Notes

Acrobatic squirrels learn how to jump and also find tree limbs with no plummeting.
The risk for adverse immune-mediated reactions, associated with the administration of certain immunotherapeutic agents, should be mitigated early. Infusion reactions to monoclonal antibodies and other biopharmaceuticals, known as cytokine release syndrome, can arise from the release of cytokines via the drug target cell, as well as the recruitment of immune effector cells. While several in vitro cytokine release assays have been proposed up to date, many of them lack important blood components, required for this response to occur. The blood endothelial cell chamber model is an in vitro assay, composed of freshly drawn human whole blood and cultured human primary endothelial cells. Herein, its potential to study the compatibility of immunotherapeutics with the human immune system was studied by evaluating three commercially available monoclonal antibodies and bacterial endotoxin lipopolysaccharide. We demonstrate that the anti-CD28 antibody TGN1412 displayed an adaptive cytokine release profile and a distinct IL-2 response, accompanied with increased CD3+ cell recruitment. Alemtuzumab exhibited a clear cytokine response with a mixed adaptive/innate source (IFNγ, TNFα and IL-6). Its immunosuppressive nature is observed in depleted CD3+ cells. Cetuximab, associated with low infusion reactions, showed a very low or absent stimulatory effect on proinflammatory cytokines. In contrast, bacterial endotoxin demonstrated a clear innate cytokine response, defined by TNFα, IL-6 and IL-1β release, accompanied with a strong recruitment of CD14+CD16+ cells. Therefore, the blood endothelial cell chamber model is presented as a valuable in vitro tool to investigate therapeutic monoclonal antibodies with respect to cytokine release and vascular immune cell recruitment.
Papillary thyroid cancer (PTC) is heterogeneous cancer with many different immune cells involved in its pathogenesis. L Antigen Family Member 3 (LAGE3) is an ESO/LAGE gene family member that has not been extensively studied in PTC.

Comprehensive bioinformatics analyses of LAGE3 were based on The Cancer Genome Atlas, Gene Expression Omnibus, and Genomics of Drug Sensitivity in Cancer (GDSC) databases. We also performed RNA-sequencing on 78 paired samples from local PTC patients.

We observed that LAGE3 was significantly up-regulated in most solid tumor types, including PTC compared with corresponding normal tissues. The high level of LAGE3 was also significantly associated with advanced malignancy. LAGE3 expression was significantly associated with cancer-related pathways, biochemical metabolism, and immune-related terms. Further, tumor microenvironment analysis indicated LAGE3 was positively correlated with different immune cells infiltrating levels and the activity of different steps of the cancer-immunity cycle. Analyses based on the GDSC database revealed that low levels of LAGE3 might be resistant to WZ3105, I-BET-762, and PHA-793887. In addition, the experimental results validated that knocking down LAGE3 could affect proliferation, migration, and invasion in the PTC cell lines.

This study discloses that LAGE3 plays an oncogenic and cancer-immunological role, also providing novel PTC biological and clinical implications.
This study discloses that LAGE3 plays an oncogenic and cancer-immunological role, also providing novel PTC biological and clinical implications.
Bipolar disorder (BD) might be associated in disturbances in brain networks. However, little is known about the abnormalities in structural brain connectivity which might be related to vulnerability to BD and predictive of the emergence of manic symptoms. No previous study has investigated the effect of subthreshold syndromes on structural dysconnectivity in offspring of parents with BD (BDoff).

We investigated diffusion weighted images of 70 BDoff and 48 healthy controls (HC). click here Nineteen of the 70 BDoff had presented with subthreshold syndromes indicating a clinical high-risk (BDoff-CHR) and other 51 BDoff had no such history (BDoff-non-CHR). Global and regional network properties, rich club organization and inter-regional connectivity in BDoff and healthy controls were investigated using graph analytical methods and network-based-statistics (NBS).

Global properties of WM networks appeared to be intact in BDoff-CHR and BDoff-non-CHR. link2 However, decreased regional connectivity in right occipito-parietal areloping BD who had experienced subthreshold mood symptoms.
Investigate the relation between age, baseline neurological and functional status, and survival after out-of-hospital cardiac arrest (OHCA).

Data analysis from the Jerusalem District Resuscitation Study. Patients >80 years and those 18-80 years with OHCA from 4/2005-12/2010 were compared.

survival at four time points; secondary outcomes neurological and functional status at hospital discharge, and relationship between survival, age and pre-arrest activities of daily living (ADL) and Cerebral Performance Category (CPC) scores (higher scores indicate worse function in both).

3,211 patients (1,259 >80 years, 1952 aged 18-80) with median follow-up 5.9 years (range 0.1-11.1 years) were included. Survival was better for younger patients at all four time points, including 7.8% versus 2.5% at hospital discharge, 4.6% versus 0.2% at late follow-up. Functional status at discharge was also better, 4.8±5.4 versus 9.0±4.7, p<0.001, and more young patients had CPC1/2, 60.7% versus 32.2%, p=0.004. Older patients who survived to emergency department admission had increased mortality per year of age (2.6%, hazard ratio [HR] 1.026, 95% confidence interval [CI] 1.006-1.048 versus 1.7%, HR 1.017, 95% CI 1.010-1.025), per point in pre-arrest ADL (3.0%, HR 1.030, 95% CI 1.007-1.054 versus 5.8%, HR 1.058, 95% CI 1.036-1.080), and per point in pre-arrest CPC (24%, HR 1.242, 95% CI 1.097-1.406 versus 37%, HR 1.370 95% CI 1.232-1.524).

Patient independence before arrest may be a more crucial determinant of resuscitation outcome than older age alone. Discussion of end-of-life preferences is particularly important for older individuals with functional and cognitive decline.
Patient independence before arrest may be a more crucial determinant of resuscitation outcome than older age alone. Discussion of end-of-life preferences is particularly important for older individuals with functional and cognitive decline.
Previous studies of perceived ageism among older people have focused on younger age groups with the respondents' mean age far below 80.

To explore the perceptions of poor societal treatment of older people among home-dwelling people aged 75-100+ and how their perceptions are associated with demographic characteristics, health, functioning, and wellbeing.

In the Helsinki Aging Study, a random sample of 2,917 home-dwelling people aged 75-104 received a postal questionnaire inquiring about their health, wellbeing and experiences. The response rate was 74%. We asked 'How in your opinion are older people treated in Finland?' (well/moderately/poorly) and categorized the respondents according to their responses. A multivariable forward stepwise ordered logistic regression model was used to determine the independent associations of the variables on the ordinal level of perceptions of treatment.

Of the participants, 1,653 responded to the index item. Of these, only 13% thought that older people are treated well in society, and 66% and 21% were of the opinion that older people are treated moderately or poorly in society, respectively. Perceived poor societal treatment was more common among women, the younger respondents, and those with lower incomes, as well as family caregivers and those with lower self-rated health and lower psychological wellbeing. Those who were able to walk outside unassisted and those with a regular hobby perceived poor societal treatment more often.

Several demographic factors, self-rated health, psychological wellbeing and better functioning were associated with perceptions of poor treatment among the oldest-old.
Several demographic factors, self-rated health, psychological wellbeing and better functioning were associated with perceptions of poor treatment among the oldest-old.
To find possible predictive factors to predict the failure of conservative treatment of non-tubal ectopic pregnancy. For that purpose, we assessed the rate of failure, complications and need for additional interventions of the different primary treatment regimens in non-tubal ectopic pregnancies that occurred in our center.

Retrospective single-center study conducted at Hospital Clínic of Barcelona (Spain). Conservative treatment regimens included medical (systemic single or multiple dose methotrexate; ultrasound-guided intrasaccular injection of methotrexate or chloride potassium; surgical (oophorectomy in case of ovarian ectopic pregnancy, surgical curettage). The main outcome measures were success of primary treatment and the need for additional interventions. The secondary outcomes were success rate of conservative treatment, incidence of complications, days to discharge from the hospital, days until negative β-hCG, days until complete resolution of the process. Possible predictor factors for primary may be used as predictive factors of failure of conservative treatment.
To describe the proportions of asymptomatic, mild and severe diseases in infected pregnant women admitted for delivery. To compare maternal, fetal and neonatal outcomes of SARS-CoV-2 infected pregnant women with those of non-infected patients.

Through an universal PCR testing for SARS-COV-2 at admission (not symptoms-based), this prospective cohort study enrolled all pregnant women admitted for delivery between 16th of June and the 16th of August 2020 in the West French Guiana Hospital Center.

507 pregnant women were included during the study period, of which 137 (27 %) were infected with SARS-COV-2. On admission, only 34/137 (24.8 %) of these patients presented with clinical symptoms. Among asymptomatic women, 16 /103 (15 %) became symptomatic after diagnosis. Throughout the delivery hospitalization and follow-up, 87/137 (63.5 %) remained always asymptomatic, 45/137 (32.8 %) developed a mild COVID-19 and 5/137 (3.6 %) developed a severe infection. link3 SARS-CoV-2 infected patients were more likely to have pen admitted for delivery and diagnosed with a SARS-COV-2 infection through an universal screening were symptomatic in only a quarter of cases. Their risks of post-partum hemorrhage, transfusion and admission to ICU were higher than those of uninfected patients. They also presented a higher risk of intra-uterine fetal demise. There were no other differences in maternal, obstetrical or neonatal outcomes.The antimicrobial and therapeutic efficacy of bacteriophages is currently limited, mostly due to rapid emergence of phage-resistance and the inability of most phage isolates to bind and infect a broad range of clinical strains. Here, we discuss how phage therapy can be improved through recent advances in genetic engineering. First, we outline how receptor-binding proteins and their relevant structural domains are engineered to redirect phage specificity and to avoid resistance. Next, we summarize how phages are reprogrammed as prokaryotic gene therapy vectors that deliver antimicrobial 'payload' proteins, such as sequence-specific nucleases, to target defined cells within complex microbiomes. Finally, we delineate big data- and novel artificial intelligence-driven approaches that may guide the design of improved synthetic phage in the future.
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