A poorly understood feature of the tauopathies is their very different clinical presentations. The frontotemporal lobar degeneration (FTLD) spectrum is dominated by motor and emotional/psychiatric ...abnormalities, whereas cognitive and memory deficits are prominent in the early stages of Alzheimer’s disease (AD). We report two novel mouse models overexpressing different human tau protein constructs. One is a full-length tau carrying a double mutation P301S/G335D; line 66 (L66) and the second is a truncated 3-repeat tau fragment which constitutes the bulk of the PHF core in AD corresponding to residues 296–390 fused with a signal sequence targeting it to the endoplasmic reticulum membrane (line 1; L1). L66 has abundant tau pathology widely distributed throughout the brain, with particularly high counts of affected neurons in hippocampus and entorhinal cortex. The pathology is neuroanatomically static and declines with age. Behaviourally, the model is devoid of a higher cognitive phenotype but presents with sensorimotor impairments and motor learning phenotypes. L1 displays a much weaker histopathological phenotype, but shows evidence of neuroanatomical spread and amplification with age that resembles the Braak staging of AD. Behaviourally, the model has minimal motor deficits but shows severe cognitive impairments affecting particularly the rodent equivalent of episodic memory which progresses with advancing age. In both models, tau aggregation can be dissociated from abnormal phosphorylation. The two models make possible the demonstration of two distinct but nevertheless convergent pathways of tau molecular pathogenesis. L1 appears to be useful for modelling the cognitive impairment of AD, whereas L66 appears to be more useful for modelling the motor features of the FTLD spectrum. Differences in clinical presentation of AD-like and FTLD syndromes are therefore likely to be inherent to the respective underlying tauopathy, and are not dependent on presence or absence of concomitant APP pathology.
An uncommon clinical entity mimicking necrotizing enterocolitis (NEC) is allergic enterocolitis secondary to cow's milk protein allergy. Although milk protein allergy is the most common food allergy ...among infants and young children, the incidence and prevalence of this disease entity presenting as enterocolitis in neonates is not well documented. We report this case of milk protein-associated allergic enterocolitis to highlight the unusual recurrent presentation as NEC, (with recurrent pneumatosis, bloody stools) managed successfully with modification of milk formula.
The genus Micromonas comprises distinct genetic clades that commonly dominate eukaryotic phytoplankton community from polar to tropical waters. This phytoplankter is also recurrently infected by ...abundant and genetically diverse prasinoviruses. Here we report on the interplay between prasinoviruses and Micromonas with regard to the genetic diversity of this host. For 1 year, we monitored the abundance of three clades of Micromonas and their viruses in the Western English Channel, both in the environment using clade‐specific probes and flow cytometry, and in the laboratory using clonal strains of Micromonas clades to assay for their viruses by plaque‐forming units. We showed that the seasonal fluctuations of Micromonas clades were closely mirrored by the abundance of their corresponding viruses, indicating that the members of Micromonas genus are susceptible to viral infection, regardless of their genetic affiliation. The characterization of 45 viral isolates revealed that Micromonas clades are attacked by specific virus populations, which exhibit distinctive clade specificity, life strategies and genetic diversity. However, some viruses can also cross‐infect different host clades, suggesting a mechanism of horizontal gene transfer within the Micromonas genus. This study provides novel insights into the impact of viral infection for the ecology and evolution of the prominent phytoplankter Micromonas.
Upon antigen recognition, T cells form either static (synapses) or migratory (kinapses) contacts with antigen-presenting cells. Addressing whether synapses and kinapses result in distinct T cell ...receptor (TCR) signals has been hampered by the inability to simultaneously assess T cell phenotype and behavior. Here, we introduced dynamic in situ cytometry (DISC), a combination of intravital multiphoton imaging and flow cytometry-like phenotypic analysis. Taking advantage of CD62L shedding as a marker of early TCR signaling, we examined how T cells sense TCR ligands of varying affinities in vivo. We uncovered three modes of antigen recognition: synapses with the strongest TCR signals, kinapses with robust signaling, and kinapses with weak signaling. As illustrated here, the DISC approach should provide unique opportunities to link immune cell behavior to phenotype and function in vivo.
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► TCR ligand affinity controls synapse versus kinapse formation ► TCR signaling can be tracked in vivo in conjunction with cell behavior by DISC ► Distinct thresholds of pMHC affinity regulate T cell dynamics and TCR signaling ► Kinapses can result in robust or weak TCR signaling in vivo
Stress maneuvers inspired by arthroscopic techniques have been previously studied for MRA of shoulder, hip, knee and wrist. Axial traction in MRA of the wrist is advantageous to study intrinsic ...ligaments and cartilage, but seems useless to assess tendons or nerves disorders. Based on our experience and a well-chosen iconography, we would like to emphasize the contribution of axial traction in MRA of wrist disorders.
Population growth in the Southeast has driven withdrawals for municipal water beyond the limits of local supplies. With few options left for development of virgin sources, a number of urban areas are ...looking toward demand management and additional supplies by reallocating storage in reservoirs that were built primarily or in part for hydropower. Hydropower has become a lesser part of the mix of energy sources, and the question arises as to value of water for that purpose relative to its value for municipal use. Three cases are used to examine the issue. Effects of withdrawal for municipal water supply on output of electric energy are estimated. Benefits of foregone energy are evaluated using the least cost alternative for replacement, and benefits for municipal water are estimated using costs for development of new sources. Benefits for use as municipal water are found to be considerably higher than benefits for hydroelectric energy at existing prices, even higher than the least cost alternative for replacement. Given the spatial distribution of the cases, that finding would appear to hold in general across the region.
Tendinopathy is a frequent and ubiquitous disease developing early disorganized collagen fibers with neo-angiogenesis on histology. Peritendinous injection of corticosteroid is the commonly accepted ...strategy despite the absence of inflammation in tendinopathy. Platelet-rich plasma (PRP) might be a useful strategy to rapidly accelerate healing of the tendinopathy but there is a lack ok knowledge about the amount of PRP to be injected and the opportunity of a second injection in case of partial pain relief. The aim of our study was to assess the potential therapeutic effect of early second PRP intra-tendinous to treat persistent painful tendon tear and tendinosis in a long-term follow-up by ultrasonography (US) and clinical data in case of incomplete efficiency of first PRP treatment injection.
Twenty-four consecutive patients referred for US treatment of tendon tear or tendinosis (T+) were included retrospectively. All had previously received a single intra-tendinous injection of PRP under US guidance (PRPT+) and benefited of a second PRP injection (PRPT2+) under US guidance in order to treat persistent painful. US and clinical data were collected for each anatomic compartment for upper and lower limbs before treatment (D0), 6weeks (W6) after first treatment, 6weeks (W12) after second treatment and until 32-month follow-up. We used Mac Nemar test and regression model to compare US and clinical data.
The residual US size of lesions was not significantly lower at W12 after PRPT2+ as compared to W6 (P=0.86 in upper and P=NS in lower member) independently of age (P=0.22), gender (P=0.97) and kind of tendinopathy (P=NS). Quick dash test values and WOMAC values were not significantly lower in PRPT+ at W12 (average: 21.5months) as compared to W6 (P>0.66) and long-term follow-up (P>0.75) independently of age (P=0.39), gender (P=0.63) and kind of tendinopathy (P=NS). Nevertheless, comparison between D0 and long-term follow-up (LTF) functionnal score was statistically significant (p<0.001 in upper and lower member).
Our study suggests that second early intra-tendinous PRP injection under US guidance does not permit rapid decrease of tendinopathy area in US, nor does it quickly improve clinical pain and functional data in case of incomplete efficiency of first PRP injection. However, in long-term follow-up, patients improved their ability to mobilize pathologic tendons.
Background: Plasma B‐type natriuretic peptide (BNP) assay is recommended as a diagnostic tool in emergency‐room patients with acute dyspnea. In the intensive care unit (ICU), the utility of this ...peptide remains a matter of debate. The objectives of this study were to determine whether cut‐off values for BNP and N‐terminal‐proBNP (NT‐proBNP) reliably diagnosed right and/or left ventricular failure in patients with shock or acute respiratory distress, and whether non‐cardiac factors led to an increase in these markers.
Methods: Plasma BNP and NT‐proBNP levels and echocardiographic parameters of cardiac dysfunction were determined in 41 patients within 24 h of the onset of shock or acute respiratory distress.
Results: BNP and NT‐proBNP levels were higher in the 25 patients with heart failure than in the other 16 patients: 491.7 ± 418 pg/ml vs. 144.3 ± 128 pg/ml and 2874.4 ± 2929 pg/ml vs. 762.7 ± 1128 pg/ml, respectively (P < 0.05). In the diagnosis of cardiac dysfunction, BNP > 221 pg/ml and NT‐proBNP > 443 pg/ml had 68% and 84% sensitivity, respectively, and 88% and 75% specificity, respectively, but there was a substantial overlap of BNP and NT‐proBNP values between patients with and without heart failure. BNP and NT‐proBNP were elevated, but not significantly, in patients with isolated right ventricular dysfunction. Patients with renal dysfunction and normal heart function had significantly higher levels of BNP (258.6 ± 144 pg/ml vs. 92.4 ± 84 pg/ml) and NT‐proBNP (2049 ± 1320 pg/ml vs. 118 ± 104 pg/ml) than patients without renal dysfunction.
Conclusion: Both BNP and NT‐proBNP can help in the diagnosis of cardiac dysfunction in ICU patients, but cannot replace echocardiography. An elevated BNP or NT‐proBNP level merely indicates the presence of a ‘cardiorenal distress’ and should prompt further investigation.
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