Force, speed, and oxygen consumption in Thoroughbred and draft horses

Thoroughbred (TB) and draft horses (DH) havelong been selected for tasks of very different intensities andforce-speed relationships. To study their adaptations, we measuredO₂ consumption and related variables in three TB and four DH during progressive exercise tests ona level treadmill. The horses exerted a draft force of 0, 5, 10, 15, or20% of their body weight at speeds that increased by 2 m/s every 3 minuntil they could not maintain that speed. We found that TB could exertthe same draft forces as DH and, at each force, TB achieved about twicethe speed, twice the external power, and twice theO₂ consumption as DH; thus the twobreeds had the same gross efficiencies. We also found maximalO₂ consumption of TB to be abouttwice that of DH (134 vs. 72 ml · kg¹ · min¹,respectively), suggesting adaptations to high-intensity exercise. Peakefficiency was reached at lower speeds in DH than in TB, suggestingadaptations to high-force, low-speed exercise. These differencesbetween TB and DH in force-speed and aerobic capacities and in speedfor peak efficiency likely reflect different contraction velocities inlocomotor muscles.

     

Intérêt de la tomographie par émission de positons (TEP) au 18FDG dans le suivi des patients traités pour carcinome épidermoïde des voies aérodigestives supérieures (VADS) en rémission clinique

IntroductionPosttreatment follow-up of head and neck squamous cell carcinoma (HNSCC) recurrence is a diagnostic challenge. Tissue distortions from radiation and surgery can obscure early detection of recurrence by conventional follow-up approaches such as physical examination (PE), computed tomography, and magnetic resonance imaging. A number of studies have shown that ¹⁸Fluoro-fluorodeoxyglucose (¹⁸FDG) Positron emission tomography (PET) may be an effective technique for the detection of persistent, recurrent, and distant metastatic HNSCC after treatment. The aim of this prospective study was to determine the benefits (sensitivity, specificity, predictive values, and accuracy) of ¹⁸FDG PET using hybrid PET–Computed tomography system (PET/CT) in the detection of HNSCC subclinical locoregional recurrence and distant metastases, in patients 12 months after curative treatment with a negative conventional follow up.Materials and MethodsNinety-one patients cured from head and neck squamous cell carcinoma (HNSCC) without any clinical element for recurrence were included. Whole-body ¹⁸FDG PET/CT examination was performed 11.6 ± 4.4 months after the end of the treatment. The gold standard was histopathology or 6 months imaging follow-up.ResultsThe whole-body ¹⁸FDG PET/CT of the 91 patients in this study consisted of 52 negative and 39 positive results. Nine of these patients who exhibited abnormal ¹⁸FDG uptake in head and neck area did not have subsequently proven recurrent HNSCC (false positive). Thirty had proven recurrence (true positive). All 52 patients with negative readings of ¹⁸FDG PET/CT remained free of disease at 6 months (true negative). The sensitivity and specificity of ¹⁸FDG PET/CT in this study for the diagnosis of HNSCC recurrence were 100% (30/30) and 85% (52/61) respectively. The positive predictive value was 77% (30/39). The negative predictive value was 100% (52/52). The overall accuracy was 90% (82/91).ConclusionThe results of our study confirm the high effectiveness of ¹⁸FDG PET/CT in assessment of HNSCC recurrence. It suggests that this modality is more accurate than conventional follow-up PE alone in the assessment of patient recurrence after previous curative treatment for HNSCC. Therefore, a PET study could be systematically proposed at 12 months after the end of the treatment.     

CFTR transgene expression in primary DeltaF508 epithelial cell cultures from human nasal polyps following gene transfer with cationic phosphonolipids

Cystic fibrosis (CF) is the most common autosomal lethal recessive disorder in the Caucasian population. The major cause of mortality is lung disease, owing to the failure of a functional protein from the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Today, even though the knowledge about the CFTR genomic is extensive, no efficient treatment has been developed yet. In this context, gene therapy represents a potential important advance on condition that it could develop efficient and safe transfection agents. Even though viral vectors have been used in most clinical trials owing to their high transfection efficiency, random integration and immunogenicity are still critical side effects. Consequently, all of these drawbacks brought forth the development of nonviral transfection systems. Although they engender few toxicity and immunogenicity problems, their low transfection efficiency is a hurdle that must be overcome. Over the past decade, we have developed an original family of monocationic lipids, cationic phosphonolipids, whose efficiency has been previously demonstrated both in vitro and in vivo. In this report, we observe that a new cationic phosphonolipid (KLN 30) can lead to the restoration of the CFTR protein following the ex vivo transfection of epithelial cells issuing from a F508 homozygous patient. The transgene expression and the cytotoxicity correlate with the charge ratio of the lipoplex. A kinetic study was performed, and a luminescent signal was detected until 35 d after transfection.     

High N-Terminal Pro-B-Type Natriuretic Peptide Levels Are Associated with Reduced Heart Rate Variability in Acute Myocardial Infarction

Aim

We investigated the relationships between the autonomic nervous system, as assessed by heart rate variability (HRV) and levels of N-terminal Pro-B-type Natriuretic Peptide (Nt-proBNP) in patients with acute myocardial infarction (MI).

Methods and Results

The mean of standard deviation of RR intervals (SDNN), the percentage of RR intervals with >50 ms variation (pNN50), square root of mean squared differences of successive RR intervals (rMSSD), and frequency domain parameters (total power (TP), high frequency and low frequency power ratio (LF/HF)) were assessed by 24 h Holter ECG monitoring. 1018 consecutive patients admitted <24 h for an acute MI were included. Plasma Nt-proBNP (Elecsys, Roche) was measured from blood samples taken on admission. The median (IQR) Nt-proBNP level was 681(159–2432) pmol/L. Patients with the highest quartile of Nt-proBNP were older, with higher rate of risk factors and lower ejection fraction. The highest Nt-proBNP quartile group had the lowest SDNN, LF/HF and total power but similar pNN50 and rMSSD levels. Nt-proBNP levels correlated negatively with SDNN (r = −0.19, p<0.001), LF/HF (r = −0.37, p<0.001), and LF (r = −0.29, p<0.001) but not HF (r = −0.043, p = 0.172). Multiple regression analysis showed that plasma propeptide levels remained predictive of LF/HF (B(SE) = −0.065(0.015), p<0.001)), even after adjustment for confounders.

Conclusions

In conclusion, our population-based study highlights the importance of Nt-proBNP levels to predict decreased HRV after acute MI.     

Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study

Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs]) whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs); instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.     

Durability and Effectiveness of Maraviroc-Containing Regimens in HIV-1-Infected Individuals with Virological Failure in Routine Clinical Practice

Introduction

Limited data are available on the durability and effectiveness of maraviroc in routine clinical practice. We assessed the durability of maraviroc-containing regimens during a 30-month period, as well as their immunovirological and clinical efficacy, according to viral tropism in treatment-experienced individuals with viral load (VL) >50 copies/ml in the French Hospital Database on HIV.

Methods

Virological success was defined as VL<50 copies/ml, immunological success as a confirmed increase of at least 100 CD4 cells/mm³ measured twice at least one month apart, and clinical failure as hospitalization for a non-AIDS event, an AIDS event, or death. Multivariable Cox regression models adjusted for potential confounders were used to assess the influence of viral tropism on durability, the immunovirological responses, and clinical outcome.

Results

356 individuals started maraviroc with VL>50 copies/ml of whom 223 harbored R5 viruses, 44 non-R5 viruses and 89 viruses of unknown tropism. Individuals with non-R5 viruses were more likely than individuals with R5 viruses to discontinue maraviroc (75% vs 34%, p<0.0001). At 30 months, the estimated rates of virological and immunological success were respectively 89% and 51% in individuals with R5 viruses and 48% and 23% in individuals with non-R5 viruses. In multivariable analysis, non-R5 viruses were associated with a lower likelihood of both virological success (hazard ratio (HR): 0.42; 95% confidence interval (CI), 0.25–0.70) and immunological success (HR: 0.37; 95% CI, 0.18–0.77). No difference in clinical outcome was found between individuals with R5 and non-R5 viruses. The effectiveness of maraviroc-containing regimens in individuals with unknown viral tropism was not significantly different from that in individuals with R5 viruses. A limitation of the study is the absence of genotypic susceptibility score.

Conclusion

In this observational study, maraviroc-containing regimens yielded high rates of viral suppression and immunological responses in individuals with R5 viruses in whom prior regimens had failed.     

CFTR transgene expression in primary ΔF508 epithelial cell cultures from human nasal polyps following gene transfer with cationic phosphonolipids

Cystic fibrosis (CF) is the most common autosomal lethal recessive disorder in the Caucasian population. The major cause of mortality is lung disease, owing to the failure of a functional protein from the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Today, even though the knowledge about the CFTR genomic is extensive, no efficient treatment has been developed yet. In this context, gene therapy represents a potential important advance on condition that it could develop efficient and safe transfection agents. Even though viral vectors have been used in most clinical trials owing to their high transfection efficiency, random integration and immunogenicity are still critical side effects. Consequently, all of these drawbacks brought forth the development of nonviral transfection systems. Although they engender few toxicity and immunogenicity problems, their low transfection efficiency is a hurdle that must be overcome. Over the past decade, we have developed an original family of monocationic lipids, cationic phosphonolipids, whose efficiency has been previously demonstrated both in vitro and in vivo. In this report, we observe that a new cationic phosphonolipid (KLN 30) can lead to the restoration of the CFTR protein following the ex vivo transfection of epithelial cells issuing from a ΔF508 homozygous patient. The transgene expression and the cytotoxicity correlate with the charge ratio of the lipoplex. A kinetic study was performed, and a luminescent signal was detected until 35 d after transfection.     

Phylogenetic and functional analysis of Aspergillus fumigatus MGTC, a fungal protein homologous to a bacterial virulence factor

MgtC is important for the survival of several bacterial pathogens in macrophages and for growth under magnesium limitation. Among eukaryotes, a gene homologous to mgtC was found only in the pathogenic fungus Aspergillus fumigatus. Our data show that the A. fumigatus MgtC (AfuMgtC) protein does not have the same function as the bacterial MgtC proteins.