Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019).

OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

COVID-19: relationship between atmospheric temperature and daily new cases growth rate.

Purpose: The novel coronavirus (severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)) first appeared in Wuhan, China, in December 2019, and rapidly spread across the globe. Since most respiratory viruses are known to show a seasonal pattern of infection, it has been hypothesised that SARS-CoV-2 may be seasonally dependent as well. The present study looks at a possible effect of atmospheric temperature, which is one of the suspected factors influencing seasonality, on the evolution of the pandemic. Basic procedures: Since confirming a seasonal pattern would take several more months of observation, we conducted an innovative day-to-day micro-correlation analysis of nine outbreak locations, across four continents and both hemispheres, in order to examine a possible relationship between atmospheric temperature (used as a proxy for seasonality) and outbreak progression. Main findings: There was a negative correlation between atmospheric temperature variations and daily new cases growth rates, in all nine outbreaks, with a median lag of 10 days. Principal conclusions: The results presented here suggest that high temperatures might dampen SARS-CoV-2 propagation, while lower temperatures might increase its transmission. Our hypothesis is that this could support a potential effect of atmospheric temperature on coronavirus disease progression, and potentially a seasonal pattern for this virus, with a peak in the cold season and rarer occurrences in the summer. This could guide government policy in both the Northern and Southern hemispheres for the months to come.

Differential expression of coxsackievirus and adenovirus receptor in endomyocardial tissue of patients with myocarditis.

Recent studies demonstrated that the expression of coxsackievirus and adenovirus receptor (CAR) is implicated in the pathophysiology of myocarditis. The aim of the present study was to assess the association between active and borderline myocarditis and CAR expression in endomyocardial tissues, and analyze the association between CAR expression and treatment response. An analytic, cross­sectional, retrospective study was performed in 26 patients with myocarditis and 10 control subjects without heart disease. Myocardial biopsies were obtained and CAR transcription was measured by reverse transcription­quantitative polymerase chain reaction analysis. The association between CAR mRNA levels and the response to immunosuppressive or conventional therapy (treatment responders, n=17; non­responders, n=9) or with the type of histological myocarditis (active myocarditis, n=16; borderline myocarditis, n=10) was analyzed. CAR transcription levels were significantly lower (P=0.012) in patients with myocarditis compared with controls, and a significant decrease was observed (P=0.023) in CAR mRNA levels among patients with borderline myocarditis compared with the no myocarditis group. Patients responding to therapy exhibited higher CAR mRNA levels (P=0.036) compared with patients not responding to treatment, as evaluated based on clinical and echocardiographic criteria (immunosuppressive therapy, n=8; conventional therapy, n=1). Myocarditis in non­responders was associated with fewer clinical manifestations and lower CAR mRNA levels. A significant difference was only found regarding the use of oral steroids in patients with active myocarditis who responded to treatment (P=0.02), with no difference in borderline myocarditis. In conclusion, the transcriptional level of CAR is low in the endomyocardial tissue of patients with myocarditis, and it is lower in borderline myocarditis and in non­responder patients. These findings may enable early identification of patients who may benefit from treatment and timely determination of prognosis.

LifePrint: a novel k-tuple distance method for construction of phylogenetic trees.

PURPOSE: Here we describe LifePrint, a sequence alignment-independent k-tuple distance method to estimate relatedness between complete genomes. METHODS: We designed a representative sample of all possible DNA tuples of length 9 (9-tuples). The final sample comprises 1878 tuples (called the LifePrint set of 9-tuples; LPS9) that are distinct from each other by at least two internal and noncontiguous nucleotide differences. For validation of our k-tuple distance method, we analyzed several real and simulated viroid genomes. Using different distance metrics, we scrutinized diverse viroid genomes to estimate the k-tuple distances between these genomic sequences. Then we used the estimated genomic k-tuple distances to construct phylogenetic trees using the neighbor-joining algorithm. A comparison of the accuracy of LPS9 and the previously reported 5-tuple method was made using symmetric differences between the trees estimated from each method and a simulated "true" phylogenetic tree. RESULTS: The identified optimal search scheme for LPS9 allows only up to two nucleotide differences between each 9-tuple and the scrutinized genome. Similarity search results of simulated viroid genomes indicate that, in most cases, LPS9 is able to detect single-base substitutions between genomes efficiently. Analysis of simulated genomic variants with a high proportion of base substitutions indicates that LPS9 is able to discern relationships between genomic variants with up to 40% of nucleotide substitution. CONCLUSION: Our LPS9 method generates more accurate phylogenetic reconstructions than the previously proposed 5-tuples strategy. LPS9-reconstructed trees show higher bootstrap proportion values than distance trees derived from the 5-tuple method.

Effects of income and wealth on GHQ depression and poor self rated health in white collar women and men in the Whitehall II study.

STUDY OBJECTIVE: To determine whether measures of income and wealth are associated with poor self rated health and GHQ depression. DESIGN: Whitehall II study of London based civil servants re-interviewed between 1997-1999; 7162 participants. MAIN RESULTS: A twofold age adjusted difference in morbidity was observed between the top and bottom of the personal income hierarchy for both sexes. For household income and particularly for wealth these associations are stronger. After adjusting for health at baseline the associations between personal income and both health outcomes are reduced by about 40%-60%. For household income the attenuation is somewhat smaller and for wealth is about 30%. Adjusting for other sociodemographic factors leads to further attenuation of the effects. CONCLUSIONS: The associations between income, particularly personal income, and morbidity can be largely accounted for by pre-existing health and other measures of social position. The strong independent association between household wealth-a measure of income earned over decades and across generations-and morbidity are likely to be related to a set of early and current material and psychosocial benefits.

[Semi-automatic acquisition and processing of mechanocardiograms]. / Acquisition et traitement semi-automatique des mécanocardiogrammes.

Like echocardiography and radio-isotope techniques, mechanocardiography has a special place in the evaluation of left ventricular function in heart disease. This recognized technique can be easily performed by clinicians or pharmacologists or in aerospace medicine. A programme has been developed from micro-processor material (HP 9845 S - SP 9835 - HP 6940 B multi-programmer) already in use in the department. After sampling at 700 Hz and quantification, this programme can reproduce a complete mechanocardiographic tracing consisting of ECG, phonocardiogram, carotidogram and apexogram . The first derivative of the apex cardiogram is calculated numerically and visualized. The characteristic events of the systolic phase of the apex cardiogram are then checked manually or semi-automatically by the operator. After confirmation, the calculations are performed and are edited with the tracings. This system eliminates the need for a recorder, as the tracings can be stored on cassette or diskette and recalled later for statistical analysis. These programmes make the interpretation of the mechanocardiographic tracings considerably simpler and faster.

Comparison of geometrical models for evaluating left ventricular wall motion from cineangiograms.

Regional wall motion of the left ventricle (LV) has been analyzed from contrast ventriculograms by using 4 methods based on different geometrical frameworks. Two of them utilize moving internal reference systems, the center of mass (CMM) and the long axis (LAM) methods; the two other ones use fixed external reference systems, the area-based (ABM) and the Palo Alto (PAM) methods. The techniques were applied on a set of 81 patients: 42 were normal and composed the group I; 22 had a single vessel obstruction greater than 75% of the left anterior descending coronary artery (group II) with old necrosis or active ischemia of the LV anterior wall; 17 had a single vessel obstruction greater than 75% of the right coronary artery (group III) with old necrosis or active ischemia of the LV inferior wall. ABM and PAM showed the highest specificities and sensitivities on the studied sample. Therefore, we believe these two methods, of the techniques tested, are the best to quantitate wall motion from cineangiograms.

Subcostal M-mode computerised echocardiography. An alternative or complementary approach to parasternal echocardiography?

Subcostal M-mode echocardiography has been suggested as a method for assessment of left ventricular size and function. Parasternal and subcostal measurements (direct and derived) of left ventricular function were compared in 30 healthy young subjects. We calculated instantaneous left ventricular diameter and wall thickness every 10 ms for both the subcostal and parasternal approaches using a computer program for echocardiographic digitisation and compensation. All variables were filtered to calculate instantaneous first derivative (velocity) and logarithmic derivative (normalised velocity). The program provided normal values for computerised variables of left ventricular function from the subcostal approach. It was found that there was no identity and no correlation or a poor one between subcostal and parasternal left ventricular internal diameters and volumes. The parietal wall thickness was significantly greater using the subcostal approach, and the comparative velocities study showed striking variations between the two approaches, especially in diastole, where the peak lateral wall thinning rate was 20% lower than the posterior thinning rate. We conclude that for a normal and young population, the subcostal and standard parasternal data cannot be used interchangeably for precise studies of left ventricular function. The subcostal approach, however, provides useful complementary information about lateral wall motion.

Production of S-Methylthioacetate by Brevibacterium linens.

Volatile sulfur compounds production by eight strains of Brevibacterium linens isolated from cheeses was demonstrated: methanethiol, dimethyldisulfide, and 2,3,4-trithiapentane. Four of these strains also produced S-methylthioacetate, an important aroma component of smear-coated cheeses. It is the first demonstrated microbiological production of a thioester.