Individual adherence to mass drug administration in neglected tropical disease control: A probability model conditional on past behaviour

We present a general framework which describes the systematic (binary) scenario of individuals either taking treatment or not for any reason, over the course of mass drug administration (MDA)—which we refer to as ‘adherence’ and ‘non-adherence’. The probability models developed can be informed by observed adherence behaviour as well as employed to explore how different patterns influence the impact of MDA programmes, by the use of mathematical models of transmission and control. We demonstrate the interpretative value of the developed probability model employing a dataset collected in the TUMIKIA project, a randomised trial of deworming strategies to control soil-transmitted helminths (STH) by MDA conducted in coastal Kenya. We stratify our analysis by age and sex, although the framework which we introduce here may be readily adapted to accommodate other stratifications. Our findings include the detection of specific patterns of non-adherence in all age groups to varying extents. This is particularly apparent in men of ages 30+. We then demonstrate the use of the probability model in stochastic individual-based simulations by running two example forecasts for the elimination of STH transmission employing MDA within the TUMIKIA trial setting with different adherence patterns. This suggested a substantial reduction in the probability of elimination (between 23-43%) when comparing observed adherence patterns with an assumption of independence, with important implications for programmes. The results here demonstrate the considerable impact and utility of considering non-adherence on the success of MDA programmes to control neglected tropical diseases (NTDs).     

Improved procedure for the anion-exchange isolation of urinary organic acids

DEAE-Sephadex equilibrated in 0.5 M triethylammonium acetate is suitable for the quantitative isolation of lactonisable organic acids. Mono-, di- and tricarboxylic acids can be eluted sequentially from DEAE-Sephadex by the use of 0.5 M triethylamine, 0.5 M triethylamine—0.1 M acetic acid, and 1.5 M pyridinium acetate.     

Abnormal deoxyribose metabolites in the urine of a child with a possible new inborn error of metabolism

The urinary extract of a child investigated because of strabismus was found to contain large amounts of a compound which was identified using gas chromatography/mass spectrometry as 2-deoxyerythropentono-1,4-lactone. This lactone has not been observed previously in urinary extracts. When ion-exchange chromatography was used to isolate the organic acids from urine, the major peaks obtained by gas chromatography were shown to be 2-deoxyerythropentonic acid, 2-deoxyerythropentono-1,5-lactone and 2-deoxyerythropentono-1,4,lactone. Another abnormal metabolite, 2-deoxyribitol, was also excreted by the patient although this compound could not be detected in the urine of normal children. It is proposed that these unusual compounds accumulate in the urine of this child as a result of a defect in the catabolism of 2-deoxyribose.     

Pelodera (syn. Rhabditis) strongyloides as a cause of dermatitis – a report of 11 dogs from Finland

Background  

Pelodera (Rhabditis) strongyloides is a small saprophytic nematode that lives in decaying organic matter. On rare occasions, it can invade the mammalian skin, causing a pruritic, erythematous, alopecic and crusting dermatitis on skin sites that come into contact with the ground. Diagnosis of the disease is based on case history (a dog living outdoors on damp straw bedding) with characteristic skin lesions and on the demonstration of typical larvae in skin scrapings or biopsy. Pelodera (rhabditic) dermatitis cases have been reported mainly from Central European countries and the United States.     

Age‐dependent racemization of serine residues in a human chaperone protein

Racemization is one of the most abundant modifications in long‐lived proteins. It has been proposed that the accumulation of such modifications over time could lead to changes in tissues and ultimately human age‐related diseases. Serine is one of the main amino acids involved in racemization; however, the site of D‐Ser in any aged protein has yet to be reported. In this study, racemization of two residues, Ser 59 and Ser 62, has been demonstrated in an unstructured region of the small heat shock protein, αA‐crystallin. αA‐crystallin is also the most abundant structural protein in the human lens. D‐Ser increased linearly with age in normal lenses, until it accounted for approximately 35% of the Ser at both sites by the age of 75 years. In agreement with a possible role in human age‐related disease, levels were significantly higher in cataract lenses. It is likely that such prevalent age‐related changes contribute to the denaturation of α‐crystallin, and therefore its ability to act as a chaperone. Racemization of amino acids, such as serine, in flexible regions of long‐lived proteins, could be associated with the development of human age‐related conditions such as cataract.     

Spontaneous Cleavage of Proteins at Serine Residues

Long-lived proteins are found at several sites in the body and they undergo numerous changes as a result of prolonged exposure to physiological conditions. Truncation is a common modification and many cleavages appear to be non-enzymatic, however little is known about the processes involved. In this study we demonstrate, using synthetic peptides that incorporate the sequence of a protein that is known to cleave in older lenses, that truncation on the N-terminal side of serine residues can occur at neutral pH. A mechanism that incorporates an N,O-acyl shift, which is analogous to intein cleavage, is proposed. Such cleavages may explain the origin of abundant peptides derived from crystallins in aged human lenses.