A Neonate with Recurrent Vomiting and Generalized Hypotonia Diagnosed with a Deficiency of Dihydropyrimidine Dehydrogenase

Deficiency of dihydropyrimidine dehydrogenase (DPD) is a rare inborn error of pyrimidine metabolism. To date, only about 50 patients are known worldwide. The clinical picture is varied and is not yet fully described. Most patients are diagnosed at the age of 1–3 years. We present a patient diagnosed 8 weeks postpartum.

The female patient presented in the first 3 days after birth with agitation, choking, and vomiting. Six weeks later, the patient presented again with vomiting and insufficient weight gain. Metabolic screening of urine showed a strongly increased excretion of uracil and thymine, with no other abnormalities. This suggested a deficiency of DPD which was confirmed by enzyme analysis in peripheral blood mononucleair (PBM) cells (patient: activity <0.01 nmol/mg/h; controls: 9.9 ± 2.8 nmol/mg/h). The patient was homozygous for the IVS14+1G>A mutation.

MRI of the brain showed some cerebral atrophy; myelinization appeared normal. Many patients with DPD-deficiency suffer from convulsions and mental retardation, some show microcephaly, feeding difficulties, autism, and hypertonia. Our patient showed feeding difficulties and in the second half-year she developed slight motor retardation and generalized hypotonia. Further observation of the development of the patient may shed more light on the relationship between clinical symptoms and DPD deficiency. DPD deficiency may present in newborns with vomiting and hypotonia as the main symptoms.     

Considerations on the performance of immunocastrated male pigs

With the ongoing social pressure on surgical castration of pigs, an increase in the population of pigs that are either not castrated or immunocastrated (IC) can be expected. In both cases, their nutrient requirements and performance will differ from surgically castrated pigs and will require changes in their management. Immunocastration is performed by giving two injections of a modified gonadotrophin-releasing hormone component along with an adjuvant, at least 4 weeks apart. This paper describes the reported differences in growth performance and carcass quality of IC male pigs in comparison with boars (BO) and barrows (BA). Theoretically, IC pigs remain physiologically boar until the second vaccination and therefore, growth may be comparable with BO until this second vaccination. From then on, IC male pigs consume more feed than BO and grow faster when fed ad libitum. IC showed a faster growth and better feed conversion ratio than BA. When fed restrictedly, BO grow faster and more efficiently than BA and IC. IC have a lower carcass yield than BA and BO, whereas meat percentage is intermediate.     

Perspectives on the use of multiple sclerosis risk genes for prediction

Objective

A recent collaborative genome-wide association study replicated a large number of susceptibility loci and identified novel loci. This increase in known multiple sclerosis (MS) risk genes raises questions about clinical applicability of genotyping. In an empirical set we assessed the predictive power of typing multiple genes. Next, in a modelling study we explored current and potential predictive performance of genetic MS risk models.

Materials and Methods

Genotype data on 6 MS risk genes in 591 MS patients and 600 controls were used to investigate the predictive value of combining risk alleles. Next, the replicated and novel MS risk loci from the recent and largest international genome-wide association study were used to construct genetic risk models simulating a population of 100,000 individuals. Finally, we assessed the required numbers, frequencies, and ORs of risk SNPs for higher discriminative accuracy in the future.

Results

Individuals with 10 to 12 risk alleles had a significantly increased risk compared to individuals with the average population risk for developing MS (OR 2.76 (95% CI 2.02–3.77)). In the simulation study we showed that the area under the receiver operating characteristic curve (AUC) for a risk score based on the 6 SNPs was 0.64. The AUC increases to 0.66 using the well replicated 24 SNPs and to 0.69 when including all replicated and novel SNPs (n = 53) in the risk model. An additional 20 SNPs with allele frequency 0.30 and ORs 1.1 would be needed to increase the AUC to a slightly higher level of 0.70, and at least 50 novel variants with allele frequency 0.30 and ORs 1.4 would be needed to obtain an AUC of 0.85.

Conclusion

Although new MS risk SNPs emerge rapidly, the discriminatory ability in a clinical setting will be limited.     

Can light-saturated photosynthesis in lowland tropical forests be estimated by one light level?

Leaf-level net photosynthesis (A_n) estimates and associated photosynthetic parameters are crucial for accurately parameterizing photosynthesis models. For tropical forests, such data are poorly available and collected at variable light conditions. To avoid over- or underestimation of modeled photosynthesis, it is critical to know at which photosynthetic photon flux density (PPFD) photosynthesis becomes light-saturated. We studied the dependence of A_n on PPFD in two tropical forests in French Guiana. We estimated the light saturation range, including the lowest PPFD level at which A_sat (A_n at light saturation) is reached, as well as the PPFD range at which A_sat remained unaltered. The light saturation range was derived from photosynthetic light-response curves, and within-canopy and interspecific differences were studied. We observed wide light saturation ranges of A_n. Light saturation ranges differed among canopy heights, but a PPFD level of 1,000 µmol m⁻² s⁻¹ was common across all heights, except for pioneer trees species that did not reach light saturation below 2,000 µmol m⁻² s⁻¹. A light intensity of 1,000 µmol m⁻² s⁻¹ sufficed for measuring A_sat of climax species at our study sites, independent of the species or the canopy height. Because of the wide light saturation ranges, results from studies measuring A_sat at higher PPFD levels (for upper canopy leaves up to 1,600 µmol m⁻² s⁻¹) are comparable with studies measuring at 1,000 µmol m⁻² s⁻¹.     

Longevity Relatives Count score identifies heritable longevity carriers and suggests case improvement in genetic studies

Loci associated with longevity are likely to harbor genes coding for key players of molecular pathways involved in a lifelong decreased mortality and decreased/compressed morbidity. However, identifying such loci is challenging. One of the most plausible reasons is the uncertainty in defining long‐lived cases with the heritable longevity trait among long‐living phenocopies. To avoid phenocopies, family selection scores have been constructed, but these have not yet been adopted as state of the art in longevity research. Here, we aim to identify individuals with the heritable longevity trait by using current insights and a novel family score based on these insights. We use a unique dataset connecting living study participants to their deceased ancestors covering 37,825 persons from 1,326 five‐generational families, living between 1788 and 2019. Our main finding suggests that longevity is transmitted for at least two subsequent generations only when at least 20% of all relatives are long‐lived. This proves the importance of family data to avoid phenocopies in genetic studies.     

Exposure to the Proton Scavenger Glycine under Alkaline Conditions Induces Escherichia coli Viability Loss

Our previous work described a clear loss of Escherichia coli (E. coli) membrane integrity after incubation with glycine or its N-methylated derivatives N-methylglycine (sarcosine) and N,N-dimethylglycine (DMG), but not N,N,N-trimethylglycine (betaine), under alkaline stress conditions. The current study offers a thorough viability analysis, based on a combination of real-time physiological techniques, of E. coli exposed to glycine and its N-methylated derivatives at alkaline pH. Flow cytometry was applied to assess various physiological parameters such as membrane permeability, esterase activity, respiratory activity and membrane potential. ATP and inorganic phosphate concentrations were also determined. Membrane damage was confirmed through the measurement of nucleic acid leakage. Results further showed no loss of esterase or respiratory activity, while an instant and significant decrease in the ATP concentration occurred upon exposure to either glycine, sarcosine or DMG, but not betaine. There was a clear membrane hyperpolarization as well as a significant increase in cellular inorganic phosphate concentration. Based on these results, we suggest that the inability to sustain an adequate level of ATP combined with a decrease in membrane functionality leads to the loss of bacterial viability when exposed to the proton scavengers glycine, sarcosine and DMG at alkaline pH.     

Continuous High-resolution Microscopic Observation of Replicative Aging in Budding Yeast

We demonstrate the use of a simple microfluidic setup, in which single budding yeast cells can be tracked throughout their entire lifespan. The microfluidic chip exploits the size difference between mother and daughter cells using an array of micropads. Upon loading, cells are trapped underneath these micropads, because the distance between the micropad and cover glass is similar to the diameter of a yeast cell (3-4 μm). After the loading procedure, culture medium is continuously flushed through the chip, which not only creates a constant and defined environment throughout the entire experiment, but also flushes out the emerging daughter cells, which are not retained underneath the pads due to their smaller size. The setup retains mother cells so efficiently that in a single experiment up to 50 individual cells can be monitored in a fully automated manner for 5 days or, if necessary, longer. In addition, the excellent optical properties of the chip allow high-resolution imaging of cells during the entire aging process.     

Infections in Children Admitted with Complicated Severe Acute Malnutrition in Niger

Background

Although malnutrition affects thousands of children throughout the Sahel each year and predisposes them to infections, there is little data on the etiology of infections in these populations. We present a clinical and biological characterization of infections in hospitalized children with complicated severe acute malnutrition (SAM) in Maradi, Niger.

Methods

Children with complicated SAM hospitalized in the intensive care unit of a therapeutic feeding center, with no antibiotics in the previous 7 days, were included. A clinical examination, blood, urine and stool cultures, and chest radiography were performed systematically on admission.

Results

Among the 311 children included in the study, gastroenteritis was the most frequent clinical diagnosis on admission, followed by respiratory tract infections and malaria. Blood or urine culture was positive in 17% and 16% of cases, respectively, and 36% had abnormal chest radiography. Enterobacteria were sensitive to most antibiotics, except amoxicillin and cotrimoxazole. Twenty-nine (9%) children died, most frequently from sepsis. Clinical signs were poor indicators of infection and initial diagnoses correlated poorly with biologically or radiography-confirmed diagnoses.

Conclusions

These data confirm the high level of infections and poor correlation with clinical signs in children with complicated SAM, and provide antibiotic resistance profiles from an area with limited microbiological data. These results contribute unique data to the ongoing debate on the use and choice of broad-spectrum antibiotics as first-line treatment in children with complicated SAM and reinforce the call for an update of international guidelines on management of complicated SAM based on more recent data.