Clinical characteristics of Plasmodium falciparum infection among symptomatic patients presenting to a major urban military hospital in Cameroon.

BACKGROUND: Urban malaria has received insufficient attention in the literature. The prevalence and clinical characteristics of Plasmodium falciparum infection amongst patients presenting with suspected malaria were investigated at a major urban hospital in Douala, Cameroon with a particular focus on anaemia. METHODS: A cross-sectional, 18-week demographic and clinical survey was conducted of patients presenting to the Emergency Department of Douala Military Hospital with suspected malaria, largely defined by the presence or recent history of fever. Venous samples were tested for P. falciparum using rapid diagnostic tests and PCR, and anaemia was defined by haemoglobin level according to WHO definitions. Likelihood ratios (LR), odds ratios (OR), and population attributable risk percent (PARP) were calculated. RESULTS: Participants were ages 8 months to 86 years, 51% were women (257/503), and all districts of Douala were represented. Overall, 38.0% (n = 189/497) were anaemic, including 5.2% (n = 26/497) with severe anaemia. Anaemia prevalence was significantly higher (OR: 2.20, 95% CI 1.41-3.45) among children < 15 years (53.1%, n = 52/98) compared to adults (34%, n = 133/392). Plasmodium falciparum was detected in 37.2% by nested PCR. Among all participants, several factors were associated with clinically significant LR for P. falciparum infection, including age 10-14 years (positive LR: 3.73), living in the island district of Douala VI (positive LR: 3.41), travel to any of three northern regions (positive LR: 5.11), and high fever > 40 °C at presentation (positive LR: 4.83). Among all participants, 8.7% of anaemia was associated with P. falciparum infection, while the PARP was 33.2% among those < 15 years of age and 81.0% among 10-14-year-olds. CONCLUSIONS: The prevalence of P. falciparum infection in the urban hospital was high. Mirroring trends in many rural African settings, older children had the highest positivity rate for P. falciparum infection. Anaemia was also common in all age groups, and for those 10-14 years of age, 80% of the risk for anaemia was associated with P. falciparum infection. Malaria rates in major urban population centres can be high, and more research into the multifactorial causes of anaemia across the age spectrum are needed.

Muscle development and regeneration controlled by AUF1-mediated stage-specific degradation of fate-determining checkpoint mRNAs.

AUF1 promotes rapid decay of mRNAs containing 3' untranslated region (3'UTR) AU-rich elements (AREs). AUF1 depletion in mice accelerates muscle loss and causes limb girdle muscular dystrophy. Here, we demonstrate that the selective, targeted degradation by AUF1 of key muscle stem cell fate-determining checkpoint mRNAs regulates each stage of muscle development and regeneration by reprogramming each myogenic stage. Skeletal muscle stem (satellite) cell explants show that Auf1 transcription is activated with satellite cell activation by stem cell regulatory factor CTCF. AUF1 then targets checkpoint ARE-mRNAs for degradation, progressively reprogramming the transcriptome through each stage of myogenesis. Transition steps in myogenesis, from stem cell proliferation to differentiation to muscle fiber development, are each controlled by fate-determining checkpoint mRNAs, which, surprisingly, were found to be controlled in their expression by AUF1-targeted mRNA decay. Checkpoint mRNAs targeted by AUF1 include Twist1, decay of which promotes myoblast development; CyclinD1, decay of which blocks myoblast proliferation and initiates differentiation; and RGS5, decay of which activates Sonic Hedgehog (SHH) pathway-mediated differentiation of mature myotubes. AUF1 therefore orchestrates muscle stem cell proliferation, self-renewal, myoblast differentiation, and ultimately formation of muscle fibers through targeted, staged mRNA decay.

Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs).

Non-communicable diseases (NCDs) are medical conditions that, by definition, are non-infectious and non-transmissible among people. Much of current NCDs are generally due to genetic, behavioral, and metabolic risk factors that often include excessive alcohol consumption, smoking, obesity, and untreated elevated blood pressure, and share many common signal transduction pathways. Alterations in cell and physiological signaling and transcriptional control pathways have been well studied in several human NCDs, but these same pathways also regulate expression and function of the protein synthetic machinery and mRNA translation which have been less well investigated. Alterations in expression of specific translation factors, and disruption of canonical mRNA translational regulation, both contribute to the pathology of many NCDs. The two most common pathological alterations that contribute to NCDs discussed in this review will be the regulation of eukaryotic initiation factor 2 (eIF2) by the integrated stress response (ISR) and the mammalian target of rapamycin complex 1 (mTORC1) pathways. Both pathways integrally connect mRNA translation activity to external and internal physiological stimuli. Here, we review the role of ISR control of eIF2 activity and mTORC1 control of cap-mediated mRNA translation in some common NCDs, including Alzheimer's disease, Parkinson's disease, stroke, diabetes mellitus, liver cirrhosis, chronic obstructive pulmonary disease (COPD), and cardiac diseases. Our goal is to provide insights that further the understanding as to the important role of translational regulation in the pathogenesis of these diseases.

AUF1 gene transfer increases exercise performance and improves skeletal muscle deficit in adult mice.

Muscle function and mass begin declining in adults long before evidence of sarcopenia and include reduced mitochondrial function, although much remains to be characterized. We found that mRNA decay factor AU-rich mRNA binding factor 1 (AUF1), which stimulates myogenesis, is strongly reduced in skeletal muscle of adult and older mice in the absence of evidence of sarcopenia. Muscle-specific adeno-associated virus (AAV)8-AUF1 gene therapy increased expression of AUF1, muscle function, and mass. AAV8 AUF1 muscle gene transfer in 12-month-old mice increased the levels of activated muscle stem (satellite) cells, increased muscle mass, reduced markers of muscle atrophy, increased markers of mitochondrial content and muscle fiber oxidative capacity, and enhanced exercise performance to levels of 3-month-old mice. With wild-type and AUF1 knockout mice and cultured myoblasts, AUF1 supplementation of muscle fibers was found to increase expression of Peroxisome Proliferator-activated Receptor Gamma Co-activator 1-alpha (PGC1α), a major effector of skeletal muscle mitochondrial oxidative metabolism. AUF1 stabilized and increased translation of the pgc1α mRNA, which is strongly reduced in adult muscle in the absence of AUF1 supplementation. Skeletal muscle-specific gene transfer of AUF1 therefore restores muscle mass, increases exercise endurance, and may provide a therapeutic strategy for age-related muscle loss.

Atypical hypoplastic left ventricular syndrome in a calf.

An 8-day-old male Angus calf was presented to the University of Illinois, Veterinary Teaching Hospital, Urbana, IL, for lethargy, weakness, and poor suckle reflex. Clinical evaluation revealed a strong left-sided heart murmur and a split S2 sound. The calf died within 48 hours. Necropsy revealed a combination of the following cardiac defects: left ventricular hypoplasia, high ventricular septal defect, left auricular atresia with mitral valve aplasia, patent foramen ovale, patent ductus arteriosus, and pulmonary trunk atresia. Mild suppurative pneumonia with pulmonary edema and congestion were also present. This combination of defects appears to be similar to the hypoplastic left heart syndrome in humans and is reported here for the first time in cattle.

West Nile virus infection in free-ranging squirrels in Illinois.

West Nile virus (WNV) infection was diagnosed in 13 gray squirrels (Sciurus carolinensis) and 3 fox squirrels (Sciurus niger) that were observed with neurologic signs before death or found dead. All 16 had gliosis throughout all sections of the brain. Most had lymphoplasmacytic encephalitis or meningoencephalitis, many with admixed neutrophils. Neuronal necrosis and neuronophagia were also prominent features. West Nile virus antigen was demonstrated in the brain, spleen, heart or kidney in 10 of 13 gray squirrels and 3 of 3 fox squirrels by immunohistochemistry. Nucleic acid amplification tests (NAATs) confirmed the presence of WNV in the brain or spinal cord of 10/10 gray squirrels and 1/3 fox squirrels tested. Viral levels were quantified in various tissues of selected gray squirrels, and titers were highest in spleen and brain, with no virus detected in serum. This is the first description of lesions associated with WNV infection in gray and fox squirrels.

New records of hair follicle mites (Demodecidae) from North American Cervidae.

Individuals of three species of cervids, with varying degrees of alopecia, were examined for ectoparasites: Rocky Mountain elk (Cervus elaphus nelsoni) and mule deer (Odocoileus hemionus hemionus) in Colorado and white-tailed deer (Odocoileus virginianus) in South Dakota. Hair follicle mites were recovered and identified as Demodex kutzeri, a species originally described from the European red deer (Cervus elaphus, from Austria) and the sika deer (Cervus nippon pseudaxis, captive in Germany). These findings expand the geographic range of D. kutzeri to North America and extend its host range to include the genus Odocoileus. Thus, the host range for D. kutzeri spans two subfamilies of cervids. Additionally, D. kutzeri was identified in material from a white-tailed deer collected in South Carolina in 1971, indicating this parasite has been present, but unrecognized, on US cervids for some time.