Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru

Introduction

The disease burden and risk factors for respiratory syncytial virus (RSV) and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear.

Materials and Methods

We conducted a prospective, household-based cohort study of children aged <3 years living in remote rural highland communities in San Marcos, Cajamarca, Peru. Acute respiratory illnesses (ARI), including lower respiratory tract infection (LRTI), were monitored through weekly household visits from March 2009 through September 2011. Nasal swabs collected during ARI/LRTI were tested for RSV, MPV, and other respiratory viruses using real-time RT-PCR. Incidence rates and rate ratios were calculated using mixed effects Poisson regression.

Results

Among 892 enrolled children, incidence rates of RSV and MPV ARI were 30 and 17 episodes per 100 child-years, respectively. The proportions of RSV and MPV ARI that presented as LRTI were 12.5% and 8.9%, respectively. Clinic visits for ARI and hospitalizations were significantly more frequent (all p values <0.05) among children with RSV (clinic 41% and hospital 5.3%) and MPV ARI (38% and 3.5%) when compared with other viral infections (23% and 0.7%) and infections without virus detected (24% and 0.6%). In multivariable analysis, risk factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03), the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38), residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2^nd compared to 1^st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3^rd compared to 1^st quartile residents). Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01).

Conclusion

In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional studies to control infections by these viruses among young children from developing countries.     

Genetic Differentiation in Insular Lowland Rainforests: Insights from Historical Demographic Patterns in Philippine Birds

Phylogeographic studies of Philippine birds support that deep genetic structure occurs across continuous lowland forests within islands, despite the lack of obvious contemporary isolation mechanisms. To examine the pattern and tempo of diversification within Philippine island forests, and test if common mechanisms are responsible for observed differentiation, we focused on three co-distributed lowland bird taxa endemic to Greater Luzon and Greater Negros-Panay: Blue-headed Fantail (Rhipidura cyaniceps), White-browed Shama (Copsychus luzoniensis), and Lemon-throated Leaf-Warbler (Phylloscopus cebuensis). Each species has two described subspecies within Greater Luzon, and a single described subspecies on Greater Negros/Panay. Each of the three focal species showed a common geographic pattern of two monophyletic groups in Greater Luzon sister to a third monophyletic group found in Greater Negros-Panay, suggesting that common or similar biogeographic processes may have produced similar distributions. However, studied species displayed variable levels of mitochondrial DNA differentiation between clades, and genetic differentiation within Luzon was not necessarily concordant with described subspecies boundaries. Population genetic parameters for the three species suggested both rapid population growth from small numbers and geographic expansion across Luzon Island. Estimates of the timing of population expansion further supported that these events occurred asynchronously throughout the Pleistocene in the focal species, demanding particular explanations for differentiation, and support that co-distribution may be secondarily congruent.     

Post-operative small pelvic field radiation therapy in patients with intermediate risk early stage cervix cancer: a safe and efficient treatment modality

BackgroundThe treatment of early stage cervical cancer has different therapeutic options. Adjuvant external beam radiotherapy for surgically treated intermediate risk cervical cancer patients has shown acceptable oncological outcomes with a low incidence of toxicity. The aim of this study was to analyze the oncological outcomes and safety of adjuvant small pelvic field radiotherapy in surgically treated stage IB1-2 cervical cancer patients who met the Sedlis intermediate-risk criteria.Materials and methodsA retrospective cohort study was carried out with 28 patients treated from 2007 to November 2019 with biopsy proven intermediate risk stage IB1–2 cervical cancer previously treated with radical hysterectomy and bilateral lymphadenectomy who received adjuvant small pelvic field radiotherapy. The primary endpoints were local and distant control and overall survival. Secondary endpoints were acute and late gastrointestinal and genitourinary toxicity. Survival curves were analyzed using the Kaplan-Meier method.ResultsAfter a median follow up period of 41.5 (27.5–80.5) months, adjuvant small pelvic field radiotherapy showed a 100% overall survival rate, 81.82% disease free survival and 86.36% local recurrence-free survival with no incidence of grade 3 or 4 acute or late toxicity. Three patients suffered from relapse, 1 in the vaginal cuff, 1 in the retrovesical area and 1 patient in the retroperitoneal area.ConclusionsAdjuvant small pelvic field radiotherapy is an efficient and safe treatment option that offers excellent oncological outcomes to surgically treated intermediate-risk stage IB1–2 cervical cancer patients with an excellent toxicity profile.     

The fermentation of sugarcane molasses by Dekkera bruxellensis and the mobilization of reserve carbohydrates

The yeast Dekkera bruxellensis is considered to be very well adapted to industrial environments, in Brazil, USA, Canada and European Countries, when different substrates are used in alcoholic fermentations. Our previous study described its fermentative profile with a sugarcane juice substrate. In this study, we have extended its physiological evaluation to fermentation situations by using sugarcane molasses as a substrate to replicate industrial working conditions. The results have confirmed the previous reports of the low capacity of D. bruxellensis cells to assimilate sucrose, which seems to be the main factor that can cause a bottleneck in its use as fermentative yeast. Furthermore, the cells of D. bruxellensis showed a tendency to deviate most of sugar available for biomass and organic acids (lactic and acetic) compared with Saccharomyces cerevisiae, when calculated on the basis of their respective yields. As well as this, the acetate production from molasses medium by both yeasts was in marked contrast with the previous data on sugarcane juice. Glycerol and ethanol production by D. bruxellensis cells achieved levels of 33 and 53 % of the S. cerevisiae, respectively. However, the ethanol yield was similar for both yeasts. It is worth noting that this yeast did not accumulate trehalose when the intracellular glycogen content was 30 % lower than in S. cerevisiae. The lack of trehalose did not affect yeast viability under fermentation conditions. Thus, the adaptive success of D. bruxellensis under industrial fermentation conditions seems to be unrelated to the production of these reserve carbohydrates.     

Cytochrome c1 exhibits two binding sites for cytochrome c in plants

In plants, channeling of cytochrome c molecules between complexes III and IV has been purported to shuttle electrons within the supercomplexes instead of carrying electrons by random diffusion across the intermembrane bulk phase. However, the mode plant cytochrome c behaves inside a supercomplex such as the respirasome, formed by complexes I, III and IV, remains obscure from a structural point of view. Here, we report ab-initio Brownian dynamics calculations and nuclear magnetic resonance-driven docking computations showing two binding sites for plant cytochrome c at the head soluble domain of plant cytochrome c₁, namely a non-productive (or distal) site with a long heme-to-heme distance and a functional (or proximal) site with the two heme groups close enough as to allow electron transfer. As inferred from isothermal titration calorimetry experiments, the two binding sites exhibit different equilibrium dissociation constants, for both reduced and oxidized species, that are all within the micromolar range, thus revealing the transient nature of such a respiratory complex. Although the docking of cytochrome c at the distal site occurs at the interface between cytochrome c₁ and the Rieske subunit, it is fully compatible with the complex III structure. In our model, the extra distal site in complex III could indeed facilitate the functional cytochrome c channeling towards complex IV by building a “floating boat bridge” of cytochrome c molecules (between complexes III and IV) in plant respirasome.     

Identification of an elongation factor 1Bγ protein with glutathione transferase activity in both yeast and mycelial morphologies from human pathogenic Blastoschizomyces capitatus

Blastoschizomyces capitatus is an uncommon, opportunistic pathogenic fungus, which causes invasive and disseminated infections. This microorganism is normally present in both environmental and normal human flora. Within a host, B. capitatus is able to grow in both unicellular yeast and multicellular filamentous growth forms. In this study, we obtained in vitro morphological conversion of B. capitatus from yeast-to-mycelial phase to investigate the presence and expression of glutathione transferase (GST) enzymes in both cell forms. A protein with GST activity using the model substrate 1-chloro-2,4-dinitrobenzene was detected in both morphologies and identified by tandem mass spectrometry as a eukaryotic elongation factor 1Bγ (eEF1Bγ) protein, a member of the GST superfamily. No significant difference in GST-specific activity and kinetic constants were observed between mycelial and yeast forms, indicating that eEF1Bγ protein did not show differential expression between the two phases.     

Mechanisms underlying hypertriglyceridemia in rats with monosodium l-glutamate-induced obesity: Evidence of XBP-1/PDI/MTP axis activation

Non-alcoholic fatty liver disease (NAFLD) is intimately associated with insulin resistance and hypertriglyceridemia, whereas many of the mechanisms underlying this association are still poorly understood. In the present study, we investigated the relationship between microsomal triglyceride transfer protein (MTP) and markers of endoplasmic reticulum (ER) stress in the liver of rats subjected to neonatal monosodium l-glutamate (MSG)-induced obesity. At age 120 days old, the MSG-obese animals exhibited hyperglycemia, hypertriglyceridemia, insulin resistance, and liver steatosis, while the control (CTR) group did not. Analysis using fast protein liquid chromatography of the serum lipoproteins revealed that the triacylglycerol content of the very low-density lipoprotein (VLDL) particles was twice as high in the MSG animals compared with the CTR animals. The expression of ER stress markers, GRP76 and GRP94, was increased in the MSG rats, promoting a higher expression of X-box binding protein 1 (XBP-1), protein disulfide isomerase (PDI), and MTP. As the XBP-1/PDI/MTP axis has been suggested to represent a significant lipogenic mechanism in the liver response to ER stress, our data indicate that hypertriglyceridemia and liver steatosis occurring in the MSG rats are associated with increased MTP expression.