Intellectual disability, unusual facial morphology and hand anomalies in sibs

Here we report on a Portuguese family with three sisters who shared moderate intellectual disability, unusual facial morphology (short palpebral fissures; broad nasal tip; thin upper and lower vermillion; broad and pointed chin) and hand anomalies in two of them (short left third and fifth right metacarpals in one case; marked syndactyly between the third and fourth fingers in another). One of the sisters had microcephaly and short stature, and the other two were obese. Obesity and somewhat similar facial features were also present in the otherwise healthy mother. Despite the overlap with several known syndromes (Albright osteodystrophy; Filippi syndrome; Rubinstein-Taybi syndrome; microdeletion 2q37), we suggest this condition is previously unreported, and most likely displays an autosomal recessive pattern of inheritance

Combined liver-kidney transplantation and the effect of preformed lymphocytotoxic antibodies

Thirty-eight sequentially placed liver and kidney allografts were evaluated with respect to patient and graft survival, and the influence of preformed lymphocytotoxic antibodies was analysed. The results suggest that the survival rate of combined liver and kidney transplantation is similar to the survival rate of liver transplantation alone. Sequentially placed kidney allografts may be protected from hyperacute rejection in the presence of donor specific lymphocytotoxic antibodies, but not in all instances. Both patient and kidney allograft survival was lower in positive crossmatch patients (33% and 17% respectively) than in negative crossmatch patients (78% and 75%). High levels of panel reactive antibodies (>10%) also appeared to have a deleterious effect on survival, although the majority of the patients who failed also had a positive crossmatch. Although preformed lymphocytotoxic antibodies are not an absolute contraindication to combined liver-kidney transplantation, they do appear to have a deleterious effect on long-term graft survival. However, more correlation with clinical parameters is needed. © 1994

Abundance of unknots in various models of polymer loops

A veritable zoo of different knots is seen in the ensemble of looped polymer chains, whether created computationally or observed in vitro. At short loop lengths, the spectrum of knots is dominated by the trivial knot (unknot). The fractional abundance of this topological state in the ensemble of all conformations of the loop of $N$ segments follows a decaying exponential form, $\sim \exp (-N/N_0)$, where $N_0$ marks the crossover from a mostly unknotted (ie topologically simple) to a mostly knotted (ie topologically complex) ensemble. In the present work we use computational simulation to look closer into the variation of $N_0$ for a variety of polymer models. Among models examined, $N_0$ is smallest (about 240) for the model with all segments of the same length, it is somewhat larger (305) for Gaussian distributed segments, and can be very large (up to many thousands) when the segment length distribution has a fat power law tail.Comment: 13 pages, 6 color figure

Rapid monitoring of anti-tuberculosis therapy using fluorescein diacetate microscopy: a simple method to determine infectiousness and screen for drug resistance

Background: Tuberculosis treatment and infection control are hampered by difficulty assessing mycobacterial viability to determine infectiousness and early treatment response. TB culture takes weeks; molecular tests are technically demanding; and acid-fast staining cannot differentiate live from dead tuberculosis. / Objectives: To develop and evaluate a simple slide-microscopy test to rapidly determine tuberculosis viability. / Methods: A protocol was optimized to stain viable but not dead tuberculosis in decontaminated sputum dried onto microscope slides and stained with the vital stain fluorescein diacetate (FDA). The reliability of this FDA slide microscopy for determining the concentration of viable tuberculosis in sputum was then compared with quantitative culture. / Results-laboratory evaluation: In untreated patients, tuberculosis auramine staining was unaffected whether sputum was fresh or had been sterilized by boiling, whereas FDA stained only un-boiled, viable tuberculosis. Quantification of viable tuberculosis by culture was reliably predicted by FDA, but not by auramine microscopy. / Results-clinical evaluation : Sequential sputums were collected from 35 patients before and after 3, 6 and 9 days of first-line tuberculosis treatment. Culture quantification of viable mycobacteria in sputum was predicted by slide microscopy with FDA (r2=0.77) but not auramine (r2=0.33). Quantification of viable tuberculosis in sputum by both quantitative culture and FDA microscopy fell 10-100 fold during the first nine days of treatment in all patients with drug-susceptible tuberculosis, whereas there was little change for patients with MDRTB. Specifically, 70% of samples from patients with drug-susceptible tuberculosis had a decline in the FDA count of viable tuberculosis of at least 0.2 logs/treatment-day, compared with none of the samples from MDRTB patients (P1 month required for culture. This simple and inexpensive technique rapidly assessed patient infectiousness on treatment, potentially guiding infection control measures. FDA staining also revealed differences in early treatment response between non-MDR and MDRTB and may allow early field screening for MDRTB and impending treatment failure

In vitro digestion and stability assessment of b-lactoglobulin/riboflavin nanostructures

B-Lactoglobulin (b-Lg) is the major protein fraction of bovine whey serum and a primary gelling agent. b-Lg has a high nutritional value, is stable at low pH being highly resistant to proteolytic degradation in the stomach, besides, it has the ability of acting as an encapsulating agent. This study aims at assessing the ability of b-Lg nanostructures to associate a nutraceutical - i.e. riboflavin - and release it in a controlled manner throughout an in vitro gastrointestinal (GI) system. For this reason b-Lg nanostructures loaded with riboflavin were critically characterized in terms of their morphology (i.e. size, polydispersity, -potential and shape) by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and efficiency to associate to riboflavin through spectrofluorimetry. Furthermore, these nanocomplexes were evaluated in an in vitro GI model, simulating the physiological conditions. Stable b-Lg nanostructures were obtained at pH 6, of spherical shape, characterized by particle size of 172±1 nm, low polydispersity (i.e. PDI of 0.06±0.02), -potential of -32±3 mV and association efficiency (AE) of 26±1 %. b-Lg nanostructures showed to be stable upon their passage throughout stomach (i.e. particle size, PDI and potential of 248±10 nm, 0.18±0.03 and 18±3 mV, respectively). Concerning their passage throughout the intestine, such nanostructures were mostly degraded in the duodenum. Regarding riboflavin, a release of about 11 % was observed after their passage through stomach, while 35 %, 38 % and 5 % were the released percentages of the total riboflavin associated observed after passage through duodenum, jejunum and ileum, respectively. Hence,b-Lg nanostructures showed to be suitable carriers for riboflavin until the intestine, where their degradation occurs. b-Lg also showed to be structurally stable, under food simulant conditions (yoghurt simulant, composed of 3 % acetic acid), over 14 days, with a protective effect upon riboflavin activity, releasing it in a 7 day period.Oscar L. Ramos, Ricardo N. Pereira and Ana C. Pinheiro gratefully acknowledge their Post-Doctoral grants (SFRH/BPD/80766/2011, SFRH/BPD/81887/2011 and SFRH/BPD/101181/2014, respectively) and Ana I. Bourbon gratefully acknowledge her Doctoral grant (SFRH/BD/73178/2010) to Fundacao para a Ciencia e a Tecnologia (FCT). The authors would like to acknowledge to Francisco Figueiredo from the Institute for Molecular and Cell Biology (IBMC), University of Porto, for assistance in taking the TEM pictures. The authors thank the FCT Strategic Project of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684), the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462), and the project "BioInd e Biotechnology and Bioengineering for improved Industrial and Agro-Food processes", REF. NORTE-07-0124-FEDER-000028, co-funded by the Programa Operacional Regional do Norte (ON. 2 - O Novo Norte), QREN, FEDER

Identification and quantification of microplastics in wastewater using focal plane array-based reflectance micro-FT-IR imaging

Microplastics (<5 mm) have been documented in environmental samples on a global scale. While these pollutants may enter aquatic environments via wastewater treatment facilities, the abundance of microplastics in these matrices has not been investigated. Although efficient methods for the analysis of microplastics in sediment samples and marine organisms have been published, no methods have been developed for detecting these pollutants within organic-rich wastewater samples. In addition, there is no standardized method for analyzing microplastics isolated from environmental samples. In many cases, part of the identification protocol relies on visual selection before analysis, which is open to bias. In order to address this, a new method for the analysis of microplastics in wastewater was developed. A pretreatment step using 30% hydrogen peroxide (H2O2) was employed to remove biogenic material, and focal plane array (FPA)-based reflectance micro-Fourier-transform (FT-IR) imaging was shown to successfully image and identify different microplastic types (polyethylene, polypropylene, nylon-6, polyvinyl chloride, polystyrene). Microplastic-spiked wastewater samples were used to validate the methodology, resulting in a robust protocol which was nonselective and reproducible (the overall success identification rate was 98.33%). The use of FPA-based micro-FT-IR spectroscopy also provides a considerable reduction in analysis time compared with previous methods, since samples that could take several days to be mapped using a single-element detector can now be imaged in less than 9 h (circular filter with a diameter of 47 mm). This method for identifying and quantifying microplastics in wastewater is likely to provide an essential tool for further research into the pathways by which microplastics enter the environment.This work is funded by a NERC (Natural Environment Research Council) CASE studentship (NE/K007521/1) with contribution from industrial partner Fera Science Ltd., United Kingdom. The authors would like to thank Peter Vale, from Severn Trent Water Ltd, for providing access to and additionally Ashley Howkins (Brunel University London) for providing travel and assistance with the sampling of the Severn Trent wastewater treatment plant in Derbyshire, UK. We are grateful to Emma Bradley and Chris Sinclair for providing helpful suggestions for our research

Ancient DNA of guinea pigs (Cavia spp.) indicates a probable new center of domestication and pathways of global distribution

Guinea pigs (Cavia spp.) have a long association with humans. From as early as 10,000 years ago they were a wild food source. Later, domesticated Cavia porcellus were dispersed well beyond their native range through pre-Columbian exchange networks and, more recently, widely across the globe. Here we present 46 complete mitogenomes of archaeological guinea pigs from sites in Peru, Bolivia, Colombia, the Caribbean, Belgium and the United States to elucidate their evolutionary history, origins and paths of dispersal. Our results indicate an independent centre of domestication of Cavia in the eastern Colombian Highlands. We identify a Peruvian origin for the initial introduction of domesticated guinea pigs (Cavia porcellus) beyond South America into the Caribbean. We also demonstrate that Peru was the probable source of the earliest known guinea pigs transported, as part of the exotic pet trade, to both Europe and the southeastern United States. Finally, we identify a modern reintroduction of guinea pigs to Puerto Rico, where local inhabitants use them for food. This research demonstrates that the natural and cultural history of guinea pigs is more complex than previously known and has implications for other studies regarding regional to global-scale studies of mammal domestication, translocation, and distribution.Fil: Lord, E.. Stockholms Universitet; Suecia. University of Otago; Nueva ZelandaFil: Collins, C.. University of Otago; Nueva ZelandaFil: deFrance, S.. University of Florida; Estados UnidosFil: LeFebvre, M. J.. University of Florida; Estados UnidosFil: Pigière, F.. Universidad de Dublin; IrlandaFil: Eeckhout, P.. Université Libre de Bruxelles; BélgicaFil: Erauw, C.. Université Libre de Bruxelles; BélgicaFil: Fitzpatrick, S. M.. State University of Oregon; Estados UnidosFil: Healy, P. F.. Trent University; CanadáFil: Martínez Polanco, M. F.. Muséum National d'Histoire Naturelle; Francia. Universitat Rovira I Virgili; España. Institut Català de Paleoecologia Humana i Evolució Social; EspañaFil: Garcia, J. L.. Stetson University; Estados UnidosFil: Ramos Roca, E.. Universidad de los Andes. Facultad de Ciencias Sociales. Departamento de Antropología; ColombiaFil: Delgado Burbano, Miguel Eduardo. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Área Antropológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. School of Life Sciences and Human Phenome Institute Fudan University; ChinaFil: Sánchez Urriago, A.. Instituto Colombiano de Antropología e Historia; ColombiaFil: Peña Léon, G. A.. Universidad Nacional de Colombia; ColombiaFil: Toyne, J. M.. University of Florida; Estados UnidosFil: Dahlstedt, A.. Arizona State University; Estados UnidosFil: Moore, K. M.. State University of Pennsylvania; Estados UnidosFil: Laguer Diaz, C.. University of Florida; Estados UnidosFil: Zori, C.. Baylor University; Estados UnidosFil: Matisoo-Smith, E.. University of Otago; Nueva Zeland

Simulated 21st century's increase in oceanic suboxia by CO2-enhanced biotic carbon export

The primary impacts of anthropogenic CO2 emissions on marine biogeochemical cycles predicted so far include ocean acidification, global warming induced shifts in biogeographical provinces, and a possible negative feedback on atmospheric CO2 levels by CO2‐fertilized biological production. Here we report a new potentially significant impact on the oxygen‐minimum zones of the tropical oceans. Using a model of global climate, ocean circulation, and biogeochemical cycling, we extrapolate mesocosm‐derived experimental findings of a pCO2‐sensitive increase in biotic carbon‐to‐nitrogen drawdown to the global ocean. For a simulation run from the onset of the industrial revolution until A.D. 2100 under a “business‐as‐usual” scenario for anthropogenic CO2 emissions, our model predicts a negative feedback on atmospheric CO2 levels, which amounts to 34 Gt C by the end of this century. While this represents a small alteration of the anthropogenic perturbation of the carbon cycle, the model results reveal a dramatic 50% increase in the suboxic water volume by the end of this century in response to the respiration of excess organic carbon formed at higher CO2 levels. This is a significant expansion of the marine “dead zones” with severe implications not only for all higher life forms but also for oxygen‐sensitive nutrient recycling and, hence, for oceanic nutrient inventories

Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents and young adults (BREATHER): Extended follow-up results of a randomised, open-label, non-inferiority trial

BACKGROUND: Weekends off antiretroviral therapy (ART) may help engage HIV-1-infected young people facing lifelong treatment. BREATHER showed short cycle therapy (SCT; 5 days on, 2 days off ART) was non-inferior to continuous therapy (CT) over 48 weeks. Planned follow-up was extended to 144 weeks, maintaining original randomisation. METHODS: BREATHER was an open-label, non-inferiority trial. Participants aged 8-24yrs with virological suppression on efavirenz-based first-line ART were randomised 1:1, stratified by age and African/non-African sites, to remain on CT or change to SCT. The Kaplan-Meier method was used to estimate the proportion of participants with viral rebound (confirmed VL≥50 copies/mL) under intent-to-treat at 48 weeks (primary outcome), and in extended follow-up at 96, 144, and 192 weeks. SCT participants returned to CT following viral rebound, 3 VL blips or discontinuation of efavirenz. FINDINGS: Of 199 participants (99 SCT, 100 CT), 97 per arm consented to extended follow-up. Median follow-up was 185.3 weeks (IQR 160.9-216.1). 69 (70%) SCT participants remained on SCT at last follow-up. 105 (53%) were male, baseline median age 14 years (IQR 12-18), median CD4 count 735 cells/μL (IQR 576-968). 16 SCT and 16 CT participants had confirmed VL≥50 copies/mL by the end of extended follow-up (HR 1.00, 95% CI 0.50-2.00). Estimated difference in percentage with viral rebound (SCT minus CT) by week 144 was 1.9% (90% CI -6.6-10.4; p = 0.72) and was similar in a per-protocol analysis. There were no significant differences between arms in proportions of participants with grade 3/4 adverse events (18 SCT vs 16 CT participants; p = 0.71) or ART-related adverse events (10 vs 12; p = 0.82). 20 versus 8 serious adverse events (SAEs) were reported in 16 SCT versus 4 CT participants, respectively (p = 0.005 comparing proportions between groups; incidence rate ratio 2.49, 95%CI 0.71-8.66, p = 0.15). 75% of SAEs (15 SCT, 6 CT) were hospitalisations for a wide range of conditions. 3 SCT and 6 CT participants switched to second-line ART following viral failure (p = 0.50). CONCLUSIONS: Sustainable non-inferiority of virological suppression in young people was shown for SCT versus CT over median 3.6 years. Standard-dose efavirenz-based SCT is a viable option for virologically suppressed HIV-1 infected young people on first-line ART with 3-monthly VL monitoring. TRIAL REGISTRATION: EudraCT 2009-012947-40 ISRCTN 97755073 ClinicalTrials.gov NCT01641016