The impacts of seasonal variation and climate on food utilization in a population of critically endangered cotton-top tamarins (Saguinus oedipus) in Colombia: A 22-year longitudinal study.

To examine how precipitation patterns and climate change impact feeding choices made by a population of critically endangered cotton-top tamarins (Saguinus oedipus), we examined 22 years of feeding data (1999-2020) from 21 groups collected at Parque Natural Regional Bosque Seco El Ceibal Mono Tití in Santa Catalina, Colombia. We describe the diet and examine the role of seasonal rainfall and annual variation in rainfall on diet. Rainfall is highly seasonal (mean annual rainfall 1562 mm [range 940-2680 mm]) with a dry, early rainy, and late rainy season in each year. Over 80 species of plants formed part of the fruit, nectar, and exudate components of the diet. Fruits, although available year-round, were more commonly available and consumed during the late rainy seasons (August-November). Exudates were consumed more frequently in the dry season (December-March) and invertebrate consumption was stable across the year. Nectar feeding from a single species (Combretum fruticosum) peaked in November. Rainfall varied over the years, with 13 years exceeding the 99% confidence intervals for mean rainfall. Ten of these extreme years (both drought and extremely wet) occurred in the last 11 years. Fruit consumption did not vary between extreme and average years, but cotton-top tamarins consumed more invertebrates and exudates in wet years. Presently, cotton-top tamarins appear to be able to cope with these extreme variations in rainfall due to their highly varied diet. However, the forests that these primates depend upon for survival are threatened by human exploitation making it critically important to maintain a generalist feeding strategy for survival as many fruiting trees that compose a large proportion of the diet are removed. As conservation efforts continue, plant species consumed by cotton-top tamarins provide useful data when selecting species for habitat restoration programs.

Prevalence of underweight, wasting and stunting among young children with a significant cognitive delay in 47 low-income and middle-income countries.

BACKGROUND: Undernutrition in early childhood is associated with a range of negative outcomes across the lifespan. Little is known about the prevalence of exposure to undernutrition among young children with significant cognitive delay. METHOD: Secondary analysis of data collected on 161 188 three- and four-year-old children in 47 low-income and middle-income countries in Rounds 4-6 of UNICEF's Multiple Indicator Cluster Surveys. Of these, 12.3% (95% confidence interval 11.8-12.8%) showed evidence of significant cognitive delay. RESULTS: In both middle-income and low-income countries, significant cognitive delay was associated with an increased prevalence of exposure to three indicators of undernutrition (underweight, wasting and stunting). Overall, children with significant cognitive delay were more than twice as likely than their peers to be exposed to severe underweight, severe wasting and severe stunting. Among children with significant cognitive delay (and after controlling for country economic classification group), relative household wealth was the strongest and most consistent predictor of exposure to undernutrition. CONCLUSIONS: Given that undernutrition in early childhood is associated with a range of negative outcomes in later life, it is possible that undernutrition in early childhood may play an important role in accounting for health inequalities and inequities experienced by people with significant cognitive delay in low-income and middle-income countries.

The impact of flow PRA on outcome in pediatric heart recipients in modern era: An analysis of the Pediatric Heart Transplant Study database.

Data from patients in the Pediatric Heart Transplant Study (PHTS) registry transplanted between 2010 and 2014 were analyzed to determine the association between HLA antibody (PRA) determined by SPA using Luminex or flow cytometry with a positive retrospective cross-match and the post-transplant outcomes of acute rejection and graft survival. A total of 1459 of 1596 (91%) recipients had a PRA reported pretransplant; 26% had a PRA > 20%. Patients with a PRA > 20% were more likely to have CHD, prior cardiac surgery, ECMO support at listing, and waited longer for transplantation than patients with a PRA <20%. Patients with higher PRA% determined by SPA were predictive of a positive retrospective cross-match determined by flow cytometric method (P < .001). A PRA > 50% determined by SPA was independently associated with worse overall graft survival after first month of transplant in both unadjusted and adjusted for all other risk factors. In this large multicenter series of pediatric heart transplant recipients, an elevated PRA determined by SPA remains a significant risk factor in the modern era.

Mast cells and exosomes in hyperoxia-induced neonatal lung disease.

Chronic lung disease of prematurity (CLD) is a frequent sequela of premature birth and oxygen toxicity is a major associated risk factor. Impaired alveolarization, scarring, and inflammation are hallmarks of CLD. Mast cell hyperplasia is a feature of CLD but the role of mast cells in its pathogenesis is unknown. We hypothesized that mast cell hyperplasia is a consequence of neonatal hyperoxia and contributes to CLD. Additionally, mast cell products may have diagnostic and prognostic value in preterm infants predisposed to CLD. To model CLD, neonatal wild-type and mast cell-deficient mice were placed in an O2 chamber delivering hyperoxic gas mixture [inspired O2 fraction (FiO2 ) of 0.8] (HO) for 2 wk and then returned to room air (RA) for an additional 3 wk. Age-matched controls were kept in RA (FiO2 of 0.21). Lungs from HO mice had increased numbers of mast cells, alveolar simplification and enlargement, and increased lung compliance. Mast cell deficiency proved protective by preserving air space integrity and lung compliance. The mast cell mediators ß-hexosaminidase (ß-hex), histamine, and elastase increased in the bronchoalveolar lavage fluid of HO wild-type mice. Tracheal aspirate fluids (TAs) from oxygenated and mechanically ventilated preterm infants were analyzed for mast cell products. In TAs from infants with confirmed cases of CLD, ß-hex was elevated over time and correlated with FiO2 Mast cell exosomes were also present in the TAs. Collectively, these data show that mast cells play a significant role in hyperoxia-induced lung injury and their products could serve as potential biomarkers in evolving CLD.

Overweight and obesity among children at risk of intellectual disability in 20 low and middle income countries.

BACKGROUND: Children with intellectual disability (ID) in high income countries are at significantly greater risk of obesity than their non-disabled peers. We aimed to estimate the prevalence of overweight and obesity in 3 to 4-year-old children who are/are not at risk of ID in low and middle income countries. METHOD: Secondary analysis of Round 4 and 5 UNICEF Multiple Indicator Cluster Surveys (MICS) from 20 low and middle income countries that included a total of 83 597 3 to 4-year-old children. RESULTS: Few differences in risk of overweight or obesity were apparent between 3 and 4-year-old children identified as being at risk/not at risk of ID in 20 low and middle income countries. In the two countries where statistically significant differences were observed, prevalence of overweight/obesity was lower among children at risk of ID. CONCLUSIONS: These results stand in stark contrast to evidence from high income countries which suggest that children with ID are at significantly increased risk of obesity when compared to their non-intellectually disabled peers.

Increased intracranial pressure in mini-pigs exposed to simulated solar particle event radiation.

Changes in intracranial pressure (ICP) during space flight have stimulated an area of research in space medicine. It is widely speculated that elevations in ICP contribute to structural and functional ocular changes, including deterioration in vision, which is also observed during space flight. The aim of this study was to investigate changes in OP occurring as a result of ionizing radiation exposure (at doses and dose-rates relevant to solar particle event radiation). We used a large animal model, the Yucatan mini-pig, and were able to obtain measurements over a 90 day period. This is the first investigation to show long term recordings of ICP in a large animal model without an invasive craniotomy procedure. Further, this is the first investigation reporting increased ICP after radiation exposure.

A systematic review and meta-analysis of environmental contaminant exposure impacts on weight loss and glucose regulation during calorie-restricted diets in preclinical studies: Persistent organic pollutants may impede glycemic control.

Epidemiological evidence links chemical exposure with type 2 diabetes (T2DM) risk and prevalence. Chemical exposure may therefore also limit success of weight loss or restoration of glycemic control during calorie restricted diets. Few human studies examine this hypothesis. This systematic review and clustered meta-analysis examines preclinical evidence that exposure to anthropogenic environmental contaminants impedes weight loss and resumption of glycemic control during calorie restriction. Of five eligible papers from 212 unique citations, four used C57BL/6 mice and one used Sprague Dawley rats. In four the animals received high fat diets to induce obesity and impaired glycemic control. All examined persistent organic pollutants (POPs). Polychlorinated biphenyl (PCB) 77 exposure did not affect final mass (standardised mean difference (SMD) = -0.35 [-1.09, 0.39]; n = 5 (experiments); n = 3 (papers)), or response to insulin in insulin tolerance tests (SMD = -1.54 [-3.25, 0.16] n = 3 (experiments); n = 2 (papers)), but impaired glucose control in glucose tolerance tests (SMD = -1.30 [-1.96, -0.63]; n = 6 (experiments); n = 3 (papers)). The impaired glycemic control following perfluoro-octane sulphonic acid (PFOS) exposure and enhanced mass loss following dichlorodiphenyltrichloroethane (DDT) exposure have not been replicated. Animal studies thus suggest some chemical groups, especially PCB and PFOS, could impair glucose control management during calorie restriction, similar to conclusions from limited existing clinical studies. We discuss the research that is urgently required to inform weight management services that are now the mainstay prevention initiative for T2DM.

Complete genome sequence of a novel papillomavirus in Siamese fighting fish (Betta splendens) from Trinidad and Tobago.

Here, we announce the complete genome of a previously undescribed papillomavirus from a betta fish, Betta splendens. The genome is 5,671 bp with a GC content of 38.2%. Variants were detected in public databases. This genome is most similar to papillomaviruses that infect sea bass (52.9 % nucleotide identity).

Genetic diversity of MHC class I loci in six non-model frogs is shaped by positive selection and gene duplication.

Comparative studies of major histocompatibility complex (MHC) genes across vertebrate species can reveal the evolutionary processes that shape the structure and function of immune regulatory proteins. In this study, we characterized MHC class I sequences from six frog species representing three anuran families (Hylidae, Centrolenidae and Ranidae). Using cDNA from our focal species, we amplified a total of 79 unique sequences spanning exons 2-4 that encode the extracellular domains of the functional alpha chain protein. We compared intra- and interspecific nucleotide and amino-acid divergence, tested for recombination, and identified codon sites under selection by estimating the rate of non-synonymous to synonymous substitutions with multiple codon-based maximum likelihood methods. We determined that positive (diversifying) selection was acting on specific amino-acid sites located within the domains that bind pathogen-derived peptides. We also found significant signals of recombination across the physical distance of the genes. Finally, we determined that all the six species expressed two or three putative classical class I loci, in contrast to the single locus condition of Xenopus laevis. Our results suggest that MHC evolution in anurans is a dynamic process and that variation in numbers of loci and genetic diversity can exist among taxa. Thus, the accumulation of genetic data for more species will be useful in further characterizing the relative importance of processes such as selection, recombination and gene duplication in shaping MHC loci among amphibian lineages.

From financial hardship to child difficulties: main and moderating effects of perceived social support.

BACKGROUND: There is an unequivocal relationship between socio-economic status and child well-being. The Family Stress Model of economic hardship proposes that this relationship is mediated by financial hardship, parenting stress and parenting behaviours. In this study, the Family Stress Model is tested and analysis is extended to examine main and moderating effects of social support. METHODS: A survey incorporating well-validated measures of financial hardship, parenting stress, parenting behaviours and child difficulties was sent to 1296 parents who had utilized universal family support services in Alberta, Canada. A total of 923 parents (71%) responded. Hierarchical linear regression was employed to investigate the mediating roles of financial hardship, parenting stress and parenting behaviours, and to investigate main and moderating influences of parental social support. RESULTS: The study findings generally support the Family Stress Model. The relationship between socio-economic status and child difficulties was mediated by financial hardship and parenting stress. Higher levels of parental social support were associated with lower levels of parenting stress, ineffective parenting and child difficulties. Parental social support was important irrespective of parenting stress levels. CONCLUSIONS: The study findings add to the now critical mass of data showing that parent-child health and well-being is inextricably linked with parental social support. While there is a burgeoning literature on parent training, far less research attention has been given to the development and evaluation of strategies to strengthen parents' social relationships. This is an important direction for future research.

The use of long acting subcutaneous levonorgestrel (LNG) gel depot as an effective contraceptive option for cotton-top tamarins (Saguinus oedipus).

Cotton-top tamarins (Saguinus oedipus) are a critically endangered species that have been bred successfully in captivity for many years. For two decades, the Cotton-top Tamarin SSP(©) has been challenged with a high rate of reproduction combined with a history of contraceptive failures and nonrecommended births using the current Depo Provera(®) (medroxyprogesterone acetate) injection followed by MGA (melengestrol acetate) implant contraception combination. To address these issues we have developed and tested the use of levonorgestrel (LNG) as an effective contraception option for cotton-top tamarins. LNG was delivered in an injectable, gel matrix consisting of polylactic-co-glycolic acid, triethyl citrate and N-methylpyrrolidone. This gel matrix forms a biodegradable depot at the subcutaneous injection site providing slow release of the active ingredient. Gel matrix composition and LNG concentration were adjusted in four gel formulations to maximize the duration of contraceptive efficacy while minimizing immediate post-injection increases in fecal LNG concentration. LNG treatment (68.44 ± 8.61 mg/kg) successfully eliminated ovarian cycles (fecal pregnanediol-3-glucuronide (PdG) and estrone conjugates (E(1) C)) for 198.8 ± 70.3 days (formulation four; range 19-50 weeks). It was demonstrated that subcutaneous LNG depot injection was an effective, reversible contraceptive option for the management of cotton-top tamarins in captivity.

Verification and Validation of Digital Pathology (Whole Slide Imaging) for Primary Histopathological Diagnosis: All Wales Experience.

AIMS: The study is aimed to verify Aperio AT2 scanner for reporting on the digital pathology platform (DP) and to validate the cohort of pathologists in the interpretation of DP for routine diagnostic histopathological services in Wales, United Kingdom. MATERIALS METHODS AND RESULTS: This was a large multicenter study involving seven hospitals across Wales and unique with 22 (largest number) pathologists participating. 7491 slides from 3001 cases were scanned on Leica Aperio AT2 scanner and reported on digital workstations with Leica software of e-slide manager. A senior pathology fellow compared DP reports with authorized reports on glass slide (GS). A panel of expert pathologists reviewed the discrepant cases under multiheader microscope to establish ground truth. 2745 out of 3001 (91%) cases showed complete concordance between DP and GS reports. Two hundred and fifty-six cases showed discrepancies in diagnosis, of which 170 (5.6%) were deemed of no clinical significance by the review panel. There were 86 (2.9%) clinically significant discrepancies in the diagnosis between DP and GS. The concordance was raised to 97.1% after discounting clinically insignificant discrepancies. Ground truth lay with DP in 28 out of 86 clinically significant discrepancies and with GS in 58 cases. Sensitivity of DP was 98.07% (confidence interval [CI] 97.57-98.56%); for GS was 99.07% (CI 98.72-99.41%). CONCLUSIONS: We concluded that Leica Aperio AT2 scanner produces adequate quality of images for routine histopathologic diagnosis. Pathologists were able to diagnose in DP with good concordance as with GS. STRENGTHS AND LIMITATIONS OF THIS STUDY: Strengths of this study - This was a prospective blind study. Different pathologists reported digital and glass arms at different times giving an ambience of real-time reporting. There was standardized use of software and hardware across Wales. A strong managerial support from efficiency through the technology group was a key factor for the implementation of the study. LIMITATIONS: This study did not include Cytopathology and in situ hybridization slides. Difficulty in achieving surgical pathology practise standardization across the whole country contributed to intra-observer variations.

Developing an effective community conservation program for cotton-top tamarins (Saguinus oedipus) in Colombia.

Developing effective conservation programs that positively impact the survival of a species while considering the needs of local communities is challenging. Here we present an overview of the conservation program developed by Proyecto Tití to integrate local communities in the conservation of Colombia's critically endangered primate, the cotton-top tamarin (Saguinus oedipus). Our comprehensive assessment of the threats effecting the long-term survival of the cotton-top tamarin allowed us to establish the primary components of our program. Proyecto Tití has three areas of emphasis: (1) scientific studies detailing the biology and long-term survival of the cotton-top tamarin, (2) conservation education programs to increase public awareness and conservation knowledge, and (3) community empowerment programs that demonstrate a valuable economic incentive to protecting wildlife and forested areas in Colombia. This integrated approach to conservation that involves local communities in activities that benefit individuals, as well as wildlife, has proven to be remarkably effective in protecting cotton-top tamarins and their forested habitat. Our bindes program, which uses small cook stoves made from clay, has demonstrated a marked reduction in the number of trees that have been harvested for firewood. Developing environmental entrepreneurs, who create products made from recycled plastic for sale in national and international markets, has had a significant impact in reducing the amount of plastic that has been littering the environment and threatening the health of wildlife, while creating a stable economic income for rural communities. Proyecto Tití has provided economic alternatives to local communities that have dramatically reduced the illegal capture of cotton-top tamarins and forest destruction in the region that has positively impacted the long-term survival of this critically endangered primate.

Kaposi's sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients.

Kaposi's sarcoma-associated herpesvirus (KSHV) was found in the bone marrow dendritic cells of multiple myeloma patients but not in malignant plasma cells or bone marrow dendritic cells from normal individuals or patients with other malignancies. In addition the virus was detected in the bone marrow dendritic cells from two out of eight patients with monoclonal gammopathy of undetermined significance (MGUS), a precursor to myeloma. Viral interleukin-6, the human homolog of which is a growth factor for myeloma, was found to be transcribed in the myeloma bone marrow dendritic cells. KSHV may be required for transformation from MGUS to myeloma and perpetuate the growth of malignant plasma cells.

Litter size and infant survivorship in wild groups of cotton-top tamarins (Saguinus oedipus) in Colombia.

Cotton-top tamains (Saguinus oedipus) are a critically endangered primate found only in Colombia. Efforts to conserve this species are centered on developing effective management plans that integrate biological information regarding population dynamics and factors that influence their survival. This study documented infants born to wild cotton-top tamarin females from 1994-2008 at two distinct field sites in northern Colombia. Our studies have shown that wild cotton-top tamarins typically give birth to one litter each year and infant survival to 6 months of age was greater in the wild than has been reported in captive colonies. However, similar to reports from captive colonies, litter size of wild cotton-top tamarins ranges from 1-3 infants, with twin litters most common. Here we report the first occurrence of triplet litters in nearly 20 years of observing wild cotton-top tamarin groups. Over the first 3 months of life, wild-born infants exhibited highest mortality during the first week of life, similar to reports from captive colonies. Infant survival in the wild also increases with successive litters as it does in captivity. However, inter-birth interval, group size, and the number of adult males in the group did not appear to influence infant survival in the wild. The value of such long-term data from field studies aids in the information that can be used to model future population trends and develop effective conservation plans for this critically endangered primate.

Decline in microbial activity does not necessarily indicate an end to biodegradation in MSW-biowaste: a case study.

The aim of this study was to examine whether a decline in microbial activity (i.e., CO(2) output) during the biodegradation of municipal solid waste (MSW) indicated an end to biodegradation and the appearance of a stable, final product. As the organic fraction of MSW was biodegraded in an 8 clamp Cambridge Batch System composter, CO(2) output declined by 50% and moisture content at the end of the process was <20%. Levels of biodegradable material remaining in the product were determined by the dynamic respiration index (DRI) method but despite 151 days in the composting system biodegradable material was still present at levels (24130mgO(2)/kgdry matter (DM)) which exceeded draft EU biowaste directive (2001) guidelines (10,000mgO(2)/kgDM). Further laboratory based incubations demonstrated that microbial activity and hence biodegradation of organic material could be restarted if moisture levels were adjusted suggesting that dehydration limited microbial activity. Low levels of microbial activity alone did not therefore indicate and end to biodegradation, biodegradable material was not exhausted and the final product was not stable which has serious implications for its end-use.

Does a third head of the rectus femoris muscle exist?

Current anatomical texts describe only two tendinous origins of the rectus femoris muscle. The authors identified one older reference in which a third head of the rectus femoris muscle was briefly described. In order to confirm the existence of this head, 48 adult cadavers (96 sides) underwent detailed dissection of the proximal attachments of the rectus femoris muscle. Of these sides 83% were found to harbour a recognised third head of the rectus femoris muscle. This additional head was found to attach deeply to the iliofemoral ligament and superficially with the tendon of the gluteus minimus muscle as it attached into the femur. This tendon attached to the anterior aspect of the greater trochanter in an inferolateral direction compared to the straight head. The mean length and width of the third head was 2 cm and 4 cm, respectively. The mean thickness was found to be 3 mm. Most commonly this third head was bilaterally absent or bilaterally present. However, 4.2% were found only on left sides and 5.2% were found only on right sides. The angle created between the reflected and third heads was approximately 60 degrees. Two sides (both left sides with one female and one male specimen) were found to have third heads that were bilaminar. These bilaminar third heads had a distinct layer attaching to the underlying iliofemoral ligament and a superficial layer blending with the gluteus minimus tendon to insert onto the greater trochanter. Although the function of such an attachment is speculative, the clinician may wish to consider this structure in the interpretation of imaging or in surgical procedures in this region, as in our study it was present on the majority of sides.

In vitro cytoreductive effects on multiple myeloma cells induced by bisphosphonates.

In a double blind randomized study, the bisphosphonate drug Pamidronate (Aredia) significantly protected Durie-Salmon stage III multiple myeloma patients from osteolytic bone disease. In the patient sub-group on salvage chemotherapy. Pamidronate treatment was also significantly associated with prolonged survival. To test if this drug could induce direct antitumor effects, we exposed myeloma cells to increasing concentrations of Pamidronate or a more potent bisphosphonate, Zoledronate. A concentration- and time-dependent cytotoxic effect was detected on four of five myeloma cell lines as well as three specimens obtained directly from myeloma patients. Zoledronate-induced cytotoxicity was significantly greater than that of Pamidronate. Cytotoxicity could not be explained by bisphosphonate-induced chelation of extracellular calcium or secondary decrease in production of the myeloma growth factor interleukin-6. Morphological examination, DNA electrophoresis and cell cycle analysis indicated that the bisphosphonate-induced cytotoxic effect consisted of a combination of cytostasis and apoptotic myeloma cell death. Enforced expression of BCL-2 protected against the apoptotic death but not against cytostasis. Most cytotoxic effects were seen between 10 and 100 microM of drug. The results suggest a possible direct anti-tumor effect in myeloma patients treated with bisphosphonates which may participate in their significantly increased survival. This hypothesis should now be further tested in clinical trials.

A phase I dose-ranging trial of monthly infusions of zoledronic acid for the treatment of osteolytic bone metastases.

Bisphosphonates are potent inhibitors of bone resorption and provide a therapeutic benefit for patients with bone metastases. Zoledronic acid is a highly potent, nitrogen-containing bisphosphonate. In the present trial, we assessed the safety and tolerability of increasing doses of zoledronic acid and its effects on urinary markers of bone resorption in cancer patients with bone metastases. Fifty-nine cancer patients with bone metastases were enrolled sequentially into one of 8 treatment groups in the core protocol. Each patient received a 5-min i.v. infusion of 0.1, 0.2, 0.4, 0.8, 1.5, 2, 4, or 8 mg zoledronic acid monthly for 3 months. Patients were monitored for clinical findings, adverse events, electrocardiograms, markers of bone resorption, as well as routine hematology, blood chemistries, and urinalysis. Thirty patients who demonstrated a radiographic response to treatment or stable disease in the core protocol were enrolled in a humanitarian extension protocol and continued to receive monthly infusions. Zoledronic acid was well tolerated at all dose levels. Adverse events reported by >10% of patients included skeletal pain, nausea, fatigue, upper respiratory tract infection, constipation, headache, diarrhea, and fever. Three patients in the core protocol and one patient in the extension protocol experienced grade 3 skeletal pain, "flu-like" symptoms, or hypophosphatemia, which were possibly related to treatment; all recovered completely. Adverse events were reported with similar frequency across all of the dosage groups. Zoledronic acid resulted in sustained, dose-dependent decreases in urinary markers of bone resorption. Zoledronic acid was safe and well tolerated and demonstrated potent inhibition of bone resorption.

Compost liquor bioremediation using waste materials as biofiltration media.

Compost liquor results from the percolation of precipitation through composting waste; the release of liquids from high moisture content feedstocks; and as a result of runoff from hard surfaces and machinery. This research aimed to establish the potential for waste materials to act as media for low-cost compost liquor biofilters. Six types of potential biofilter media were packed into experimental biofilters (1 m long x 0.11 m diameter) and irrigated with compost liquor (organic loading rate of 0.6 kg/m3/d) for three months. The pH, BOD5, NH3/NH4+, and phytotoxicity of the effluent was monitored regularly. Natural, organic materials (oversize, compost and wood mulch) performed best, when compared to synthetic materials such as polystyrene packaging or inert materials such as broken brick. On average, the best media achieved 78% removal of both BOD5 and ammoniacal nitrogen during the study period. Although significant improvements in liquor quality were achieved, the effluent remained heavily polluted.