We performed this study to longitudinally compare rates of stunting, wasting and underweight among low birthweight (LBW), non-LBW, and/or small-for-gestational age (SGA) and non-SGA infants in Leyte, ...The Philippines and factors that predicted catch up. Birthweights of 357 infants born in Leyte, The Philippines were obtained within 48 hours of delivery and infants were evaluated at one, six and 12 months. Newborns were classified as LBW, SGA, or both. We derived length-for-age, weight-for-length and weight-for-age Z-scores using WHOAnthro. Generalized estimating equations models were used to compare the differences in prevalence and mean Z-scores for these growth and nutritional outcomes, with separate models made with LBW and SGA as distinct primary predictors. We compared the longitudinal risk of stunting, wasting and underweight during infancy among LBW versus non-LBW and SGA versus non-SGA infants, while also evaluating key potential confounding, explanatory and modifying covariates. Overall, 9.0% of infants were born prematurely, 14.0% of infants were LBW and 22.9% were SGA. LBW infants had significantly increased odds of stunting, wasting and underweight persisting to 12 months of age, and SGA infants had significantly increased odds of stunting and underweight. LBW and SGA infants had higher rates of weight-for-length gain in the first month of life. Maternal educational attainment and exclusive breastfeeding decreased the risk of stunting and undernutrition. In this setting, LBW and SGA infants have higher rates of growth stunting and undernutrition during the first year of life and do not exhibit catch-up growth by 12 months of age. Clinical Trial Registration NCT00486863
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE:To estimate whether there is a gender difference in scholarly productivity among academic gynecologic oncologists.
METHODS:In this cross-sectional study, the academic rank and gender of ...gynecologic oncology faculty in the United States were determined from online residency and fellowship directories and departmental web sites. Each individualʼs h-index and years of publication were determined from Scopus (a citation database of peer-reviewed literature). The h-index is a quantification of an authorʼs scholarly productivity that combines the number of publications with the number of times the publications have been cited. We generated descriptive statistics and compared rank, gender, and productivity scores.
RESULTS:Five hundred seven academic faculty within 137 U.S. teaching programs were identified. Of these, 215 (42%) were female and 292 (58%) were male. Men had significantly higher median h-indices than women, 16 compared with 8, respectively (P<.001). Women were more likely to be of junior academic rank with 63% of assistant professors being female compared with 20% of full professors. When stratifying h-indices by gender and academic rank, men had significantly higher h-indices at the assistant professor level (7 compared with 5, P<.001); however, this difference disappeared at the higher ranks. Stratifying by the years of active publication, there was no significant difference between genders.
CONCLUSION:Female gynecologic oncologists at the assistant professor level had lower scholarly productivity than men; however, at higher academic ranks, they equaled their male counterparts. Women were more junior in rank, had published for fewer years, and were underrepresented in leadership positions.
LEVEL OF EVIDENCE:III
The utility of cells cultured from the mitral valve as models of myxomatous diseases needs to be properly validated. In this study valve interstitial cells (VICs) and valve endothelial cells (VECs) ...were cultured from normal and diseased canine mitral valves in 2% (v/v) or 10% FBS media, in the presence of TGFβ1, 2 and 3, the TGFβ RI kinase inhibitor SB431542 and TGFβ neutralising antibodies, 5HT and the 5HT2RB antagonist LY272015. Cultures were examined by morphology, transcriptomic profiling, protein expression of the cell specific markers αSMA and SM22α (VICs), and CD31 (VECs), deposition of proteoglycans (PG), the PG versican, and the TGFβs themselves. VECs derived from normal valves were CD31+/αSMA-, but those from diseased valves were αSMA+, indicating endothelial-to-mesenchymal (EndoMT) transition had occurred. The TGFβs induced EndoMT in normal VECs, and this was abolished by SB431542, with significant changes in αSMA, CD31 and HAS2 expression (P<0.05). Normal VICs cultured in 10% FBS media were αSMA+ (activated myofibroblast (disease) phenotype), but were αSMA- when grown in 2% FBS. VICs from diseased dogs were αSMA+ in 2% FBS (retention of the activated myofibroblast disease phenotype), with significantly increased TGFβ1 expression (P<0.05) compared to normal cells. Treatment of normal and diseased VICs with the TGFβs significantly increased expression of αSMA, SM22α, versican, the TGFβs themselves, and deposition of PGs (P<0.05), with TGFβ1 being the most potent activator. These effects were either abolished or markedly reduced by SB431542 and a pan-TGFβ neutralizing antibody (P<0.05). SB431542 also markedly reduced αSMA expression in VICs from diseased valves, but 5HT and LY272015 had no effect on VIC phenotype. Transcriptomic profiling identified clear differences in gene expression for the different conditions and treatments that partially matched that seen in native diseased valve tissue, including changes in expression of ACTA2 (αSMA), 5HTR2B, TAGLN (SM22α) and MYH10 (SMemb), gene ontology terms and canonical signalling pathways. Normal and diseased VICs and normal VECs from canine mitral valves can be successfully grown in culture with retention of phenotype, which can be manipulated using TGFβ1 and the TGFβ RI kinase inhibitor SB431542. This optimized cell system can now be used to model MMVD to elucidate disease mechanisms and identify key regulators of disease progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PREMISE OF THE STUDY:
Symbioses are almost universal, but little is known about how symbiont abundance can affect host performance. Many orchids undergo vegetative dormancy and frequent and ...protracted dormancy have been associated with population declines. If mycorrhizal fungi affect host plant performance, those effects are likely to alter patterns of vegetative dormancy. The goal of this study was to determine whether the abundance of mycorrhizal fungi is related to the likelihood of entering dormancy and whether fungal abundance varied with dormancy duration in the federally listed threatened orchid Isotria medeoloides.
METHODS:
We studied three populations of the threatened North American terrestrial orchid Isotria medeoloides using long‐term emergence data and evaluated the relationship between the abundance of associated mycorrhizal fungi (Russulaceae) and orchid dormancy and emergence. Mycorrhizal fungi in soil adjacent to orchids were quantified in two ways. First, ectomycorrhizal (ECM) fungi on adjacent root tips were identified using DNA sequencing to determine their phylogenetic relationship to fungi that are known to form mycorrhizae with I. medeoloides. Second, we extracted DNA from soil samples and used quantitative real‐time PCR to estimate the abundance of Russulaceae hyphae adjacent to each orchid.
KEY RESULTS:
We found that the abundance of Russulaceae, both in the soil and on nearby ECM root tips, was significantly related to orchid prior emergence. Both abundance and prior emergence history were predictive of future emergence.
CONCLUSIONS:
These results suggest that the abundance of mycorrhizal fungi can influence orchid population dynamics and is an essential component of orchid conservation.
Myxomatous mitral valve disease (MMVD) is the single most important acquired cardiovascular disease of the dog. Much is known about the cellular changes and the contribution of activated ...myofibroblasts (valve interstitial cells (aVICs) to the valve extra-cellular matrix remodelling characteristic of the disease. However, little is known on how aVIC survival might contribute to disease pathogenesis. This study examined the temporal (disease severity-dependent) and spatial distribution of aVICs in MMVD valves, the expression of a range of apoptosis-related genes in cultured VICs from both normal (quiescent VIC (qVIC) and diseased (aVIC) valves, and the differential effects of doxorubicin treatment, as a trigger of apoptosis, on expression of the same genes. Activated myofibroblasts were identified in normal valves at the valve base only (the area closest to the annulus), and then became more numerous and apparent along the valve length as the disease progressed, with evidence of cell survival at the valve base. There were no significant differences in basal gene expression comparing qVICs and aVICs for CASP3, FAS, BID, BAX, BCL2, CASP8, DDIAS, XIAP and BIRC5. After doxorubicin treatment (2 mM) for 8 h there was significant difference (P < .05) in the expression of BID, BCL2, DDIAS, and CASP8, but when assessed for interactions using a mixed model ANOVA only CASP8 was significantly different because of treatment (P < .05). These data suggest aVIC survival in MMVD valves may be a consequence of heightened resistance of aVICs to apoptosis, but would require confirmation examining expression of the relevant proteins.
•Activated myofibroblasts are persistent in myxomatous mitral valve disease (MMVD).•Apoptosis gene expression are comparable in normal and diseased mitral valve VICs.•Doxorubicin induces differential expression of apoptotic genes in normal and diseased VICs.•CASP8 expression is significantly different in diseased VICs treated with doxorubicin.•Activated myofibroblast persistence in MMVD may be due to resistance to apoptosis.
Aims
Women with gestational diabetes mellitus (GDM) require postpartum glucose screening, as they have a 70% lifetime risk of developing Type 2 diabetes mellitus. However, less than half complete ...postpartum screening.
Methods
We conducted a retrospective chart review of patients who delivered at our institution from 2001 to 2019. Inclusion criteria were patients with gestational diabetes who were at least 18 years old and had delivered an infant at >24 weeks of gestation. Our primary outcome was completion of postpartum gestational diabetes screening.
Results
The majority of patients (62%) did not complete screening. After adjusted risk ratio analyses, the only variables that remained significantly associated with an increased likelihood of completing screening were Asian race and having prenatal care at one particular community health center, which served a predominantly Asian population.
Conclusions
This community health center protocol for scheduling patients with GDM that complied with recommendations for postpartum care, indicating that evidence‐based methods can improve maternal health.
Mitochondrial oxidative phosphorylation (OXPHOS) dysfunction is implicated in a growing spectrum of diseases, from neurodegeneration to cancer. Where tissues or transformed cells are available, ...respirometry and enzymology allow a sophisticated analysis of OXPHOS with modest-cost equipment. The isolation of organelle fractions is also invaluable for determining association of proteins of interest. Here we revisit and consolidate methods to measure whole cell mitochondrial ATP synthesis, respiration, isolation of mitochondria from cultured cells and tissues, and OXPHOS enzymology. We also explain common pitfalls, guide optimisation of the methods for new users, and provide full laboratory protocols in Supplementary materials.
Associations between chronic diabetes complications and mitochondrial dysfunction represent a subject of major importance, given the diabetes pandemic and high personal and socioeconomic costs of ...diabetes and its complications. Modelling diabetes complications in inbred laboratory animals is challenging due to incomplete recapitulation of human features, but offer mechanistic insights and preclinical testing. As mitochondrial-based oxidative stress is implicated in human diabetic complications, herein we evaluate diabetes in a unique mouse model that harbors a mitochondrial DNA from a divergent mouse species (the 'xenomitochondrial mouse'), which has mild mitochondrial dysfunction and increased oxidative stress. We use the streptozotocin-induced diabetes model with insulin supplementation, with 20-weeks diabetes. We compare C57BL/6 mice and the 'xenomitochondrial' mouse, with measures of heart and kidney function, histology, and skin oxidative stress markers. Compared to C57BL/6 mice, the xenomitochondrial mouse has increased diabetic heart and kidney damage, with cardiac dysfunction, and increased cardiac and renal fibrosis. Our results show that mitochondrial oxidative stress consequent to divergent mtDNA can worsen diabetes complications. This has implications for novel therapeutics to counter diabetes complications, and for genetic studies of risk, as mtDNA genotypes may contribute to clinical outcomes.
OBJECTIVE To evaluate eicosanoid concentrations in freshly prepared canine packed RBCs (PRBCs) and to assess changes in eicosanoid concentrations in PRBC units over time during storage and under ...transfusion conditions. DESIGN Prospective study. SAMPLE 25 plasma samples from 14 healthy Greyhounds. PROCEDURES Plasma samples were obtained during PRBC preparation (donation samples), and the PRBC units were then stored at 4°C until used for transfusion (≤ 21 days later; n = 17) or mock transfusion if expired (22 to 24 days later; 8). Immediately prior to use, 100 mL of saline (0.9% NaCl) solution was added to each unit and a pretransfusion sample was collected. A posttransfusion sample was collected after transfusion or mock transfusion. Concentrations of arachidonic acid, prostaglandin (PG) F
, PGE
, PGD
, thromboxane B
, 6-keto-PGF
, and leukotriene B
were measured by liquid chromatography-mass spectrometry and analyzed statistically. RESULTS Median arachidonic acid concentration was significantly decreased in posttransfusion samples, compared with the concentration in donation samples. Median PGF
, 6-keto-PGF
, and leukotriene B
concentrations were significantly increased in pretransfusion samples, compared with those in donation samples. Median PGF
, thromboxane B
, and 6-keto-PGF
concentrations were significantly increased in posttransfusion samples, compared with those in pretransfusion samples. Duration of PRBC storage had significant associations with pretransfusion and posttransfusion arachidonic acid and thromboxane B
concentrations. CONCLUSIONS AND CLINICAL RELEVANCE Concentrations of several proinflammatory eicosanoids increased in PRBC units during storage, transfusion, or both. Accumulation of these products could potentially contribute to adverse transfusion reactions, and investigation of the potential association between eicosanoid concentrations in PRBCs and the incidence of transfusion reactions in dogs is warranted.
Accumulation of neurotoxic amyloid-β (Aβ) is central to the pathology of Alzheimer's disease (AD). Elucidating the mechanisms of Aβ accumulation will therefore expedite the development of ...Aβ-targeting AD therapeutics. We examined activity of an Aβ-degrading protease (matrix metalloprotease 2) to investigate whether biochemical factors consistent with conditions in the AD brain contribute to Aβ accumulation by altering Aβ sensitivity to proteolytic degradation. An Aβ amino acid mutation found in familial AD, Aβ interactions with zinc (Zn), and increased Aβ hydrophobicity all strongly prevented Aβ degradation. Consistent to all of these factors is the promotion of specific Aβ aggregates where the protease cleavage site, confirmed by mass spectrometry, is inaccessible within an amyloid structure. These data indicate decreased degradation due to amyloid formation initiates Aβ accumulation by preventing normal protease activity. Zn also prevented Aβ degradation by the proteases neprilysin and insulin degrading enzyme. Treating Zn-induced Aβ amyloid with the metal-protein attenuating compound clioquinol reversed amyloid formation and restored the peptide's sensitivity to degradation by matrix metalloprotease 2. This provides new data indicating that therapeutic compounds designed to modulate Aβ-metal interactions can inhibit Aβ accumulation by restoring the catalytic potential of Aβ-degrading proteases.
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