ABSTRACT
Human consumption of long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) is below recommendations, and enriching chicken meat (by incorporating LC n-3 PUFA into broiler diets) is a ...viable means of increasing consumption. Fish oil is the most common LC n-3 PUFA supplement used but is unsustainable and reduces the oxidative stability of the mat. The objective of this experiment was to compare fresh fish oil (FFO) with fish oil encapsulated (EFO) in a gelatin matrix (to maintain its oxidative stability) and algal biomass at a low (LAG, 11), medium (MAG, 22), or high (HAG, 33 g/kg of diet) level of inclusion. The C22:6n-3 contents of the FFO, EFO, and MAG diets were equal. A control (CON) diet using blended vegetable oil was also made. As-hatched 1-d-old Ross 308 broilers (144) were reared (21 d) on a common starter diet then allocated to treatment pens (4 pens per treatment, 6 birds per pen) and fed treatment diets for 21 d before being slaughtered. Breast and leg meat was analyzed (per pen) for fatty acids, and cooked samples (2 pens per treatment) were analyzed for volatile aldehydes. Concentrations (mg/100 g of meat) of C20:5n-3, C22:5n-3, and C22:6n-3 were (respectively) CON: 4, 15, 24; FFO: 31, 46, 129; EFO: 18, 27, 122; LAG: 9, 19, 111; MAG: 6, 16, 147; and HAG: 9, 14, 187 (SEM: 2.4, 3.6, 13.1) in breast meat and CON: 4, 12, 9; FFO: 58, 56, 132; EFO: 63, 49, 153; LAG: 13, 14, 101; MAG: 11, 15, 102; HAG: 37, 37, 203 (SEM: 7.8, 6.7, 14.4) in leg meat. Cooked EFO and HAG leg meat was more oxidized (5.2 mg of hexanal/kg of meat) than the other meats (mean 2.2 mg/kg, SEM 0.63). It is concluded that algal biomass is as effective as fish oil at enriching broiler diets with C22:6 LC n-3 PUFA, and at equal C22:6n-3 contents, there is no significant difference between these 2 supplements on the oxidative stability of the meat that is produced.
The aim of this study was to identify modifiable risk factors associated with mortality in patients requiring revision total hip arthroplasty (THA) for periprosthetic hip fracture.
The electronic ...records of consecutive patients undergoing revision THA for periprosthetic hip fracture between December 2011 and October 2018 were reviewed. The data which were collected included age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, the preoperative serum level of haemoglobin, time to surgery, operating time, blood transfusion, length of hospital stay, and postoperative surgical and medical complications. Univariate and multivariate logistic regression analyses were used to determine independent modifiable factors associated with mortality at 90 days and one year postoperatively.
A total of 203 patients were identified. Their mean age was 78 years (44 to 100), and 108 (53%) were female. The median time to surgery was three days (interquartile range (IQR) 2 to 5). The mortality rate at one year was 13.8% (n = 28). The commonest surgical complication was dislocation (n = 22, 10.8%) and the commonest medical complication within 90 days of surgery was hospital-acquired pneumonia (n = 25, 12%). Multivariate analysis showed that the rate of mortality one year postoperatively was five-fold higher in patients who sustained a dislocation (odds ratio (OR) 5.03 (95% confidence interval (CI) 1.60 to 15.83); p = 0.006). The rate of mortality was also four-fold higher in patients who developed hospital-acquired pneumonia within 90 days postoperatively (OR 4.43 (95% CI 1.55 to 12.67); p = 0.005). There was no evidence that the time to surgery was a risk factor for death at one year.
Dislocation and hospital-acquired pneumonia following revision THA for a periprosthetic fracture are potentially modifiable risk factors for mortality. This study suggests that surgeons should consider increasing constraint to reduce the risk of dislocation, and the early involvement of a multidisciplinary team to reduce the risk of hospital-acquired pneumonia. We found no evidence that the time to surgery affected mortality, which may allow time for medical optimization, surgical planning, and resource allocation. Cite this article:
2020;102-B(5):580-585.
Polygenic inheritance plays a central role in Parkinson disease (PD). A priority in elucidating PD etiology lies in defining the biological basis of genetic risk. Unraveling how risk leads to ...disruption will yield disease-modifying therapeutic targets that may be effective. Here, we utilized a high-throughput and hypothesis-free approach to determine biological processes underlying PD using the largest currently available cohorts of genetic and gene expression data from International Parkinson’s Disease Genetics Consortium (IPDGC) and the Accelerating Medicines Partnership-Parkinson’s disease initiative (AMP-PD), among other sources. We applied large-scale gene-set specific polygenic risk score (PRS) analyses to assess the role of common variation on PD risk focusing on publicly annotated gene sets representative of curated pathways. We nominated specific molecular sub-processes underlying protein misfolding and aggregation, post-translational protein modification, immune response, membrane and intracellular trafficking, lipid and vitamin metabolism, synaptic transmission, endosomal–lysosomal dysfunction, chromatin remodeling and apoptosis mediated by caspases among the main contributors to PD etiology. We assessed the impact of rare variation on PD risk in an independent cohort of whole-genome sequencing data and found evidence for a burden of rare damaging alleles in a range of processes, including neuronal transmission-related pathways and immune response. We explored enrichment linked to expression cell specificity patterns using single-cell gene expression data and demonstrated a significant risk pattern for dopaminergic neurons, serotonergic neurons, hypothalamic GABAergic neurons, and neural progenitors. Subsequently, we created a novel way of building de novo pathways by constructing a network expression community map using transcriptomic data derived from the blood of PD patients, which revealed functional enrichment in inflammatory signaling pathways, cell death machinery related processes, and dysregulation of mitochondrial homeostasis. Our analyses highlight several specific promising pathways and genes for functional prioritization and provide a cellular context in which such work should be done.
Aims: To evaluate the expression of the intermediate filament desmin in reactive mesothelium and malignant mesothelioma and to compare its utility with five other previously reported immunomarkers ...claimed to be of use in distinguishing reactive from neoplastic mesothelium.
Methods and results: Sixty cases of malignant pleural mesothelioma and 40 cases of reactive mesothelial hyperplasia formed the study group. Cases were immunohistochemically stained with desmin, epithelial membrane antigen (EMA), p53, Bcl‐2, P‐glycoprotein and platelet‐derived growth factor receptor (PDGF‐R) β‐chain by the avidin–biotin complex method. The cohort of malignant pleural mesotheliomas were immunoreactive to desmin, EMA and p53 in 6/60 (10%), 48/60 (80%) and 27/60 (45%), respectively. In comparison, the cohort of reactive mesothelial hyperplasias were immunoreactive to desmin, EMA and p53 in 34/40 (85%), 8/40 (20%) and 0/40 (0%), respectively. In a smaller cohort (n = 15) of malignant pleural mesotheliomas, Bcl‐2, P‐glycoprotein and PDGF‐R β‐chain were expressed in 0/15 (0%), 2/15 (13%) and 15/15 (100%), respectively. In a small cohort (n = 15) of reactive mesothelial hyperplasias, Bcl‐2, P‐glycoprotein and PDGF‐R β‐chain were immunoreactive in 0/15 (0%), 0/15 (0%) and 6/15 (40%), respectively.
Conclusions: Desmin and EMA appear to be the most useful markers in distinguishing benign from malignant mesothelial proliferations. Desmin appears to be preferentially expressed in reactive mesothelium and EMA appears to be preferentially expressed in neoplastic mesothelium. The complementary use of both markers is advocated in ascertaining the nature of mesothelial proliferations. Immunohistochemical detection of mutated p53 oncoprotein appeared to be of less utility in this study on account of the low marker sensitivity for malignant mesothelioma. However, p53 antibody may be of use as a second‐line marker of neoplastic mesothelium within a standard immunohistochemical panel of antibodies. In this study, Bcl‐2, P‐glycoprotein and PDGF‐R β‐chain appear to be of no use in distinguishing reactive from neoplastic mesothelium, although more formal evaluation of these markers is required.
GRM3, a metabotropic glutamate receptor-modulating synaptic glutamate, is a promising schizophrenia candidate gene. In a family-based association study, a common GRM3 haplotype was strongly ...associated with schizophrenia (P = 0.0001). Within this haplotype, the A allele of single-nucleotide polymorphism (SNP) 4 (hCV11245618) in intron 2 was slightly overtransmitted to probands (P = 0.02). We studied the effects of this SNP on neurobiological traits related to risk for schizophrenia and glutamate neurotransmission. The SNP4 A allele was associated with poorer performance on several cognitive tests of prefrontal and hippocampal function. The physiological basis of this effect was assessed with functional MRI, which showed relatively deleterious activation patterns in both cortical regions in control subjects homozygous for the SNP4 A allele. We next looked at SNP4′s effects on two indirect measures of prefrontal glutamate neurotransmission. Prefrontal N-acetylaspartate, an in vivo MRI measure related to synaptic activity and closely correlated with tissue glutamate, was lower in SNP4 AA homozygotes. In postmortem human prefrontal cortex, AA homozygotes had lower mRNA levels of the glial glutamate transporter EAAT2, a protein regulated by GRM3 that critically modulates synaptic glutamate. Effects of SNP4 on prefrontal GRM3 mRNA and protein levels were marginal. Resequencing revealed no missense or splice-site SNPs, suggesting that the intronic SNP4 or related haplotypes may exert subtle regulatory effects on GRM3 transcription. These convergent data point to a specific molecular pathway by which GRM3 genotype alters glutamate neurotransmission, prefrontal and hippocampal physiology and cognition, and thereby increased risk for schizophrenia.
CHARGE syndrome is a well-established multiple-malformation syndrome with distinctive consensus diagnostic criteria. Characteristic associated anomalies include ocular coloboma, choanal atresia, ...cranial nerve defects, distinctive external and inner ear abnormalities, hearing loss, cardiovascular malformations, urogenital anomalies, and growth retardation. Recently, mutations of the chromodomain helicase DNA-binding protein gene
CHD7 were reported to be a major cause of CHARGE syndrome. We sequenced the
CHD7 gene in 110 individuals who had received the clinical diagnosis of CHARGE syndrome, and we detected mutations in 64 (58%). Mutations were distributed throughout the coding exons and conserved splice sites of
CHD7. Of the 64 mutations, 47 (73%) predicted premature truncation of the protein. These included nonsense and frameshift mutations, which most likely lead to haploinsufficiency. Phenotypically, the mutation-positive group was more likely to exhibit cardiovascular malformations (54 of 59 in the mutation-positive group vs. 30 of 42 in the mutation-negative group;
P
=.014), coloboma of the eye (55 of 62 in the mutation-positive group vs. 30 of 43 in the mutation-negative group;
P
=.022), and facial asymmetry, often caused by seventh cranial nerve abnormalities (36 of 56 in the mutation-positive group vs. 13 of 39 in the mutation-negative group;
P
=.004). Mouse embryo whole-mount and section in situ hybridization showed the expression of
Chd7 in the outflow tract of the heart, optic vesicle, facio-acoustic preganglion complex, brain, olfactory pit, and mandibular component of the first branchial arch. Microarray gene-expression analysis showed a signature pattern of gene-expression differences that distinguished the individuals with CHARGE syndrome with
CHD7 mutation from the controls. We conclude that cardiovascular malformations, coloboma, and facial asymmetry are common findings in CHARGE syndrome caused by
CHD7 mutation.
The von Willebrand factor (VWF) gene is highly polymorphic, with variants correlated with VWF antigen levels, adhesion activity, clearance and factor VIII binding. VWF mutations are detected in ...patients with von Willebrand disease (VWD), whereas polymorphic variants could be associated with thrombosis. However, information on the ethnic diversity of VWF variants and their association with diseases is limited.
To characterize novel VWF variants from different ethnicities in the general population.
We analyzed samples from 1092 subjects of 14 ethnicities available in the 1000 Genomes database for VWF variants and their potential functional impacts.
We identified 2728 SNPs and 91 insertions and deletions that had a high level of ethnic diversity, with Africans having the highest number of variants. The highest level of diversity was found in the D' and D2 domains. Among 94 non-synonymous variants, 31 were predicted to be deleterious, including 19 that were previously associated with VWD. Most of these 'VWD variants' had allele frequencies consistent with disease incidence in European subjects, but some had a significantly higher frequency in other ethnicities. The mutations R2185Q, H817Q and M740I associated with type 1 and type 2N VWD were present in more than 13% of African subjects.
These results highlight the complexity of VWF variations in different ethnic groups and emphasize the importance of interrogating variations on multiple ethnic backgrounds for associations with bleeding and thrombosis.
Hypotension is common after spinal local anaesthesia for caesarean section. However, the substandard treatment of spinal hypotension and associated complications are responsible for up to two-thirds ...of deaths that occur in South Africa (SA) for caesarean section under spinal anaesthesia. In some cases, spinal hypotension may be predicted by simple parameters such as age >25 years, preoperative heart rate >90 bpm and preoperative mean arterial pressure <90 mmHg. Heart rate variability and point-of-care echocardiography also predict hypotension with greater accuracy, but are limited by equipment and training issues. Spinal anaesthesia is absolutely contraindicated if the parturient is hypovolaemic. Left lateral tilt is still advised, despite the absence of strong supporting evidence. The dose of spinal bupivacaine should not be reduced in obese patients. Crystalloid co-loading is an adequate fluid strategy in most cases, but is of limited efficacy in the prevention of hypotension. It is imperative that immediately after the patient is placed supine, close attention is paid to communication with her, heart rate changes and pulse volume. Early intervention with phenylephrine is the first-line approach for hypotension if heart rate is preserved under spinal anaesthesia. Phenylephrine infusions (25 - 50 μg/min) are easy to administer, maintain baseline maternal haemodynamics and are applicable to the SA context. The vigilant use of phenylephrine boluses (50 - 100 μg), targeting maternal heart rate as a surrogate for cardiac output, is also effective. Noradrenaline has been used successfully to prevent spinal hypotension, but evidence does not yet suggest practice change. Local and international guidelines have recently been published.
Because ambient temperature strongly influences reproduction in frogs, the seasonal timing of frog calling provides a sensitive index of biotic response to climate change. Over the last century, ...daily temperatures increased during 5 of the 8 months key to gametogenesis in frogs and toads near Ithaca, New York (U.S.A.). Earliest dates of calling frogs recorded by Albert Hazen Wright between 1900 and 1912 near Ithaca were compared to those from the New York State Amphibian and Reptile Atlas Project for 1990-1999 for the three counties surrounding Ithaca. Four species are now calling 10-13 days earlier, two are unchanged, and none is calling later. The data suggest that climate has warmed in central New York State during this century and has resulted in earlier breeding in some amphibians-a possible first indication of biotic response to climate change in eastern North America.
Background: There have been few inter-observer studies of diffuse parenchymal lung disease (DPLD), but the recent ATS/ERS consensus classification provides a basis for such a study. Methods: A method ...for categorising numerically the percentage likelihood of these differential diagnoses was developed, and the diagnostic confidence of pathologists using this classification and the reproducibility of their diagnoses were assessed. Results: The overall kappa coefficient of agreement for the first choice diagnosis was 0.38 (n = 133 biopsies), increasing to 0.43 for patients (n = 83) with multiple biopsies. Weighted kappa coefficients of agreement, quantifying the level of probability of individual diagnoses, were moderate to good (mean 0.58, range 0.40–0.75). However, in 18% of biopsy specimens the diagnosis was given with low confidence. Over 50% of inter-observer variation related to the diagnosis of non-specific interstitial pneumonia and, in particular, its distinction from usual interstitial pneumonia. Conclusion: These results show that the ATS/ERS classification can be applied reproducibly by pathologists who evaluate DPLD routinely, and support the practice of taking multiple biopsy specimens.
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