•Relative tissue expression of caprine SIRT3 was higher (p≤0.05) in muscle, followed by uterus, liver and ovary.•Two novel non-synonymous SNPs (c.802C > T and c.835 G > A) were detected in exon 6 of ...caprine SIRT3 by PCR-SSCP.•Diplotypes of exon 6 fragment had a significant (p ≤ 0.01) association with body weight in goats.
Sirtuin3 (SIRT3), a NAD+ dependent deacetylase, play a predominant role to control various metabolic processes involved in mammalian energy homeostasis. A study was conducted on two native goat breeds of Kerala, Malabari and Attappady Black, to analyze the tissue expression profile of caprine SIRT3, detect potential polymorphisms in exon 6 of SIRT3 and to study their association with production traits in goats. The mRNA isolated from ovary, uterus, liver and muscle of Malabari and Attappady Black goats were subjected to quantitative PCR (qPCR). Relative expression of caprine SIRT3 was significantly (p ≤ 0.05) higher in muscle, followed by uterus, liver and ovary. DNA was isolated from a total of 282 goats (176 Malabari and 106 Attappady Black) which exhibited three distinct banding patterns (PP, PQ and PR) for exon 6 fragment of SIRT3, on PCR-SSCP analysis. Sequencing the representative PCR products revealed the presence of two novel non-synonymous SNPs (c.802C > T and c.835 G > A) in the amplicon. The effect of the amino acid substitution on protein function was predicted by PolyPhen-2 tool which indicated that the amino acid change at position 802 was probably damaging and that at position 835 was benign. Further association analysis revealed that the diplotypes of exon 6 fragment had a significant (p ≤ 0.01) association with body weight. PR diplotpye was observed to be superior to PP and PQ diplotypes. All these results highlight the role of SIRT3 in growth traits and thus SIRT3 may be considered as a potential candidate gene for the production traits of goats.
Medication error in developed countries is of primary concern when there is a question of adversity to a patient's health, but in developing countries like India, it is just a term and its ...significance is undervalued. The incidence of medication error is essential to estimate the proper medical care provided in the healthcare system.
The main objective of the study is to determine the incidences of medication error in critical care unit and to evaluate its risk outcomes.
This is a prospective observational study conducted over a period of 6 months in a critical care unit of a tertiary care hospital. Medication chart review method was opted for data collection. The medication errors were mainly classified as prescription, transcription, indenting, dispensing, and administration error. A total of 6,705 charts were reviewed. The NCCMERP risk index was used to evaluate the outcome of errors.
Of the total 6,705 charts, 410 medication errors were found, i.e., 6.11%. The most common error is transcription error that constitutes 44.1% of the total errors, followed by prescription error 40%, and administration error 14%. The frequency of indenting and dispensing errors is negligible with 1.5% and 0.5%, respectively. The main causes of medication errors are due to incomplete prescription 50.2% and wrong doses 22.9%. In drug class, antibiotics and antihypertensive agents are most prone to medication error. About 87.1% errors belonged to the Category B of National Coordinating Council for Medication Error Reporting and Prevention risk index.
Majority of the errors are transcription errors followed by prescription and administration errors. Consultant doctors have to be more vigilant during prescribing and verifying the medication charts. Clinical pharmacists should act as a checkpoint at each step of medication process to identify and prevent medication errors.
Zirpe KG, Seta B, Gholap S, Aurangabadi K, Gurav SK, Deshmukh AM,
Incidence of Medication Error in Critical Care Unit of a Tertiary Care Hospital: Where Do We Stand? Indian J Crit Care Med 2020;24(9):799-803.
Screening mammography and magnetic resonance imaging (MRI) are recommended for women with ATM, CHEK2, and PALB2 pathogenic variants. However, there are few data to guide screening regimens for these ...women.
To estimate the benefits and harms of breast cancer screening strategies using mammography and MRI at various start ages for women with ATM, CHEK2, and PALB2 pathogenic variants.
This comparative modeling analysis used 2 established breast cancer microsimulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate different screening strategies. Age-specific breast cancer risks were estimated using aggregated data from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium for 32 247 cases and 32 544 controls in 12 population-based studies. Data on screening performance for mammography and MRI were estimated from published literature. The models simulated US women with ATM, CHEK2, or PALB2 pathogenic variants born in 1985.
Screening strategies with combinations of annual mammography alone and with MRI starting at age 25, 30, 35, or 40 years until age 74 years.
Estimated lifetime breast cancer mortality reduction, life-years gained, breast cancer deaths averted, total screening examinations, false-positive screenings, and benign biopsies per 1000 women screened. Results are reported as model mean values and ranges.
The mean model-estimated lifetime breast cancer risk was 20.9% (18.1%-23.7%) for women with ATM pathogenic variants, 27.6% (23.4%-31.7%) for women with CHEK2 pathogenic variants, and 39.5% (35.6%-43.3%) for women with PALB2 pathogenic variants. Across pathogenic variants, annual mammography alone from 40 to 74 years was estimated to reduce breast cancer mortality by 36.4% (34.6%-38.2%) to 38.5% (37.8%-39.2%) compared with no screening. Screening with annual MRI starting at 35 years followed by annual mammography and MRI at 40 years was estimated to reduce breast cancer mortality by 54.4% (54.2%-54.7%) to 57.6% (57.2%-58.0%), with 4661 (4635-4688) to 5001 (4979-5023) false-positive screenings and 1280 (1272-1287) to 1368 (1362-1374) benign biopsies per 1000 women. Annual MRI starting at 30 years followed by mammography and MRI at 40 years was estimated to reduce mortality by 55.4% (55.3%-55.4%) to 59.5% (58.5%-60.4%), with 5075 (5057-5093) to 5415 (5393-5437) false-positive screenings and 1439 (1429-1449) to 1528 (1517-1538) benign biopsies per 1000 women. When starting MRI at 30 years, initiating annual mammography starting at 30 vs 40 years did not meaningfully reduce mean mortality rates (0.1% 0.1%-0.2% to 0.3% 0.2%-0.3%) but was estimated to add 649 (602-695) to 650 (603-696) false-positive screenings and 58 (41-76) to 59 (41-76) benign biopsies per 1000 women.
This analysis suggests that annual MRI screening starting at 30 to 35 years followed by annual MRI and mammography at 40 years may reduce breast cancer mortality by more than 50% for women with ATM, CHEK2, and PALB2 pathogenic variants. In the setting of MRI screening, mammography prior to 40 years may offer little additional benefit.
The rhoptry proteome of Eimeria tenella sporozoites Oakes, Richard D.; Kurian, Dominic; Bromley, Elizabeth ...
International journal for parasitology,
February 2013, 2013-Feb, 2013-02-00, 20130201, Letnik:
43, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Display omitted .
► Nine independent preparations of Eimeria tenella sporozoite rhoptries were analysed. ► Mass spectrometry was carried out on 1-DE and 2-DE separated proteins. ► 347 targets were ...identified including orthologues of known RONs and ROPs and novel proteins. ► Many of the RON proteins were differentially expressed between parasite stages. ► Two ROP kinases were found in the sporozoite rhoptry proteome.
Proteins derived from the rhoptry secretory organelles are crucial for the invasion and survival of apicomplexan parasites within host cells. The rhoptries are club-shaped organelles that contain two distinct subpopulations of proteins that localise to separate compartments of the organelle. Proteins from the neck region (rhoptry neck proteins, RON) are secreted early in invasion and a subset of these is critical for the formation and function of the moving junction between parasite and host membranes. Proteins from the bulb compartment (rhoptry protein, ROP) are released later, into the nascent parasitophorous vacuole where they have a role in modifying the vacuolar environment, and into the host cell where they act as key determinants of virulence through their ability to interact with host cell signalling pathways, causing an array of downstream effects. In this paper we present the results of an extensive proteomics analysis of the rhoptry organelles from the coccidian parasite, Eimeria tenella, which is a highly pathogenic parasite of the domestic chicken causing severe caecal coccidiosis. Several different classes of rhoptry protein have been identified. First are the RON proteins that have varying degrees of similarity to proteins of Toxoplasma gondii and Neospora caninum. For some RON families, E. tenella expresses more than one gene product and many of the individual RON proteins are differentially expressed between the sporozoite and merozoite developmental stages. The E. tenella sporozoite rhoptry expresses only a limited repertoire of proteins with homology to known ROP proteins from other coccidia, including just two secreted ROP kinases, both of which appear to be equipped for catalytic activity. Finally, a large number of hitherto undescribed proteins that map to the sporozoite rhoptry are identified, many of which have orthologous proteins encoded within the genomes of T. gondii and N. caninum.
The human dopaminergic system is vital for a broad range of neurological processes, including the control of voluntary movement. Here we report a proband presenting with clinical features of dopamine ...deficiency: severe infantile parkinsonism-dystonia, characterised by frequent oculogyric crises, dysautonomia and global neurodevelopmental impairment. CSF neurotransmitter analysis was unexpectedly normal. Triome whole-genome sequencing revealed a homozygous variant (c.110C>A, (p.T37K)) in DRD1, encoding the most abundant dopamine receptor (Dsub.1 ) in the central nervous system, most highly expressed in the striatum. This variant was absent from gnomAD, with a CADD score of 27.5. Using an in vitro heterologous expression system, we determined that DRD1-T37K results in loss of protein function. Structure-function modelling studies predicted reduced substrate binding, which was confirmed in vitro. Exposure of mutant protein to the selective Dsub.1 agonist Chloro APB resulted in significantly reduced cyclic AMP levels. Numerous Dsub.1 agonists failed to rescue the cellular defect, reflected clinically in the patient, who had no benefit from dopaminergic therapy. Our study identifies DRD1 as a new disease-associated gene, suggesting a crucial role for the Dsub.1 receptor in motor control.
Breast Cancer Risk Reduction, Version 2.2015 Bevers, Therese B; Ward, John H; Arun, Banu K ...
Journal of the National Comprehensive Cancer Network
13, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Breast cancer is the most frequently diagnosed malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. To assist women who are at increased risk of ...developing breast cancer and their physicians in the application of individualized strategies to reduce breast cancer risk, NCCN has developed these guidelines for breast cancer risk reduction.
Gliomas are a group of primary brain tumors, the most common and aggressive subtype of which is glioblastoma. Glioblastoma has a median survival of just 15 months after diagnosis. Only previous ...exposure to ionizing radiation and particular inherited genetic syndromes are accepted risk factors for glioma; the vast majority of cases are thought to occur spontaneously. Previous observational studies have described associations between several risk factors and glioma, but studies are often conflicting and whether these associations reflect true casual relationships is unclear because observational studies may be susceptible to confounding, measurement error and reverse causation. Mendelian randomization (MR) is a form of instrumental variable analysis that can be used to provide supporting evidence for causal relationships between exposures (e.g., risk factors) and outcomes (e.g., disease onset). MR utilizes genetic variants, such as single nucleotide polymorphisms (SNPs), that are robustly associated with an exposure to determine whether there is a causal effect of the exposure on the outcome. MR is less susceptible to confounding, reverse causation and measurement errors as it is based on the random inheritance during conception of genetic variants that can be relatively accurately measured. In previous studies, MR has implicated a genetically predicted increase in telomere length with an increased risk of glioma, and found little evidence that obesity related factors, vitamin D or atopy are causal in glioma risk. In this review, we describe MR and its potential use to discover and validate novel risk factors, mechanistic factors, and therapeutic targets in glioma.
The prevalence and penetrance of
BRCA1
and
BRCA2
(
BRCA1/2
) mutations may differ between Asians and whites. We investigated
BRCA1/2
mutations and cancer risk factors in a clinic-based sample.
...BRCA1/2
mutation carriers were enrolled from cancer genetics clinics in Hong Kong and California according to standardized entry criteria. We compared BRCA mutation position, cancer history, hormonal and reproductive exposures. We analyzed DNA samples for single-nucleotide polymorphisms reported to modify breast cancer risk. We performed logistic regression to identify independent predictors of breast cancer. Fifty Asian women and forty-nine white American women were enrolled.
BRCA1
mutations were more common among whites (67 vs. 42 %,
p
= 0.02), and
BRCA2
mutations among Asians (58 vs. 37 %,
p
= 0.04). More Asians had breast cancer (76 vs. 53 %,
p
= 0.03); more whites had relatives with breast cancer (86 vs. 50 %,
p
= 0.0003). More whites than Asians had breastfed (71 vs. 42 %,
p
= 0.005), had high BMI (median 24.3 vs. 21.2,
p
= 0.04), consumed alcohol (2 drinks/week vs. 0,
p
< 0.001), and had oophorectomy (61 vs. 34 %,
p
= 0.01). Asians had a higher frequency of risk-associated alleles in
MAP3K1
(88 vs. 59 %,
p
= 0.005) and
TOX3/TNRC9
(88 vs. 55 %,
p
= 0.0002). On logistic regression,
MAP3K1 was
associated with increased breast cancer risk for
BRCA2,
but not
BRCA1
mutation carriers; breast density was associated with increased risk among Asians but not whites. We found significant differences in breast cancer risk factors between Asian and white
BRCA1/2
mutation carriers. Further investigation of racial differences in
BRCA1/2
mutation epidemiology could inform targeted cancer risk-reduction strategies.
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