41 research outputs found
Analysis of Salmonella enterica Serotype Paratyphi A Gene Expression in the Blood of Bacteremic Patients in Bangladesh
Salmonella enterica serotype Paratyphi A is a significant and emerging global public health problem and accounts for one fifth of all cases of enteric fever in many areas of Asia. S. Paratyphi A only infects humans, and the lack of an appropriate animal model has limited the study of S. Paratyphi A infection. In this study, we report the application of an RNA analysis method, Selective Capture of Transcribed Sequences (SCOTS), to evaluate which S. Paratyphi A genes are expressed directly in the blood of infected humans. Our results provide insight into the bacterial adaptations and modifications that S. Paratyphi A may need to survive within infected humans and suggest that similar approaches may be applied to other pathogens in infected humans and animals
Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial
Background
Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
Methods
RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
Findings
Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
Interpretation
Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population
Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial
Background
Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.
Methods
RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and
ClinicalTrials.gov
,
NCT00541047
.
Findings
Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths.
Interpretation
Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.
Funding
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society
Not Available
Not AvailableClimate change associated heat stress was
established to be the crucial factor, which negatively
influences animal production. The animals possess several
adaptive mechanisms which are helpful for their survival in
harsh environmental conditions, but while doing so their
productive performances are compromised. Among the
various mechanisms, which helps to maintain homeostasis in
animals, Physiological adaptability was considered one of the
primary response mechanisms by which the heat stressed
animals survive the heat stress. This review is therefore an
attempt to provide the audience an updated review on the
subject to signify the importance of physiological responses in
animals and their role in surviving the stressful environment.
Respiration rate (RR), pulse rate (PR), rectal temperature
(RT), sweating rate (SR) and skin temperature (ST) are the
cardinal physiological variables which helps to maintain the
heat balance and homeostasis in the stressed animals. Among
the various physiological variables, RR, RT and ST were
established to be ideal indicators for quantifying heat stress in
several farm animals. Therefore, these variables can be
effectively used to assess the severity of heat stress in
livestock. Although these variables are considered significant
in establishing the heat stress impact in animals, a wide
genetic variation was also established in these response
mechanisms. Further, variations in physiological adaptability
were also established between indigenous, cross bred and pure
bred animals. The indigenous livestock breeds were tipped to
be exhibiting less physiological variability as compared to
their counterparts. These discussions vividly indicate the
importance of studying in detail the physiological adaptive
mechanisms in different farm animals and these efforts can
help the farming community to identify the suitable agroclimatic zone specific livestock breeds which can go in long
way to help to ensure climate resilient livestock production.Not Availabl
Not Available
Not AvailableA study was conducted to assess comparatively the growth performance of three different indigenous goat breeds during exposure to summer heat stress. The primary objective of the study was to observe the heat stress impact on the growth performance based on the body weight changes, allometric measurements, growth hormone (GH) concentration and peripheral blood mononuclear cell (PBMC) Insulin-like growth factor-1 (IGF-1) mRNA expression pattern during the summer season in comparison with the local breed (Osmanabadi). Thirty-six ten-month- to one-year-old female goats of Osmanabadi, Malabari and Salem Black breeds were randomly divided into six groups, OC (n = 6; Osmanabadi control), OHS (n = 6; Osmanabadi heat stress), MC (n = 6; Malabari control), MHS (n = 6; Malabari heat stress), SBC (n = 6; Salem Black control) and SBHS (n = 6; Salem Black heat stress). Body weight was recorded at weekly intervals, whereas other growth and allometric measurements and blood collection were carried out at fortnightly intervals. Breed factor significantly (p < .05) influenced only few growth variables such as body weight, body mass index (BMI) and body condition score (BCS). However, heat stress treatment significantly (p < .05) reduced all growth parameters expect BMI. Further, the heat stress significantly (p < .01) increased plasma GH concentration in goats with significantly higher (p < .05) concentration recorded in OHS. Among the stress groups, the lower (p < .05) PBMC IGF-1 mRNA expression was recorded in OHS, while the higher (p < .05) expression was observed in SBHS indicating the extreme adaptive capability of Salem Black breed. Thus, the results indicated that the Salem Black breed performed much better compared to both Osmanabadi and Malabari breeds indicating the superior ability of this breed to adapt to heat stress challenges. The results also indicated that plasma GH and IGF-1 gene may act as ideal biomarkers for assessing the heat stress impact on growth performance in indigenous goats.ICAR-NIAN
Not Available
Not AvailableAgrobiodiversity in drylands consisting of large number of field crops, horticultural crops, grasses, shrubs and
multi-purpose trees plays a very critical role in providing food, fodder, nutritional and environmental security
to the inhabitants of drylands. Despite several bio-physical constraints, the drylands support high human and
livestock population with limited resources resulting in over-exploitation of the natural resources. moreover,
drylands are more vulnerable to global warming-mediated climate changes such as intense drought, sudden
rainfall burst, high ambient temperature and appearance of new unforeseen diseases and pests. In addition to
other technological interventions, the management of agro-biodiversity in drylands is expected to be a key factor
for sustainability, food and fodder security and for improving livelihood in drylands.
Genetic resources of dryland species include local landraces, improved elite material, traditional cultivars, genetic
stocks and wild relatives of coarse cereals (pearl millet, barley, sorghum, maize and small millets), legumes
(chickpea, mungbean, mothbean, clusterbean), horticultural crops, grasses, shrubs, medicinal plants and multipurpose trees. A large numberof exotic and indigenous germplasm accessions are conserved in National Gene
Bank or Field Gene Banks at the ICAR-National Bureau of Plant Genetic Resources (NPBGR) and elsewhere
across globe. Characterization of genetic resources using prescribed descriptors has largely indicated existence of
large variation for phenotypic, phenological, nutritional and stress-adaptation traits among available germplasm.
research conducted so far has indicated that the genetic resources from drylands hold a unique advantage as they
have evolved over centuries by natural and human selection under drought, high temperature or saline conditions.
they are better adapted to the local conditions and would contribute in enhancing the resilience at the farm level.
these resources could be of immense importance especially as sources of native genes conditioning resistance
to various biotic and abiotic stresses and also make unique study material to understand the mechanism of
adaptation to abiotic stresses. they could also serve as an excellent genomic resource for isolation of candidate
genes for tolerance to climatic and edaphic stresses for accelerating further genetic improvement. However, only
a very small fraction of these accessions has been utilized so far because of operational difficulties in dealing
with large number of germplasm accessions. the development of core and mini-core in recent past is expected
to improve this situation. Formation of trait-specific gene pools is also likely to enhance the utilization of genetic
resources to a greater extent.
there are multiple and complex challenges for agrobiodiversity in drylands due to habitat destruction, high
grazing/browsing pressure, invasion of other species, unsustainable exploitation of natural resources and dilution
of customary conservation practices. Critical assessment is needed for identifying geographical and trait-diversity
gaps using GIS and other modern tools.
additional explorations are needed in the regions where collection gaps have been indicated. Ex situconservation
of genetic resources from such regions and distribution of germplasm to the stakeholders on regular basis would
remain very crucial especially in the present scenario of climate change. Developing e-resources with detailed
information like passport data, characterization and evaluation data with respect to individual accessions would
certainly help in enhancing the utilization of genetic resources to broaden crop genetic base which is very
essential to reduce the chances of disease epidemics and to adapt to the effects of climate change.Not Availabl
Not Available
Not AvailableThe primary objective of the study was to compare the impact of heat stress on meat production characteristics of Osmanabadi and Salem Black breed goats based on changes in carcass characteristics, meat quality attributes, plasma leptin concentration, skeletal muscle myostatin and heat shock protein 70 (HSP70) gene expression patterns. The goats were randomly distributed into four groups: OSC (n = 6; Osmanabadi Control), OSHS (n = 6; Osmanabadi Heat Stress), SBC (n = 6; Salem Black Control) and SBHS (n = 6; Salem Black Heat Stress). The animals were slaughtered at the end of the study and their meat characteristics were assessed. This study established the impact of heat stress on a wide variety of carcass and meat quality characteristics in OS and SB goat breeds. The results from the study also provided some crucial evidence for a better resilience capacity of Salem Black breed as compared to Osmanabadi goats in maintaining the meat production during heat stress. The study also established plasma leptin and HSP70 genes to be the ideal biomarkers to reflect the impact of heat stress on meat characteristics in indigenous goats.ICAR-National Institute of Animal Nutrition and Physiolog