105 research outputs found
Identification of novel targets of diabetic nephropathy and PEDF peptide treatment using RNA-seq
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology
Characterization and Control of the Microbial Community Affiliated with Copper or Aluminum Heat Exchangers of HVAC Systems
Microbial growth in heating ventilation and air-conditioning (HVAC) systems with the subsequent contamination of indoor air is of increasing concern. Microbes and the subsequent biofilms grow easily within heat exchangers. A comparative study where heat exchangers fabricated from antimicrobial copper were evaluated for their ability to limit microbial growth was conducted using a full-scale HVAC system under conditions of normal flow rates using single-pass outside air. Resident bacterial and fungal populations were quantitatively assessed by removing triplicate sets of coupons from each exchanger commencing the fourth week after their installation for the next 30 weeks. The intrinsic biofilm associated with each coupon was extracted and characterized using selective and differential media. The predominant organisms isolated from aluminum exchangers were species of Methylobacterium of which at least three colony morphologies and 11 distinct PFGE patterns we found; of the few bacteria isolated from the copper exchangers, the majority were species of Bacillus. The concentrations and type of bacteria recovered from the control, aluminum, exchangers were found to be dependent on the type of plating media used and were 11,411–47,257 CFU cm−2 per coupon surface. The concentration of fungi was found to average 378 CFU cm−2. Significantly lower concentrations of bacteria, 3 CFU cm−2, and fungi, 1 CFU cm−2, were recovered from copper exchangers regardless of the plating media used. Commonly used aluminum heat exchangers developed stable, mixed, bacterial/fungal biofilms in excess of 47,000 organisms per cm2 within 4 weeks of operation, whereas the antimicrobial properties of metallic copper were able to limit the microbial load affiliated with the copper heat exchangers to levels 99.97 % lower during the same time period
The genomes of two key bumblebee species with primitive eusocial organization
Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation
Initial findings from a novel population-based child mortality surveillance approach: a descriptive study.
--- - Label: BACKGROUND NlmCategory: BACKGROUND content:
"Sub-Saharan Africa and south Asia contributed 81% of 5\xC2\xB79
million under-5 deaths and 77% of 2\xC2\xB76 million stillbirths
worldwide in 2015. Vital registration and verbal autopsy data
are mainstays for the estimation of leading causes of death, but
both are non-specific and focus on a single underlying cause. We
aimed to provide granular data on the contributory causes of
death in stillborn fetuses and in deceased neonates and children
younger than 5 years, to inform child mortality prevention
efforts." - Label: METHODS NlmCategory: METHODS content: "The
Child Health and Mortality Prevention Surveillance (CHAMPS)
Network was established at sites in seven countries (Baliakandi,
Bangladesh; Harar and Kersa, Ethiopia; Siaya and Kisumu, Kenya;
Bamako, Mali; Manhi\xC3\xA7a, Mozambique; Bombali, Sierra Leone;
and Soweto, South Africa) to collect standardised,
population-based, longitudinal data on under-5 mortality and
stillbirths in sub-Saharan Africa and south Asia, to improve the
accuracy of determining causes of death. Here, we analysed data
obtained in the first 2 years after the implementation of CHAMPS
at the first five operational sites, during which surveillance
and post-mortem diagnostics, including minimally invasive tissue
sampling (MITS), were used. Data were abstracted from all
available clinical records of deceased children, and relevant
maternal health records were also extracted for stillbirths and
neonatal deaths, to incorporate reported pregnancy or delivery
complications. Expert panels followed standardised procedures to
characterise causal chains leading to death, including
underlying, intermediate (comorbid or antecedent causes), and
immediate causes of death for stillbirths, neonatal deaths, and
child (age 1-59 months) deaths." - Label: FINDINGS NlmCategory:
RESULTS content: Between Dec 10, 2016, and Dec 31, 2018, MITS
procedures were implemented at five sites in Mozambique, South
Africa, Kenya, Mali, and Bangladesh. We screened 2385 death
notifications for inclusion eligibility, following which 1295
families were approached for consent; consent was provided for
MITS by 963 (74%) of 1295 eligible cases approached. At least
one cause of death was identified in 912 (98%) of 933 cases (180
stillbirths, 449 neonatal deaths, and 304 child deaths); two or
more conditions were identified in the causal chain for 585
(63%) of 933 cases. The most common underlying causes of
stillbirth were perinatal asphyxia or hypoxia (130 [72%] of 180
stillbirths) and congenital infection or sepsis (27 [15%]). The
most common underlying causes of neonatal death were preterm
birth complications (187 [42%] of 449 neonatal deaths),
perinatal asphyxia or hypoxia (98 [22%]), and neonatal sepsis
(50 [11%]). The most common underlying causes of child deaths
were congenital birth defects (39 [13%] of 304 deaths), lower
respiratory infection (37 [12%]), and HIV (35 [12%]). In 503
(54%) of 933 cases, at least one contributory pathogen was
identified. Cytomegalovirus, Escherichia coli, group B
Streptococcus, and other infections contributed to 30 (17%) of
180 stillbirths. Among neonatal deaths with underlying
prematurity, 60% were precipitated by other infectious causes.
Of the 275 child deaths with infectious causes, the most common
contributory pathogens were Klebsiella pneumoniae (86 [31%]),
Streptococcus pneumoniae (54 [20%]), HIV (40 [15%]), and
cytomegalovirus (34 [12%]), and multiple infections were common.
Lower respiratory tract infection contributed to 174 (57%) of
304 child deaths. - Label: INTERPRETATION NlmCategory:
CONCLUSIONS content: Cause of death determination using MITS
enabled detailed characterisation of contributing conditions.
Global estimates of child mortality aetiologies, which are
currently based on a single syndromic cause for each death, will
be strengthened by findings from CHAMPS. This approach adds
specificity and provides a more complete overview of the chain
of events leading to death, highlighting multiple potential
interventions to prevent under-5 mortality and stillbirths. -
Label: FUNDING NlmCategory: BACKGROUND content: Bill &
Melinda Gates Foundation
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
Summary Low-dose exposures to common environmental chemicals that are deemed safe individually may be combining to instigate carcinogenesis, thereby contributing to the incidence of cancer. This risk may be overlooked by current regulatory practices and needs to be vigorously investigated
Recommended from our members
Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?
Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested
Initial findings from a novel population-based child mortality surveillance approach: a descriptive study.
BACKGROUND: Sub-Saharan Africa and south Asia contributed 81% of 5·9 million under-5 deaths and 77% of 2·6 million stillbirths worldwide in 2015. Vital registration and verbal autopsy data are mainstays for the estimation of leading causes of death, but both are non-specific and focus on a single underlying cause. We aimed to provide granular data on the contributory causes of death in stillborn fetuses and in deceased neonates and children younger than 5 years, to inform child mortality prevention efforts. METHODS: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network was established at sites in seven countries (Baliakandi, Bangladesh; Harar and Kersa, Ethiopia; Siaya and Kisumu, Kenya; Bamako, Mali; Manhiça, Mozambique; Bombali, Sierra Leone; and Soweto, South Africa) to collect standardised, population-based, longitudinal data on under-5 mortality and stillbirths in sub-Saharan Africa and south Asia, to improve the accuracy of determining causes of death. Here, we analysed data obtained in the first 2 years after the implementation of CHAMPS at the first five operational sites, during which surveillance and post-mortem diagnostics, including minimally invasive tissue sampling (MITS), were used. Data were abstracted from all available clinical records of deceased children, and relevant maternal health records were also extracted for stillbirths and neonatal deaths, to incorporate reported pregnancy or delivery complications. Expert panels followed standardised procedures to characterise causal chains leading to death, including underlying, intermediate (comorbid or antecedent causes), and immediate causes of death for stillbirths, neonatal deaths, and child (age 1-59 months) deaths. FINDINGS: Between Dec 10, 2016, and Dec 31, 2018, MITS procedures were implemented at five sites in Mozambique, South Africa, Kenya, Mali, and Bangladesh. We screened 2385 death notifications for inclusion eligibility, following which 1295 families were approached for consent; consent was provided for MITS by 963 (74%) of 1295 eligible cases approached. At least one cause of death was identified in 912 (98%) of 933 cases (180 stillbirths, 449 neonatal deaths, and 304 child deaths); two or more conditions were identified in the causal chain for 585 (63%) of 933 cases. The most common underlying causes of stillbirth were perinatal asphyxia or hypoxia (130 [72%] of 180 stillbirths) and congenital infection or sepsis (27 [15%]). The most common underlying causes of neonatal death were preterm birth complications (187 [42%] of 449 neonatal deaths), perinatal asphyxia or hypoxia (98 [22%]), and neonatal sepsis (50 [11%]). The most common underlying causes of child deaths were congenital birth defects (39 [13%] of 304 deaths), lower respiratory infection (37 [12%]), and HIV (35 [12%]). In 503 (54%) of 933 cases, at least one contributory pathogen was identified. Cytomegalovirus, Escherichia coli, group B Streptococcus, and other infections contributed to 30 (17%) of 180 stillbirths. Among neonatal deaths with underlying prematurity, 60% were precipitated by other infectious causes. Of the 275 child deaths with infectious causes, the most common contributory pathogens were Klebsiella pneumoniae (86 [31%]), Streptococcus pneumoniae (54 [20%]), HIV (40 [15%]), and cytomegalovirus (34 [12%]), and multiple infections were common. Lower respiratory tract infection contributed to 174 (57%) of 304 child deaths. INTERPRETATION: Cause of death determination using MITS enabled detailed characterisation of contributing conditions. Global estimates of child mortality aetiologies, which are currently based on a single syndromic cause for each death, will be strengthened by findings from CHAMPS. This approach adds specificity and provides a more complete overview of the chain of events leading to death, highlighting multiple potential interventions to prevent under-5 mortality and stillbirths. FUNDING: Bill & Melinda Gates Foundation
Mortality Surveillance Methods to Identify and Characterize Deaths in Child Health and Mortality Prevention Surveillance Network Sites
Despite reductions over the past 2 decades, childhood
mortality remains high in low- and middle-income countries in
sub-Saharan Africa and South Asia. In these settings, children
often die at home, without contact with the health system, and
are neither accounted for, nor attributed with a cause of death.
In addition, when cause of death determinations occur, they
often use nonspecific methods. Consequently, findings from
models currently utilized to build national and global estimates
of causes of death are associated with substantial uncertainty.
Higher-quality data would enable stakeholders to effectively
target interventions for the leading causes of childhood
mortality, a critical component to achieving the Sustainable
Development Goals by eliminating preventable perinatal and
childhood deaths. The Child Health and Mortality Prevention
Surveillance (CHAMPS) Network tracks the causes of under-5
mortality and stillbirths at sites in sub-Saharan Africa and
South Asia through comprehensive mortality surveillance,
utilizing minimally invasive tissue sampling (MITS), postmortem
laboratory and pathology testing, verbal autopsy, and clinical
and demographic data. CHAMPS sites have established facility-
and community-based mortality notification systems, which aim to
report potentially eligible deaths, defined as under-5 deaths
and stillbirths within a defined catchment area, within 24-36
hours so that MITS can be conducted quickly after death. Where
MITS has been conducted, a final cause of death is determined by
an expert review panel. Data on cause of death will be provided
to local, national, and global stakeholders to inform strategies
to reduce perinatal and childhood mortality in sub-Saharan
Africa and South Asia
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology
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