To explore the incidence and complexity of women presenting for maternity care who require concurrent cancer care, and to report the birth outcomes of these women.
A retrospective audit of women ...attending a 'high risk' maternal medicine clinic at an Australian tertiary maternity hospital between 1 October 2021 and 30 April 2023 was conducted. The inclusion criteria were a diagnosis of cancer and a concurrent pregnancy, or a diagnosis of cancer prior to the current pregnancy. Clinic lists and coding data were screened via the electronic medical record to identify potential subjects. Data were collected from the individual maternity and neonatal records.
Forty of 705 (5.7%) women attending the maternal medicine clinic met the inclusion criteria, of which ten had a new diagnosis of cancer in pregnancy and 30 presented for maternity care after a previous diagnosis of cancer. Cancer therapy during pregnancy included surgery and chemotherapy. Most pregnancies (92.5%) resulted in term deliveries (≥37 weeks gestation). Four neonates were preterm, and one was small-for-gestational-age. Caesarean section delivery and post-partum haemorrhage were more common than expected, but the rate of other adverse pregnancy outcomes was consistent with the background population. Over half of neonates required neonatal intensive care unit / special care nursery admission but the indications for admission were common, self-limiting conditions, and the length of stay was short (mean <5.0 days).
Approximately 6% of women attending the maternal medicine clinic had a current or previous diagnosis of cancer. Most pregnancies resulted in term deliveries and neonatal outcomes were excellent.
Anticancer agents can impair ovarian function, resulting in premature menopause and associated long-term health effects. Ovarian toxicity is not usually adequately assessed in trials of anticancer ...agents, leaving an important information gap for patients facing therapy choices. This American Society of Clinical Oncology (ASCO) statement provides information about the incorporation of ovarian toxicity measures in trial design. ASCO recommends: (1) measurement of ovarian toxicity in relevant clinical trials of anticancer agents that enrol post-pubertal, pre-menopausal patients; (2) collection of ovarian function measures at baseline and at 12–24 months after anticancer agent cessation, as a minimum, and later in line with the trial schedule; and (3) assessment of both clinical measures and biomarkers of ovarian function. ASCO recognises that routine measurement of ovarian toxicity and function in cancer clinical trials will add additional complexity and burden to trial resources but asserts that this issue is of such importance to patients that it cannot continue to be overlooked.
The Lancet Breast Cancer Commission Coles, Charlotte E; Earl, Helena; Anderson, Benjamin O ...
The Lancet (British edition),
05/2024, Letnik:
403, Številka:
10439
Journal Article
Recenzirano
Over a 2-year period, we brainstormed ideas, scoped the literature, obtained funding for dedicated pilot research that provided new data, and produced this Commission report to reduce the effects ...that breast cancer has on society. Costs and suffering can be financial, physical, psychological, emotional, and social, they affect children, families, local communities, and wider society, can occur at all stages of breast cancer, and are evident even within health-care services that are free at the point of delivery. Equitable access to early diagnosis and treatment is a fundamental need for all individuals to improve their breast cancer survival and quality of life. In collaboration with the WHO Global Breast Cancer Initiative, we call for action to deliver stage-shifting, as a sustained decline in breast cancer mortality rates is achieved by diagnosing at least 60% of invasive cancers at stages I–II.
Elucidating the mechanisms that sustain asthmatic inflammation is critical for precision therapies. We found that interleukin-6- and STAT3 transcription factor-dependent upregulation of Notch4 ...receptor on lung tissue regulatory T (T
) cells is necessary for allergens and particulate matter pollutants to promote airway inflammation. Notch4 subverted T
cells into the type 2 and type 17 helper (T
2 and T
17) effector T cells by Wnt and Hippo pathway-dependent mechanisms. Wnt activation induced growth and differentiation factor 15 expression in T
cells, which activated group 2 innate lymphoid cells to provide a feed-forward mechanism for aggravated inflammation. Notch4, Wnt and Hippo were upregulated in circulating T
cells of individuals with asthma as a function of disease severity, in association with reduced T
cell-mediated suppression. Our studies thus identify Notch4-mediated immune tolerance subversion as a fundamental mechanism that licenses tissue inflammation in asthma.
Acid-catalyzed multiphase chemistry of isoprene epoxydiols (IEPOX) on sulfate aerosol produces substantial amounts of water-soluble secondary organic aerosol (SOA) constituents, including ...2-methyltetrols, methyltetrol sulfates, and oligomers thereof in atmospheric fine particulate matter (PM2.5). These constituents have commonly been measured by gas chromatography interfaced to electron ionization mass spectrometry (GC/EI-MS) with prior derivatization or by reverse-phase liquid chromatography interfaced to electrospray ionization high-resolution mass spectrometry (RPLC/ESI-HR-MS). However, both techniques have limitations in explicitly resolving and quantifying polar SOA constituents due either to thermal degradation or poor separation. With authentic 2-methyltetrol and methyltetrol sulfate standards synthesized in-house, we developed a hydrophilic interaction liquid chromatography (HILIC)/ESI-HR-quadrupole time-of-flight mass spectrometry (QTOFMS) protocol that can chromatographically resolve and accurately measure the major IEPOX-derived SOA constituents in both laboratory-generated SOA and atmospheric PM2.5. 2-Methyltetrols were simultaneously resolved along with 4-6 diastereomers of methyltetrol sulfate, allowing efficient quantification of both major classes of SOA constituents by a single non-thermal analytical method. The sum of 2-methyltetrols and methyltetrol sulfates accounted for approximately 92%, 62%, and 21% of the laboratory-generated β-IEPOX aerosol mass, laboratory-generated δ-IEPOX aerosol mass, and organic aerosol mass in the southeastern U.S., respectively, where the mass concentration of methyltetrol sulfates was 171-271% the mass concentration of methyltetrol. Mass concentrations of methyltetrol sulfates were 0.39 and 2.33 μg m-3 in a PM2.5 sample collected from central Amazonia and the southeastern U.S., respectively. The improved resolution clearly reveals isomeric patterns specific to methyltetrol sulfates from acid-catalyzed multiphase chemistry of β- and δ-IEPOX. We also demonstrate that conventional GC/EI-MS analyses overestimate 2-methyltetrols by up to 188%, resulting (in part) from the thermal degradation of methyltetrol sulfates. Lastly, C5-alkene triols and 3-methyltetrahydrofuran-3,4-diols are found to be largely GC/EI-MS artifacts formed from thermal degradation of 2-methyltetrol sulfates and 3-methyletrol sulfates, respectively, and are not detected with HILIC/ESI-HR-QTOFMS.
Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, ...Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.
Asthma disproportionately affects African American/Black (AA/B) and Hispanic/Latinx (H/L) patients and individuals with low socioeconomic status (SES), but the relationship between SES and asthma ...morbidity within these racial/ethnic groups is inadequately understood.
To determine the relationship between SES and asthma morbidity among AA/B and H/L adults with moderate to severe asthma using multidomain SES frameworks and mediation analyses.
We analyzed enrollment data from the PeRson EmPowered Asthma RElief randomized trial, evaluating inhaled corticosteroid supplementation to rescue therapy. We tested for direct and indirect relationships between SES and asthma morbidity using structural equation models. For SES, we used a latent variable defined by poverty, education, and unemployment. For asthma morbidity, we used self-reported asthma exacerbations in the year before enrollment (corticosteroid bursts, emergency room/urgent care visits, or hospitalizations), and Asthma Control Test scores. We tested for mediation via health literacy, perceived stress, and self-reported discrimination. All models adjusted for age, sex, body mass index, ethnicity, and comorbidities.
Among 990 AA/B and H/L adults, low SES (latent variable) was directly associated with hospitalizations (β = 0.24) and worse Asthma Control Test scores (β = 0.20). Stress partially mediated the relationship between SES and increased emergency room/urgent care visits and worse asthma control (β = 0.03 and = 0.05, respectively). Individual SES domains were directly associated with asthma morbidity. Stress mediated indirect associations between low educational attainment and unemployment with worse asthma control (β = 0.05 and = 0.06, respectively).
Lower SES is directly, and indirectly through stress, associated with asthma morbidity among AA/B and H/L adults. Identification of stressors and relevant management strategies may lessen asthma-related morbidity among these populations.
Cigarette smoke aggravates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the underlying mechanisms remain unclear. Here, they show that benzoapyrene in cigarette ...smoke extract facilitates SARS-CoV-2 infection via upregulating angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Benzoapyrene trans-activates the promoters of ACE2 and TMPRSS2 by upregulating nuclear receptor subfamily 4 A number 2 (NR4A2) and promoting its binding of NR4A2 to their promoters, which is independent of functional genetic polymorphisms in ACE2 and TMPRSS2. Benzoapyrene increases the susceptibility of lung epithelial cells to SARS-CoV-2 pseudoviruses and facilitates the infection of authentic Omicron BA.5 in primary human alveolar type II cells, lung organoids, and lung and testis of hamsters. Increased expression of Nr4a2, Ace2, and Tmprss2, as well as decreased methylation of CpG islands at the Nr4a2 promoter are observed in aged mice compared to their younger counterparts. NR4A2 knockdown or interferon-λ2/λ3 stimulation downregulates the expression of NR4A2, ACE2, and TMPRSS2, thereby inhibiting the infection. In conclusion, benzoapyrene enhances SARS-CoV-2 infection by boosting NR4A2-induced ACE2 and TMPRSS2 expression. This study elucidates the mechanisms underlying the detrimental effects of cigarette smoking on SARS-CoV-2 infection and provides prophylactic options for coronavirus disease 2019, particularly for the elderly population.
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