Neonatal weight loss and gain patterns in caesarean section born infants : integrative systematic review

There is evidence that caesarean section delivery can impact on neonatal weight loss and weight gain patterns in the first 5 days of life. We conducted an integrative systematic review to examine the association of mode of delivery on early neonatal weight loss. Pubmed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Excerpta Medica dataBASE, and Medical Literature Analysis and Retrieval System Online were searched for relevant papers published before June 2019. Reference lists from the relevant papers were then backwards and forwards searched. As neonatal weight loss was reported in different formats, a meta‐analysis could not be carried out. Most studies did not distinguish between elective and emergency caesarean sections or instrumental and nonassisted vaginal deliveries. Seven papers were included. All papers except one found that caesarean section was associated with higher weight loss in the early days of life. Two papers presented data from studies on babies followed up to 1 month. One study found that on day 25, babies born by caesarean section had significantly higher weight gain than those born vaginally, while another found that by day 28, babies born vaginally gained more weight per day (11.9 g/kg/day) than those born by caesarean section (10.9 g/kg/day; p = .02). Overall, infants born by caesarean section lost more weight than those born vaginally, but due to the small number of studies included, more are needed to look at this difference and why it may occur. This discrepancy in weight between the two groups may be corrected over time, but future studies will need larger sample sizes and longer follow‐up periods to examine this

Combretazet-3 a novel synthetic cis-stable combretastatin-A4-azetidinone hybrid with enhanced stabilityand therapeutic efficacy in colon cancer

In recent years an extensive series of synthetic combretastatin A-4 (CA-4)-azetidinone (β-lactam) hybrids were designed and synthesised with a view to improve the stability, therapeutic efficacy and aqueous solubility of CA-4. Lead compounds containing a 3,4,5-trimethoxy aromatic ring at position 1 and a variety of substitution patterns at positions 3 and 4 of the β-lactam ring were screened in three adenocarcinoma-derived colon cancer cell lines (CT-26, Caco-2 and the CA-4 resistant cell line, HT-29). In both CT-26 and Caco-2 cells all β-lactam analogues analysed displayed potent therapeutic efficacy within the nanomolar range. Substitution of the ethylene bridge of CA-4 with the β-lactam ring together with the aforementioned aryl substitutions improved the therapeutic efficacy of CA-4 up to 300‑fold in the combretastatin refractory HT-29 cells. The lead compound combretazet-3 (CAZ-3); chemical name [4-(3-hydroxy-4-methoxyphenyl)-3-(4-hydroxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one] demonstrated improved chemical stability together with enhanced therapeutic efficacy as compared with CA-4 whilst maintaining the natural biological properties of CA-4. Furthermore, CAZ-3 demonstrated significant tumour inhibition in a murine model of colon cancer. Our results suggest that combretastatin-azetidinone hybrids represent an effective novel therapy for the treatment of combretastatin resistant carcinomas

Parents’ beliefs about their influence on children’s scientific and religious views: Perspectives from Iran, China and the United States

Parents in Iran, China and the United States were asked 1) about their potential influence on their children's religious and scientific views and 2) to consider a situation in which their children expressed dissent. The Iranian and US parents endorsed their influence on children's beliefs in both domains. By contrast, Chinese parents claimed more influence in the domain of science than religion. Most parents spoke of influencing their children via Parent-only mechanisms in each domain (e.g., discussion, teaching), although US parents did spontaneously note Multiple sources for the transmission of religious views (e.g., church, other influential adults). Parents proposed a similar stance towards children’s dissenting religious and scientific views. Chinese and US parents were more likely to express Supportive approaches and Iranian parents were more likely to express a Directive approach by comparison. The present research informs our understanding of the cultural transmission of views about science and religion

Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors

Aim: The aim of the study was to assess the prognostic performance of a 6-gene molecular score (OncoMasTR Molecular Score [OMm]) and a composite risk score (OncoMasTR Risk Score [OM]) and to conduct a within-patient comparison against four routinely used molecular and clinicopathological risk assessment tools: Oncotype DX Recurrence Score, Ki67, Nottingham Prognostic Index and Clinical Risk Category, based on the modified Adjuvant! Online definition and three risk factors: patient age, tumour size and grade. Methods: Biospecimens and clinicopathological information for 404 Irish women also previously enrolled in the Trial Assigning Individualized Options for Treatment [Rx] were provided by 11 participating hospitals, as the primary objective of an independent translational study. Gene expression measured via RT-qPCR was used to calculate OMm and OM. The prognostic value for distant recurrence-free survival (DRFS) and invasive disease-free survival (IDFS) was assessed using Cox proportional hazards models and Kaplan-Meier analysis. All statistical tests were two-sided ones. Results: OMm and OM (both with likelihood ratio statistic [LRS] P Discussion: Both OncoMasTR scores were significantly prognostic for DRFS and IDFS and provided additional prognostic information to the molecular and clinicopathological risk factors/tools assessed. OM was also the most accurate risk classification tool for identifying DR. A concise 6-gene signature with superior risk stratification was shown to increase prognosis reliability, which may help clinicians optimise treatment decisions. Trial registration: ClinicalTrials.gov NCT02050750 NCT00310180.</p

Prevalence of problem alcohol use among patients attending primary care for methadone treatment

<p>Abstract</p> <p>Background</p> <p>Problem alcohol use is associated with adverse health outcomes among current or former heroin users and primary care is providing methadone treatment for increasing numbers of this population. This study aimed todetermine the prevalence of problem alcohol use among current or former heroin users attending primary care for methadone treatment and to describe the socio-demographic characteristics and health service utilisation characteristics associated with problem alcohol uses.</p> <p>Methods</p> <p>We conducted a cross sectional survey of patients sampled from a national database of patients attending general practice for methadone treatment. Participants were recruited by their general practitioner and data was collected using an interviewer-administered questionnaire, which included the Alcohol Use Disorders Identification Test ('AUDIT'), with a score of >7 considered abnormal (ie 'AUDIT positive cases') and socio-demographic, medical and substance use characteristics.</p> <p>Results</p> <p>We interviewed 196 patients (71% of those invited, 31% of those sampled, 11% of the national database). The median age was 32 years, 55% were hepatitis C positive, 79% had used illicit drugs in the previous month and 68% were male. Sixty-eight 'AUDIT positive' cases were identified (prevalence of 35%, 95% CI = 28–41%) and these were more likely to have attended a local Emergency Department in the previous year (p < 0.05) and less likely to have attended a hospital clinic in the previous year (p < 0.05). Twenty-seven (14%) scored 20 or higher indicating possible alcohol dependence.</p> <p>Conclusion</p> <p>Problem alcohol use has a high prevalence among current or former heroin users attending primary care for methadone treatment and interventions that address this issue should be explored as a priority. Interventions that address problem alcohol use in this population should be considered as a priority, although the complex medical and psychological needs of this population may make this challenging.</p

Metformin is a metabolic modulator and radiosensitiser in rectal cancer

Resistance to neoadjuvant chemoradiation therapy, is a major challenge in the management of rectal cancer. Increasing evidence supports a role for altered energy metabolism in the resistance of tumours to anti-cancer therapy, suggesting that targeting tumour metabolism may have potential as a novel therapeutic strategy to boost treatment response. In this study, the impact of metformin on the radiosensitivity of colorectal cancer cells, and the potential mechanisms of action of metformin-mediated radiosensitisation were investigated. Metformin treatment was demonstrated to significantly radiosensitise both radiosensitive and radioresistant colorectal cancer cells in vitro. Transcriptomic and functional analysis demonstrated metformin-mediated alterations to energy metabolism, mitochondrial function, cell cycle distribution and progression, cell death and antioxidant levels in colorectal cancer cells. Using ex vivo models, metformin treatment significantly inhibited oxidative phosphorylation and glycolysis in treatment naïve rectal cancer biopsies, without affecting the real-time metabolic profile of non-cancer rectal tissue. Importantly, metformin treatment differentially altered the protein secretome of rectal cancer tissue when compared to non-cancer rectal tissue. Together these data highlight the potential utility of metformin as an anti-metabolic radiosensitiser in rectal cancer

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

Summary Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886) we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralising antibody titres (NAbT) using a live virus microneutralization assay against wild-type (WT), Delta, Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titres and T cell responses after the fourth vaccine dose increases compared to those after the third vaccine dose. Patients who received B cell-depleting therapies within 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination