CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Diminished growth and lower adiposity in hyperglycemic very low birth weight neonates at 4 months corrected age.

OBJECTIVE: Characterize the relationship between neonatal hyperglycemia and growth and body composition at 4 months corrected age (CA) in very low birth weight (VLBW) preterm infants. STUDY DESIGN: A prospective study of VLBW appropriate-for-gestation infants (N=53). All blood glucose measurements in the first 14 days and nutritional intake and illness markers until discharge were recorded. Standard anthropometrics and body composition via air displacement plethysmography were measured near term CA and 4 months CA. Relationships between hyperglycemia and anthropometrics and body composition were examined using multivariate linear regression. RESULTS: Infants with >5 days of hyperglycemia were lighter (5345 vs 6455 g, P⩽0.001), shorter (57.9 vs 60.9 cm, P⩽0.01), had smaller occipital-frontal head circumference (39.4 vs 42.0 cm, P⩽0.05) and were leaner (percent body fat 15.0 vs 23.8, P⩽0.01) at 4 months CA than those who did not have hyperglycemia, including after correcting for nutritional and illness factors. CONCLUSIONS: Neonatal hyperglycemia in VLBW infants is associated with decreased body size and lower adiposity at 4 months CA independent of nutritional deficit, insulin use and illness. Downregulation of the growth hormone axis may be responsible. These changes may influence long-term growth and cognitive development.

Body composition at birth in preterm infants between 30 and 36 weeks gestation.

BACKGROUND: The American Academy of Pediatrics calls for aggressive management of preterm infants to achieve body composition approximating that of the healthy infant in utero. Air displacement plethysmography (ADP) has been validated for assessment of body composition in preterm infants and could be used to monitor their nutritional status during hospitalization. Comparative datasets on body composition at birth among healthy, live-born preterm infants are lacking. OBJECTIVE: The aim of this study is to provide the first descriptive fat mass (FM) and fat-free mass (FFM) data from healthy newborn preterm infants at birth as a proxy for healthy in utero body composition. METHODS: Body mass and volume were obtained using ADP within 72 h of birth in 98 singleton, appropriate-for-gestational-age preterm infants. FM and FFM were calculated using the Fomon equation. RESULTS: Measurement with ADP was feasible and well tolerated by infants as young as 30 weeks gestation and <72 h of age. FFM and FM increased linearly over the gestational age range period at rates of 171 and 46 g week(-1) , respectively. Mean values obtained by ADP by gestational week were similar to the previously published reference data from chemical analysis on stillbirths. CONCLUSIONS: Body composition assessment using ADP is feasible in newborn preterm infants and provides group estimates similar to that of the reference fetus. In the future, integrating body composition information into the nutritional management of preterm infants may help to identify new strategies to optimize growth and development in this vulnerable population.

Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol.

The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic-pituitary-adrenal (HPA) function on cognition in healthy, older adults, which may reflect developmental, functional or neurodegenerative effects of the serotonin transporter polymorphism. We investigated whether 5-HTT genotype interacts with cumulative life stress and HPA-axis measures of waking and diurnal cortisol slope to impact cognition in 154 non-depressed, older adults. Structural images of hippocampal volume were acquired on a subsample of 56 participants. The 5-HTT s allele was associated with both significantly lower delayed recall and higher waking cortisol levels. Presence of the s allele interacted with higher waking cortisol to negatively impact memory. We also observed a significant interaction of higher waking cortisol and the s allele on lower hippocampal volume. Smaller hippocampi and higher cortisol were associated with lower delayed recall only in s allele carriers. No impact or interactions of cumulative life stress with 5-HTT or cortisol were observed. This is the first investigation to identify an association of the 5-HTT s allele with poorer memory function in older adults. The interactive effects of the s allele and waking cortisol levels on reduced hippocampal volume and lower memory suggest that the negative effect of the serotonin polymorphism on memory is mediated by the HPA axis. Further, given the significant association of the s allele with higher waking cortisol in our investigation, future studies may be needed to evaluate the impact of the serotonin transporter polymorphism on any neuropsychiatric or behavioral outcome which is influenced by HPA axis function in older adults.

Sterilizing immunity against experimental Helicobacter pylori infection is challenge-strain dependent.

The development of a murine model of Helicobacter pylori infection through serial in vivo passage of candidate strains has enabled a quantitative assessment of vaccine efficacy. In this study we compare infection with and protection against challenge from both CagA(+) type I, and CagA(-) type II in vivo adapted isolates. In vivo passage of a type II H. pylori isolate resulted in a highly infectious strain (X47-2AL), capable of reproducibly infecting mice to high density (10(7) CFU/g of gastric tissue). Similarly adapted type I strains were found to colonize mice at a significantly lower level (10(4)-10(5) CFU/g tissue). Mucosal immunization with recombinant urease (rUre) significantly protected animals against both types. Protection against X47-2AL was characterized by a > or =100-fold (or 2 log) reduction in bacterial density. However, the presence of a residual infection highlighted the inability to achieve sterilizing immunity against this strain. The level of protection appeared independent of challenge dose, and was stable for up to 6 months, all animals exhibiting a low-level residual infection that did not recrudesce with time. Similarly immunized mice challenged with isolates representing the residual infection were also protected, confirming that they did not represent a sub-population of H. pylori that could escape immunity. Immunization and challenge studies with type I adapted-isolates, demonstrated a similar 2-3 log reduction in the bacterial burden, but that in this instance resulted in sterilizing immunity. These results suggest varied specificity for the murine host by different Helicobacter strains that can influence the outcome of both infection and immunity.

Chlamydia trachomatis infection does not enhance local cellular immunity against concurrent Candida vaginal infection.

Although Th1-type cell-mediated immunity (CMI) is the predominant host defense mechanism against mucosal Candida albicans infection, CMI against a vaginal C. albicans infection in mice is limited at the vaginal mucosa despite a strong Candida-specific Th1-type response in the draining lymph nodes. In contrast, Th1-type CMI is highly effective against an experimental Chlamydia trachomatis genital tract infection. This study demonstrated through two independent designs that a concurrent Candida and Chlamydia infection could not accelerate or modulate the anti-Candida CMI response. Together, these results suggest that host responses to these genital tract infections are independent and not influenced by the presence of the other.

Three polymorphisms in the 3' UTR of the TRAIL (TNF-related apoptosis-inducing ligand) gene.

Screening of the TRAIL (TNF-related apoptosis inducing ligand/Apo-2L) gene revealed three single nucleotide polymorphisms (SNPs) in the 3' UTR at nucleotides 1525G/A, 1588G/A, and 1591C/T. Over 50 individuals from each of two populations, Caucasian and African Americans, were genotyped for these three polymorphisms and allele frequencies were determined.

Differential regulation of CD4 lymphocyte recruitment between the upper and lower regions of the genital tract during Chlamydia trachomatis infection.

Genital infection with Chlamydia trachomatis results in both the local recruitment of protective immune responses and an inflammatory infiltrate that may also participate in tubal pathology. As a beginning to understanding the etiology of immune system-mediated tubal pathology, we evaluated the regional recruitment of lymphocyte subsets to different areas of the female genital tract (GT) over the course of a murine infection with the mouse pneumonitis agent of Chlamydia trachomatis (MoPn). Using flow cytometric techniques we found that the CD4 lymphocyte subset was preferentially recruited to the upper GT (oviduct and uterine horn) over the lower GT (cervical-vaginal region) throughout the course of MoPn infection. The influx of CD4 cells also correlated with the expression of endothelial cell adhesion molecules (ECAMs) and in vitro lymphocyte adherence in the upper GT. Interestingly, the expression of ECAMs in the lower GT was not maintained longer than 7 days after infection, even in the presence of viable chlamydiae. Taken together, these data suggest that regulatory mechanisms of lymphocyte recruitment differ between the upper and lower regions of the GT and may influence the clearance of chlamydiae and the development of tubal pathology.

An analysis of the qualitative factors which influence young people's acceptance of orthodontic care.

INTRODUCTION AND METHOD: The qualitative data volunteered as responses to open questions in a self-administered questionnaire study were analysed to identify the psychological factors influencing young people's behaviour in relation to orthodontic care and to gain an understanding of the psychological factors which influence adolescents' acceptance of orthodontic care. The study was conducted in all Walsall and Dudley secondary schools. RESULTS AND DISCUSSION: The responses of the young people who were in year 10 of education with an average age of 15.0 years demonstrated the importance of personal constructs, peer group and media influences, parental influences, conflicting messages, teasing, symptom perception, appearance and self-image, and interpersonal relationships in determining whether or not young people either seek and accept or reject orthodontic treatment. CONCLUSION: The study concluded that it is essential that clinicians involve patients fully and honestly in discussions concerning their orthodontic therapy in order to enable them to make a considered consent.

Rectal and intranasal immunizations with recombinant urease induce distinct local and serum immune responses in mice and protect against Helicobacter pylori infection.

To determine the optimal inductive sites for immunization against Helicobacter pylori infection, the protective efficacy of recombinant urease (rUre) was assessed for mice given the vaccine by either the oral (p.o.), intranasal (i.n.), or rectal route. When mice were immunized with rUre (25 microg p.o. or rectally or 10 microg i.n.) plus heat-labile toxin from Escherichia coli as the mucosal adjuvant, all routes afforded protection against challenge with H. pylori, as indicated by a significant reduction in gastric urease activity (P < 0.0005) compared to that of sham-immunized controls. Quantitative H. pylori culture of stomach tissue demonstrated a >97% reduction in bacterial burden in mice immunized by all routes (P < 0.05). Induction of antiurease immunoglobulin A (IgA) levels in gastric luminal secretions after p.o. immunization was greater than after i.n. administration (means, 6.0 and 1.02 ng/ml, respectively) and was dependent upon challenge with H. pylori. However, immunization by the rectal route resulted in the generation of the highest levels of gastric antiurease IgA (mean, 40. 89 ng/ml), which was detectable prior to challenge with H. pylori. Immunohistochemical staining of stomach tissue for cells secreting urease-specific antibody and CD4(+) T cells showed levels of recruitment to be dependent upon challenge with H. pylori and equivalent for all routes. These results identify both the rectum and nasal passages as suitable inductive sites for urease immunization.