Cross-tissue and generation predictability of relative Wolbachia densities in the mosquito Aedes aegypti.

BACKGROUND: The insect endosymbiotic bacterium Wolbachia is being deployed in field populations of the mosquito Aedes aegypti for biological control. This microbe prevents the replication of human disease-causing viruses inside the vector, including dengue, Zika and chikungunya. Relative Wolbachia densities may in part predict the strength of this 'viral blocking' effect. Additionally, Wolbachia densities may affect the strength of the reproductive manipulations it induces, including cytoplasmic incompatibility (CI), maternal inheritance rates or induced fitness effects in the insect host. High rates of CI and maternal inheritance and low rates of fitness effects are also key to the successful spreading of Wolbachia through vector populations and its successful use in biocontrol. The factors that control Wolbachia densities are not completely understood. METHODS: We used quantitative PCR-based methods to estimate relative density of the Wolbachia wAlbB strain in both the somatic and reproductive tissues of adult male and female mosquitoes, as well as in eggs. Using correlation analyses, we assessed whether densities in one tissue predict those in others within the same individual, but also across generations. RESULTS: We found little relationship among the relative Wolbachia densities of different tissues in the same host. The results also show that there was very little relationship between Wolbachia densities in parents and those in offspring, both in the same and different tissues. The one exception was with ovary-egg relationships, where there was a strong positive association. Relative Wolbachia densities in reproductive tissues were always greater than those in the somatic tissues. Additionally, the densities were consistent in females over their lifetime regardless of tissue, whereas they were generally higher and more variable in males, particularly in the testes. CONCLUSIONS: Our results indicate that either stochastic processes or local tissue-based physiologies are more likely factors dictating Wolbachia densities in Ae. aegypti individuals, rather than shared embryonic environments or heritable genetic effects of the mosquito genome. These findings have implications for understanding how relative Wolbachia densities may evolve and/or be maintained over the long term in Ae. aegypti.

Ischaemic bowel perforation secondary to a gravid uterus in a patient with treated inflammatory bowel disease and an ileoanal pouch: a case report.

The diagnosis of visceral perforation during pregnancy is often delayed and the management complex. A 32-year-old primigravid woman in her second trimester presented with abdominal pain and a pre-existing ileoanal pouch. Initial imaging was negative but later imaging was suggestive of serious pathology. At laparotomy, a caesarean section was performed. Peritonitis was encountered secondary to two discrete perforations in the small bowel separate from her pouch. Histology found an ischaemic perforation secondary to a pressure effect from the gravid uterus. In pregnancy, ileoanal pouches may make the interconnected bowel vulnerable to the pressure effect of the gravid uterus and perforation. Pregnant women with such a surgical history who develop symptoms suggestive of bowel perforation should have rapid imaging and their clinical team should consider early definitive surgical intervention.

Pediatric lung function testing during a pandemic: An international perspective.

The COVID pandemic has passed its first peak for now in many countries while some are still on the rise, with some facing a second wave of cases. Precautions and infection control measures for both pediatric and adult pulmonary function testing (PFT) have been a topic of debate during the pandemic. Many centers had to close their PFT laboratories during the initial periods of the pandemic and are reopening as the numbers of new cases are decreasing. This review aims to summarize different practices of PFT laboratory management in different countries, including patient appointments, personal protective equipment, testing room requirements and telemedicine during and immediately following the COVID pandemic.

Early post-conception maternal cortisol, children's HPAA activity and DNA methylation profiles.

The hypothalamic-pituitary-adrenal axis (HPAA) plays a critical role in the functioning of all other biological systems. Thus, studying how the environment may influence its ontogeny is paramount to understanding developmental origins of health and disease. The early post-conceptional (EPC) period could be particularly important for the HPAA as the effects of exposures on organisms' first cells can be transmitted through all cell lineages. We evaluate putative relationships between EPC maternal cortisol levels, a marker of physiologic stress, and their children's pre-pubertal HPAA activity (n=22 dyads). Maternal first-morning urinary (FMU) cortisol, collected every-other-day during the first 8 weeks post-conception, was associated with children's FMU cortisol collected daily around the start of the school year, a non-experimental challenge, as well as salivary cortisol responses to an experimental challenge (all Ps5% change in children's buccal epithelial cells' DNA methylation for 867 sites, while children's HPAA activity was associated with five CpG sites. Yet, no CpG sites were related to both, EPC cortisol and children's HPAA activity. Thus, these epigenetic modifications did not statistically mediate the observed physiological links. Larger, prospective peri-conceptional cohort studies including frequent bio-specimen collection from mothers and children will be required to replicate our analyses and, if our results are confirmed, identify biological mechanisms mediating the statistical links observed between maternal EPC cortisol and children's HPAA activity.

Blood and nasal epigenetics correlate with allergic rhinitis symptom development in the environmental exposure unit.

BACKGROUND: Epigenetic alterations may represent new therapeutic targets and/or biomarkers of allergic rhinitis (AR). Our aim was to examine genome-wide epigenetic changes induced by controlled pollen exposure in the environmental exposure unit (EEU). METHODS: 38 AR sufferers and eight nonallergic controls were exposed to grass pollen for 3 hours on two consecutive days. We interrogated DNA methylation at baseline and 3 hours in peripheral blood mononuclear cells (PBMCs) using the Infinium Methylation 450K array. We corrected for demographics, cell composition, and multiple testing (Benjamini-Hochberg) and verified hits using bisulfite PCR pyrosequencing and qPCR. To extend these findings to a clinically relevant tissue, we investigated DNA methylation and gene expression of mucin 4 (MUC4), in nasal brushings from a separate validation cohort exposed to birch pollen. RESULTS: In PBMCs of allergic rhinitis participants, 42 sites showed significant DNA methylation changes of 2% or greater. DNA methylation changes in tryptase gamma 1 (TPSG1), schlafen 12 (SLFN12), and MUC4 in response to exposure were validated by pyrosequencing. SLFN12 DNA methylation significantly correlated with symptoms (P < 0.05), and baseline DNA methylation pattern was found to be predictive of symptom severity upon grass allergen exposure (P = 0.029). Changes in MUC4 DNA methylation in nasal brushings in the validation cohort correlated with drop in peak nasal inspiratory flow (Spearman's r = 0.314, P = 0.034), and MUC4 gene expression was significantly increased (P < 0.0001). CONCLUSION: This study revealed novel and rapid epigenetic changes upon exposure in a controlled allergen challenge facility, and identified baseline epigenetic status as a predictor of symptom severity.

Birth weight and postnatal microbial exposures predict the distribution of peripheral blood leukocyte subsets in young adults in the Philippines.

The immune system not only provides protection against infectious disease but also contributes to the etiology of neoplastic, atopic, and cardiovascular and metabolic diseases. Prenatal and postnatal nutritional and microbial environments have lasting effects on multiple aspects of immunity, indicating that immune processes may play important roles in the developmental origins of disease. The objective of this study is to evaluate the association between birth weight and the distribution of leukocyte (white blood cell) subsets in peripheral blood in young adulthood. Postnatal microbial exposures were also considered as predictors of leukocyte distribution. Participants (n=486; mean age=20.9 years) were drawn from a prospective birth cohort study in the Philippines, and analyses focused on the following cell types: CD4 T lymphocytes, CD8 T lymphocytes, B lymphocytes, natural killer cells, monocytes, granulocytes. Higher birth weight was a strong predictor of higher proportion of CD4 T lymphocytes (B=0.12, s.e.=0.041, P=0.003), lower proportion of CD8 T lymphocytes (B=-0.874, s.e.=0.364, P=0.016), higher CD4:CD8 ratio (B=1.964, s.e.=0.658, P=0.003), and higher B lymphocytes (B=0.062, s.e.=0.031, P=0.047). Measures of microbial exposure in infancy were negatively associated with proportions of B lymphocytes and granulocytes, and lower CD4:CD8 ratio. Leukocytes are the key regulators and effectors of innate and specific immunity, but the origins of variation in the distribution of cell type across individuals are not known. Our findings point toward nutritional and microbial exposures in infancy as potentially important determinants of immune-phenotypes in adulthood, and they suggest that leukocyte distribution is a plausible mechanism through which developmental environments have lasting effects on disease risk in adulthood.

BECon: a tool for interpreting DNA methylation findings from blood in the context of brain.

Tissue differences are one of the largest contributors to variability in the human DNA methylome. Despite the tissue-specific nature of DNA methylation, the inaccessibility of human brain samples necessitates the frequent use of surrogate tissues such as blood, in studies of associations between DNA methylation and brain function and health. Results from studies of surrogate tissues in humans are difficult to interpret in this context, as the connection between blood-brain DNA methylation is tenuous and not well-documented. Here, we aimed to provide a resource to the community to aid interpretation of blood-based DNA methylation results in the context of brain tissue. We used paired samples from 16 individuals from three brain regions and whole blood, run on the Illumina 450 K Human Methylation Array to quantify the concordance of DNA methylation between tissues. From these data, we have made available metrics on: the variability of cytosine-phosphate-guanine dinucleotides (CpGs) in our blood and brain samples, the concordance of CpGs between blood and brain, and estimations of how strongly a CpG is affected by cell composition in both blood and brain through the web application BECon (Blood-Brain Epigenetic Concordance; https://redgar598.shinyapps.io/BECon/). We anticipate that BECon will enable biological interpretation of blood-based human DNA methylation results, in the context of brain.

Is Abdominal Fat Distribution Measured by Axial CT Imaging an Indicator of Complications and Mortality in Acute Pancreatitis?

BACKGROUND: Obesity is an important risk-stratifying co-morbidity for many pathological conditions. Controversy exists about its influence in outcomes after acute pancreatitis (AP). This study assessed abdominal fat distribution (subcutaneous, retroperitoneal and intra-abdominal) measured using computer tomography (CT) images and related it to outcomes in patients with AP. METHODS: The case notes of patients admitted with AP were identified from computerised records from 2008 to the 2013. Image analysis software was used to assess the individual abdominal fat distributions from CT images. RESULTS: A total of 79 patients were included. There was no relationship between fat distribution and either severity of, or mortality from, AP. Fat distribution was not found to be an independent risk factor on multivariate analysis. There was, however, a positive correlation between retroperitoneal and intra-abdominal fat with APACHE II scores, Ranson and Glasgow score and Multiple Organ Dysfunction score (MODS) on various days following admission (r = 0.421, p = 0.0008; r = 0.469, p < 0.0001; r = 0.398, p = 0.007; r = 0.336, p = 0.011, respectively). On multiple logistical regression analysis, the only variables associated with mortality were Balthazar Severity Index, MODS and EWS with a p value of <0.0001, 0.0019 and 0.0481, respectively. CONCLUSIONS: Obese patients have worse predicted outcomes as measured by the EWS, MODS and Ranson scores. Abdominal fat distribution, however, was not shown to be directly related to AP severity or mortality. The addition of fat parameters may be of use in prognostic CT severity index models, but from this data, it does not appear to be an independent risk factor of adverse outcome.

A comparison of fentanyl with pethidine for pain relief during childbirth: a randomised controlled trial.

OBJECTIVE: To compare the efficacy of fentanyl administered via the subcutaneous (s.c.) or intranasal (i.n.) route with intramuscular (i.m.) pethidine in labouring women requesting analgesia. DESIGN: A randomised controlled trial three-armed, parallel-design. SETTING: A regional hospital and the largest tertiary maternity centre in South Australia. SAMPLE: One hundred and fifty-six healthy parturients birthing at term. METHODS: Women were randomised to receive s.c. fentanyl (n = 53), i.n. fentanyl (n = 52), or i.m. pethidine (n = 51). The outcomes were analysed by intention-to-treat. MAIN OUTCOME MEASURES: Pain scores measured before and 30 minutes after opioid administration. RESULTS: All groups reported clinically significant reductions in pain scores (mean range 1.2-1.6; P < 0.001), with no significant differences between groups. Significantly more women in the fentanyl groups reported satisfaction with using the study drug again, compared with women receiving i.m. pethidine (82.9% i.n. fentanyl, 80.6% s.c. fentanyl, and 44.0% i.m. pethidine; P < 0.01). Women in the fentanyl groups experienced less sedation (i.n. fentanyl 7.3%, s.c. fentanyl 2.9%, i.m. pethidine 44%; P ≤ 0.03), shorter labours by at least 2 hours (P < 0.05), and fewer difficulties establishing breastfeeding (78.8% i.m. pethidine, 39.4% i.n. fentanyl, and 44.0% s.c. fentanyl; P < 0.01). Neonates in the pethidine group were more likely to require nursery admission (P < 0.02). CONCLUSIONS: Fentanyl administered by s.c. and i.n. routes is as efficacious in relieving labour pain as i.m. pethidine, but resulted in greater satisfaction, less sedation, shorter labour, fewer nursery admissions, and fewer difficulties in establishing breastfeeding. Fentanyl appears to be a suitable alternative to pethidine when providing parenteral pain relief to labouring women.

Gallbladder agenesis.

This case report describes unusual congenital biliary anatomy encountered at a routine laparoscopic cholecystectomy. Imaging obtained prior to surgery (ultrasonography and magnetic resonance cholangiopancreatography) had been misleading. The case highlights the importance of careful dissection even with anticipated normal anatomy.

Imaging of indeterminate pancreatic cystic lesions: a systematic review.

BACKGROUND: Pancreatic cystic lesions are an increasing problem and investigation of these cysts can be fraught with difficulty. There is currently no gold standard for diagnosis or surveillance. This review was undertaken to determine the present reliability of the characterisation, assessment of malignant potential and diagnosis of pancreatic cystic lesions using available imaging modalities. METHODS: A Medline search using the terms 'pancreatic', 'pancreas', 'cyst', 'cystic', 'lesions', 'imaging', 'PET'. 'CT', 'MRI' and 'EUS' was performed. Publications were screened to include studies examining the performance of CT, MRI, MRCP, EUS and 18-FDG PET in the determination of benign or malignant cysts, cyst morphology and specific diagnoses. RESULTS: Nineteen studies were identified that met the inclusion criteria. 18-FDG PET had a sensitivity and specificity of 57.0-94.0% and 65.0-97.0% and an accuracy of 94% in determining benign versus malignant cysts. CT had a sensitivity and specificity of 36.3-71.4% and 63.9-100% in determining benign disease but had an accuracy of making a specific diagnosis of 39.0-44.7%. MRI had a sensitivity and specificity of 91.4-100.0% and 89.7% in assessing main pancreatic duct communication. CONCLUSION: CT is a good quality initial investigation to be used in conjunction with clinical data. MRCP can add useful information regarding MPD communication but should be used judiciously. PET may have a role in equivocal cases to determine malignancy. Further examination of CT-PET in this patient group is warranted.

Assessment of reproducibility and accuracy in templating hybrid total hip arthroplasty using digital radiographs.

In 20 patients undergoing hybrid total hip arthroplasty, the reproducibility and accuracy of templating using digital radiographs were assessed. Digital images were manipulated using either a ten-pence coin as a marker to scale for magnification, or two digital-line methods using computer software. On-screen images were templated with standard acetate templates and compared with templating performed on hard-copy digital prints. The digital-line methods were the least reliable and accuracy of sizing compared with the inserted prostheses varied between -1.6% and +10.2%. The hard-copy radiographs showed better reproducibility than the ten-pence coin method, but were less accurate with 3.7% undersizing. The ten-pence coin method was the most accurate, with no significant differences for offset or acetabulum, and undersizing of only 0.9%. On-screen templating of digital radiographs with standard acetate templates is accurate and reproducible if a radiopaque marker such as a ten-pence coin is included when the original radiograph is taken.

Cadaver studies and their impact on the understanding of human adiposity.

The skinfold thickness is a much-used measurement for monitoring adiposity in a wide range of medical, health, occupational and sport science disciplines. Misconceptions abound, however, in its use, particularly that of purportedly predicting body 'fat' as opposed to 'adipose tissue'. To obtain data to investigate body composition and the extent to which anthropometry can be justifiably used to predict whole-body adiposity, an extensive dissection study was undertaken on 34 cadavers. In addition, to pre-empt questions on the applicability of cadaver data to living subjects, 40 elderly in vivo subjects of the same age range were compared with the cadaver population. No significant macro-morphological differences were found between males or females in the morbid and in vivo groups. Significant findings affect our previous understanding of the predictability of whole-body 'fat'. Skinfold compressibility was by no means constant; skin thickness varied with location in both sexes, females having thinner skin than males; there were significant sex differences in adipose tissue patterning. An identical thickness of adipose tissue did not necessarily contain the same concentrations of fat. Despite this variability, a relationship was demonstrated between aggregate skinfold measures and subcutaneous adipose tissue mass (as opposed to subcutaneous fat), this relationship being more evident in men. A strong relationship was found between subcutaneous adiposity and whole-body adiposity, and between direct skinfold depth measures and whole-body adiposity. The amount of visceral adipose tissue was the same in men and women, but in the men this represented a greater proportion of their total body adiposity. Further, the use of waist-to-hip girth ratio (WHR) was identified as an important predictor of health risk. These findings demonstrate that it is not sustainable to introduce a non-quantifiable error by transforming anthropometric values (skinfolds) into predictions of percentage body fat. If subcutaneous adiposity can be predicted, then an excellent indication of overall adiposity could be obtained. Currently, skinfold measurement can yield a reasonable indication of comparative subcutaneous adiposity (better in men than in women). In neither gender is this prediction completely reliable due to both inter- and intra-individual differences in the skinfold measurement procedure.

Developing an accurate system of measuring colour in a venous leg ulcer in order to assess healing.

OBJECTIVE: To develop a standardised method of assessing venous ulceration, based on the colour of an ulcer bed and the surrounding skin. METHOD: This pilot study involved taking three sequential digital photographs during an episode of care and measuring the colour using image analysis software. Ten episodes of care were used for data collection. RESULTS: Based on previous research, a threshold of < or =3 degrees of colour and 3% of saturation was selected to indicate the reliability of the system. The mean of the colour measurements was inside the reliability threshold when measuring an ulcer bed, but outside the threshold for measuring the surrounding skin. CONCLUSION: The results indicate that the system provides consistent visual representation of a venous leg ulcer.

Egg size-number trade-off and a decline in oviposition site choice quality: female Pararge aegeria butterflies pay a cost of having males present at oviposition.

Once mated, the optimal strategy for females of the monandrous butterfly, Pararge aegeria, is to avoid male contact and devote as much time as possible to ovipositing, as there is little advantage for females to engage in multiple matings. In other butterfly species the presence of males during egg laying has been shown to affect aspects of oviposition behavior and it has been suggested that repeated interference from males has the potential to reduce reproductive output. The aim of this study was to assess the effects of male presence during oviposition on reproductive output and behavior of a population of P. aegeria obtained from Madeira Island, Portugal, and maintained in the laboratory. Two experiments were performed where females were housed individually in small cages. Experiment 1 examined how social factors influenced the egg laying behavior of females. To do this the presence or absence of males was manipulated and egg size and number was measured over the first 14 days of oviposition. It was observed that when males were present during oviposition females made a trade-off between egg size and number. Experiment 2 examined how social factors affected oviposition site choice. Again, male presence/absence was manipulated, but in this experiment where the female laid her egg in relation to host quality was scored, and the size of the egg laid was measured. In the absence of males females selectively positioned their larger eggs on good quality host plants. However, selective oviposition was no longer observed when females were in the presence of males. We suggest that P. aegeria females from the Madeira Island population are adapted for a flexible oviposition strategy, governed by external cues, allowing a trade-off between egg size and number when the time available for egg laying is limiting.

Relationships between visceral, trunk and whole-body adipose tissue weights by cadaver dissection.

BACKGROUND: Despite the important association of central adiposity and cardiovascular and other risk factors, there are only three reported values for directly weighed visceral adipose tissue (AT). All other reported values are based on medical imaging techniques. OBJECTIVE: The study aimed to investigate the relationships between visceral, trunk and total AT weights in older men and women. METHODS: Data was obtained from the combination of two studies involving the complete dissection of 15 male and 16 female cadavers (age range 55-94 years) and allowed for compartmentation into skin, AT, muscle, bone and a residual component, divided over six body segments: head, trunk, legs and arms. Visceral AT was separated from trunk subcutaneous AT. All tissues were weighed. RESULTS: Visceral AT weights ranged from 0.3 to 5.8 kg. Mean values were 3.00 +/- 1.52 kg (mean +/- SE) for the men and 3.24 +/- 1.67 kg for the women. These were not significantly different (p = 0.68), but visceral AT weight, expressed as a percentage of total body AT weight was significantly greater (p = 0.02) in the men (16.8 +/- 5.4%) than in the women (12.9 +/- 3.5%). Correlations between visceral AT weight and the weight of subcutaneous AT of the trunk were highly significant (men, r = 0.70, women, r = 0.81, p < 0.005), with similar slopes for the two sexes. The correlation coefficients of visceral with total body AT weights were even greater (men, r = 0.83 and women, r = 0.96, p < 0.0001). CONCLUSIONS: In this sample of older Belgians, visceral AT is strongly related to total body adiposity, corresponding to an increment of about 200 g of visceral AT for every kilogram of total AT in men and about 180 g in women. Because of this relationship, techniques such as skinfold calipers and ultrasound for assessing whole body fatness from measurement of only the subcutaneous layer are thus able to account for visceral adiposity.

Cadaver-assessed validity of anthropometric indicators of adipose tissue distribution.

Although the waist-to-hip ratio (WHR) has emerged as the best anthropometric indicator of the body's adipose tissue distribution, it has never been directly validated. Waist and hip girths, and triceps and subscapular skinfold thickness were measured in 12 male and 13 female cadavers aged 55-94 y. Adipose tissue from the upper limbs, lower limbs, subcutaneous trunk and intra-abdominal regions was then separated by dissection and weighed. Adipose volumes were also determined by hydrostatic weighing. The following adipose tissue mass ratios (and corresponding volume ratios) were derived: trunk to sum of lower limbs, trunk to sum of upper and lower limbs, intra-abdominal to sum of lower limbs and intra-abdominal to sum of upper and lower limbs. Centrality index (CI-subscapular-to-triceps skinfold ratio) and WHR were regressed on the tissue mass and volume ratios of the 25 cadavers. WHR was significantly related to mass and volume ratios for the 12 men (R2=36.0-57.5%, P<0.05), except for intra-abdominal to sum of upper and lower limbs (R(2)=26.3%, P=0.09), but none of these relations was significant in the women. CI was significantly related to all mass and volume ratios only for men and women combined (R(2)=16.2-21.8%, P<0.05). The WHR was better related to all mass and volume ratios than the CI. These results, especially the strong association between WHR and the ratio of intra-abdominal to lower limb adipose masses (R(2)=35.4%, P=0.002), demonstrate a clear relation between the selected anthropometric variables (hip and waist girths, and subscapular and triceps skinfolds) and adipose tissue distribution, thus validating the use of WHR as an important predictor of health risk.

Issues in adolescent health: a challenge for nursing.

The young people of today are the greatest investment we as adults have in our future. The care and nurturing we afford the adolescent is just as important as that which we afford to children or the elderly. Although most adolescents have a preoccupation with their bodies, they do not always engage in activities that will protect and develop them. Adolescents are often exposed to peer pressure, the effects of which may impact negatively on their behaviour and their health. Many adolescent health and behavioural issues evolve from developmental changes and can manifest in a confrontational attitude toward society, parents and others. They are hormonally 'fully charged', and their adolescent sexuality can have enormous effects on their future physical, psychosocial, moral and sexual development. Nurses have a pivotal role to play in ensuring children and adolescents learn the facts relating to the consequences of engaging in unhealthy behaviour and lifestyle. Nurses must also encourage parents to model and reinforce good health practices, such as serving balanced and nutritious meals at regular times and planning positive family activities. In this paper we review some of the salient issues in adolescent health today.