Diffusion-weighted MRI in paediatric neuroimaging.

Diffusion-weighted imaging (DWI) is a well-established technique in neuroimaging, but the diagnostic value of DWI outside the setting of acute infarct and abscess is sometimes under-recognised particularly in paediatric neuroimaging. DWI also plays an important role in the evaluation of intracranial infection, brain tumours, demyelinating diseases, and metabolic disorders. DWI can assist in the early detection and characterisation of intraocular and skull-base pathology. The cases presented in this article demonstrate the utility of DWI in paediatric neuroimaging. DWI can improve diagnostic sensitivity and in conjunction with other magnetic resonance imaging (MRI) sequences can aid in early diagnosis and management. Obtaining an early diagnosis may avoid potential complications and improve patient outcome.

Spectrum of Neuroradiologic Findings Associated with Monogenic Interferonopathies.

The genetic interferonopathies are a heterogeneous group of disorders thought to be caused by the dysregulated expression of interferons and are now commonly considered in the differential diagnosis of children presenting with recurrent or persistent inflammatory phenotypes. With emerging therapeutic options, recognition of these disorders is increasingly important, and neuroimaging plays a vital role. In this article, we discuss the wide spectrum of neuroradiologic features associated with monogenic interferonopathies by reviewing the literature and illustrate these with cases from our institutions. These cases include intracerebral calcifications, white matter T2 hyperintensities, deep WM cysts, cerebral atrophy, large cerebral artery disease, bilateral striatal necrosis, and masslike lesions. A better understanding of the breadth of the neuroimaging phenotypes in conjunction with clinical and laboratory findings will enable earlier diagnosis and direct therapeutic strategies.

Evaluation of DISORDER: Retrospective Image Motion Correction for Volumetric Brain MRI in a Pediatric Setting.

BACKGROUND AND PURPOSE: Head motion causes image degradation in brain MR imaging examinations, negatively impacting image quality, especially in pediatric populations. Here, we used a retrospective motion correction technique in children and assessed image quality improvement for 3D MR imaging acquisitions. MATERIALS AND METHODS: We prospectively acquired brain MR imaging at 3T using 3D sequences, T1-weighted MPRAGE, T2-weighted TSE, and FLAIR in 32 unsedated children, including 7 with epilepsy (age range, 2-18 years). We implemented a novel motion correction technique through a modification of k-space data acquisition: Distributed and Incoherent Sample Orders for Reconstruction Deblurring by using Encoding Redundancy (DISORDER). For each participant and technique, we obtained 3 reconstructions as acquired (Aq), after DISORDER motion correction (Di), and Di with additional outlier rejection (DiOut). We analyzed 288 images quantitatively, measuring 2 objective no-reference image quality metrics: gradient entropy (GE) and MPRAGE white matter (WM) homogeneity. As a qualitative metric, we presented blinded and randomized images to 2 expert neuroradiologists who scored them for clinical readability. RESULTS: Both image quality metrics improved after motion correction for all modalities, and improvement correlated with the amount of intrascan motion. Neuroradiologists also considered the motion corrected images as of higher quality (Wilcoxon z = -3.164 for MPRAGE; z = -2.066 for TSE; z = -2.645 for FLAIR; all P < .05). CONCLUSIONS: Retrospective image motion correction with DISORDER increased image quality both from an objective and qualitative perspective. In 75% of sessions, at least 1 sequence was improved by this approach, indicating the benefit of this technique in unsedated children for both clinical and research environments.

Genomic instability of TnSMU2 contributes to Streptococcus mutans biofilm development and competence in a cidB mutant.

Streptococcus mutans is a key pathogenic bacterium in the oral cavity and a primary contributor to dental caries. The S. mutans Cid/Lrg system likely contributes to tolerating stresses encountered in this environment as cid and/or lrg mutants exhibit altered oxidative stress sensitivity, genetic competence, and biofilm phenotypes. It was recently noted that the cidB mutant had two stable colony morphologies: a "rough" phenotype (similar to wild type) and a "smooth" phenotype. In our previously published work, the cidB rough mutant exhibited increased sensitivity to oxidative stress, and RNAseq identified widespread transcriptomic changes in central carbon metabolism and oxidative stress response genes. In this current report, we conducted Illumina-based genome resequencing of wild type, cidB rough, and cidB smooth mutants and compared their resistance to oxidative and acid stress, biofilm formation, and competence phenotypes. Both cidB mutants exhibited comparable aerobic growth inhibition on agar plates, during planktonic growth, and in the presence of 1 mM hydrogen peroxide. The cidB smooth mutant displayed a significant competence defect in BHI, which was rescuable by synthetic CSP. Both cidB mutants also displayed reduced XIP-mediated competence, although this reduction was more pronounced in the cidB smooth mutant. Anaerobic biofilms of the cidB smooth mutant displayed increased propidium iodide staining, but corresponding biofilm CFU data suggest this phenotype is due to cell damage and not increased cell death. The cidB rough anaerobic biofilms showed altered structure relative to wild type (reduced biomass and average thickness) which correlated with decreased CFU counts. Sequencing data revealed that the cidB smooth mutant has a unique "loss of read coverage" of ~78 kb of DNA, corresponding to the genomic island TnSMU2 and genes flanking its 3' end. It is therefore likely that the unique biofilm and competence phenotypes of the cidB smooth mutant are related to its genomic changes in this region.

The Bone Does Not Predict the Brain in Sturge-Weber Syndrome.

BACKGROUND AND PURPOSE: It has been hypothesized that skull marrow signal alteration may represent an early disease manifestation of Sturge-Weber syndrome before development of its intracranial manifestations. We alternatively hypothesized that intraosseous changes are associated with the overlying port-wine stain rather than the intracranial stigmata of Sturge-Weber syndrome and hence are not a predictor of brain involvement. MATERIALS AND METHODS: MR imaging of children presenting with port-wine stain and/or Sturge-Weber syndrome between 1998 and 2017 was evaluated by 2 pediatric neuroradiologists for marrow signal abnormality and pial angioma and other Sturge-Weber syndrome features: ocular hemangioma, atrophy, and white matter changes (advanced myelination). Groups were divided into port-wine stain-only (without intracranial Sturge-Weber syndrome features) and Sturge-Weber syndrome (the presence of cerebral pial angioma). The χ2 test was performed to evaluate the association between port-wine stain and bone marrow changes and between osseous change and pial angioma. RESULTS: We reviewed 139 cases: 40 with port-wine stain-only and 99 with Sturge-Weber syndrome with pial angioma. Fifteen of 99 cases of Sturge-Weber syndrome had no port-wine stain. In the port-wine stain-only cohort, 78% had ipsilateral bony changes and 17% had no intraosseous changes. In the Sturge-Weber syndrome cohort, 84/99 had associated port-wine stain, 91% (P < .01) had bony changes ipsilateral to the port-wine stain or had no bone changes in the absence of port-wine stain, and 77% (P = .27) had bony changes ipsilateral to a cerebral pial angioma. Eighty percent of patients with Sturge-Weber syndrome who lacked a port-wine stain also lacked marrow changes. Five patients with bilateral port-wine stain and bilateral marrow changes had only a unilateral pial angioma. CONCLUSIONS: Intraosseous marrow changes are strongly associated with facial port-wine stain; no significant association was found between pial angioma and bone marrow changes.

The Neonatal Microbiome and Its Partial Role in Mediating the Association between Birth by Cesarean Section and Adverse Pediatric Outcomes.

BACKGROUND: Cesarean sections (CS) are among the most commonly performed surgical procedures in the world. Epidemiologic data has associated delivery by CS with an increased risk of certain adverse health outcomes in children, such as asthma and obesity. OBJECTIVE: To explore what is known about the effect of mode of delivery on the development of the infant microbiome and discuss the potentially mediating role of CS-related microbial dysbiosis in the development of adverse pediatric health outcomes. Recommendations for future inquiry are also provided. METHODS: This study provides a narrative overview of the literature synthesizing the findings of literature retrieved from searches of PubMed and other computerized databases and authoritative texts. RESULTS: Emerging evidence suggests that mode of delivery is involved in the development of the neonatal microbiome and may partially explain pediatric health outcomes associated with birth by CS. Specifically, the gut microbiome of vaginally delivered infants more closely resembles their mothers' vaginal microbiome and thus more commonly consists of potentially beneficial microbiota such as Lactobacillus, Bifidobacterium, and Bacteroides. Conversely, the microbiome of infants born via CS shows an increased prevalence of either skin flora or potentially pathogenic microbial communities such as Klebsiella, Enterococcus, and Clostridium. CONCLUSIONS: Mode of delivery plays an important role in the development of the postnatal microbiome but likely tells only part of the story. More comprehensive investigations into all the pre- and perinatal factors that have the potential to contribute to the neonatal microbiome are warranted.

Modification of the Streptococcus mutans transcriptome by LrgAB and environmental stressors.

The Streptococcus mutans Cid/Lrg system is central to the physiology of this cariogenic organism, affecting oxidative stress resistance, biofilm formation and competence. Previous transcriptome analyses of lytS (responsible for the regulation of lrgAB expression) and cidB mutants have revealed pleiotropic effects on carbohydrate metabolism and stress resistance genes. In this study, it was found that an lrgAB mutant, previously shown to have diminished aerobic and oxidative stress growth, was also much more growth impaired in the presence of heat and vancomycin stresses, relative to wild-type, lrgA and lrgB mutants. To obtain a more holistic picture of LrgAB and its involvement in stress resistance, RNA sequencing and bioinformatics analyses were used to assess the transcriptional response of wild-type and isogenic lrgAB mutants under anaerobic (control) and stress-inducing culture conditions (aerobic, heat and vancomycin). Hierarchical clustering and principal components analyses of all differentially expressed genes revealed that the most distinct gene expression profiles between S. mutans UA159 and lrgAB mutant occurred during aerobic and high-temperature growth. Similar to previous studies of a cidB mutant, lrgAB stress transcriptomes were characterized by a variety of gene expression changes related to genomic islands, CRISPR-C as systems, ABC transporters, competence, bacteriocins, glucosyltransferases, protein translation, tricarboxylic acid cycle, carbohydrate metabolism/storage and transport. Notably, expression of lrgAB was upregulated in the wild-type strain under all three stress conditions. Collectively, these results demonstrate that mutation of lrgAB alters the transcriptional response to stress, and further support the idea that the Cid/Lrg system acts to promote cell homeostasis in the face of environmental stress.

Assessing need for district nursing: study findings.

To determine whether an appropriate level of nursing care is being provided in the community, this study aimed to explore whether patients' needs are being identified through the referral system and whether those needs are being met.

Cutaneous herpes simplex infections.

OBJECTIVE: To review the clinical features and natural history of cutaneous herpes simplex infections associated with genital herpes. DESIGN: A retrospective case note study of all patients presenting to James Pringle House with this condition between 1983-1987. SUBJECTS: 123 patients were identified. RESULTS: The commonest sites involved were the buttocks 64/186 (34%), suprapubic area 28/186 (15%) and thigh 14/186 (7.5%). Thirty five of the 123 (28%) patients had more than one anatomical site involved. Genital and extragenital recurrences occurred with similar frequency. DISCUSSION: Extragenital cutaneous herpes simplex is not uncommon. Lesions may occur virtually anywhere on the body. HSV should always be considered in the differential diagnosis of vesiculating skin lesions.

The use of the Nominal Group Technique in research with community nurses.

The use of group-based techniques to generate ideas and offer solutions to problems is commonplace in many disciplines and for many purposes. What were originally useful adjuncts to market research have become valuable and illuminating tools in education, policy and research. This paper will describe the use of one such technique, the Nominal Group Technique, and its practical application in bridging the gap between researchers and practitioners in one particular study of community nursing.

Evolutionary change in the use of skills within the district nursing team: a study in two Health Board areas in Scotland.

Grade mix within the district nursing team in the United Kingdom has changed markedly over the last 10 years but the relationship between grade mix and skill mix has received only intermittent research attention. This study adopted an ethnographic approach and aimed to explore the way in which grade and skill are taken into account in the delegation of nursing care. After gaining ethical approval, a total of 76 members of 21 district nursing teams in two areas were observed and interviewed. Delegation practices were found to vary both within and between areas and considerable differences were uncovered in the responsibilities allocated to more junior and unqualified team members. The developing role of nursing auxiliaries is discussed in relation to the role of the G grade sister, resource constraints and the standards of patient care. The paper concludes by arguing that the supervision and leadership role provided by the G grade sister should be fully recognized and safeguarded.

The management of recurrent genital herpes infection in pregnancy: a postal survey of obstetric practice.

OBJECTIVE: To determine clinical practice amongst obstetricians in the UK in the antepartum and intrapartum management of pregnant women with recurrent genital herpes infection. METHODS: All Members and Fellows of the Royal College of Obstetricians and Gynaecologists resident in the UK were sent a questionnaire requesting information concerning their management of pregnant women with recurrent genital herpes infection. RESULTS: There was a 76% response rate to the questionnaire. Of the 1201 obstetricians who responded, only 369 (31%) admitted to having a formal policy governing the management of herpes in pregnancy within their unit. However, regular screening was advocated by 718 (60%), of whom 463 (64%) performed regular antenatal swabs for viral culture. At the time of presentation in labour 974 obstetricians (81%) routinely examined the genitals for evidence of a recurrence. When asked in what circumstances caesarean section would be considered an appropriate method of delivery in women with genital herpes infection, 1107 (92%) felt that visible active lesions at the time of labour was sufficient. However, when the membranes had been ruptured for more than four hours in the presence of genital lesions, only 678 (56%) considered this an indication for caesarean section. Caesarean section was more likely to be considered appropriate in this situation by obstetricians who performed antenatal screening (chi 2 = 30.38, P < 0.0001). Five hundred and ninety-six obstetricians (50%) felt that a positive viral culture obtained at antenatal screening from the most recent occasion prior to presentation in labour was an indication for caesarean section, although of this group 192 (32%) said they did not perform antenatal screening by viral culture. The reporting of a recurrence by the patient without visible evidence of disease was considered an appropriate indication for caesarean section by 438 respondents (36%). Maternal request for caesarean section regardless of recurrences at delivery was considered an acceptable indication for operative delivery by 745 obstetricians (62%). CONCLUSIONS: 1. There seems to be little agreement amongst obstetricians in the UK regarding the management of recurrent genital herpes infection in pregnancy. 2. The management possibilities are reviewed and suggestions are made for a more cohesive approach to the problem.

The effect of suppressive oral acyclovir on the psychological morbidity associated with recurrent genital herpes.

OBJECTIVES: To assess the psychological impact of recurrent genital herpes and to determine if longterm acyclovir has any impact on this morbidity. SETTING AND SUBJECTS: Patients with frequently recurring genital herpes attending a department of genitourinary medicine who were considered suitable for longterm acyclovir. METHODS: Patients completed an 80 item, self-administered psychological questionnaire before starting acyclovir and every three months for one year. Treatment was then stopped and three months later a further questionnaire was completed. The questionnaire consisted of the General Health Questionnaire (GHQ); the Hospital Anxiety and Depression Questionnaire (HADQ); Illness Attitude Scales and Illness Concern. Data were analysed by McNemar's test for changes in proportions and by Wilcoxon's test for changes in scores. RESULTS: 102 patients were recruited: 55 men, and 47 women. Eighty two (80%) patients completed three months treatment, 75 (74%) six months, 64 (63%) nine months and 61 (60%) a year. Fifty (49%) of the original 102 patients completed the three months post treatment follow up. At first visit 63% (64/102) were designated as GHQ "cases". Within three months this decreased to 26% (21/82). McNemar's test showed that 67% (34/51) of the patients who were initially classified as GHQ "cases" became "noncases" after three months (p < 0.0001). There was a significant decrease in the proportion of HAD anxiety cases from visit one to visit two (p < 0.0001) and a decrease in illness concern scores from visit one to visit two (p < 0.0001). All these decreases were maintained throughout the years treatment with acyclovir. CONCLUSIONS: There is a substantial morbidity associated with frequently recurring genital herpes. However, acyclovir suppression significantly reduces illness concern and anxiety and is a useful addition to the treatment of this infection.

A prospective study of the psychological impact on patients with a first episode of genital herpes.

OBJECTIVES: To assess the psychological impact of first episode of genital herpes, and to determine whether this changes over time. SETTING AND SUBJECTS: The Departments of Genitourinary Medicine (GUM), and Dermatology, Middlesex Hospital London. The study group consisted of patients attending the department of GUM with a clinically proven first episode of genital herpes. Two control groups were recruited; firstly patients without herpes attending the GUM Department and secondly patients attending the Dermatology Department out patients with chronic dermatoses. METHODS: Patients and controls completed an 87 item, self-administered psychological questionnaire at 3 monthly intervals for a year. The questionnaire consisted of the General Health Questionnaire (GHQ); the Hospital Anxiety and Depression Questionnaire (HADQ); Illness Attitude Scales and Illness Concern. Patients were also asked questions about their sexual behaviour. RESULTS: Ninety one patients (68 women, 23 men) with genital herpes, 61 GUM controls (42 women, 19 men) and 56 dermatology controls (36 women, 20 men) participated. There were no statistically significant demographic differences between patients and controls. At first visit the proportion of patients classified as "cases" by the GHQ (GHQ cases) were similar for primary herpes patients 62% (56/91) and Dermatology controls 52% (29/56) while a significantly smaller proportion of GUM controls 34% (21/61) were classified as GHQ cases. The primary herpes group were significantly more concerned about their illness than either the GUM controls or the Dermatology controls (p < 0.002). The proportion of primary herpes patients classified as "cases" by the GHQ reduced significantly over the initial three month period with 67% of patients classified as "cases" at their first visit becoming "noncases" after three months (p < 0.0001). Also 50% of those classified as "cases" at first visit by the HADQ become "noncases" after the initial three months (p = 0.007). The illness concern scores also decreased significantly from visit one to visit two (means 14.7 vs. 12.3; p < 0.0001). CONCLUSION: The diagnosis of a first episode of genital herpes has a profound emotional effect on patients. If they do not have recurrent episodes, their emotional state improves. For those who do have recurrences, the level of anxiety and concern remains as high as at the time of their first diagnosis. Clinicians must be sensitive to the emotional impact such a diagnosis may bring.

Dosage and safety of long-term suppressive acyclovir therapy for recurrent genital herpes.

131 patients with frequently recurring genital herpes were treated for 1 year with reducing doses of oral acyclovir. The time to first recurrence in patients who commenced therapy on 400 mg twice a day was statistically significantly shorter than those on 200 mg four times a day (p less than 0.02) and as the total daily dose and frequency of therapy were lowered so the time to first recurrence was shortened. By the end of 60 days on 200 mg once a day (the lowest daily dose) 56% of patients had recurrences. Patients showed a marked reduction in the frequency of recurrence during therapy (from a mean of 1.1 per 28 days before to 0.11 during treatment, p = 0.0001). After stopping treatment the frequency of recurrences (0.71 per 28 days) was significantly less than the pre-treatment period (p = 0.001). No important side-effects were seen. It is concluded that long-term suppression with acyclovir is safe and effective for patients with recurrent genital herpes.

Suppression of frequently recurring genital herpes: acyclovir v inosine pranobex.

The suppressive action of acyclovir and inosine pranobex was compared in a randomised double blind controlled trial in patients with frequently recurring genital herpes. Fourteen patients received acyclovir and 17 inosine pranobex. Treatment continued for 12 weeks. The time to the first recurrence was significantly longer and the frequency of recurrences significantly less in the recipients of acyclovir. No important side effects were noted. It is concluded that acyclovir is the treatment of choice to suppress often recurring genital herpes.

A randomised placebo controlled trial of suppressive acyclovir in late pregnancy in women with recurrent genital herpes infection.

OBJECTIVE: To evaluate the efficacy and safety of a suppressive course of acyclovir in late pregnancy in women with recurrent genital herpes infection on the incidence of viral shedding, herpes lesion development and caesarean section for recurrent genital herpes. DESIGN: Double-blind, randomised placebo controlled clinical trial. SETTING: A department of genitourinary medicine in Sheffield and an antenatal clinic in London. POPULATION: Pregnant women with recurrent genital herpes infection at < 36 weeks of gestation. METHODS: Participating women were given acyclovir 200 mg four times a day (or matching placebo) from 36 weeks of gestation until the time of delivery. Women were seen weekly and viral cultures were obtained from the cervix and vulva. Decisions regarding mode of delivery were left to the discretion of the attending obstetrician. MAIN OUTCOME MEASURES: Delivery by caesarean section for recurrent genital herpes infection. Number of episodes of recurrent genital herpes infection and number of episodes of asymptomatic viral shedding during the treatment period. In addition blood was taken at two weekly intervals to determine acyclovir levels. RESULTS: The total number of women recruited was 63 (31 received acyclovir and 32 received placebo). The number of women undergoing delivery by caesarean section for recurrent herpes at the time of delivery was 12 (19%). The odds ratio for delivery by caesarean section in women taking acyclovir, compared with those taking placebo, was 0.44 (95% CI 0.09-1.59). The odds ratio for clinical recurrences during treatment was 0.10 (95% confidence interval 0.00-0.86) and the odds ratio for clinical recurrence or asymptomatic shedding during treatment was 0.32 (95% CI 0.05-1.56). CONCLUSION: This trial was unable to demonstrate that acyclovir can significantly decrease the number of caesarean section deliveries; however, the number of clinical recurrences was significantly reduced. Two episodes of asymptomatic virus shedding both occurred in women taking acyclovir. At the present time there is little evidence to suggest that acyclovir should be used outside randomised controlled trials for the suppression of recurrent genital herpes infection during pregnancy.