The effectiveness of personalised food choice advice tailored to an individual's socio-demographic, cognitive characteristics, and sensory preferences.

Personalised dietary advice has become increasingly popular, currently however most approaches are based on an individual's genetic and phenotypic profile whilst largely ignoring other determinants such as socio economic and cognitive variables. This paper provides novel insights by testing the effectiveness of personalised healthy eating advice concurrently tailored to an individual's socio-demographic group, cognitive characteristics, and sensory preferences. We first used existing data to build a synthetic dataset based on information from 3654 households (Study 1a), and then developed a cluster model to identify individuals characterised by similar socio-demographic, cognitive, and sensory aspects (Study 1b). Finally, in Study 2 we used the characteristics of 8 clusters to build 8 separate personalised food choice advice and assess their ability to motivate the increased consumption of fruit and vegetables and decreased intakes of saturated fat and sugar. We presented 218 participants with either generic UK Government "EatWell" advice, advice that was tailored to their allocated cluster (matched personalised), or advice tailored to a different cluster (unmatched personalised). Results showed that, when compared to generic advice, participants that received matched personalised advice were significantly more likely to indicate they would change their diet. Participants were similarly motivated to increase vegetable consumption and decrease saturated fat intake when they received unmatched personalised advice, potentially highlighting the power of providing alternative food choices. Overall, this study demonstrated that the power of personalizing food choice advice, based on a combination of individual characteristics, can be more effective than current approaches in motivating dietary change. Our study also emphasizes the viability of addressing population health through automatically delivered web-based personalised advice.

Healthcare and housing provision for a UK homeless community: a qualitative service evaluation.

OBJECTIVES: Homelessness is both a significant determinant and consequence of health and social inequalities. To better meet healthcare needs, dedicated mental health and general nurses were implemented to deliver outreach healthcare to people experiencing homelessness in one United Kingdom (UK) county. During COVID-19, the UK Government also instructed local authorities to accommodate individuals sleeping rough and have a national target to end rough sleeping. This qualitative study explored experiences of this nurse-let outreach service and housing journeys during and beyond COVID-19 among people experiencing homelessness. STUDY DESIGN: Face-to-face, narrative storytelling interviews were conducted via opportunistic sampling in community settings. Individuals with recent or current experiences of homelessness were eligible. METHODS: Participants were informed about the study via known professionals and introduced to the researcher. Eighteen narrative interviews were conducted, transcribed, and analysed using reflective thematic analysis. RESULTS: Individuals described complex journeys in becoming and being homeless. The nurse-led outreach service provided integral support, with reported benefits to person-centred and accessible care and improved outcomes in health and well-being. After being housed, individuals valued housing necessities and described new responsibilities. However, some participants did not accept or stay in housing provisions where they perceived risks. CONCLUSIONS: Interviewed participants perceived that the dedicated nurse-led outreach service improved their access to care and health outcomes. In the absence of dedicated provisions, mainstream healthcare should ensure flexible processes and collaborative professional working. Local authorities must also be afforded increased resources for housing, as well as integrated support, to reduce social and health inequalities.

Nonopioid Analgesics for the Perioperative Geriatric Patient: A Narrative Review.

Management of acute perioperative pain in the geriatric patient can be challenging as the physiologic and pharmacokinetic changes associated with aging may predispose older patients to opioid-related side effects. Furthermore, elderly adults are more susceptible to postoperative delirium and postoperative cognitive dysfunction, which may be exacerbated by both poorly controlled postoperative pain and commonly used pain medications. This narrative review summarizes the literature published in the past 10 years for several nonopioid analgesics commonly prescribed to the geriatric patient in the perioperative period. Nonopioid analgesics are broken down as follows: medications prescribed throughout the perioperative period (acetaminophen and nonsteroidal anti-inflammatory drugs), medications limited to the acute perioperative setting ( N -methyl-D-aspartate receptor antagonists, dexmedetomidine, dexamethasone, and local anesthetics), and medications to be used with caution in the geriatric patient population (gabapentinoids and muscle relaxants). Our search identified 1757 citations, but only 33 specifically focused on geriatric analgesia. Of these, only 21 were randomized clinical trials' and 1 was a systematic review. While guidance in tailoring pain regimens that focus on the use of nonopioid medications in the geriatric patient is lacking, we summarize the current literature and highlight that some nonopioid medications may extend benefits to the geriatric patient beyond analgesia.

COVID-19 stressors, wellbeing and health behaviours: a cross-sectional study.

BACKGROUND: Following the implementation of pandemic response measures, concerns arose regarding the impact for population health and wellbeing. METHODS: This study reports findings from a survey (N = 2510) conducted in Warwickshire (UK) during August and September 2020, and for the first time investigates behaviours which may worsen or mitigate the association between COVID-19-related stressors and wellbeing. RESULTS: Increased stressors were associated with lower mental wellbeing and higher loneliness. Participants with a mental health condition reported lower wellbeing, as did younger groups, women and participants not in employment. To cope with restrictions, more participants engaged in healthier behaviours over unhealthy behaviours, and relaxing reduced the association between stressors and poor wellbeing. Some participants reported increasing alcohol and unhealthy dietary behaviours to cope with restrictions, however, these behaviours did not mitigate the impact of COVID-19 stressors and were instead negatively associated with wellbeing. Around half of participants helped neighbours during the pandemic, a behaviour positively associated with wellbeing particularly among older adults. CONCLUSION: These findings contribute understanding about how various positive and negative health behaviours may mitigate or worsen the impact of COVID-19 on wellbeing, and how public health interventions may effectively target behaviours and groups in similar populations.

Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.

Approximately 1% of the global population is affected by intellectual disability (ID), and the majority receive no molecular diagnosis. Previous studies have indicated high levels of genetic heterogeneity, with estimates of more than 2500 autosomal ID genes, the majority of which are autosomal recessive (AR). Here, we combined microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES) to identify disease genes/mutations in 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID. We identified definite or candidate mutations (or CNVs) in 51% of families in 72 different genes, including 26 not previously reported for ARID. The new ARID genes include nine with loss-of-function mutations (ABI2, MAPK8, MPDZ, PIDD1, SLAIN1, TBC1D23, TRAPPC6B, UBA7 and USP44), and missense mutations include the first reports of variants in BDNF or TET1 associated with ID. The genes identified also showed overlap with de novo gene sets for other neuropsychiatric disorders. Transcriptional studies showed prominent expression in the prenatal brain. The high yield of AR mutations for ID indicated that this approach has excellent clinical potential and should inform clinical diagnostics, including clinical whole exome and genome sequencing, for populations in which consanguinity is common. As with other AR disorders, the relevance will also apply to outbred populations.

Undergraduate radiology education: foundation doctors' experiences and preferences.

AIM: To assess foundation doctors' experiences of undergraduate radiology teaching within the UK and preferences for radiology teaching delivery. MATERIALS AND METHODS: This was a retrospective multicentre study of foundation doctors. A questionnaire, designed using the Royal College of Radiologists Undergraduate Radiology Curriculum, was completed to determine how prepared foundation doctors felt in image interpretation by their undergraduate teaching. For this, agreement with statements was graded using a five-point Likert scale. Open and closed questions were used to assess preferences for teaching delivery. RESULTS: The study involved 150 foundation doctors from 29 medical schools. The majority "strongly agreed" or "agreed" that undergraduate training gave them confidence in interpreting most basic chest and abdominal radiographs. Confidence was less for skeletal radiographs and trauma computed tomography (CT). Seventy-seven percent wished they had had more radiology teaching. The three most important topics to be included in teaching were chest radiograph, CT, and abdominal radiograph interpretation. Small group teaching and integration into clinical teaching received the highest number of votes for preferred teaching delivery method. Ninety-two percent felt radiologists were best suited to deliver teaching. CONCLUSION: In general, foundation doctors felt undergraduate teaching prepared them well for chest and abdominal radiograph interpretation, but less so for skeletal radiography and CT. The majority felt more undergraduate radiology teaching would be beneficial, and that this should be delivered by radiologists in either small group sessions or integrated into clinical teaching.

Adult care providers' perspectives on the transition to adult care for emerging adults with Type 1 diabetes: a cross-sectional survey.

AIMS: To assess adult diabetes care providers' current transition practices, knowledge about transition care, and perceived barriers to implementation of best practices in transition care for emerging adults with Type 1 diabetes mellitus. METHODS: We administered a 38-item web-based survey to adult diabetes care providers identified through the Québec Endocrinologist Medical Association and Diabetes Québec. RESULTS: Fifty-three physicians responded (35%). Fewer than half of all respondents (46%) were familiar with the American Diabetes Association's transition care position statement. Approximately one-third of respondents reported a gap of >6 months between paediatric and adult diabetes care. Most (83%) believed communication with the paediatric team was adequate; however, only 56% reported receiving a medical summary and 2% a psychosocial summary from the paediatric provider. Respondents believed that the paediatric team should improve emerging adults' preparation for transition care by developing their self-management skills and improve teaching about the differences between paediatric and adult-oriented care. Only 31% had a system for identifying emerging adults lost to follow-up in adult care. Perceived barriers included difficulty accessing psychosocial services, emerging adults' lack of motivation, and inadequate transition preparation. Most (87%) were interested in having additional resources, including a self-care management tool and a registry to track those lost to follow-up. CONCLUSIONS: Our findings highlight the need to better engage adult care providers into transition care practices. Despite adult physicians' interest in transition care, implementation of transition care recommendations and resources in clinical care remains limited. Enhanced efforts are needed to improve access to mental health services within the adult healthcare setting.

A comparison of computer-assisted detection (CAD) programs for the identification of colorectal polyps: performance and sensitivity analysis, current limitations and practical tips for radiologists.

AIM: To directly compare the accuracy and speed of analysis of two commercially available computer-assisted detection (CAD) programs in detecting colorectal polyps. MATERIALS AND METHOD: In this retrospective single-centre study, patients who had colorectal polyps identified on computed tomography colonography (CTC) and subsequent lower gastrointestinal endoscopy, were analysed using two commercially available CAD programs (CAD1 and CAD2). Results were compared against endoscopy to ascertain sensitivity and positive predictive value (PPV) for colorectal polyps. Time taken for CAD analysis was also calculated. RESULTS: CAD1 demonstrated a sensitivity of 89.8%, PPV of 17.6% and mean analysis time of 125.8 seconds. CAD2 demonstrated a sensitivity of 75.5%, PPV of 44.0% and mean analysis time of 84.6 seconds. CONCLUSION: The sensitivity and PPV for colorectal polyps and CAD analysis times can vary widely between current commercially available CAD programs. There is still room for improvement. Generally, there is a trade-off between sensitivity and PPV, and so further developments should aim to optimise both. Information on these factors should be made routinely available, so that an informed choice on their use can be made. This information could also potentially influence the radiologist's use of CAD results.

Reducing interruptions during duty radiology shifts, assessment of its benefits and review of factors affecting the radiology working environment.

AIM: To investigate and reduce the number of inappropriate interruptions to the duty radiology registrar, as well as subjectively assess the effect of reducing interruptions and identify other methods of improving the duty working environment. MATERIALS AND METHODS: A pre- and post-intervention prospective quantitative study and post-intervention retrospective qualitative study of duty radiology registrars was performed at a tertiary referral centre. The first cycle of the quantitative study was performed prior to implementation of a telephone triage system. The second cycle and qualitative study were performed afterwards. RESULTS: The average number of interruptions per day dropped by 43.7% after the intervention. Moreover, inappropriate interruptions dropped from one in three to one in five interruptions. Improvement was demonstrated following the intervention for perceived patient safety, workload, reporting efficiency, reporting accuracy, work satisfaction, and stress. The most common hindrance to a good working environment was interruptions (36%). The most common suggestion for improvement was improved comfort (33%). CONCLUSION: The present study demonstrates that a telephone triage system can substantially reduce the number of interruptions to the duty radiologist. It also demonstrates that reducing interruptions in radiology has the potential to improve the working environment in many ways.

Attenuated behaviour in Cornelia de Lange and fragile X syndromes.

BACKGROUND: Catatonia-like presentations in people with autism have been increasingly recognised within research and diagnostic guidelines. The recently developed Attenuated Behaviour Questionnaire has identified that attenuated behaviour [autistic catatonia] is very prevalent in people with autism spectrum disorders (ASDs) and associated with repetitive behaviour. In the current study, we investigated attenuated behaviour within two genetic syndromes associated with ASD and examined ASD and repetitive behaviour as longitudinal predictors of attenuated behaviour. METHOD: The Attenuated Behaviour Questionnaire was completed by parents/carers of 33 individuals with Cornelia de Lange syndrome (CdLS) and 69 with fragile X syndrome (FXS). Information collected from the same informants 4 years previously was utilised to examine ASD and repetitive behaviour as predictors of later attenuated behaviour, controlling for age, gender and ability. RESULTS: Catatonia-like attenuated behaviour was reported for individuals with CdLS (30.3%) and FXS (11.6%). Slowed movement was more prevalent in people with CdLS. No other phenotypic differences were observed. Across the two groups, repetitive behaviour predicted the presence of attenuated behaviour 4 years later, after controlling for age, gender and ability. CONCLUSIONS: Attenuated behaviour can be identified in individuals with CdLS and FXS and may have an effect on both adaptive behaviour and quality of life. Repetitive behaviours predicted subsequent risk within both groups and should be assessed by services as part of a pro-active strategy of support.

Investigating the level of glaucoma awareness and perception of its risk factors in Anambra State, Nigeria.

OBJECTIVES: The purpose of this study was to investigate the level of awareness of glaucoma and perception of its risk factors in Anambra State, and to examine and evaluate the health seeking behaviour of this target population and its relationship with the development glaucoma. STUDY DESIGN: This is a qualitative study that utilised face-to-face semi-structured interviews to investigate the level of glaucoma awareness in the state. METHODS: Purposive, non-random sampling technique was used to recruit the participants, and data were collected from 28 participants [aged 21-73 years] using semi-structured interview. The resulting data were analysed using Nvivo 10 software and Interpretative phenomenological analysis framework. RESULTS: Of the 28 interviewees, 15 (53.6%) live in urban areas, and 13 (46.4%) live in the rural areas; 11 (39.3%) of the participants were male and 17 (60.7%) were females. In this study, people with more education, and people that live in the urban areas tend to have heard about glaucoma compared with people with less education, and who live in the rural areas; although this sample was too small to make substantive claims. Glaucoma was perceived as 'a dangerous eye disease that can cause blindness if not treated early; serious eye problem; an incurable eye problem that can eventually result to blindness, and a dangerous eye problem that can easily render a person blind'. Four a priori themes and ten emergent themes were identified. CONCLUSIONS: There is low awareness of glaucoma in this population, and this encourages people to indulge in certain risk behaviours that could predispose them to glaucoma. Therefore, providing sustained health promotion programmes and improved eye care services could help this population immensely in the current struggle against glaucoma blindness.

Does compliance with healthy lifestyle behaviours cluster within individuals in Australian primary school-aged children?

BACKGROUND: The 3 "movement behaviours" of sleep, screen time, and physical activity are associated with a wide range of health outcomes in children. This study examined whether these behaviours cluster together within individuals in Australian primary school children. METHODS: Three datasets including 4,449 9- to 11-year-old children were interrogated-(a) Obesity Prevention and Lifestyle (OPAL), (b) the International Study of Children, Obesity, Lifestyle and Environment (ISCOLE), and (c) the National Children's Nutrition and Physical Activity Survey (NCNPAS). The surveys measured movement behaviours using different instruments (accelerometry, use of time recall, and questionnaires) and different operationalizations of compliance. Observed frequencies of compliance with various combinations of guidelines were compared with expected frequencies based on the assumption of independence, using chi-square tests. RESULTS: Compliance with the sleep guidelines was relatively high (72%, 75%, and 79% in the OPAL, ISCOLE, and NCNPAS datasets, respectively), and compliance with the screen (18%, 35%, and 22%) and physical activity (33%, 57%, and 87%) guidelines was generally lower. Against expectation, there was no evidence of clustering in any of the datasets (p > .99). CONCLUSIONS: Compliance with movement behaviour guidelines does not cluster within individuals in 9- to 11-year-old Australian children. It may be unlikely that fostering compliance with one guideline will have a flow-on effect to the others. Temporal trade-offs (i.e., the need to choose one movement behaviour above another) in the 24-hr day may contribute to the lack of clustering.

A Hybrid Readout Solution for GaN-Based Detectors Using CMOS Technology.

Gallium nitride (GaN) and its alloys are becoming preferred materials for ultraviolet (UV) detectors due to their wide bandgap and tailorable out-of-band cutoff from 3.4 eV to 6.2 eV. GaN based avalanche photodiodes (APDs) are particularly suitable for their high photon sensitivity and quantum efficiency in the UV region and for their inherent insensitivity to visible wavelengths. Challenges exist however for practical utilization. With growing interests in such photodetectors, hybrid readout solutions are becoming prevalent with CMOS technology being adopted for its maturity, scalability, and reliability. In this paper, we describe our approach to combine GaN APDs with a CMOS readout circuit, comprising of a linear array of 1 × 8 capacitive transimpedance amplifiers (CTIAs), implemented in a 0.35 µm high voltage CMOS technology. Further, we present a simple, yet sustainable circuit technique to allow operation of APDs under high reverse biases, up to ≈80 V with verified measurement results. The readout offers a conversion gain of 0.43 µV/e-, obtaining avalanche gains up to 10³. Several parameters of the CTIA are discussed followed by a perspective on possible hybridization, exploiting the advantages of a 3D-stacked technology.

Validity of short food questionnaire items to measure intake in children and adolescents: a systematic review.

BACKGROUND: Short food questions are appealing to measure dietary intakes. METHODS: A review of studies published between 2004 and 2016 was undertaken and these were included in the present study if they reported on a question or short item questionnaire (≤50 items, data presented as ≤30 food groups) measuring food intake or food-related habits, in children (aged 6 months to 18 years), and reported question validity or reliability. Thirty studies met the inclusion criteria. RESULTS: Most questions assessed foods or food groups (n = 29), with the most commonly assessed being fruit (n = 22) or vegetable intake (n = 23), dairy foods and discretionary foods (n = 20 studies each). Four studies assessed food habits, with the most common being breakfast and meal frequency (n = 4 studies). Twenty studies assessed reliability, and 25 studies determined accuracy and were most commonly compared against food records. Evaluation of question performance relied on statistical tests such as correlation. CONCLUSIONS: The present study has identified valid and reliable questions for the range of key food groups of interest to public health nutrition. Questions were more likely to be reliable than accurate, and relatively few questions were both reliable and accurate. Gaps in repeatable and valid short food questions have been identified that will provide direction for future tool development.

Paradoxical physiological responses to propranolol in a Rett syndrome patient: a case report.

BACKGROUND: Rett Syndrome (RTT), caused by a loss-of-function in the epigenetic modulator: X-linked methyl-CpG binding protein 2 (MeCP2), is a pervasive neurological disorder characterized by compromised brain functions, anxiety, severe mental retardation, language and learning disabilities, repetitive stereotyped hand movements and developmental regression. An imbalance in the sympathetic and the parasympathetic nervous system (dysautonomia) and the resulting autonomic storms is a frequent occurrence in patients with RTT. The prototypical beta blocker propranolol has been used to manage sympathetic hyperactivity in patients with RTT. CASE PRESENTATION: A 13 year old girl with RTT was referred to the Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust. Her clinical picture included disordered breathing with concomitant hyperventilation and apnoea, epilepsy, scoliosis, no QT prolongation (QT/QTc [372/467 ms on automated electrocardiogram [ECG], but manually calculated to be 440 ms]), no cardiac abnormalities (PR interval: 104 ms, QRS duration: 78 ms), and generalised anxiety disorder (ICD-10-CM Diagnosis Code F41.1). She was also constipated and was fed via percutaneous endoscopic gastrostomy (PEG). To manage the dysautonomia, propranolol was given (5 mg and 10 mg) and in parallel her physiological parameters, including heart rate, skin temperature and skin transpiration, were monitored continuously for 24 h as she went about her activities of daily living. Whilst her skin temperature increased and skin transpiration decreased, unexpectedly there was a significant paradoxical increase in the patient's average heart rate following propranolol treatment. CONCLUSION: Here, we present a unique case of a paradoxical increase in heart rate response following propranolol treatment for managing dysautonomia in a child with RTT. Further studies are warranted to better understand the underlying dysautonomia in patients with RTT and the impact this might have on treatment strategies in rare disorders such as RTT.

Prevalence and socio-economic distribution of eating, physical activity and sedentary behaviour among South Australian children in urban and rural communities: baseline findings from the OPAL evaluation.

OBJECTIVE: To identify current prevalence and sociodemographic distribution of adherence to national diet and physical activity and sedentary behaviour guidelines among Australian primary school children. STUDY DESIGN: Cross-sectional survey of children (n = 4637, 9-11 years) participating at baseline in the South Australian Obesity Prevention and Lifestyle (OPAL) programme evaluation. METHODS: Self-reported diet, physical activity (PA) and screen time (ST) behaviours were assessed via questionnaire. Children were classified as meeting or not meeting each guideline (two or more serves of fruit, five or more serves of vegetables, two or less serves of discretionary food, ≥60 min of PA, and ≤2 h of ST per day). RESULTS: Although 65% of children met fruit recommendations, only 22% met vegetable recommendations (17% consumed no vegetables). Approximately one-quarter (28%) of children met discretionary food recommendations. Only 17% of children met the ST recommendations and 33% met PA recommendations. Less than 1% of children met all five recommendations. Rural children were more likely to meet both PA (OR = 1.45, 95% CI: 1.21-1.74, P < 0.001) and ST (OR = 1.37, 95% CI: 1.14-1.66, P < 0.01) recommendations than urban counterparts. Children at least socio-economic disadvantage performed better than those at greatest disadvantage for most behaviours. CONCLUSION: Improvement in Australian children's diet and physical activity and sedentary behaviours, particularly urban children and those at greatest socio-economic disadvantage, is urgently warranted.

Single Photon Counting UV Solar-Blind Detectors Using Silicon and III-Nitride Materials.

Ultraviolet (UV) studies in astronomy, cosmology, planetary studies, biological and medical applications often require precision detection of faint objects and in many cases require photon-counting detection. We present an overview of two approaches for achieving photon counting in the UV. The first approach involves UV enhancement of photon-counting silicon detectors, including electron multiplying charge-coupled devices and avalanche photodiodes. The approach used here employs molecular beam epitaxy for delta doping and superlattice doping for surface passivation and high UV quantum efficiency. Additional UV enhancements include antireflection (AR) and solar-blind UV bandpass coatings prepared by atomic layer deposition. Quantum efficiency (QE) measurements show QE > 50% in the 100-300 nm range for detectors with simple AR coatings, and QE ≅ 80% at ~206 nm has been shown when more complex AR coatings are used. The second approach is based on avalanche photodiodes in III-nitride materials with high QE and intrinsic solar blindness.

Activation of muscarinic receptors by ACh release in hippocampal CA1 depolarizes VIP but has varying effects on parvalbumin-expressing basket cells.

KEY POINTS: Optogenetically released acetylcholine (ACh) from medial septal afferents activates muscarinic receptors on both vasoactive intestinal peptide-expressing (VIP) and parvalbumin-expressing (PV) basket cells (BCs) in mouse hippocampal CA1. ACh release depolarized VIP BCs whereas PV BCs depolarized, hyperpolarized or produced biphasic responses. Depolarizing responses in VIP or PV BCs resulted in increased amplitudes and frequencies of spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 pyramidal neurons. The instantaneous frequency of sIPSCs that result from excitation of VIP or PV BCs primarily occurred within the low gamma frequency band (25-50 Hz). We investigated the effect of acetylcholine release on mouse hippocampal CA1 perisomatically projecting interneurons. Acetylcholine was optogenetically released in hippocampal slices by expressing the excitatory optogenetic protein oChIEF-tdTomato in medial septum/diagonal band of Broca cholinergic neurons using Cre recombinase-dependent adeno-associated virally mediated transfection. The effect of optogenetically released acetylcholine was assessed on interneurons expressing Cre recombinase in vasoactive intestinal peptide (VIP) or parvalbumin (PV) interneurons using whole cell patch clamp methods. Acetylcholine released onto VIP interneurons that innervate pyramidal neuron perisomatic regions (basket cells, BCs) were depolarized by muscarinic receptors. Although PV BCs were also excited by muscarinic receptor activation, they more frequently responded with hyperpolarizing or biphasic responses. Muscarinic receptor activation resulting from ACh release increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in downstream hippocampal CA1 pyramidal neurons with peak instantaneous frequencies occurring in both the gamma and theta bandwidths. Both PV and VIP BCs contributed to the increased sIPSC frequency in pyramidal neurons and optogenetic suppression of PV or VIP BCs inhibited sIPSCs occurring in the gamma range. Therefore, we propose acetylcholine release in CA1 has a complex effect on CA1 pyramidal neuron output through varying effects on perisomatically projecting interneurons.

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome.

UNLABELLED: Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point. INTRODUCTION: Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome. METHODS: VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry. RESULTS: Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), -0.5 ± 1.1; p = 0.001) and at 3 months (-0.6 ± 1.1; p < 0.001), but not at 6 months (-0.3 ± 1.3; p = 0.066) or 12 months (-0.3 ± 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup (N = 16; 25 %) had LS BMD Z-scores that were ≤-1.0 at 12 months. In these children, each additional 1,000 mg/m(2) of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, -0.71 to -0.07; p = 0.017). CONCLUSIONS: The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤-1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.

The development of bone mineral lateralization in the arms.

UNLABELLED: Bone mineral content (BMC) is known to be greater in the dominant arm after the age of 8 years. We studied a group of children and found that BMC sidedness gradually increased up to the age of 6 years and then remained stable into late adolescence. INTRODUCTION: Bone mineral content (BMC) exhibits sidedness in the arms after the age of 8 years, but it is not known whether BMC is greater in the dominant arm from birth or whether lateralization develops in early childhood. To address this, we examined bone mineral status in relation to handedness and age. METHODS: Subjects (N = 158) were children recently initiating glucocorticoids for underlying disease (leukemia 43 %, rheumatic conditions 39 %, nephrotic syndrome 18 %). Handedness was determined by questionnaire and BMC by dual-energy X-ray absorptiometry. RESULTS: Median age was 7.2 years (range, 1.5 to 17.0 years), 49 % was male, and the spine BMD Z-score was -0.9 (SD, 1.3). By linear regression, BMC sidedness in the arms was significantly related to age (r = 0.294, p = 0.0005). Breakpoint analysis revealed two lines with a knot at 6.0 years (95 % CI, 4.5-7.5 years). The formula for the first line was: dominant:nondominant arm BMC ratio = 0.029 × age [in years] + 0.850 (r = 0.323, p = 0.017). The slope of the second line was not different from 0 (p = 0.332), while the slopes for the two lines were significantly different (p = 0.027). CONCLUSIONS: These results show that arm BMC sidedness in this patient group develops up to age 6 years and then remains stable into late adolescence. This temporal profile is consistent with mechanical stimulation of the skeleton in response to asymmetrical muscle use as handedness becomes manifest.