The smartphone as a tool to screen for scoliosis, applicable by everyone.

PURPOSE (MAIN PURPOSES AND RESEARCH QUESTION): The purpose of this study is to assess the accuracy and precision of the smartphone with application and casing (Scolioscreen) compared to the Scoliometer. METHODS: The Axial Trunk Rotation (ATR) was measured in adolescent scoliosis patients visiting the outpatient clinic while performing the Adam Forward Bending Test. The Scolioscreen measurements were performed by the orthopedic surgeon and a parent. They were compared to the measurement with the Scoliometer by the orthopedic surgeon, the gold standard. The accuracy was determined with the Pearson's correlation coefficient, and precision was determined by assessing the intra- and inter-variability with the intra-class correlation coefficient (ICC). RESULTS: Fifty patients with adolescent idiopathic scoliosis (44 girls) were included with a mean age of 14.1 years and a mean Cobb angle of 38.5°. The accuracy of both the parents and orthopedic surgeon was excellent with a Pearson correlation coefficient of 0.92 and 0.97, respectively. All the ICC's, both intra- and inter-observer, were over 0.92 demonstrating excellent precision. CONCLUSION: This study confirms the accuracy and precision of the Scolioscreen when measuring the ATR on patients with AIS. Therefore, the Scoliometer can be replaced by the more easily available Scolioscreen which can be used by both physician and parents.

Proteome and secretome profiling of zinc availability in Cryptococcus neoformans identifies Wos2 as a subtle influencer of fungal virulence determinants.

BACKGROUND: Fungal infections impact over 25% of the global population. For the opportunistic fungal pathogen, Cryptococcus neoformans, infection leads to cryptococcosis. In the presence of the host, disease is enabled by elaboration of sophisticated virulence determinants, including polysaccharide capsule, melanin, thermotolerance, and extracellular enzymes. Conversely, the host protects itself from fungal invasion by regulating and sequestering transition metals (e.g., iron, zinc, copper) important for microbial growth and survival. RESULTS: Here, we explore the intricate relationship between zinc availability and fungal virulence via mass spectrometry-based quantitative proteomics. We observe a core proteome along with a distinct zinc-regulated protein-level signature demonstrating a shift away from transport and ion binding under zinc-replete conditions towards transcription and metal acquisition under zinc-limited conditions. In addition, we revealed a novel connection among zinc availability, thermotolerance, as well as capsule and melanin production through the detection of a Wos2 ortholog in the secretome under replete conditions. CONCLUSIONS: Overall, we provide new biological insight into cellular remodeling at the protein level of C. neoformans under regulated zinc conditions and uncover a novel connection between zinc homeostasis and fungal virulence determinants.

STRAWB2 (Stress and Wellbeing After Childbirth): a randomised controlled trial of targeted self-help materials to prevent post-traumatic stress disorder following childbirth.

OBJECTIVES: To test whether providing psychological self-help materials would significantly lower the incidence of post-traumatic stress disorder (PTSD) at 6-12 weeks postnatally. DESIGN: Open-label randomised controlled trial, with blinded outcome assessment. SETTING: Community midwifery services in two National Health Service (NHS) trusts in the North West. SAMPLE: A cohort of 2419 women receiving normal NHS postnatal care. METHODS: Midwives screened women for traumatic birth experience; 678 women who screened positively (28.1%) were randomly allocated to self-help with usual care (n = 336) or to usual care alone (n = 342). The self-help materials were a leaflet and online film designed to prevent the development of PTSD after trauma exposure through explaining how to manage early psychological responses. MAIN OUTCOME MEASURE: The primary outcome was a composite of diagnostic and subdiagnostic PTSD at 6-12 weeks postnatally using the gold-standard Clinician-Administered PTSD Scale (CAPS-5) interview. RESULTS: Of the 678 women correctly randomised plus the nine women randomised in error, 478 (70.5%) were followed up. Diagnostic or subdiagnostic PTSD rates at follow-up did not differ between groups who received self-help (26.7%, 65/243) or usual care alone (26.2%, 64/244) (intention-to-treat analysis: RR 1.02, 95% CI 0.68-1.53). Findings remained consistent in the per-protocol analysis (RR 1.04, 95% CI 0.85-1.27). Women viewed the materials very positively. There were no adverse effects. Health economic micro-costing indicated implementation would be very low cost. CONCLUSIONS: Many women experience a traumatic birth and risk developing PTSD, but self-help strategies without professional support are insufficient and should not be routinely introduced. TWEETABLE ABSTRACT: Self-help information alone does not reduce the number of women developing PTSD after a traumatic childbirth.

One-year follow-up of conservative management of appendicitis: results from a single centre during extended lockdown in the COVID-19 pandemic.

INTRODUCTION: Conservative management with antibiotics was recommended by the UK Surgical Royal Colleges early in the COVID-19 pandemic as the first-line treatment for acute uncomplicated appendicitis. METHODS: This is a prospective single-centre cohort study of patients aged 16 years or over, diagnosed clinically and confirmed radiologically with acute appendicitis in a secondary care setting who were initially treated conservatively with antibiotics. The primary outcome was the response to conservative management with antibiotics. Secondary outcomes were: antibiotic duration; operative rates; surgical approach (open, laparoscopic or conversion to open); complication rates; COVID-19 positive rate; rates of readmission within 12 months; and length of hospital stay. RESULTS: A total of 109 patients were included in the study, 67 of whom were male. Median age was 37 (range 17-93) years. A further 28 patients were excluded because of a decision to manage operatively on the index admission or because of other diagnoses. Thirty-three patients (30.3%) had surgery on the index admission after failed conservative management and 15 (13.8%) had surgery on readmission. On histology, 32/48 patients (66.7%) had a diagnosis of complicated appendicitis and 18/48 (37.5%) had a confirmed appendicolith. CONCLUSIONS: There was a high readmission rate (47/109; 43.1%) for surgery, a radiological drain or conservative management within the first year following initial conservative management. There is a significant risk of recurrence of symptoms, particularly in the presence of an appendicolith. Laparoscopic appendicectomy should be the first-line treatment, with conservative management reserved for patients with acute uncomplicated appendicitis who are COVID-19 positive or have comorbidities.

Creative potential: mental well-being impact assessment of the Liverpool 2008 European capital of culture programme.

OBJECTIVES: Culture has a number of potential impacts upon health and well-being. This project was undertaken to assess the potential impacts of the Liverpool 2008 European Capital of Culture programme upon mental well-being, so that positive effects can be maximized and negative impacts reduced, in order that health and well-being are promoted and inequalities are reduced. STUDY DESIGN: A mental well-being impact assessment (MWIA) toolkit has been developed, and was piloted in this study. MWIA uses a sequence of procedures designed to systematically assess the effect of projects, programmes and policies upon people's mental well-being and health. METHODS: The MWIA toolkit was used to explore the potential positive and negative impacts on mental well-being of a sample of projects and policies from the European Capital of Culture programme. This was achieved by asking stakeholders to answer a series of questions, holding participative workshops, constructing a community profile and reviewing the research literature. Recommendations were developed which aim to enhance the impact of the programme on people's mental well-being. RESULTS: As expected, both positive and negative impacts of the European Capital of Culture programme on mental well-being were identified. Fourteen themes were identified as emerging from the workshops, screening and reviewing the research evidence. Based on these data, 33 recommendations were developed by the project steering group and have been presented to the Liverpool Culture Company. CONCLUSIONS: The process of conducting the assessment, particularly its participatory nature and its awareness-raising role, had impacts upon mental well-being. The findings demonstrate the potential for the Culture Company programme to have a profound impact upon mental well-being, and highlight areas which could be addressed to optimize the impact of the programme.

Gemcitabine and pemetrexed administered in rapid sequence as front-line chemotherapy for advanced non-small-cell lung cancer: a phase II clinical trial.

BACKGROUND: Previous studies of the gemcitabine-pemetrexed combination in patients with late-stage non-small-cell lung cancer (NSCLC) utilized a 90-min delay between gemcitabine and pemetrexed administration. This phase II study evaluated activity when these agents were administered in rapid succession. MATERIALS AND METHODS: Chemonaive patients with late-stage NSCLC received gemcitabine 1250 mg/m(2) on days 1 and 8, with pemetrexed 500 mg/m(2) immediately following day 8 gemcitabine every 21 days for six cycles, folic acid, B(12), and steroid prophylaxis. RESULTS: Fifty-four enrolled patients (53 treated) completed a median of four cycles. Median dose intensity was 84% (gemcitabine) and 83% (pemetrexed); 68% of patients required dose adjustments. Response was as follows: complete response, 0; partial response, 7 (13%); stable disease, 29 (54%); progressive disease, 9 (17%); and unknown/unavailable, 9 (17%). Median progression-free and overall survival was 4.6 and 12.4 months, respectively. Common grade 3 or 4 toxic effects were as follows: neutropenia (40%); fatigue and dyspnea (21% each); pneumonia (17%); febrile neutropenia and thrombocytopenia (11% each); and anemia (6%). CONCLUSIONS: The gemcitabine-pemetrexed combination is minimally active in late-stage NSCLC, with a high incidence of grade 3 or 4 toxic effects requiring frequent dose adjustments. A gemcitabine dose <1250 mg/m(2) warrants consideration for future trials exploring this doublet. Administering day 8 pemetrexed immediately after gemcitabine does not appear to negatively impact therapeutic index.

Phytoextraction of cadmium and zinc from arable soils amended with sewage sludge using Thlaspi caerulescens: development of a predictive model.

The objectives of this study were to assess the potential for using Thlaspi caerulescens as a phytoextraction plant and develop a user-advice model, which can predict the frequency of phytoextraction operation required under prescribed conditions. Pot and field trials were conducted using soil collected from a dedicated sewage sludge disposal facility. Soil amendments (sulphuric acid, potassium chloride and EDTA) intended to increase Cd solubility were also tested. Predictive models of Cd and Zn uptake were developed which were able to reproduce the observed pH-dependence of Cd uptake with an apparent maximum around pH 6. Chemical treatments did not significantly increase the uptake of Cd. The periodic use of phytoextraction with T. caerulescens to maintain soils below statutory metal concentration limits, when modern sewage sludges are repeatedly applied, seems very attractive given the non-intrusive and cost-effective nature of the process. The major limitations lie with the large-scale husbandry of T. caerulescens.

Quantitative Synthetic MRI in Children: Normative Intracranial Tissue Segmentation Values during Development.

BACKGROUND AND PURPOSE: Synthetic MR imaging is a new technique to create absolute R1 relaxivity (1/T1), R2 relaxivity (1/T2), and proton-density maps using a single multiple-spin-echo saturation recovery sequence. These relaxivity maps allow rapid automated intracranial segmentation of tissue types. To assess its utility in children, we created a normative data base of intracranial volume and brain parenchymal, GM, WM, CSF, and myelin volumes in a pediatric population with normal brain MRI findings using synthetic MR imaging. MATERIALS AND METHODS: All multiple-spin-echo saturation recovery sequences containing brain MR imaging examinations performed during 34 months were retrospectively reviewed. Abnormal examination findings were excluded following a detailed radiographic and clinical chart review. The remaining normal examination findings were then quantitatively analyzed with synthetic MR imaging. Intracranial, brain parenchymal, GM, WM, CSF, and myelin volumes were plotted versus age. Qualitative assessment of segmentation accuracy was performed. Selected abnormal examination findings were compared with these normative curves. RESULTS: One hundred twenty-two MRI examinations with normal findings were included of individuals ranging from 0.1 to 21.5 years of age (median, 11.8 years). Resulting normative data plots compared favorably with previously published data obtained using more onerous techniques. Differentiation from pathologic states was possible using quantitative values in select cases. CONCLUSIONS: A pediatric data base of normal intracranial tissue volumes using a single sequence and rapid software analysis has been compiled and correlates with previously published data. This provides a framework for clinical interpretation of quantitative synthetic MR images during development. Improved age-based segmentation algorithms in young children are needed.

Neuropathological changes in Down's syndrome hippocampal formation. Effect of age and apolipoprotein E genotype.

BACKGROUND: The neuropathological changes of Alzheimer's disease occur universally in individuals with Down's syndrome as they reach middle age and worsen with increasing age. Thus, evaluation of patients of various ages with Down's syndrome allows one to construct a life history of the development of neuropathological changes associated with Alzheimer's disease at various points in the disease process. METHODS: We have used semiquantitative scales and quantitative computerized image analysis techniques to analyze the characteristics of neurofibrillary tangle formation and A beta amyloid deposition in the hippocampal formation and inferior temporal gyrus in 36 individuals with Down's syndrome ranging in age from 4 to 73 years. RESULTS: Neurofibrillary tangles occur in a hierarchical distribution in a circumscribed set of neuronal fields, affecting the entorhinal cortex, area CA1/subiculum, then other hippocampal subfields. Although amyloid deposition occurs more evenly in a more widespread distribution, it also accumulates over the years 30 to 50. Surprisingly, examination of the patients available older than 50 years showed no trend toward continued increased deposition of amyloid. Within this group, however, individuals who had inherited the apolipoprotein E (Apo E) epsilon 4 genotype contained more than twice the amyloid burden of individuals who did not inherit the Apo E epsilon 4 genotype. COMMENT: This large series of cases confirms earlier observations that had suggested early vulnerability of entorhinal cortex and CA1/subiculum for neurofibrillary tangles and a more widespread but specific topography of A beta deposition. Moreover, it demonstrates quantitatively that the lesions increase to a certain level and then apparently reach a plateau. The level of amyloid deposition in Down's syndrome is higher than in sporadic Alzheimer's disease. Inheritance of the Apo E epsilon 4 genotype appears to be an additional (independent) risk factor for developing higher levels of amyloid accumulation.

Treatment of spasmodic torticollis with amantadine: a double-blind study.

Ten patients with spasmodic torticollis participated in a double-blind crossover trial of amantadine hydrochloride for a period of 2 months each. A further regimen of combined amantadine and haloperidol was tried with three patients after the conclusion of the double-blind trial. There were no therapeutic benefits of either treatment. Half of the patients reported minor side effects that resolved promptly when amantadine was discontinued.

Normal cerebral arteriography in patients with spontaneous subarachnoid hemorrhage.

Previous studies have reported that 18 to 27% of patients with spontaneous subarachnoid hemorrhage have normal cerebral arteriograms. Our series of 220 patients from three hospitals demonstrated normal arteriograms in only 16 (7%). Recent improvements in neuroradiologic techniques, such as femoral catheterization, magnification angiography, oblique and basal projections, and subtraction most probably contribute to the improved yield. Nonvisualization of a cerebral aneurysm probably represents the most common explanation for a normal cerebral arteriogram.

Reduced apolipoprotein epsilon 4 allele frequency in the oldest old Alzheimer's patients and cognitively normal individuals.

Recent genetic studies show that the apolipoprotein E epsilon 4 allele (ApoE-epsilon 4) is a risk factor for Alzheimer's disease (AD). If ApoE-epsilon 4 individuals develop AD as they get older, we would expect a decrease in ApoE-epsilon 4 allele frequency with increasing age. We found a marked decline in ApoE-epsilon 4 allele frequency with advancing age in both AD and cognitively normal controls (p < 0.003), although in all age groups the ApoE-epsilon 4 allele was overrepresented (p < 0.0001). Nonetheless, a few cognitively normal nonagenarians were ApoE-epsilon 4 positive. Thus, our data support two new conclusions: (1) the ApoE-epsilon 4 associated risk for AD is age-dependent, probably due to censoring by the earlier development of AD in ApoE-epsilon 4 individuals, and (2) despite the ApoE-epsilon 4 associated risk for AD, it is possible to reach extreme old age with normal cognition.

Soil phosphate status modifies response of mycorrhizal and non-mycorrhizal Senecio vulgaris L. to infection by the rust, Puccinia lagenophorae Cooke.

The impact of rust infection (Puccinia lagenophorae Cooke) on growth of mycorrhizal and non-mycorrhizal Senecio vulgaris L. was examined under three levels of phosphorus fertilization. Seeds were then collected from infected and control plants and germination, seed chemistry and offspring vigour were examined. Rust infection did not become established on plants which were phosphorus limited, but on hosts fed with medium or high levels of P, the proportion of total leaf number exhibiting infection was a function of leaf production. Capitula production was decreased by rust infection and increased by mycorrhizal colonization in plants fed with a medium concentration of P. In plants fed with a high P concentration, leaf number was reduced by rust infection of mycorrhizal plants, whilst rust was deleterious to both mycorrhizal and non-mycorrhizal plants grown with a medium P supply. However, the effects of the rust were less marked in the mycorrhizal plants. Seed production and weight were unaffected by fungal treatments, although percentage germination of the resultant seeds was reduced by maternal mycorrhizal colonization and enhanced in seed from rusted, mycorrhizal plants grown at high soil P. The amount of total C, N and P was also reduced by maternal mycorrhizal infection at high soil P and increased in seeds from rusted, mycorrhizal mothers. Vigour of offspring produced from treated mother plants was influenced by mycorrhizal × phosphorus and rust × phosphorus interactions with respect to bud and leaf numbers. Mycorrhizal infection of mother plants grown with a medium P supply benefited the offspring as increased leaf and bud production was observed, but rusted mothers at the same P level produced offspring with reduced leaf number and potential fecundity.

Interactions between arbuscular mycorrhizal fungi and foliar-feeding insects in Plantago lanceolata L.

A field experiment was conducted to investigate whether infection by arbuscular mycorrhizal (AM) fungi has any effect on herbivory by foliar-feeding insects. Plants of PI ant ago laureolata L. were grown in a randomized block design and natural levels of mycorrhizal infection reduced by the application of the granular fungicide iprodione. Plant growth responses were examined and herbivore bioassays performed by rearing both a chewing and sucking insect on the leaves of mycorrhizal and fungicide-treated plants. Fungicide application successfully reduced mycorrhizal infection, and this led to reductions in foliar biomass, caused by lower leaf number. However, fungicide-treated plants suffered consistently higher levels of damage by centralist chewing and leaf-mining insects, which colonized the plants. The chewing insect bioassay confirmed the field results, in that larvae of Arttia caja L. (Lepidoptera: Arctiidae) consumed more leaf material from plants in which infection was reduced. There was no evidence that AM fungi altered food quality for the chewing insect. Instead, infection caused an increase in the carbon/nutrient balance, which in turn led to increased levels of the carbon-based feeding deterrents, aucubin and catalpol, The sucking insect, Mvzus perskae (Sulzer) reacted in an opposite fashion to the ehewtr. with performance being greater on mycorrhizal plants. Again, there was no evidence that an alteration in food Quality was the cause, and in this case infection may result in changes in leaf morphology which benefit the insect. We suggest that under conditions of high light and low nutrient availability. AM infection can alter the carbon/nutrient balance of plants, leading to an increased allocation to carbon-based defences. This can have important consequences for insect herbivore performance and the patterns of herbivory in field situations.

Hypothalamic serotonin in treatments for feeding disorders and depression as studied by brain microdialysis.

Microdialysis was used to measure changes in extracellular serotonin in the hypothalamus of rats while they engaged in feeding behavior or received drug treatments used to treat feeding disorders and affective disorders in humans. Hypothalamic serotonin increased significantly relative to controls in response to (1) intraperitoneal tryptophan after food deprivation, (2) the smell of food and eating a meal, (3) a conditioned taste aversion, (4) d-fenfluramine and fluoxetine, and (5) an amphetamine challenge test after chronic low doses of lithium. In some cases, increases correlated with nonspecific behavioral arousal were seen in the hippocampus. The results suggest that diet, drug, and behavioral therapies, alone or combined, can be used to preferentially modify hypothalamic serotonin in the control of behavioral, emotional, and endocrine problems.

Routine multipurpose gas chromatographic assay for urinary corticosteroids.

THE USE OF A ROUTINE ASSAY FOR URINARY STEROIDS IS DESCRIBED THAT IS THOUGHT TO SATISFY THE FOLLOWING NEEDS: the measurement of low levels of 17-hydroxycorticosteroid excretion; the assessment of adrenocortical activity during prednisolone therapy; the diagnosis of the adrenogenital syndrome and the monitoring of its treatment using any available urine specimen; the very early diagnosis of pregnancy using any available urine specimen. It may also prove of value in the assessment of progesterone secretion and metabolism during pregnancy.

Clinical and neuropathological correlates of apolipoprotein E genotype in Alzheimer's disease. Window on molecular epidemiology.

Inheritance of the apolipoprotein E (apo E) epsilon 4 allele has recently been found to be associated with Alzheimer's disease. We have studied the clinical and neuropathological correlates of apolipoprotein E genotype in a large group of Alzheimer's patients. The primary influence on clinical presentation is a shift towards earlier age of onset in individuals who have the apo E epsilon 4 gene: no change in clinical course was observed. In neuropathological studies, we find that the major influence of apo E epsilon 4 is on increased A beta deposition. These results led to a model of the biological interaction between the apo E protein and Alzheimer's disease.

Epidemiological, clinical, and neuropathological study of apolipoprotein E genotype in Alzheimer's disease.

Our studies of the APOE genotype in AD confirm a strong association of the epsilon 4 allele with development of AD and a decreased risk associated with epsilon 2. From a clinical/neuropathological perspective, the major effects of APOE epsilon 4 are to lower the age of onset and to increase the amount of A beta deposit in the brain. Neither rate of progression nor number of neurofibrillary tangles were affected. We also carried out a longitudinal population-based assessment of the APOE genotype to determine the risk for developing cognitive impairment of someone in the general population based on APOE genotype. APOE epsilon 4 carried about 1.4-fold increased risk, and APOE epsilon 2 about 1.7-fold decreased risk. Thus, inheritance of APOE epsilon 4 is a major biological risk factor for AD, but it has limited utility as a prognostic indicator for development of dementia in an individual.