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Hypoxia‐ischaemia (HI) can result in structural brain abnormalities, which in turn can lead to behavioural deficits in various cognitive and motor domains, in both adult and paediatric populations. Cardiorespiratory arrest (CA) is a major cause of hypoxia‐ischaemia in adults, but it is relatively rare in infants and children. While the effects of adult CA on brain and cognition have been widely studied, to date, there are no studies examining the neurodevelopmental outcome of children who suffered CA early in life. Here, we studied the long‐term outcome of 28 children who suffered early CA (i.e., before age 16). They were compared to a group of control participants (n = 28) matched for age, sex and socio‐economic status. The patient group had impairments in the domains of memory, language and academic attainment (measured using standardised tests). Individual scores within the impaired range were most commonly found within the memory domain (79%), followed by academic attainment (50%), and language (36%). The patient group also had reduced whole brain grey matter volume, and reduced volume and fractional anisotropy of the white matter. In addition, lower performance on memory tests was correlated with bilaterally reduced volume of the hippocampi, thalami, and striatum, while lower attainment scores were correlated with bilateral reduction of fractional anisotropy in the superior cerebellar peduncle, the main output tract of the cerebellum. We conclude that patients who suffered early CA are at risk of developing specific cognitive deficits associated with structural brain abnormalities. Research Highlights: Our data shed light on the long‐term outcome and associated neural mechanisms after paediatric hypoxia‐ischaemia as a result of cardiorespiratory arrest.Patients had impaired scores on memory, language and academic attainment.Memory impairments were associated with smaller hippocampi, thalami, and striatum.Lower academic attainment correlated with reduced fractional anisotropy of the superior cerebellar peduncle. [ABSTRACT FROM AUTHOR]

Background: Threatened miscarriage is a common complication of pregnancy. Results of randomised controlled trials on the efficacy of progestogen in the treatment of threatened miscarriage remain inconsistent.Objective: To investigate whether the use of progestogen is associated with improved event rate of live birth and other benefits in women with threatened miscarriage.Search Strategy: Ovid MEDLINE, Ovid Embase and Cochrane CENTRAL Register of Controlled Trials from their inception until 8 July 2019.Selection Criteria: Randomised controlled trials comparing progestogen with a placebo or no treatment for pregnancy outcomes in women with threatened miscarriage.Data Collection and Analysis: Two authors independently conducted data extraction and assessed study quality. We calculated risk ratios (RR) and 95% confidence intervals using the Mantel-Haenszel approach for dichotomous outcomes.Main Results: Ten trials with a total of 5056 participants were eligible for analysis. The use of progesterone increased the incidence of live birth (RR 1.07, 95% CI 1.00-1.15; P = 0.04; I2  = 18%), with benefit only seen with the use of oral progestogen (RR 1.17, 95% CI 1.04-1.31; P = 0.008; I2  = 0%) and not with vaginal progesterone (RR 1.04, 95% CI 1.00-1.08; P = 0.07; I2  = 0%). Similarly, progestogen reduced the risk of miscarriage (RR 0.73, 95% CI 0.59-0.92), with benefit only seen with oral progestogen and not with vaginal progesterone.Conclusion: Progestogens may have benefits on live birth rate and miscarriage rate for women with threatened miscarriage. These benefits appear to be confined to the use of oral progestogen, and no statistically significant improvements were seen with vaginal progesterone.Tweetable Abstract: A meta-analysis of 10 trials found that progestogens increased live birth rates and reduced miscarriage rates for women with threatened miscarriage. [ABSTRACT FROM AUTHOR]

Candida auris is an emerging drug‐resistant yeast responsible for hospital outbreaks. This statement reviews the evidence regarding diagnosis, treatment and prevention of this organism and provides consensus recommendations for clinicians and microbiologists in Australia and New Zealand. C. auris has been isolated in over 30 countries (including Australia). Bloodstream infections are the most frequently reported infections. Infections have crude mortality of 30–60%. Acquisition is generally healthcare‐associated and risks include underlying chronic disease, immunocompromise and presence of indwelling medical devices. C. auris may be misidentified by conventional phenotypic methods. Matrix‐assisted laser desorption ionisation time‐of‐flight mass spectrometry or sequencing of the internal transcribed spacer regions and/or the D1/D2 regions of the 28S ribosomal DNA are therefore required for definitive laboratory identification. Antifungal drug resistance, particularly to fluconazole, is common, with variable resistance to amphotericin B and echinocandins. Echinocandins are currently recommended as first‐line therapy for infection in adults and children ≥2 months of age. For neonates and infants <2 months of age, amphotericin B deoxycholate is recommended. Healthcare facilities with C. auris should implement a multimodal control response. Colonised or infected patients should be isolated in single rooms with Standard and Contact Precautions. Close contacts, patients transferred from facilities with endemic C. auris or admitted following stay in overseas healthcare institutions should be pre‐emptively isolated and screened for colonisation. Composite swabs of the axilla and groin should be collected. Routine screening of healthcare workers and the environment is not recommended. Detergents and sporicidal disinfectants should be used for environmental decontamination. [ABSTRACT FROM AUTHOR]

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Objectives: This UK-wide study defines the natural history of argininosuccinic aciduria and compares long-term neurological outcomes in patients presenting clinically or treated prospectively from birth with ammonia-lowering drugs. Methods: Retrospective analysis of medical records prior to March 2013, then prospective analysis until December 2015. Blinded review of brain MRIs. ASL genotyping. Results: Fifty-six patients were defined as early-onset ( n = 23) if symptomatic < 28 days of age, late-onset ( n = 23) if symptomatic later, or selectively screened perinatally due to a familial proband ( n = 10). The median follow-up was 12.4 years (range 0-53). Long-term outcomes in all groups showed a similar neurological phenotype including developmental delay (48/52), epilepsy (24/52), ataxia (9/52), myopathy-like symptoms (6/52) and abnormal neuroimaging (12/21). Neuroimaging findings included parenchymal infarcts (4/21), focal white matter hyperintensity (4/21), cortical or cerebral atrophy (4/21), nodular heterotopia (2/21) and reduced creatine levels in white matter (4/4). 4/21 adult patients went to mainstream school without the need of additional educational support and 1/21 lives independently. Early-onset patients had more severe involvement of visceral organs including liver, kidney and gut. All early-onset and half of late-onset patients presented with hyperammonaemia. Screened patients had normal ammonia at birth and received treatment preventing severe hyperammonaemia. ASL was sequenced ( n = 19) and 20 mutations were found. Plasma argininosuccinate was higher in early-onset compared to late-onset patients. Conclusions: Our study further defines the natural history of argininosuccinic aciduria and genotype-phenotype correlations. The neurological phenotype does not correlate with the severity of hyperammonaemia and plasma argininosuccinic acid levels. The disturbance in nitric oxide synthesis may be a contributor to the neurological disease. Clinical trials providing nitric oxide to the brain merit consideration. [ABSTRACT FROM AUTHOR]

Background Hypohidrosis is defined as diminished sweating in response to an appropriate thermal or sympathetic stimulus. When encountered in a clinical setting, it necessitates an accurate documentation of its pattern and extent to prognosticate the risk of associated heat-related illnesses. This can be achieved by thermoregulatory sweat testing which includes a starch-iodine sweat test that can be administered via various methods. Objective To describe and evaluate the effectiveness and safety of a novel method of using an atomizer spray gun in administering the starch-iodine test. Methods We describe the administration of the starch-iodine test via an atomizer spray gun (Series 700 Lab Model; Mitsuba Systems, Mumbai, India). The method was utilized for the evaluation of 30 individuals who presented with symptoms of hypohidrosis. Results Application of iodinated starch powder prepared in-house with the atomizer spray gun achieved a lightweight and homogeneous coat on our patients' skin which allowed for clear visualization of the sweating pattern in areas of anhidrosis. The sharp demarcation of the pathological regions enabled the precise calculation of the affected body surface area of impaired sweating. Unlike the starch-iodine tests using the Minor and Wada methods, neither staining of the skin nor irritation was detected in this method. Conclusion We report a novel method of using an atomizer spray gun to perform the starch-iodine test in a rapid, reproducible, effective, and safe manner suitable for use in the clinical evaluation of hypohidrosis. [ABSTRACT FROM AUTHOR]

Background Adrenal vein sampling ( AVS) is useful for distinguishing unilateral versus bilateral hypersecretion in primary aldosteronism ( PA), but is technically challenging. Furthermore, the use of adrenocorticotropic hormone ( ACTH)-stimulation in AVS is controversial. We implemented a Monash Health-specific AVS protocol in 2010. Aim The audit aimed to: (i) examine the impact of a dedicated protocol on success rates of AVS at a tertiary referral centre; (ii) evaluate the impact of AVS on sub-typing of PA; and (iii) assess the utility of ACTH stimulation in AVS. Methods AVS was performed on patients with PA confirmed by positive saline suppression testing (aldosterone level >140 pmol/L post-saline infusion), with sequential sampling of adrenal and peripheral veins, pre- and post- ACTH infusion. Patients with unilateral aldosterone-producing adenoma diagnosed on successful AVS were referred for adrenalectomy. Results Between 2010 and 2014 inclusive, a total of 28 AVS procedures was performed, with complete pre- and post- ACTH data for 19 procedures. Bilateral successful cannulation rates improved post-implementation of our protocol (61% vs 41%). Of the patients, 32% had discordant imaging and AVS results: four patients with unilateral adenomas did not lateralise on AVS and were managed medically; four patients with bilateral or no adenomas on imaging, lateralised on AVS and had surgery. Overall, use of ACTH did not increase successful cannulation and tended to mask lateralisation. Conclusion AVS is crucial in subtype classification of PA and should be performed by a dedicated radiologist with a standardised protocol. AVS outcomes were not improved with the use of ACTH stimulation. [ABSTRACT FROM AUTHOR]

Background The main aims of the 16th ISBT Platelet Immunology workshop were as follows: (i) to test the ability of the laboratories in the identification of platelet alloantibodies, (ii) to compare the detection of HPA-1a alloantibodies in serum and plasma, (iii) to quantify HPA-1a alloantibodies, (iv) to measure platelet-bound HPA-1a alloantibodies in lysates, (v) to evaluate a new bead-based assay for anti- HPA-1a and anti- HPA-1b detection, (vi) to evaluate the efficiency of a human monoclonal antibody for HPA-5a phenotyping and (vii) to test the ability to genotype for HPA-1, HPA-2, HPA-3, HPA-4, HPA-5, HPA-6, HPA-9, HPA-12w, HPA-13w and HPA-15. Materials and methods Seven exercises were developed to encompass the aims of this workshop. All materials and procedures were distributed for 34 laboratories from 20 countries. Results The platelet alloantibodies identification exercise presented good results compared with previous workshops. Comparison between serum and plasma in titration study showed comparable results for HPA-1a and HPA-5b alloantibodies. For the quantitative determination of HPA-1a alloantibodies, most of the laboratories could reliably assign a similar concentration. It was also possible to identify bound anti- HPA-1a alloantibodies in cell lysates within 2 weeks. The bead assay demonstrated good reproducibility between laboratories although some anti- HPA-1a samples remain an issue. Phenotyping of HPA-5b showed high false-negative error (6%). DNA typing presented excellent results, demonstrating that DNA tests for HPA are very well established in all laboratories. Conclusions This workshop presented high complexity exercises with very good results achieved in most of the exercises and approximately 100% consensus among the participants. [ABSTRACT FROM AUTHOR]

Background and Objectives A number of DNA-based methods to genotype the alleles coding for HNA have been described, but all require the separate amplification and analysis of each allele. The aim was to develop a DNA-based method for simultaneous detection of HNA-1, HNA-3, HNA-4 and HNA-5 alleles. Materials and Methods An allele-specific primer extension method was used in combination with magnetic beads from Luminex technology. PCR-sequence-specific primers ( SSP) was used to resolve the presence of the HNA-1b allele in samples assigned by the Luminex bead assay as HNA-1a/-1b/-1c or HNA-1b/-1c. HNA allele frequencies were determined in a panel of 140 randomly selected English Caucasoid blood donors. Results HNA allelic types were compared with historical results, and 100% concordance was found. Only eight of the 97 samples used in the validation required additional testing by PCR- SSP. Allele frequencies were determined in the blood donor population as follows: 0·318 for HNA-1a, 0·668 for HNA-1b, 0·014 for HNA-1c, 0·768 for HNA-3a, 0·232 for HNA-3b, 0·882 for HNA-4a, 0·118 for HNA-4b, 0·736 for HNA-5a and 0·264 for HNA-5b. Conclusion A multiplex Luminex bead assay for the simultaneous detection of HNA-1, HNA-3, HNA-4 and HNA-5 alleles is described that enables rapid typing of donors to support HNA alloimmunized patients who require HNA-compatible blood products. [ABSTRACT FROM AUTHOR]

Background: The first gene causing early-onset generalized dystonia with brain manganese accumulation has recently been identified. Mutations in the SLC30A10 gene, encoding a manganese transporter, cause a syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia. Methods: We present 10-year longitudinal clinical features, MRI data, and treatment response to chelation therapy of the originally described patient with a proven homozygous mutation in SLC30A10. Results: The patient presented with early-onset generalized dystonia and mild hyperbilirubinemia accompanied by elevated whole-blood manganese levels. T1-sequences in MRI showed hyperintensities in the basal ganglia and cerebellum, characteristic of manganese deposition. Treatment with intravenous disodium calcium edetate led to clinical improvement and reduction of hyperintensities in brain imaging. Conclusions: We wish to highlight this rare disorder, which, together with Wilson's disease, is the only potentially treatable inherited metal storage disorder to date, that otherwise can be fatal as a result of complications of cirrhosis. © 2012 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background Adefovir and tenofovir are nucleotide analogues used as long-term therapy of chronic hepatitis B. Side effects are few, but prolonged and high-dose therapy has been associated with proximal renal tubular dysfunction ( RTD). Aim To assess the incidence of RTD during long-term nucleotide therapy of chronic hepatitis B. Methods A total of 51 patients being treated at the Clinical Center, National Institutes of Health were studied. Diagnosis of RTD required de novo appearance of at least three of five features: hypophosphataemia, hypouricaemia, serum creatinine elevation, proteinuria or glucosuria. Results Among 51 patients treated for 1-10 (mean 7.4) years with adefovir ( n = 42), tenofovir ( n = 4) or adefovir followed by tenofovir ( n = 5), 7 (14%) developed RTD. Time to onset ranged from 22 to 94 (mean 49) months with an estimated 10-year cumulative rate of 15%. All seven had low urinary percent maximal tubular reabsorption of phosphate (<82%). Patients with RTD were older (58 vs. 44 years; P = 0.01) and had lower baseline glomerular filtration rates (82 vs. 97 cc/min; P = 0.08) compared to those without; but did not differ in other features. Six patients with RTD were switched to entecavir, all subsequently had improvements in serum phosphate (2.0-3.0 mg/dL), creatinine (1.6-1.1 mg/dL), uric acid (2.7-3.8 mg/dL) and proteinuria. Conclusions Renal tubular dysfunction develops in 15% of patients treated with adefovir or tenofovir for 2-9 years and is partially reversible with change to other antivirals. Monitoring for serum phosphate, creatinine and urinalysis is prudent during long-term adefovir and tenofovir therapy. [ABSTRACT FROM AUTHOR]

Background The primary purpose of this study was to report on an evaluation of the perceptions and beliefs of service providers towards family-centred practices in 11 early intervention programmes for infants and young children in Singapore. Methods The Measure of Processes of Care for Service Providers (MPOC-SP) and Measure of Beliefs about Participation in Family-Centred Service (MBP-FCS) were administered to 213 service providers made up of teachers, therapists, psychologists and social workers providing centre-based therapy to children with special needs who were below the age of 6 years. Results Exploratory factor analyses were performed with both scales. Nineteen of the 27 MPOC-SP items were retained and supported the original four-factor structure model. The exploratory factor analyses on MBP-FCS provided a less satisfactory outcome. Fourteen of the 28 items were retained and these loaded onto four factors. The two factors relating to Beliefs about benefits of FCS and Beliefs about the absence of negative outcomes from FCS failed to emerge as separate factors. Further multiple regressions indicated that more direct work with families and positive self-efficacy in implementing FCS contributed significantly to explaining service providers' positive perception towards family-centred practice in service delivery. Conclusions This is the first time MPOC-SP and MBP-FCS were administered to a population in an Asian context. While MBP-FCS would benefit from further development work on its construct, MPOC-SP offered important insights into service providers' perspectives about family-centred practices that would have useful implications for professional and service development. [ABSTRACT FROM AUTHOR]

Objective Fetal nuchal translucency (NT) is assessed by ultrasonography as a screening tool for aneuploidy at 11 to 13 + 6 weeks' gestation. Fetuses with increased NT but apparently normal karyotype are still at higher risk of structural abnormality and a range of genetic syndromes, which may be related to major and submicroscopic chromosomal abnormalities. The aim of this study was to report the prevalence of submicroscopic chromosomal abnormalities in a cohort of apparently euploid fetuses that presented with increased NT. Methods DNA was extracted from stored chorionic villus samples from fetuses found to have increased NT (> 3.5 mm) during first-trimester screening. These samples were examined by microarray-based comparative genomic hybridization (aCGH) using a 44K oligonucleotide array specifically constructed for prenatal screening. Variations in copy number (CNVs) were reported after excluding known non-pathogenic variants and after validation with multiplex ligation-dependent probe amplification (MLPA) or real-time quantitative polymerase chain reaction (qPCR). The prevalence of pathogenic CNVs is reported and the association with NT and other ultrasound findings described. Results CNVs were reported in 6/48 (12.5%) cases by aCGH and the microdeletions or microduplications ranged from 1.1 to 7.9 Mb. Five of these were validated by MLPA/real-time qPCR and four (8.3%) were considered to be pathogenic and clinically significant. The incidence of pathogenic CNVs was 20.0% (2/10) among those cases with other sonographic anomalies and 5.3% (2/38) among those without. Conclusion aCGH allows detection of submicroscopic chromosomal abnormalities, the prevalence of which may be increased in fetuses with NT > 3.5 mm and an apparently normal karyotype. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Testing for alloantibodies against human platelet antigens (HPAs) is essential for the clinical diagnosis of fetomaternal alloimmune thrombocytopenia (FMAIT), posttransfusion purpura, and platelet (PLT) refractoriness. Most of the methods currently used for HPA alloantibody detection rely on the availability of panels of HPA-typed PLTs and some rely on validated monoclonal antibodies (MoAbs) against the PLT glycoproteins. Recombinant β3 integrins displaying the HPA-1a (rHPA-1a) or HPA-1b (rHPA-1b) epitopes have been produced as an alternative source of antigen. The suitability of these integrin fragments was evaluated for the development of an HPA-1a alloantibody screening assay, using Luminex xMAP technology.Study Design and Methods: A 3-plex bead assay was developed by coupling biotinylated rHPA-1a, rHPA-1b, and recombinant glycoprotein VI to LumAvidin microspheres. Forty patient samples referred for FMAIT diagnostic testing, which were previously screened by the MoAb-specific immobilization of PLT antigens (MAIPA) assay, were used to assess the assay.Results: The rHPA-1a- and rHPA-1b-coupled beads were able to detect HPA-1a and HPA-1b alloantibodies in all patient samples tested that were previously confirmed to contain HPA-1-specific antibodies. Furthermore, HLA Class I antibodies did not cross-react with the coupled beads.Conclusion: The 3-plex bead assay can be used to detect HPA-1a antibodies with sufficient specificity and sensitivity for use in the clinical setting of FMAIT. The development of other recombinant integrin fragments with the use of Luminex xMAP technology may assist in providing more rapid HPA antibody detection, enabling prompt diagnosis of alloimmune PLT disorders. [ABSTRACT FROM AUTHOR]

Cell senescence is a permanent growth arrest following extended proliferation. Cultured cancer cells including metastatic melanoma cells often appear immortal (proliferate indefinitely), while uncultured benign nevi (moles) show senescence markers. Here, with new explantation methods, we investigated which classes of primary pigmented lesions are typically immortal. Nevi yielded a few proliferating cells, consistent with most nevus cells being senescent. No nevus culture (0/28) appeared immortal. Some thin and thick melanoma cultures proved immortal under these conditions, but surprisingly few (4/37). All arrested cultures displayed three senescence markers in some cells: β-galactosidase, nuclear p16, and heterochromatic foci/aggregates. However, melanoma cultures also showed features of telomeric crisis (arrest because of ultrashort telomeres). Moreover, crisis markers including anaphase bridges were frequent in uncultured vertical growth-phase (VGP) melanomas. Conversely, all immortal melanoma cultures expressed telomerase reverse transcriptase and telomerase, showing aneuploidy. The findings suggest that primary melanomas are typically precrisis, with immortalization/telomere maintenance as a late event. [ABSTRACT FROM AUTHOR]

Objective Recent studies have suggested that mutations in genes encoding several hypothalamo–pituitary (H–P) transcription factors result in hypopituitarism [isolated GH deficiency (IGHD) and combined pituitary hormone deficiency (CPHD)], which may in turn be related to the neuroanatomy revealed by magnetic resonance (MR) imaging. Although studies have focused on patients with either optic nerve hypoplasia (ONH) or isolated hypopituitarism with normal optic nerves, few studies have compared the two groups. We aimed to relate the clinical phenotype of a large cohort ( n = 170) of children with congenital hypopituitarism including septo-optic dysplasia (SOD) attending a single centre to the neuroradiological and genetic findings. Design Clinical, biochemical, MR imaging and molecular data were analysed retrospectively in 170 patients with or ‘at-risk’ (with ONH) of hypopituitarism to determine predictors of hypopituitarism. Results The presence of ONH was significantly associated with an absent septum pellucidum [odds ratio (OR) 31·5, 95% confidence intervals (CI) 7·3–136·6, P < 0·001], an abnormal corpus callosum (OR 10·5, 95% CI 3·8–28·6, P < 0·001) and stalk abnormalities (OR 2·3, 95% CI 1·2–4·2, P = 0·009). The risk of hypopituitarism was 27·2 times greater in patients with an undescended posterior pituitary (95% CI 3·6–205·1, P < 0·001). Anterior pituitary hypoplasia (OR 3·1, 95% CI 1·3–7·0, P = 0·006) and an absent pituitary stalk ( P < 0·001) were also significantly associated with hypopituitarism. With respect to the type or severity of hypopituitarism, CPHD was more often associated with an abnormal corpus callosum (OR 6·1, 95% CI 1·4–27·4, P = 0·008) and stalk abnormalities (OR 2·8, 95% CI 1·3–6·1, P = 0·006). Male to female ratio was significantly greater in patients with normal optic nerves (3·3:1) as compared with those with ONH (1·2:1). The prevalence of diabetes insipidus, thyrotrophin and ACTH deficiencies was significantly greater in patients with ONH as compared with ‘idiopathic’ hypopituitarism. Mutations in pituitary transcription factors and genes regulating GH secretion were rare (5/170) in this cohort of patients with sporadic hypopituitarism. Conclusion Our data suggest that individuals presenting with ONH are at high risk for neuroradiologic and endocrine abnormalities. The neuroradiologic features are predictive not only of the presence, but also of the type, of hypopituitarism. The association of midline abnormalities with hypopituitarism in this cohort suggests a common developmental origin for these features, the aetiology of which remains unidentified in the majority of cases. [ABSTRACT FROM AUTHOR]

The presurgical evaluation of children with intractable epilepsy includes evaluation by an experienced clinician, MRI, video EEG, and functional imaging techniques to localize seizure onset. However, the contributions of each investigation to surgical decision making has not been systematically assessed. Data used for decision on eligibility for surgery on 353 children was discussed at a presurgical multidisciplinary meeting and systematically recorded. The relationships between MRI, EEG, SPECT findings, and the probability of being offered epilepsy surgery were investigated retrospectively using a quick unbiased statistical tree (QUEST). Sixteen children were offered nonresective surgery. Of the remaining, 236 (70%) were offered resective surgery. The proportion of children with a localized lesion on MRI offered resective surgery was 92%[95% CI: 88 to 95%], and EEG telemetry did not modify decision making in this group (p < 0.001). In children with bilateral MRI changes or normal scan the probability of being offered resective surgery was 78% in those with localized ictal onset on EEG compared to 9% with nonlocalized EEG (p < 0.001). SPECT did not appear to systematically influence decision making in any group. Children with medically intractable epilepsy and localized lesions on MRI may not necessarily need ictal EEG recordings or SPECT prior to offering resective surgery. More targeted use of EEG telemetry could allow more children with less obvious surgical targets to be investigated without increasing resources. [ABSTRACT FROM AUTHOR]

The neuropsychological and clinical histories of three male siblings affected by pyridoxine-dependent seizures with known homozygous antiquitin mutations are presented. Neuropsychological evaluation is reported from when the siblings were 11, 9, and 7 years of age. Two of the siblings had received early pyridoxine treatment (antenatal, 2–4wks into pregnancy) and one had received late treatment (2mo postnatal). However, there was no differential effect on cognitive outcome, with all three siblings having moderate to severe learning disability. Unlike previously reported cases that received early postnatal treatment, none of the siblings had relatively preserved non-verbal cognitive skills. Equally, their intellectual performance over time did not increase above the 1st centile despite high maintenance doses of vitamin B6 (range 16–26mg/kg/d), and mild sensory neuropathy was reported on nerve conduction studies. The findings in these siblings challenge assumptions that early and high dose pyridoxine treatment can benefit cognition in this population and suggest routine electromyography monitoring may be beneficial. [ABSTRACT FROM AUTHOR]

The management of symptomatic and asymptomatic carotid stenosis has been a hotly debated topic for decades. The publication of four randomized controlled trials of carotid endarterectomy has clarified many of the issues. Patients with symptomatic carotid stenosis >70% benefit most with an absolute risk reduction of 17% over 2 years with numbers needed to treat of 3–6, whereas in patients with asymptomatic carotid stenosis >60%, the absolute risk reduction is 1% per annum (numbers needed to treat = 14–17). There is doubt about the benefit in women >70 years of age with asymptomatic stenosis. Carotid angioplasty and stenting is in its infancy and may one day supplant carotid endarterectomy as the treatment of choice; however, currently indications for this procedure include participation in randomized controlled trials, surgically inaccessible stenosis, in patients with combined symptomatic carotid and symptomatic coronary artery disease or in patients with severe co-morbidities that preclude formal carotid endarterectomy. [ABSTRACT FROM AUTHOR]

Noradrenergic inputs to the hypothalamic paraventricular nucleus (PVN) play important roles in the regulation of neuroendocrine and autonomic functions. Previous reports show that noradrenaline increases the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in a subpopulation of type II neurones, acting via α1-adrenoceptors (ARs), but reduces this frequency in most type I and another subpopulation of type II neurones, via α2-ARs on presynaptic GABA neurones. Here, we identified the subtypes of α-ARs mediating noradrenaline-induced increases and decreases in the sIPSC frequency of PVN neurones, by using slice patch recordings from PVN neurones. In both type I and II neurones, the noradrenaline-induced decrease in sIPSC frequency was completely blocked by BRL44408 (α2A-AR antagonist) at 1-3 μM, which is approximately 1/100 of its equilibrium dissociation constant (pA2 = 8.0), but not by prazosin (20-100 μM, α2B/C-AR antagonist; pA2 = 7.5). The effect of noradrenaline was mimicked by guanfacine (α2A-AR agonist) with an EC50 of 0.1 μM. In type II neurones, the noradrenaline-induced increase in sIPSC frequency was not blocked by any of the following antagonists: RS17053 (10 μM, α1A-AR antagonist), BMY7378 (2 μM, α1D-AR antagonist), prazosin (0.1 μM, α1-AR antagonist; pA2 = 10.5), or chloroethylclonidine (10 μM, α1B/D-AR antagonist). However, the effect of noradrenaline was blocked by higher concentrations of prazosin (1 μM) or RS17053 (100 μM), suggesting the involvement of α1L-subtype, a low affinity form of α1A-ARs. Collectively, our results indicate that the α2A-, or α1L-ARs on the GABA neurones mediate the noradrenaline-induced decreases, or increases in the frequencies of the sIPSCs of PVN neurones, respectively. [ABSTRACT FROM AUTHOR]

Growth inhibition caused by fluoride was further studied by analyzing free and bound ribosomes, and the ribosomal components in corn roots. Ribosomes were isolated by differential centrifugation. Ribosomal components were analyzed by column chromatography and electrophoresis. Fluoride reduces the amounts of both free and bound ribosomes. Fluoride also modifies the RNA to protein ratio of bound ribosomes more than that of free ribosomes. Fluoride does not affect base ratios of the ribosomal RNA, but reduces its content and changes the structure of the ribosomal protein moiety. [ABSTRACT FROM AUTHOR]

Corn seeds were treated with 0.01 M sodium fluoride for various time periods. The treated seeds were germinated and grown until the seedling roots reached a standard size of 12 ±3 mm. Analyses were made for RNA and DNA contents of 3-mm seedling root tips. Determinations also were made for growth rate, rate of cell elongation, cell multiplication, and tissue maturity of 12-mm roots. RNA contents of 3-mm root tips were found to be directly proportional to the growth rates of the entire seedling root of corn seeds treated with sodium fluoride for various periods of time. The RNA content was reduced on a cell basis and was independent of the root tip cell number. The amount of DNA was not related to the growth rate of the intact seedling roots. Since fluoride reduced the number of mitotic figures, it was likely that fluoride inhibited DNA synthesis during the interphase of the mitotic cycle. Growth by cell multiplication was inhibited more than that by cell elongation in the sample treated with fluoride for a scorter period. The two types of growth, however, showed a similar level of growth reduction in the sample treated with fluoride for a longer period. Fluoride seemed to reduce the rates of cellular elongation and multiplication not more than about 40 per cent of the control value in these tissues under present experimental conditions. Fluoride also induced maturity in the seedling roots in proportion to the periods of fluoride treatment. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 71-year-old female patient diagnosed with BK virus-associated progressive multifocal leukoencephalopathy (PML). It states that the patient had difficulty in following three-step command and had paraphasia and constructional apraxia. The neurological state of the patient deteriorated and her symptoms did not improved. It also mentions that after undergoing brain biopsy, the patient died.

Thoracic ventral dural defect, and resultant idiopathic spinal cord herniation, is a rare but increasingly recognized cause of a chronic progressive thoracic myelopathy, particularly in middle-aged women. A neurosurgically confirmed case is presented, together with a review of the pathogenesis, clinical presentation, imaging features, treatment options and progress of this entity post-treatment. [ABSTRACT FROM AUTHOR]

An abstract of the article "Sonographic findings among patients receiving methotrexate while having pregnancy of unknown location subsequently diagnosed with intrauterine pregnancy," by D. Fridman and colleagues is presented.

A new pressure sensor based on fiber Bragg gratings (FBG), is described with high-pressure sensitivity. The sensor is configured by embedding the FBG in a polymer-field aluminum casing with an opening on one side, which is exposed to pressure measurand. The measured pressure response is 0.06 nm/psi that is ∼2700 times higher than the pressure response measured with a bare FBG. The linearity of the designed sensor is also shown to be good at pressures below 50 psi. This sensor has numerous potential applications in the area of low-pressure measurements. © 2007 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 60–61, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23021 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on the two cases of Streptococcus suis endocarditis among piggery workers in Australia.

We systematically summarized tuberculosis (TB)-related non-coding RNA (ncRNA) diagnostic panels, validated and compared panel performance. We searched TB-related ncRNA panels in PubMed, OVID and Web of Science up to 28 February 2020, and available datasets in GEO, SRA and EBI ArrayExpress up to 1 March 2020. We rebuilt models and synthesized the results of each model in validation sets by bivariate mixed models. Specificity at 90% sensitivity, area under curve (AUC) and inconsistence index (I 2 ) were calculated. NcRNA biofunctions were analysed. Nineteen models based on 18 ncRNA panels (miRNA, lncRNA, circRNA and snoRNA panels) and 18 datasets were included. Limited available datasets only allowed to evaluate miRNA panels further. Cui 2017 and Latorre 2015 exhibited specificity >70% at 90% sensitivity and AUC >80% in all validation sets. Cui 2017 showed higher specificity at 90% sensitivity (92%) and AUC (95%) and lower heterogeneity (I 2  = 0%) in ethological-confirmation validation sets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that most ncRNAs in panels involved in immune cell activation, oxidative stress, and Wnt and MAPK signalling pathway. Cui 2017 outperformed other models in both all available and aetiological-confirmed validation sets, meeting the criteria of target product profile of WHO. This work provided a basis for clinical choice of TB-related ncRNA diagnostic panels to a certain extent., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Threatened miscarriage is a common complication of pregnancy. Results of randomised controlled trials on the efficacy of progestogen in the treatment of threatened miscarriage remain inconsistent., Objective: To investigate whether the use of progestogen is associated with improved event rate of live birth and other benefits in women with threatened miscarriage., Search Strategy: Ovid MEDLINE, Ovid Embase and Cochrane CENTRAL Register of Controlled Trials from their inception until 8 July 2019., Selection Criteria: Randomised controlled trials comparing progestogen with a placebo or no treatment for pregnancy outcomes in women with threatened miscarriage., Data Collection and Analysis: Two authors independently conducted data extraction and assessed study quality. We calculated risk ratios (RR) and 95% confidence intervals using the Mantel-Haenszel approach for dichotomous outcomes., Main Results: Ten trials with a total of 5056 participants were eligible for analysis. The use of progesterone increased the incidence of live birth (RR 1.07, 95% CI 1.00-1.15; P = 0.04; I 2  = 18%), with benefit only seen with the use of oral progestogen (RR 1.17, 95% CI 1.04-1.31; P = 0.008; I 2  = 0%) and not with vaginal progesterone (RR 1.04, 95% CI 1.00-1.08; P = 0.07; I 2  = 0%). Similarly, progestogen reduced the risk of miscarriage (RR 0.73, 95% CI 0.59-0.92), with benefit only seen with oral progestogen and not with vaginal progesterone., Conclusion: Progestogens may have benefits on live birth rate and miscarriage rate for women with threatened miscarriage. These benefits appear to be confined to the use of oral progestogen, and no statistically significant improvements were seen with vaginal progesterone., Tweetable Abstract: A meta-analysis of 10 trials found that progestogens increased live birth rates and reduced miscarriage rates for women with threatened miscarriage., (© 2020 Royal College of Obstetricians and Gynaecologists.)