Screening for inborn errors of metabolism in high-risk children: a 3-year pilot study in Zhejiang Province, China

<p>Abstract</p> <p>Background</p> <p>Tandem mass spectrometry (MS/MS) has been available in China for 8 years. This technique makes it possible to screen for a wide range of previously unscreened inborn errors of metabolism (IEM) using a single test. This 3-year pilot study investigated the screening, diagnosis, treatment and outcomes of IEM in symptomatic infants and children.</p> <p>Methods</p> <p>All children encountered in the Newborn Screening Center of Zhejiang Province during a 3-year period with symptoms suspicious for IEM were screened for metabolic diseases. Dried blood spots were collected and analyzed by tandem mass spectrometry. The diagnoses were further confirmed by clinical symptoms and biochemical analysis. Neonatal intrahepatic cholestasis caused by citrin deficiency, ornithine transcarbamylase deficiency and primary carnitine deficiency were confirmed by DNA analysis.</p> <p>Results</p> <p>A total of 11,060 symptomatic patients (6,720 boys, 4,340 girls) with a median age of 28.8 months (range: 0.04-168.2 months) were screened. Among these, 62 were diagnosed with IEM, with a detection rate of 0.56%. Thirty-five were males and 27 females and the median age was 3.55 months (range 0.07-143.9 months). Of the 62 patients, 27 (43.5%) had aminoacidemias, 26 (41.9%) had organic acidemias and nine (14.5%) had fatty acid oxidation disorders.</p> <p>Conclusions</p> <p>Because most symptomatic patients are diagnosed at an older age, mental retardation and motor delay are difficult to reverse. Additionally, poor medication compliance reduces the efficacy of treatment. More extensive newborn screening is thus imperative for ensuring early diagnosis and enhancing the treatment efficacy of IEM.</p

Identifying critically important vascular access outcomes for trials in haemodialysis : an international survey with patients, caregivers and health professionals

BACKGROUND: Vascular access outcomes reported across haemodialysis (HD) trials are numerous, heterogeneous and not always relevant to patients and clinicians. This study aimed to identify critically important vascular access outcomes. METHOD: Outcomes derived from a systematic review, multi-disciplinary expert panel and patient input were included in a multilanguage online survey. Participants rated the absolute importance of outcomes using a 9-point Likert scale (7-9 being critically important). The relative importance was determined by a best-worst scale using multinomial logistic regression. Open text responses were analysed thematically. RESULTS: The survey was completed by 873 participants [224 (26%) patients/caregivers and 649 (74%) health professionals] from 58 countries. Vascular access function was considered the most important outcome (mean score 7.8 for patients and caregivers/8.5 for health professionals, with 85%/95% rating it critically important, and top ranked on best-worst scale), followed by infection (mean 7.4/8.2, 79%/92% rating it critically important, second rank on best-worst scale). Health professionals rated all outcomes of equal or higher importance than patients/caregivers, except for aneurysms. We identified six themes: necessity for HD, applicability across vascular access types, frequency and severity of debilitation, minimizing the risk of hospitalization and death, optimizing technical competence and adherence to best practice and direct impact on appearance and lifestyle. CONCLUSIONS: Vascular access function was the most critically important outcome among patients/caregivers and health professionals. Consistent reporting of this outcome across trials in HD will strengthen their value in supporting vascular access practice and shared decision making in patients requiring HD

Metronomic oral cyclosphosphamide as third-line systemic treatment or beyond in patients with inoperable locoregionally advanced recurrent or metastatic nasopharyngeal carcinoma

published_or_final_versio

Prognostication of serial post-intensity-modulated radiation therapy undetectable plasma EBV DNA for nasopharyngeal carcinoma

published_or_final_versio

Hydrogen bond induced change of geometry and crystallized form of copper(II) complexes: syntheses and crystal structure of complexes with Schiff-base ligands containing two imidazolyl groups

Copper(II) complexes with the Schiff base methylbis[3-(5-methylimidazol-4-ylmethyleneimino)propyl]amine (BDPA), [Cu(BDPA)][ClO4](2).H2O 1 and [Cu(BDPA)][PF6](2) 2, and with a deprotonated Schiff base ligand [H2BIPO=1,3-bis[(5-methylimidazol-4-ylmethyleneimino)propan-2-ol], {[Cu(HBIPO)]ClO4.H2O}(n) 3 and 4, have been prepared. Single-crystal structures show that 1 adopts a distorted square-pyramidal geometry with the basal plane occupied by an imidazole nitrogen, two imines and one amino nitrogen atom and the apical position by another nitrogen atom from BDPA. 2 adopts a distorted trigonal-bipyramidal geometry with two imidazole nitrogen atoms at axial positions. Both 3 and 4 adopt distorted square-pyramidal geometry with four nitrogen atoms from HBIPO in the basal plane and the apical position occupied by a deprotonated imidazole nitrogen atom from an adjacent [Cu(HBIPO)] unit, resulting in polynuclear complexes. The differences in geometry and crystallization pathway between 1 and 2, and 3 and 4, are discussed based on the crystal structures, indicating that hydrogen bonding to the basal plane imidazole group plays an important role both in the change of geometry and crystallization form of the copper(II) complexes

Developing standards for reporting implementation studies of complex interventions (StaRI): a systematic review and e-Delphi

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Reevaluation of the Value of Autoparasitoids in Biological Control

Autoparasitoids with the capacity of consuming primary parasitoids that share the same hosts to produce males are analogous to intraguild predators. The use of autoparasitoids in biological control programs is a controversial matter because there is little evidence to support the view that autoparasitoids do not disrupt and at times may promote suppression of insect pests in combination with primary parasitoids. We found that Encarsia sophia, a facultative autoparasitoid, preferred to use heterospecific hosts as secondary hosts for producing males. The autoparasitoids mated with males originated from heterospecifics may parasitize more hosts than those mated with males from conspecifics. Provided with an adequate number of males, the autoparasitoids killed more hosts than En. formosa, a commonly used parasitoid for biological control of whiteflies. This study supports the view that autoparasitoids in combination with primary parasitoids do not disrupt pest management and may enhance such programs. The demonstrated preference of an autoparasitoid for heterospecifics and improved performance of males from heterospecifics observed in this study suggests these criteria should be considered in strategies that endeavor to mass-produce and utilize autoparasitoids in the future

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Provision of smoking cessation support for pregnant women in England: results from an online survey of NHS Stop Smoking Services for Pregnant women

Background: Smoking during pregnancy is a major public health concern and an NHS priority. In 2010, 26% of UK women smoked immediately before or during their pregnancy and 12% smoked continuously. Smoking cessation support is provided through free at the point of use Stop Smoking Services for Pregnant women (SSSP). However, to date, little is known of how these services provide support across England. The aim of this study was to describe the key elements of support provided through English SSSP. Methods: SSSP managers were invited to participate in this survey by email. Data were then collected via an online questionnaire; one survey was completed for each SSSP. Up to four reminder emails were sent over a two month period. Results: 86% (121 of 141) of services completed the survey. Responding services were, on average, larger than non-responding services in terms of the number of pregnant women setting quit dates and successfully quitting (p&thinsp;&lt;&thinsp;0.01). In line with the 2010 NICE guidelines, Stop Smoking in Pregnancy and following Childbirth, one in five SSSP identified pregnant smokers using carbon monoxide (CO) testing and refer via an opt-out pathway. All services offered nicotine replacement therapy (NRT) to pregnant women and 87% of services also offered dual therapy NRT, i.e. combination of a patch and short acting NRT product.. The 2010 NICE guidelines note that services should be flexible and client-centred. Consistent with this, SSSP offer pregnant women a range of support types (median 4) including couple/family, group (open or closed) or one-to-one. These are available in a number of locations (median 5), including in community venues, clinics and women's homes. Conclusions: English Stop Smoking Services offer behavioural support and pharmacotherapy to pregnant women motivated to quit smoking. Interventions provided are generally evidence-based and delivered in a variety of both social and health care settings