The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection

Aim: To describe gut colonization in preterm infants using standard culture and 16S gene rRNA profiling, exploring differences in healthy infants and those who developed NEC/late onset sepsis (LOS). Methods: Ninety‐nine stools from 38 infants of median 27‐week gestation were cultured; 44 stools from 27 infants had their microbial profiles determined by 16S. Ordination analyses explored effects of patient variables on gut communities. Results: Standard microbiological culture identified a mean of two organisms (range 0–7), DGGE 12 (range 3–18) per patient. Enterococcus faecalis and coagulase negative staphylococci (CONS) were most common by culture (40% and 39% of specimens). Meconium was not sterile. No fungi were cultured. Bacterial community structures in infants with NEC and LOS differed from healthy infants. Infants who developed NEC carried more CONS (45% vs 30%) and less Enterococcus faecalis (31% vs 57%). 16S identified Enterobacter and Staphylococcus presence associated with NEC/LOS, respectively. Conclusions: Important differences were found in the gut microbiota of preterm infants who develop NEC/LOS. The relationship of these changes to current practices in neonatal intensive care requires further exploration.     

The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.     

LC-MS/MS测定人血浆中对乙酰氨基酚及其人体药动学和生物等效性研究

目的 建立一种快速、灵敏的高效液相色谱-串联质谱（HPLC-MS/MS）方法以测定人血浆中对乙酰氨基酚浓度,并应用于两种对乙酰氨基酚制剂的人体药代动力学和生物等效性研究。方法 以替硝唑为内标,200μL血浆样品经5倍于其体积的乙酸乙酯液液萃取,再经Waters XBridge? C18柱等度洗脱分离后导入串联质谱,以正离子多反应监测模式进行定量分析,对乙酰氨基酚和内标的选择性反应离子对分别是m/z 152→110和248→121。方法经验证后应用于19名健康受试者单剂量空腹口服两种对乙酰氨基酚制剂500mg后药代动力学和生物等效性的研究。结果 血浆中对乙酰氨基酚在0.1～8.0 μg·mL-1范围内线性良好（r2 > 0.99）,最低检测限为 0.1 μg·mL-1,提取回收率为91.0%～98.7%,日内和日间准确度分别为98.8%～111.3% （精密度：CV ? 9.03%）和94.9%～102.6% （精密度：CV ? 10.68%）。生物等效性试验中,受试制剂与参比制剂的主要药代动力学参数Cmax、AUC0-t和AUC0-∞ 几何均值比的90%置信区间分别为83.50%～105.79%,94.25%～101.54%和93.24%～101.02%,均落在生物等效可接受标准80.00%～125.00%范围内。结论 所建立测定人血浆中对乙酰氨基酚浓度的HPLC-MS/MS法具有快速灵敏、回收率高、选择性好的特点,适用于对乙酰氨基酚片人体药代动力学和生物等效性研究。受试制剂与参比制剂在人体内吸收速度和程度相似,两种制剂生物等效。     

What are Journals for?

‘The secret is comprised in three words – work, finish, publish.’Michael FaradayThere are many reasons doctors want to publish their work. For most at an early stage in their career, this may be to add a line to their curriculum vitae and advance their careers but for academics, publishing is an expectation. Many will believe they have something important to say, and wish to provoke debate and discussion; others wish to share knowledge and experiences, which in medicine can lead to a satisfying change in clinical practice. All serve to register one’s idea and educate others. However, for some, the reason is as basic as money. As we celebrate the 350th anniversary of the first academic publication, perhaps we have come full circle when it comes to why people publish?Publishing is a flourishing business. There were approximately 28,100 active scholarly peer-reviewed journals in mid-2012, collectively publishing about 1.8–1.9 million articles per year. The number of articles published each year and the number of journals have both grown steadily for more than two centuries, by about 3% and 3.5% per year respectively.¹ Journals have a responsibility to refine and define information and act as a scientific filter. Many of us will receive daily invitations in our email inbox from eclectic and new journals that are likely to take anything – is the filter now too porous? But this industry is like any other commercial activity and the supply still far outstrips the demand. Perhaps the internet revolution has merely fuelled our hunger to publish more?The launch of this exciting and innovative series about publishing coincides with the 350th celebration of the publication of the first academic journal. In the age of social media, the first question is ‘What are journals for?’, which Simon Rallison sets out to answer. Simon is Director of Publications at the Physiological Society, and was previously a journal publisher with Earthscan, Springer and Blackwell.Writing is hard work and, through this series, I hope the reader will get some useful insight into this service industry for academia.Jyoti ShahCommissioning EditorIn an age of the internet and social media, why are we still using (admittedly with refinements and improvements) a form of publication dating from 1665? What exactly is a journal in the 21st century and what role does it have to perform? Surprisingly, the academic journal has not evolved since it was invented 350 years ago.¹ The first issue of the Philosophical Transactions of the Royal Society was published in 1665, the brainchild of Henry Oldenburg and Robert Hooke. Since then, journals have digitised and now offer greater opportunity for research communication – but are authors taking advantage of what journals can offer? The academic and research community is generally very conservative about what it reads and how it views journals. There are, however, also frequent misunderstandings about the operation of journals.     

Antiidiotypic IgG crossreactive with Rh alloantibodies in red cell autoimmunity

IgG autoantibodies eluted from RBCs of antiglobulin positive normal blood donors contained at least two antibody populations, an IgG autoantibody (Ab 1), and an IgG population (Ab 2) that agglutinated RBCs coated with some Rh(D) alloantibodies. Eight of 24 autoantibody eluates tested agglutinated 3 of 10 anti-Rh(D) sensitized RBCs. The agglutinating activity was inhibited specifically by preincubation of the autoantibody eluate with the reactive anti-D. The reaction did not require the Fc domain of the anti-Rh(D), since autoantibody eluates agglutinated RBCs coated with F(ab')2 prepared from the reactive anti-D sera. These findings indicate that the RBCs of some antiglobulin- positive blood donors contain an immunoglobulin auto-antiidiotype (Ab 2) against the RBC autoantibody (Ab 1) which is demonstrable through its cross-reactivity with selected Rh(D) alloantibodies. Identification of auto-antiidiotypes in RBC autoimmunity lends support to the idiotype- antiidiotype network hypothesis of immune regulation and is consistent with the bizarre and complex serology of autoimmune hemolytic anemia. The absence of clinical hemolysis in antiglobulin-positive normal blood donors suggests that immunoglobulin idiotype-antiidiotype interactions may play a role in modulating the effects of RBC autoimmunity.     

Persistent reversed end diastolic flow in the fetal middle cerebral artery: an ominous finding

Fetal persistent middle cerebral artery reversed end diastolic flow is a rare and ominous finding. Previous cases have been associated with intracranial hemorrhage, growth restriction, anaemia, and hepatic anomaly. Intrauterine demise or early neonatal death is a common outcome. We report the case of persistent middle cerebral artery reversed end diastolic flow in a well-grown fetus at 32 weeks’ gestation resulting from acute, severe anaemia due to a large feto-maternal hemorrhage. An emergency cesarean section was performed and the neonate required advanced resuscitation and immediate blood transfusion. Postnatal magnetic resonance imaging confirmed a hemorrhagic parietal infarct and bilateral ischaemic changes in the basal ganglia. This provides further evidence that persistent middle cerebral artery reversed end diastolic flow in any fetus is an ominous finding warranting urgent diagnostic evaluation and/or delivery.     

Effects of 8 weeks of continuous positive airway pressure on abdominal adiposity in obstructive sleep apnoea

The aim of the present study was to investigate the effect of continuous positive airway pressure (CPAP) treatment on regional adipose tissue distribution in patients with moderate or severe obstructive sleep apnoea. Patients received both therapeutic and sham CPAP in a random order for 2 months each with an intervening 1-month washout. Abdominal subcutaneous, visceral and liver fat were quantified using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Liver enzymes and plasma glucose were also determined. Measurements were obtained at baseline and at the end of both treatment arms. 38 eligible patients were randomly assigned to a treatment order, with 27 patients having complete MRI/MRS data. No significant difference was observed in subcutaneous (-28.6 cm(3); p=0.49) or visceral (-16.8 cm(3); p=0.59) adipose tissue, intrahepatic lipid (-0.2%; p=0.21), or fasting glucose measurements (-0.1 mmol·L(-1); p=0.46) between treatment modalities. Alkaline phosphatase decreased (-3.1 U·L(-1); p=0.02) while on therapeutic CPAP compared with sham CPAP but other liver enzymes, including aspartate aminotransferase (0.3 U·L(-1); p=0.82), alanine aminotransferase (1.34 U·L(-1); p=0.59) and γ-glutamyltransferase (-2.3 U·L(-1); p=0.33), remained unchanged. In this first randomised, sham-controlled trial, there was no change in adipose tissue distribution after 8 weeks of therapeutic CPAP compared with 8 weeks of sham CPAP. Longer duration of CPAP use may be necessary to demonstrate a difference.     

Rapid prenatal diagnosis of beta thalassemia using DNA amplification and nonradioactive probes

We used in vitro DNA amplification by the polymerase chain reaction and nonradioactive probes for prenatal diagnosis of beta thalassemia in Chinese from the Guangdong province. Exact molecular diagnoses were made in all 20 fetuses studied over a 6-month period. We conclude that this method of prenatal diagnosis for beta thalassemia is a viable approach in many parts of the world where this disease is common.