Active observation versus interval appendicectomy after successful non-operative treatment of an appendix mass in children (CHINA study): an open-label, randomised controlled trial

BACKGROUND: Despite a scarcity of supporting evidence, most surgeons recommend routine interval appendicectomy after successful non-operative treatment of an appendix mass in children. We aimed to compare routine interval appendicectomy with active observation. METHODS: We enrolled participants in the CHildren's INterval Appendicectomy (CHINA) study, a multicentre, open-label, randomised controlled study at 19 specialist paediatric surgery centres, 17 of which were in the UK, one in Sweden, and one in New Zealand. 106 children aged 3–15 years were assigned (1:1) by weighted minimisation to interval appendicectomy or active observation with minimisation for age, trial centre, sex, and presence of a faecolith on imaging. Eligible children had acute appendicitis with an appendix mass and were successfully treated without appendicectomy or other surgical intervention. Children were excluded from the study if they had coexisting gastrointestinal disease or had a substantial coexisting medical condition or immune defect. Because of the nature of the interventions, blinding was not possible. The primary outcome was the proportion of children developing histologically proven recurrent acute appendicitis or a clinical diagnosis of recurrent appendix mass within 1 year of enrolment after successful non-operative treatment of appendix mass (active observation group) and incidence of severe complications related to interval appendicectomy. Data were analysed on an intention-to-treat basis. This study is registered with ISRCTN, number 93815412. FINDINGS: Between Aug 8, 2011, and Dec 31, 2014, we randomly assigned 106 patients, 52 patients to interval appendicectomy and 54 to active observation. Two children in the interval appendicectomy group were withdrawn due to withdrawal of consent; two in the active observation group were withdrawn because they became ineligible after allocation. Six children under active observation had histologically proven recurrent acute appendicitis. Three children in the interval appendicectomy group had severe complications. Thus, the proportion of children with histologically proven recurrent acute appendicitis under active observation was 12% (95% CI 5–23) and the proportion of children with severe complications related to interval appendicectomy was 6% (95% CI 1–17). INTERPRETATION: More than three-quarters of children could avoid appendicectomy during early follow-up after successful non-operative treatment of an appendix mass. Although the risk of complications after interval appendicectomy is low, complications can be severe. Adoption of a wait-and-see approach, reserving appendicectomy for those who develop recurrence or recurrent symptoms, results in fewer days in hospital, fewer days away from normal daily activity, and is cheaper than routine interval appendicectomy. These high-quality data will allow clinicians, parents, and children to make an evidence-based decision regarding the justification for interval appendicectomy. FUNDING: BUPA Foundation

The chronic pain coping inventory: Confirmatory factor analysis of the French version

BACKGROUND: Coping strategies are among the psychosocial factors hypothesized to contribute to the development of chronic musculoskeletal disability. The Chronic Pain Coping Inventory (CPCI) was developed to assess eight behavioral coping strategies targeted in multidisciplinary pain treatment (Guarding, Resting, Asking for Assistance, Task Persistence, Relaxation, Exercise/Stretch, Coping Self-Statements and Seeking Social Support). The present study had two objectives. First, it aimed at measuring the internal consistency and the construct validity of the French version of the CPCI. Second, it aimed to verify if, as suggested by the CPCI authors, the scales of this instrument can be grouped according to the following coping families: Illness-focused coping and Wellness-focused coping. METHOD: The CPCI was translated into French with the forward and backward translation procedure. To evaluate internal consistency, Cronbach's alphas were computed. Construct validity of the inventory was estimated through confirmatory factor analysis (CFA) in two samples: a group of 439 Quebecois workers on sick leave in the sub-acute stage of low back pain (less than 84 days after the work accident) and a group of 388 French chronic pain patients seen in a pain clinic. A CFA was also performed to evaluate if the CPCI scales were grouped into two coping families (i.e. Wellness-focused and Illness-focused coping). RESULTS: The French version of the CPCI had adequate internal consistency in both samples. The CFA confirmed the eight-scale structure of the CPCI. A series of second-order CFA confirmed the composition of the Illness-focused family of coping (Guarding, Resting and Asking for Assistance). However, the composition of the Wellness-focused family of coping (Relaxation, Exercise/Stretch, Coping Self-Statements and Seeking Social Support) was different than the one proposed by the authors of the CPCI. Also, a positive correlation was observed between Illness and Wellness coping families. CONCLUSION: The present study indicates that the internal consistency and construct validity of the French version of the CPCI were adequate, but the grouping and labeling of the CPCI families of coping are debatable and deserve further analysis in the context of musculoskeletal and pain rehabilitation

Human Cytomegalovirus Infection Upregulates the Mitochondrial Transcription and Translation Machineries.

UNLABELLED: Infection with human cytomegalovirus (HCMV) profoundly affects cellular metabolism. Like in tumor cells, HCMV infection increases glycolysis, and glucose carbon is shifted from the mitochondrial tricarboxylic acid cycle to the biosynthesis of fatty acids. However, unlike in many tumor cells, where aerobic glycolysis is accompanied by suppression of mitochondrial oxidative phosphorylation, HCMV induces mitochondrial biogenesis and respiration. Here, we affinity purified mitochondria and used quantitative mass spectrometry to determine how the mitochondrial proteome changes upon HCMV infection. We found that the mitochondrial transcription and translation systems are induced early during the viral replication cycle. Specifically, proteins involved in biogenesis of the mitochondrial ribosome were highly upregulated by HCMV infection. Inhibition of mitochondrial translation with chloramphenicol or knockdown of HCMV-induced ribosome biogenesis factor MRM3 abolished the HCMV-mediated increase in mitochondrially encoded proteins and significantly impaired viral growth under bioenergetically restricting conditions. Our findings demonstrate how HCMV manipulates mitochondrial biogenesis to support its replication. IMPORTANCE: Human cytomegalovirus (HCMV), a betaherpesvirus, is a leading cause of morbidity and mortality during congenital infection and among immunosuppressed individuals. HCMV infection significantly changes cellular metabolism. Akin to tumor cells, in HCMV-infected cells, glycolysis is increased and glucose carbon is shifted from the tricarboxylic acid cycle to fatty acid biosynthesis. However, unlike in tumor cells, HCMV induces mitochondrial biogenesis even under aerobic glycolysis. Here, we have affinity purified mitochondria and used quantitative mass spectrometry to determine how the mitochondrial proteome changes upon HCMV infection. We find that the mitochondrial transcription and translation systems are induced early during the viral replication cycle. Specifically, proteins involved in biogenesis of the mitochondrial ribosome were highly upregulated by HCMV infection. Inhibition of mitochondrial translation with chloramphenicol or knockdown of HCMV-induced ribosome biogenesis factor MRM3 abolished the HCMV-mediated increase in mitochondrially encoded proteins and significantly impaired viral growth. Our findings demonstrate how HCMV manipulates mitochondrial biogenesis to support its replication.S.K. was supported by a European Molecular Biology Organization long-term fellowship (ALTF 887-2009). M.P.W is funded by a Wellcome Trust Senior Clinical Fellowship (108070/Z/15/Z). R.J.S. is supported by MRC grant (MR/L008734/1). P.J.L . is supported by a Wellcome Trust Principal Research Fellowship, grant (WT101835). J. S. is supported by MRC Programme grant (G0701279). J.R., L. V. and M.M. are supported by MRC as part of the core funding for the Mitochondrial Biology Unit (MC_U105697135). L.V. is also supported by EMBO (ALFT 701- 2013).This is the final version of the article. It first appeared from the American Society for Microbiology via http://dx.doi.org/10.1128/mBio.00029-1

Inhibition of human cytomegalovirus replication by interferon alpha can involve multiple anti-viral factors

The shortcomings of current direct-acting anti-viral therapy against human cytomegalovirus (HCMV) has led to interest in host-directed therapy. Here we re-examine the use of interferon proteins to inhibit HCMV replication utilizing both high and low passage strains of HCMV. Pre-treatment of cells with interferon alpha (IFNα) was required for robust and prolonged inhibition of both low and high passage HCMV strains, with no obvious toxicity, and was associated with an increased anti-viral state in HCMV-infected cells. Pre-treatment of cells with IFNα led to poor expression of HCMV immediate-early proteins from both high and low passage strains, which was associated with the presence of the anti-viral factor SUMO-PML. Inhibition of HCMV replication in the presence of IFNα involving ZAP proteins was HCMV strain-dependent, wherein a high passage HCMV strain was obviously restricted by ZAP and a low passage strain was not. This suggested that strain-specific combinations of anti-viral factors were involved in inhibition of HCMV replication in the presence of IFNα. Overall, this work further supports the development of strategies involving IFNα that may be useful to inhibit HCMV replication and highlights the complexity of the anti-viral response to HCMV in the presence of IFNα

Sirenomelia in a Nigerian triplet: a case report

<p>Abstract</p> <p>Introduction</p> <p>Sirenomelia, also known as mermaid syndrome, is a very rare fatal congenital abnormality in which the legs are fused together, giving them the appearance of a mermaid's tail. It is commonly associated with abnormal kidney development, genital and rectal abnormalities. A handful of cases have been reported in other parts of the world, however, no cases have previously been reported in a Nigerian neonate. To the best of our knowledge, we believe that this is the first case reported from West Africa and in a triplet.</p> <p>Case presentation</p> <p>A 16-hour-old baby boy, the second of a set of Nigerian triplets, presented to our facility with fusion of the entire lower limbs, imperforate anus, indiscernible genital structures, single umbilical artery and a neural tube defect. His parents were from the Hausa ethnic group and not related.</p> <p>Conclusion</p> <p>Sirenomelia has not been previously described in a set of triplets, and it is hoped that this report from West Africa will give information about the non-racial predilection of this condition.</p

Static stretching of the hamstring muscle for injury prevention in football codes: a systematic review

Purpose: Hamstring injuries are common among football players. There is still disagreement regarding prevention. The aim of this review is to determine whether static stretching reduces hamstring injuries in football codes. Methods: A systematic literature search was conducted on the online databases PubMed, PEDro, Cochrane, Web of Science, Bisp and Clinical Trial register. Study results were presented descriptively and the quality of the studies assessed were based on Cochrane’s ‘risk of bias’ tool. Results: The review identified 35 studies, including four analysis studies. These studies show deficiencies in the quality of study designs. Conclusion: The study protocols are varied in terms of the length of intervention and follow-up. No RCT studies are available, however, RCT studies should be conducted in the near future

Human cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex.

Human cytomegalovirus (HCMV) is an important human pathogen and a paradigm of viral immune evasion, targeting intrinsic, innate, and adaptive immunity. We have employed two orthogonal multiplexed tandem mass tag-based proteomic screens to identify host proteins down-regulated by viral factors expressed during the latest phases of viral infection. This approach revealed that the HIV-1 restriction factor Schlafen-11 (SLFN11) was degraded by the poorly characterized, late-expressed HCMV protein RL1, via recruitment of the Cullin4-RING E3 Ubiquitin Ligase (CRL4) complex. SLFN11 potently restricted HCMV infection, inhibiting the formation and spread of viral plaques. Overall, we show that a restriction factor previously thought only to inhibit RNA viruses additionally restricts HCMV. We define the mechanism of viral antagonism and also describe an important resource for revealing additional molecules of importance in antiviral innate immunity and viral immune evasion

Sexual attitudes, pattern of communication, and sexual behavior among unmarried out-of-school youth in China

<p>Abstract</p> <p>Background</p> <p>In recent years, more adolescents are engaging in premarital sex in China. However, only a limited number of studies have explored out-of-school youth's sexual attitudes and behaviors, critical for prevention intervention development.</p> <p>Methods</p> <p>Using data from the baseline survey of a comprehensive sex education program that was conducted in a suburb of Shanghai in 2000–2002, this study describes sexual attitudes, patterns of communication on sexual matters, and premarital sexual behavior among 1,304 out-of-school youth. Multivariate logistic regression analysis was conducted to examine the factors associated with youth's premarital sexual intercourse.</p> <p>Results</p> <p>The majority (60%) of out-of-school youth held favorable attitudes towards premarital sex. Males were more likely to have favorable attitudes compared with females. Male youth generally did not communicate with either parent about sex, while one-third of female youth talked to their mothers about sexual matters. Both males and females chose their friends as the person with whom they were most likely to talk about sexual matters. About 18% of the youth reported having engaged in sexual intercourse. One-fifth of sexually active youth had always used a contraceptive method, and one-quarter had been pregnant (or had impregnated a partner). There were no gender differences in rate of premarital sex or frequency of contraceptive use. Multivariate analysis revealed that age, education, family structure, parent's discipline, attitudes towards premarital sex, pattern of communication and dating were significantly associated with youth premarital sex.</p> <p>Conclusion</p> <p>A substantial proportion of out-of-school youth engage in risky sexual behaviors. Prevention programs that empower communication and sexual negotiation skills, and promote condom use should be implemented for this vulnerable group.</p

Search for Kaluza-Klein Graviton Emission in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy Signature

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 ${pb}^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a $3+1+n$-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for $n$=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure

Measurement of the average time-integrated mixing probability of b-flavored hadrons produced at the Tevatron

We have measured the number of like-sign (LS) and opposite-sign (OS) lepton pairs arising from double semileptonic decays of $b$ and $\bar{b}$-hadrons, pair-produced at the Fermilab Tevatron collider. The data samples were collected with the Collider Detector at Fermilab (CDF) during the 1992-1995 collider run by triggering on the existence of $\mu \mu$ and $e \mu$ candidates in an event. The observed ratio of LS to OS dileptons leads to a measurement of the average time-integrated mixing probability of all produced $b$-flavored hadrons which decay weakly, $\bar{\chi} = 0.152 \pm 0.007$ (stat.) $\pm 0.011$ (syst.), that is significantly larger than the world average $\bar{\chi} = 0.118 \pm 0.005$.Comment: 47 pages, 10 figures, 15 tables Submitted to Phys. Rev.