Biocomputional construction of a gene network under acid stress in Synechocystis sp. PCC 6803

Acid stress is one of the most serious threats that cyanobacteria have to face, and it has an impact at all levels from genome to phenotype. However, very little is known about the detailed response mechanism to acid stress in this species. We present here a general analysis of the gene regulatory network of Synechocystis sp. PCC 6803 in response to acid stress using comparative genome analysis and biocomputational prediction. In this study, we collected 85 genes and used them as an initial template to predict new genes through co-regulation, protein–protein interactions and the phylogenetic profile, and 179 new genes were obtained to form a complete template. In addition, we found that 11 enriched pathways such as glycolysis are closely related to the acid stress response. Finally, we constructed a regulatory network for the intricate relationship of these genes and summarize the key steps in response to acid stress. This is the first time a bioinformatic approach has been taken systematically to gene interactions in cyanobacteria and the elaboration of their cell metabolism and regulatory pathways under acid stress, which is more efficient than a traditional experimental study. The results also provide theoretical support for similar research into environmental stresses in cyanobacteria and possible industrial applications.     

Newly discovered innate response activator B cells: crucial responders against microbial sepsis

Evaluation of: Waldmann TA, Conlon KC, Stewart DM et al. Phase 1 trial of IL-15 trans presentation blockade using humanized Mik-β-1 mAb in patients with T-cell large granular lymphocytic leukemia. Blood 121(3), 476–484 (2013).

IL-15 is a cytokine that stimulates the proliferation of NK and T cells. Previous studies have shown that IL-15 is critical to the induction of T-cell large granular lymphocyte (T-LGL) leukemia. A Phase I trial of a humanized antibody (Hu-Mikβ1) to the IL2/IL15Rβ receptor, expressed on T-LGL, is explored in this trial to evaluate the safety, pharmacokinetics, specificity and clinical efficacy of Hu-Mikβ1. The study demonstrated no toxicity and favorable saturation of IL2/IL15Rβ receptor, but no clinical efficacy in this Phase I study.     

Staphylococcus aureus nasal and pharyngeal carriage in Senegal

Nasal and pharyngeal swabs were collected from 132 patients admitted to the Principal Hospital in Dakar (Senegal), in January and February 2012. The prevalence of Staphylococcus aureus carriage was 56.1% (n = 74): 40.2% for pharyngeal samples and 36.4% for nasal samples. None of the isolates was methicillin-resistant. Carriage was independently associated with being female (p <0.01) and large households (≥15 members) (p 0.04). The luk-PV genes encoding Panton–Valentine leukocidin (PVL) were present in 26.2% of the isolates. These data highlight the importance of the oropharynx as a site of colonization, and the high prevalence of PVL-positive isolates in Senegal as compared with industrialized countries.     

Prediction of structural failure of tibial bone models under physiological loads: Effect of CT density–modulus relationships

Although finite element (FE) models can provide distinct benefits in understanding knee biomechanics, in particular the response of the knee to implants, their usefulness is limited by the modelling assumptions and input parameters. This study highlights the uncertainty of material input parameters derived from the literature and its limitation on the accuracy and usefulness of FE models of the tibia. An FE model of the intact human knee and a database of knee forces (muscles, ligaments and medial and lateral tibio-femoral contacts) were developed for walking and stair-descent activities. Ten models were constructed from ten different combinations of apparent bone density to elastic modulus material property relationships, published in the literature. Some of the published material property relationships led to predictions of bone strains in the proximal tibia which exceeded published failure criteria under loads imposed by normal activities. These relationships appear not to be applicable for the human tibia. There is a large discrepancy in proposed relationships that cover the cancellous bone density range. For FE models of the human tibia, the material relationship proposed by Morgan et al., which assumed species and anatomic site dependence, produced the most believable results for cancellous bone. In addition to casting doubt on the use of some of the published density–modulus relationships for analysis of the human proximal tibia, this study highlights the need for further experimental work to characterise the behaviour of bone with intermediate densities.     

The use of medical care and the prevalence of serious illness in an adult Prader–Willi syndrome cohort

IntroductionAdults with Prader–Willi syndrome (PWS) have an increased occurrence of several medical conditions. We report on the consequences of high morbidity rates such as prevalence rate of hospital admissions, medication use and surgery in a Dutch cohort of adults with PWS. Special attention is paid to causes and symptoms of serious illness.MethodParticipants were contacted via the Dutch Prader–Willi Parent Association and through physicians specializing in persons with ID. The persons with PWS and their main caregivers were visited at home. Information was collected through semi-structured interviews on 102 adults with PWS.ResultsThe need for medical care in the neonatal period is associated with hypotonia and feeding problems. Hospital admissions for respiratory tract infections are frequent. During childhood most hospital admissions were due to PWS syndrome specific surgery. During adolescence hospital admissions occurred for scoliosis surgery and endocrine evaluations. At adult age, hospitalization was associated with inguinal hernia surgery, diabetes mellitus, psychosis, erysipelas, water and drug intoxications. In the older group, respiratory infections were again the main reason for hospital admissions. Frequently used medications at adult age included psychotropics, laxatives, anti-diabetics and dermatologic preparations. Abnormal drinking patterns, problems with anesthesia, decreased ability to vomit, abnormal pain awareness and unpredictable fever responses were frequent and often lead to delayed diagnoses of serious conditions.DiscussionPeople with PWS are frequent users of medical-care. Reasons for hospitalization and medication use are age specific. Knowledge on the different presentation of symptoms in people with PWS is needed. In case of unexplained illness, disturbances of consciousness and behavioral changes in people with PWS, an infection should be ruled out in the first place. Information from this study may help in preventing conditions and recognizing conditions in an early stage. Adequate preventive management and treatment of PWS related morbidity, could reduce medical care use in the long term and could improve quality adjusted life years.     

“Non-filling” procedures for lip augmentation: A systematic review of contemporary techniques and their outcomes

BackgroundIdeal lip augmentation techniques have good longevity, low complication rates, and optimal functional and aesthetic results. No systematic review is currently available regarding the efficacy of lip augmentation techniques. This review will focus only on non-filling procedures for lip augmentation (NFPLAs).MethodsCurrent databases Elsevier Science Direct, PubMed, HighWire Press, Springer Standard Collection, SAGE, DOAJ, Sweetswise, Free E-Journals, Ovid Lippincott Williams & Wilkins, Willey Online Library Journals and Cochrane Plus were scrutinized and relevant article reference sections were studied for additional publications. The search heading sequence used was (“Lip” or “Mouth” or “Perioral” or “Nasolabial”) and (“Augmentation” or “Enhancement” or “Surgery” or “Lift” or “V–Y” or “Corner”).ResultsExclusion criteria applied to 6436 initial keyword-search retrievals yielded 12 articles. Eight more articles were retrieved from reference sections, for a total of 18 papers assessed. Only one article made a direct comparison of efficacy between two surgical techniques for lip augmentation, and none directly compared complications associated with different NFPLAs.ConclusionsAlthough this systematic review revealed a lack of quality data in comparing the efficacy and complications among different NFPLAs, it is important to review and pool the existing studies to better suggest proper treatment to patients.     

Outcomes after tongue–lip adhesion or mandibular distraction osteogenesis in infants with Pierre Robin sequence and severe airway obstruction

The objective was to review and compare outcomes after tongue–lip adhesion (TLA) and mandibular distraction osteogenesis (MDO) in infants with severe breathing difficulties related to Pierre Robin sequence (PRS). A single-centre retrospective (2002–2012) study was carried out; 18 infants with severe breathing difficulties related to PRS resistant to conservative treatment, who underwent TLA or MDO to correct airway obstruction, were enrolled. The primary outcome measures were successful weaning from respiratory support and resumption of full oral feeding. Nine underwent TLA and nine MDO. Eight of the nine infants who underwent MDO and all those treated with TLA were successfully weaned from respiratory support. After discharge, residual respiratory distress was diagnosed more commonly after TLA than after MDO (6/9 vs 1/9, P = 0.050). Infants resumed oral feeding sooner after MDO than after TLA (mean days after surgery to full oral feeds 44 ± 24 vs 217 ± 134, P < 0.003). The length of hospital stay was longer for infants treated with MDO than for those treated with TLA. The rate of complications was similar. Infants with severe airway obstruction related to PRS can benefit safely from either TLA or MDO. Although MDO lengthens the time to discharge, this option stabilizes airway patency of infants with PRS more efficiently and achieves full oral feeding more rapidly than TLA.