Purpose To systematically review the current evidence for conservative and surgical treatment of anterior cruciate ligament (ACL) tears in skeletally immature patients. Methods A systematic search of ...PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews (CDSR) was performed for surgical and/or conservative treatment of complete ACL tears in immature individuals. Studies with less than 6 months of follow-up were excluded. Study quality was assessed, and data were collected on clinical outcome, growth disturbance, and secondary joint damage. Results We identified 47 studies meeting the inclusion criteria. Conservative treatment was found to result in poor clinical outcomes and a high incidence of secondary defects, including meniscal and cartilage injury. Surgical treatment had only very weak evidence of growth disturbance yet strong evidence of good postoperative stability and function. No specific surgical treatment showed clearly superior outcomes, yet the studies using physeal-sparing techniques had no reported growth disturbances at all. Conclusions The current best evidence suggests that surgical stabilization should be considered the preferred treatment in immature patients with complete ACL tears. Although physeal-sparing techniques are not associated with a risk of growth disturbance, transphyseal reconstruction is an alternative with a beneficial safety profile and a minimal risk of growth disturbance. Conservative treatment commonly leads to meniscal damage and cartilage destruction and should be considered a last resort. Level of Evidence Level IV, systematic review of Level II, III, and IV studies.
Many cellular processes require proteins to be precisely positioned within the cell. In some cases this can be attributed to passive mechanisms such as recruitment by other proteins in the cell or by ...exploiting the curvature of the membrane. However, in bacteria, active self-positioning is likely to play a role in multiple processes, including the positioning of the future site of cell division and cytoplasmic protein clusters. How can such dynamic clusters be formed and positioned? Here, we present a model for the self-organization and positioning of dynamic protein clusters into regularly repeating patterns based on a phase-locked Turing pattern. A single peak in the concentration is always positioned at the midpoint of the model cell, and two peaks are positioned at the midpoint of each half. Furthermore, domain growth results in peak splitting and pattern doubling. We argue that the model may explain the regular positioning of the highly conserved structural maintenance of chromosomes complexes on the bacterial nucleoid and that it provides an attractive mechanism for the self-positioning of dynamic protein clusters in other systems.
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IJS, NUK, SBMB, UL, UM, UPUK
Inadvertent injection of contrast agent into the pancreatic duct is believed to be an important contributor to pancreatitis occurring after endoscopic retrograde cholangiopancreatography (post-ERCP ...pancreatitis, PEP). Our aim was to examine whether primary deep biliary cannulation with a guide wire is associated with a lower rate of PEP than conventional contrast-assisted cannulation.
From August 2003 to April 2006 all patients with an intact papilla who were referred for ERCP were eligible. Patients with pancreatic or ampullary cancer were excluded. Patients were randomized to undergo sphincterotomy biliary cannulation using either contrast injection or a guide wire. The ERCP fellow attempted initially for 5 minutes. If unsuccessful, the consultant attempted for 5 minutes using the same technique, followed by crossover to the other technique in the same sequence and then needle-knife sphincterotomy where appropriate. Patients were assessed clinically after the procedure, then followed up with telephone interviews after 24 hours and 30 days, and serum amylase and lipase tests after 24 hours.
Out of 1654 patients undergoing ERCP, 413 were included in the study. PEP occurred in 29/413 (7.0 %): 16 in the guide-wire arm, 13 in the contrast arm ( P = 0.48). The overall cannulation success rate was 97.3 %. Cannulation was successful without crossover in 323/413 patients (78.2 %): 167/202 (81.4 %) in the guide-wire arm and 156/211 (73.9 %) in the contrast arm ( P = 0.03). Multivariate analysis demonstrated female sex (OR = 2.7, P = 0.04), suspected sphincter of Oddi dysfunction (OR = 5.5, P = 0.01), and complete filling of the pancreatic duct with contrast agent (OR = 3.5, P = 0.02) to be independently associated with PEP. The risk of PEP increased incrementally with each attempt at the papilla (OR 1.4 per attempt, P = 0.04) to greater than 10 % after four or more attempts.
The guide-wire technique improves the primary success rate for biliary cannulation during ERCP but does not reduce the incidence of PEP compared to the conventional contrast technique. The incidence of PEP increases incrementally with each attempt at the papilla.
Trigeminal neuropathic pain (TNP) and temporomandibular disorders (TMD) are thought to have fundamentally different etiologies. It has been proposed that TNP arises through damage to, or pressure on, ...somatosensory afferents in the trigeminal nerve, whereas TMD results primarily from peripheral nociceptor activation. Because some reports suggest that neuropathic pain is associated with changes in brain anatomy, it is possible that TNP is maintained by changes in higher brain structures, whereas TMD is not. The aim of this investigation is to determine whether changes in regional brain anatomy and biochemistry occur in both conditions. Twenty-one TNP subjects, 20 TMD subjects, and 36 healthy controls were recruited. Voxel-based morphometry of T1-weighted anatomical images revealed no significant regional gray matter volume change in TMD patients. In contrast, gray matter volume of TNP patients was reduced in the primary somatosensory cortex, anterior insula, putamen, nucleus accumbens, and the thalamus, whereas gray matter volume was increased in the posterior insula. The thalamic volume decrease was only seen in the TNP patients classified as having trigeminal neuropathy but not those with trigeminal neuralgia. Furthermore, in trigeminal neuropathy patients, magnetic resonance spectroscopy revealed a significant reduction in the N-acetylaspartate/creatine ratio, a biochemical marker of neural viability, in the region of thalamic volume loss. The data suggest that the pathogenesis underlying neuropathic and non-neuropathic pain conditions are fundamentally different and that neuropathic pain conditions that result from peripheral injuries may be generated and/or maintained by structural changes in regions such as the thalamus.
This paper describes methods to analyze the brain's electric fields recorded with multichannel Electroencephalogram (EEG) and demonstrates their implementation in the software CARTOOL. It focuses on ...the analysis of the spatial properties of these fields and on quantitative assessment of changes of field topographies across time, experimental conditions, or populations. Topographic analyses are advantageous because they are reference independents and thus render statistically unambiguous results. Neurophysiologically, differences in topography directly indicate changes in the configuration of the active neuronal sources in the brain. We describe global measures of field strength and field similarities, temporal segmentation based on topographic variations, topographic analysis in the frequency domain, topographic statistical analysis, and source imaging based on distributed inverse solutions. All analysis methods are implemented in a freely available academic software package called CARTOOL. Besides providing these analysis tools, CARTOOL is particularly designed to visualize the data and the analysis results using 3-dimensional display routines that allow rapid manipulation and animation of 3D images. CARTOOL therefore is a helpful tool for researchers as well as for clinicians to interpret multichannel EEG and evoked potentials in a global, comprehensive, and unambiguous way.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
To carry out a systematic review of the literature addressing cognitive functions in first-episode psychosis (FEP), divided into domains. Although this is not a full ..."cognitive-genetics-in-schizophrenia review," we will also include putative ideas of mechanism(s) behind these impairments, focusing on how early stress, and genetic vulnerability may moderate cognitive function in psychosis.
Relevant studies were identified via computer literature searches for research published up to and including January 2013, only case-control studies were included for the neurocognitive meta-analysis.
Patients with FEP present global cognitive impairment compared to healthy controls. The largest effect size was observed for verbal memory (Cohen's d effect size = 2.10), followed by executive function (effect size = 1.86), and general IQ (effect size = 1.71). However, effect sizes varied between studies.
Cognitive impairment across domains, up to severe level based on Cohen's effect size, is present already in FEP studies. However, differences in levels of impairment are observed between studies, as well as within domains, indicating that further consolidation of cognitive impairment over the course of illness may be present. Cognitive abnormalities may be linked to a neurodevelopmental model including increased sensitivity to the negative effect of stress, as well as genetic vulnerability. More research on this field is needed.
Biaryl compounds, with two connected aromatic rings, are found across medicine, materials science and asymmetric catalysis
. The necessity of joining arene building blocks to access these valuable ...compounds has inspired several approaches for biaryl bond formation and challenged chemists to develop increasingly concise and robust methods for this task
. Oxidative coupling of two C-H bonds offers an efficient strategy for the formation of a biaryl C-C bond; however, fundamental challenges remain in controlling the reactivity and selectivity for uniting a given pair of substrates
. Biocatalytic oxidative cross-coupling reactions have the potential to overcome limitations inherent to numerous small-molecule-mediated methods by providing a paradigm with catalyst-controlled selectivity
. Here we disclose a strategy for biocatalytic cross-coupling through oxidative C-C bond formation using cytochrome P450 enzymes. We demonstrate the ability to catalyse cross-coupling reactions on a panel of phenolic substrates using natural P450 catalysts. Moreover, we engineer a P450 to possess the desired reactivity, site selectivity and atroposelectivity by transforming a low-yielding, unselective reaction into a highly efficient and selective process. This streamlined method for constructing sterically hindered biaryl bonds provides a programmable platform for assembling molecules with catalyst-controlled reactivity and selectivity.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Studies of the long-term course and outcome of psychoses tend to focus on cohorts of prevalent cases. Such studies bias samples towards those with poor outcomes, which may distort our understanding ...of prognosis. Long-term follow-up studies of epidemiologically robust first-episode samples are rare.
AESOP-10 is a 10-year follow-up study of 557 individuals with a first episode of psychosis initially identified in two areas in the UK (South East London and Nottingham). Detailed information was collated on course and outcome in three domains (clinical, social and service use) from case records, informants and follow-up interviews.
At follow-up, of 532 incident cases identified, at baseline 37 (7%) had died, 29 (6%) had emigrated and eight (2%) were excluded. Of the remaining 458, 412 (90%) were traced and some information on follow-up was collated for 387 (85%). Most cases (265, 77%) experienced at least one period of sustained remission; at follow-up, 141 (46%) had been symptom free for at least 2 years. A majority (208, 72%) of cases had been employed for less than 25% of the follow-up period. The median number of hospital admissions, including at first presentation, was 2 interquartile range (IQR) 1-4; a majority (299, 88%) were admitted a least once and a minority (21, 6%) had 10 or more admissions. Overall, outcomes were worse for those with a non-affective diagnosis, for men and for those from South East London.
Sustained periods of symptom remission are usual following first presentation to mental health services for psychosis, including for those with a non-affective disorder; almost half recover.
The pacific islands of Micronesia have experienced several outbreaks of mosquito-borne diseases over the past decade. In outbreaks on small islands, the susceptible population is usually well ...defined, and there is no co-circulation of pathogens. Because of this, analysing such outbreaks can be useful for understanding the transmission dynamics of the pathogens involved, and particularly so for yet understudied pathogens such as Zika virus. Here, we compared three outbreaks of dengue and Zika virus in two different island settings in Micronesia, the Yap Main Islands and Fais, using a mathematical model of transmission dynamics and making full use of commonalities in disease and setting between the outbreaks. We found that the estimated reproduction numbers for Zika and dengue were similar when considered in the same setting, but that, conversely, reproduction number for the same disease can vary considerably by setting. On the Yap Main Islands, we estimated a reproduction number of 8.0-16 (95% Credible Interval (CI)) for the dengue outbreak and 4.8-14 (95% CI) for the Zika outbreak, whereas for the dengue outbreak on Fais our estimate was 28-102 (95% CI). We further found that the proportion of cases of Zika reported was smaller (95% CI 1.4%-1.9%) than that of dengue (95% CI: 47%-61%). We confirmed these results in extensive sensitivity analysis. They suggest that models for dengue transmission can be useful for estimating the predicted dynamics of Zika transmission, but care must be taken when extrapolating findings from one setting to another.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The debate endures as to whether schizophrenia and bipolar disorder are separate entities or different manifestations of a single underlying pathological process. Here, we argue that this sterile ...argument obscures the fact that the truth lies somewhere in between. Thus, recent studies support a model whereby, on a background of some shared genetic liability for both disorders, patients with schizophrenia have been subject to additional genetic and/or environmental factors that impair neurodevelopment; for example, copy number variants and obstetric complications are associated with schizophrenia but not with bipolar disorder. As a result, children destined to develop schizophrenia show an excess of neuromotor delays and cognitive difficulties while those who later develop bipolar disorder perform at least as well as the general population. In keeping with this model, cognitive impairments and brain structural abnormalities are present at first onset of schizophrenia but not in the early stages of bipolar disorder. However, with repeated episodes of illness, cognitive and brain structural abnormalities accumulate in both schizophrenia and bipolar disorder, thus clouding the picture.
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