Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Trait Emotional Intelligence and Internet Gaming Disorder Among Gamers: The Mediating Role of Online Gaming Motives and Moderating Role of Age Groups

Personality differences are important determinants of problematic online behaviors. The purpose of the present study was to investigate the mediating role of loneliness, depression, and online gaming motives and moderating role of age on the relationship between trait emotional intelligence (EI) and Internet gaming disorder (IGD) via the construction of a multiple mediation model. A total of 478 online gamers completed a self-report online survey, including validated psychometric scales assessing the aforementioned constructs. Results indicated that trait EI was directly and indirectly associated with IGD and that the motive of escape was a partial mediator between trait EI and IGD among the total sample and adult gamers, but not among adolescents. Moreover, trait EI was associated with coping, skill development, fantasy, and recreation gaming motives only among total sample and adult gamers, and the escape motive was positively associated with IGD among total sample and adult gamers. However, among these relationships, only the association between trait EI and fantasy was significantly moderated by age group. Furthermore, the direct effect of trait EI was stronger among adolescent gamers when compared to adult gamers. Results showed that trait EI is inversely associated with IGD and affects gaming for different motives among adolescent and adult gamers.

     

Derivation of Power M-Mode Transcranial Doppler Criteria for Angiographic Proven MCA Occlusion

BACKGROUND: Stringent transcranial Doppler (TCD) criteria for diagnosing occlusion are needed for more reliable TCD performance at bedside in the acute stroke setting. SUBJECTS AND METHODS: At three academic stroke centers, we performed TCD examination for patients with symptoms of cerebral ischemia who underwent digital subtraction angiography (DSA). We used a standard insonation protocol with power M-mode Doppler (PMD) TCD (TCD 100 M, Spencer Technologies Inc., Seattle, WA). We collected mean flow velocity (MFV), pulsatility indices (PI), and power M-mode resistance signature (absent, high, or low) in symptomatic middle (MCA), anterior (ACA), posterior (PCA), and in affected (a), ipsilateral (i), and contralateral (c-lat) cerebral arteries. Ratios of aMCA/c-lat MCA, aMCA/iACA, and aMCA/iPCA MFV were subsequently calculated. PMD-TCD flow findings were evaluated with a receiver-operating characteristic (ROC) analysis for angiographically proven MCA occlusion. RESULTS: We studied 120 patients with acute cerebral ischemia with PMD-TCD examinations prior to or immediately after DSA. Lower aMCA velocities pointed to higher probability of occlusion (P= .055). The aMCA/iPCA MFV ratio was superior to the aMCA/iACA ratio and strongly predictive of occlusion at a threshold ratio of 0.5 (RR 2.31 CI(95) 2.13-2.51). High resistance or absent M-mode flow signatures in the proximal MCA were present in 87% of M1 and M2 MCA occlusions (probability 87%). In the presence of a low-resistance PMD signature, obtaining the aMCA/iPCA MFV ratio <0.5 increases probability of occlusion to 87%. Normal MFV ratios and low-resistance M-mode signatures are highly predictive of a negative angiogram for MCA occlusion. CONCLUSION: In acute cerebral ischemia, reliable criteria for proximal MCA occlusion have been developed based on combination of MFV ratios and M-mode flow resistance signatures. Validation of these criteria will require multicenter studies.     

Subtype determination of soma-dendritic α2-autoreceptors in slices of rat locus coeruleus

The aim of the study was to subclassify the soma-dendritic α₂-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average rate of 1 Hz. The selective α₂-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential discharge with IC₅₀ values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the right by phentolamine (0.15 μM) and rauwolscine (0.15 μM) but not by prazosin (1 μM). Apparent K _d values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent K _d values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 μM) suppressed the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored firing with EC₅₀ values of 120 and 250 nM, respectively. Prazosin (1 μM) again was ineffective. All three antagonist affinity estimates – against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the presence of oxaprotiline) – yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even at a concentration of 1 μM. These findings identify the soma-dendritic α₂-autoreceptors of the LC as the rat variant of the α_2A/D-adrenoceptor, i.e. α_2D. Not only presynaptic but also soma-dendritic α₂-autoreceptors may at least predominantly be α_2A/D throughout the nervous system. Received: 3 March 1997 / Accepted: 21 April 1997     

Severely comminuted distal radial fracture as an unsolved problem: complications associated with external fixation and pins and plaster techniques

Seventy-six patients with severely comminuted distal radial fractures were treated at two institutions, of which the overwhelming majority were Frykman class VIII. Fifteen fractures were open. Thirty patients were seen at the University Hospital; 17 had pins and plaster and 13 had external fixation. Forty-six patients were seen at Kaiser Hospital; all had pins and plaster treatment. The complication rate for those with pins and plaster at the University Hospital was 53%; the complication for external fixation rate was 62%. The affiliated-hospital complication rate was 52%. All patients with ipsilateral forearm shaft and carpal fractures developed a nonunion of the carpal fracture. Few patients maintained anatomic reduction, and many had significant intra-articular malalignment. External fixation with threaded half pins did not obviate pin problems in our series. These methods may help manage severely comminuted distal radial fractures, but complications should be anticipated and alternative treatment considered, especially when ipsilateral carpal or forearm shaft fractures are present.     

Acute carpal tunnel syndrome caused by pigmented villonodular synovitis of the wrist

An 89-year-old woman developed an acute carpal tunnel syndrome secondary to hemarthrosis associated with pigmented villonodular synovitis of the wrist. Pigmented villonodular synovitis is rare in a patient of this age and is an unusual cause of carpal tunnel syndrome.     

Comminuted intraarticular fractures of the distal radius

The comminuted intraarticular fracture of the distal radius requires early, accurate reduction of the articular surfaces and sustained restoration of anatomic position. The most commonly employed methods are pins and plaster, external fixation, percutaneous pinning, and open reduction and internal fixation. There are pitfalls, advantages, and disadvantages inherent in each method. Careful preoperative analysis of individual patients and fractures determines the therapeutic options.     

Developments in treatment of primary irresectable rectal cancer

Abstract The treatment options for primary irresectable rectal cancers are discussed. Assessment of tumour stage is the first step for an appropriate choice of treatment. Following a diagnosis of rectal cancer, a vast array of diagnostic procedures is available to determine its stage, and thereby its best treatment options. From the many (new) diagnostic options the merits and drawbacks are discussed. If a diagnosis of irresectability is made, further treatment options should include radiotherapy in most cases, some aspects of timing and application, i.e. intra-operative treatment are discussed. Chemotherapy options are manifold, the results are discussed and some new options are explored.     

Comminuted distal radius fractures.

Comminuted displaced fractures of the distal end of the radius pose a significant treatment challenge. The goal of treatment is to restore functional, painless motion of the wrist and fingers. Although satisfactory results correlate to a large extent with obtaining and maintaining normal anatomy, excessive distraction and a flexed wrist position with external fixation cause more harm than good, even if the anatomy is restored.     

SPROUT,HIPPO and CAESA: Tools for de novo structure generation and estimation of synthetic accessibility

Summary Several components of a system for structure generation are now well developed. HIPPO is a program that characterises a receptor binding site for potential target sites within the cavity that can be used in de novo design. The target sites include simple and complex hydrogen bonds, covalent bonds and bonds to metal ions. The SPROUT program for structure generation consists of two main components: the first is skeleton generation, followed by atom substitution to convert the solution skeletons to molecules. A new method of skeleton generation is presented here, where part skeletons are grown outwards from each target site. The part skeletons are then connected together to form solution skeletons. Finally the CAESA program is described, that ranks the output from SPROUT according to ease of synthesis.