[Bilateral Dislocation of the Hip Joints after a Car Accident?] / Bilaterálna traumatická luxácia bedrových klbov po autonehode?

The authors describe a case report of a 5-year-old foreign girl with a rare bilateral hip dislocation after a car accident. Young surgeons at the emergency department performed an unsuccessful closed reduction. Since the clinical and ultrasound screening of DDH of all newborns in the Slovak Republic is carried out until the age of 4-6 weeks, the treatment of dislocated hips starts early and the late diagnosed dislocations occur rarely. The aim of the study is to point at differences in DDH screening all over Europe resulting in an increased risk of misdiagnosed patients. Key words:hip dislocation, childhood, trauma, DDH, screening.

Mechanism behind Erosive Bursts In Porous Media.

Erosion and deposition during flow through porous media can lead to large erosive bursts that manifest as jumps in permeability and pressure loss. Here we reveal that the cause of these bursts is the reopening of clogged pores when the pressure difference between two opposite sites of the pore surpasses a certain threshold. We perform numerical simulations of flow through porous media and compare our predictions to experimental results, recovering with excellent agreement shape and power-law distribution of pressure loss jumps, and the behavior of the permeability jumps as a function of particle concentration. Furthermore, we find that erosive bursts only occur for pressure gradient thresholds within the range of two critical values, independent of how the flow is driven. Our findings provide a better understanding of sudden sand production in oil wells and breakthrough in filtration.

Agreeableness and Self-Consciousness as Predictors of Induced Scratching and Itch in Patients with Psoriasis.

BACKGROUND: Psoriasis (PS) is a frequent skin disease accompanied by itch, a symptom that has been shown to be related to depression and self-consciousness. PS patients describe themselves as more agreeable than healthy controls (HC), a trait that might be protective against impulsive scratching. PURPOSE: This study is the first to analyze the relationship between agreeableness and induced scratching and between depression, self-consciousness, and induced itch in PS patients. METHODS: Twenty-four PS patients and 24 HC were shown two videos: an itch-inducing experimental video (EV) and a non-itch-inducing control video (CV). Induced itch/scratching was determined by calculating the difference in itch intensity/number of scratch movements between EV and CV. Validated questionnaires were used to measure agreeableness, depression, and self-consciousness. RESULTS: In accordance with our hypothesis, in PS patients, public self-consciousness was significantly positively associated with induced itch (r = 0.564; p < 0.001), and agreeableness was significantly negatively associated with induced scratching (r = -0.444; p < 0.05). In HC, the relationship between public self-consciousness and induced itch and between agreeableness and induced scratching were positive, but not significant. CONCLUSIONS: This study showed distinct findings for PS patients and HC regarding the relationship between agreeableness and induced scratching. The relationship between public self-consciousness and induced itch was positive in both groups. The distinct finding regarding agreeableness supports the idea that scoring low on this scale might be a protective factor for scratching in PS patients. Future research should investigate mediating factors of the outlined relationships.

The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed behavioural disorder of childhood, affecting 3-5% of school-age children. The present study investigated whether the supplementation of soy-derived phosphatidylserine (PS), a naturally occurring phospholipid, improves ADHD symptoms in children. METHODS: Thirty six children, aged 4-14 years, who had not previously received any drug treatment related to ADHD, received placebo (n = 17) or 200 mg day(-1) PS (n = 19) for 2 months in a randomised, double-blind manner. Main outcome measures included: (i) ADHD symptoms based on DSM-IV-TR; (ii) short-term auditory memory and working memory using the Digit Span Test of the Wechsler Intelligence Scale for Children; and (iii) mental performance to visual stimuli (GO/NO GO task). RESULTS: PS supplementation resulted in significant improvements in: (i) ADHD (P < 0.01), AD (P < 0.01) and HD (P < 0.01); (ii) short-term auditory memory (P < 0.05); and (iii) inattention (differentiation and reverse differentiation, P < 0.05) and inattention and impulsivity (P < 0.05). No significant differences were observed in other measurements and in the placebo group. PS was well-tolerated and showed no adverse effects. CONCLUSIONS: PS significantly improved ADHD symptoms and short-term auditory memory in children. PS supplementation might be a safe and natural nutritional strategy for improving mental performance in young children suffering from ADHD.

Multi-strain probiotic improves subjective sleep quality with no impact on body composition, hemodynamics, and physical activity.

The objective of the study was to examine the impact of a multi-strain probiotic (MSP) on sleep, physical activity, and body composition changes. We used a randomised, double-blind, placebo-controlled approach with 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented daily with MSP (4 × 109 live cells Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04; Probiotical S.p.A., Novara, Italy) or placebo (PLA). In response to supplementation (after 0, 2, 4, and 6 weeks of supplementation) and 3 weeks after stopping supplementation, participants had subjective (Pittsburgh Sleep Quality Index, PSQI) and objective sleep indicators, body composition, daily physical activity and resting hemodynamics assessed. Subjective sleep quality indicators using the PSQI (sleep latency, sleep disturbance, and global PSQI score) improved ( P < 0.05) at various time points with MSP supplementation. Systolic blood pressure in PLA increased ( P < 0.05) after 6 weeks of supplementation with no change in MSP. No changes ( P > 0.05) in sleep (hours asleep, minutes awake, number of times awake) or physical activity (step count, minutes of sedentary activity, total active minutes) metrics assessed by the wearable device were observed. Additionally, no changes in resting heart rate, diastolic blood pressure, and body composition were discerned. In conclusion, MSP supplementation improved the subjective ability to fall asleep faster and disturbances experienced during sleep, which resulted in improved overall sleep quality as assessed by the PSQI. No differences in other sleep indicators, physical activity, hemodynamics, and body composition were observed during or following MSP supplementation. Registered at clinicaltrials.gov: NCT05343533.

Laparoscopic cholecystectomy in children.

UNLABELLED: In 95 children (age 6-18 y) treated for gallstones between 2002-2010, 95 laparoscopic cholecystectomies were carried out. Symptomatic cholecystolithiasis was the indication for laparoscopic cholecystectomy in most of the cases. In three patients, there was a conversion to open cholecystectomy. Postoperative complications due to failure of bile drainage arose in three patients. Restored bile drainage was secured for two biliodigestive anastomosis. Bile leak in a third patient solved a temporary biliary stent. Laparoscopic cholecystectomy is the gold standard for gallstones (Ref. 8). KEYWORDS: gallstones, laparoscopic cholecystectomy, cholecystolithiasis, bile drainage.

[Complications resulting from osteosynthesis in children after supracondylar fractures of the humerus]. / Komplikácie vyplývajúce z osteosyntézy suprakondylických zlomenín humeru u detí

INTRODUCTION: The authors carried out the analysis of the causes for re-operations after percutaneous osteosynthesis of supracondylar fractures of the humerus in children. MATERIALS AND METHODS: The authors evaluated the complications of osteosynthesis of supracondylar fractures in children hospitalized at the Clinic of Pediatric Surgery, University Hospital in Bratislava, for a 5-year period between 2007 and 2011. From the total number (395) of supracondylar fractures, 372 were treated as closed reduction and percutaneous transfixation. RESULTS: 32 (8.6%) of supracondylar fractures that were treated as closed reduction and osteosynthesis were indicated for re-operation - 8 times for signs of lesion n. ulnaris, 7 times for migration of Kirschner wires, 17 times for non-anatomical status or osteosynthesis failure. In case of lesions of nervus ulnaris, Kirschner wires were eliminated from the ulnar side and replaced either with intramedullary descendently introduced Kirschner wire to the ulnar condyle (the first option) or with three divergent Kirschner wires from radial side (the second option). In case of failed osteosynthesis, reosteosynthesis was performed using three Kirschner wires (two parallel or divergent from the radial side and one through the medial epicondyle). CONCLUSION: During the period monitored, the introduction of a differentiated approach in the treatment of supracondylar fractures of the humerus in children according to the type of fracture and the degree of displacement has significantly reduced the number of reoperations. Subsequently, it is important to notice that the decreased number of reosteosynthesis can be also assigned to the fact that the initial operation is not necessarily carried out as an urgent one (e.g. by a surgical team on night duty), but can be postponed and performed by an experienced traumatological team next day.

Disorder mapping in VCSELs using frequency-selective feedback.

We report on a simple method with a high spectral and spatial resolution for mapping variations in the cavity resonance of a plano-planar broad-area laser based on frequency-selective feedback. The demonstration experiment uses a vertical-cavity surface-emitting-laser (VCSEL), in which growth induced inhomogeneities are of particular importance. It relies only on a standalone laser with a narrow-bandwidth passive filter avoiding the need for an expensive tunable laser or high-resolution spectrometer.

Acute corticospinal tract diffusion tensor imaging predicts 6-month functional outcome after intracerebral haemorrhage.

INTRODUCTION: Diffusion tensor imaging (DTI) can assess the structural integrity of the corticospinal tract (CST) in vivo. We aimed to investigate whether CST DTI metrics after intracerebral haemorrhage (ICH) are associated with 6-month functional outcome and can improve the predictive performance of the existing ICH score. METHODS: We retrospectively included 42 patients with DTI performed within 5 days after deep supratentorial spontaneous ICH. Ipsilesional-to-contralesional ratios were calculated for fractional anisotropy (rFA) and mean diffusivity (rMD) in the pontine segment (PS) of the CST. We determined the most predictive variables for poor 6-month functional outcome [modified Rankin Scale (mRS) > 2] using the least absolute shrinkage and selection operator (LASSO) method. We calculated discrimination using optimism-adjusted estimation of the area under the curve (AUC). RESULTS: Patients with 6-month mRS > 2 had lower rFA (0.945 [± 0.139] vs 1.045 [± 0.130]; OR 0.004 [95% CI 0.00-0.77]; p = 0.04) and higher rMD (1.233 [± 0.418] vs 0.963 [± 0.211]; OR 22.5 [95% CI 1.46-519.68]; p = 0.02). Discrimination (AUC) values were: 0.76 (95% CI 0.61-0.91) for the ICH score, 0.71 (95% CI 0.54-0.89) for rFA, and 0.72 (95% CI 0.61-0.91) for rMD. Combined models with DTI and non-DTI variables offer an improvement in discrimination: for the best model, the AUC was 0.82 ([95% CI 0.68-0.95]; p = 0.15). CONCLUSION: In our exploratory study, PS-CST rFA and rMD had comparable predictive ability to the ICH score for 6-month functional outcome. Adding DTI metrics to clinical-radiological scores might improve discrimination, but this needs to be investigated in larger studies.

Characteristics of switching dynamics in a semiconductor-based cavity-soliton laser.

The switching behavior of a semiconductor cavity soliton laser is experimentally investigated, based on a vertical-cavity surface-emitting laser with frequency-selective feedback. In particular, we show the effect of frequency detuning between cavity solitons and the external injection, the temporal dynamics during ignition and erasure, and characterize the necessary injection pulse width versus its power for successful switching.

Inhibition of retinoic acid receptor signaling by Ski in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease with multiple different cytogenetic and molecular aberrations contributing to leukemic transformation. We compared gene expression profiles of 4608 genes using cDNA-arrays from 20 AML patients (nine with -7/del7q and 11 with normal karyotype) with 23 CD34+ preparations from healthy bone marrow donors. SKI, a nuclear oncogene, was highly up regulated. In a second set of 183 AML patients analyzed with real-time PCR, the highest expression level of SKI in AML with -7/del7q could be confirmed. As previously described, Ski associates with the retinoic acid receptor (RAR) complex and can repress transcription. We wanted to investigate the interference of Ski with RARalpha signaling in AML. Ski was co-immunoprecipitated and colocalized with RARalpha. We also found that overexpression of wild-type Ski inhibited the prodifferentiating effects of retinoic acid in U937 leukemia cells. Mutant Ski, lacking the N-CoR binding, was no more capable of repressing RARalpha signaling. The inhibition by wild-type Ski could partially be reverted by the histone deacetylase blocking agent valproic acid. In conclusion, Ski seems to be involved in the blocking of differentiation in AML via inhibition of RARalpha signaling.

Channelization in porous media driven by erosion and deposition.

We develop and validate a new model to study simultaneous erosion and deposition in three-dimensional porous media. We study the changes of the porous structure induced by the deposition and erosion of matter on the solid surface and find that when both processes are active, channelization in the porous structure always occurs. The channels can be stable or only temporary depending mainly on the driving mechanism. Whereas a fluid driven by a constant pressure drop in general does not form steady channels, imposing a constant flux always produces stable channels within the porous structure. Furthermore we investigate how changes of the local deposition and erosion properties affect the final state of the porous structure, finding that the larger the range of wall shear stress for which there is neither erosion nor deposition, the more steady channels are formed in the structure.

A Population Dose-Response Model for Inhaled Technosphere Insulin Administered to Healthy Subjects.

Technosphere insulin (TI), an inhaled insulin with a fast onset of action, provides a novel option for the control of prandial glucose. A euglycemic glucose clamp study was performed to compare the effects of TI and regular human insulin (RHI) on the induced glucose infusion rate (GIR) in healthy volunteers. Generation of a dose-response relationship between insulin dose and effect (expressed as AUC of GIR) was not possible from the clinical data directly. The GIR recording time was too short to capture the full effect and higher doses were not tested. Thus, a pharmacokinetic-GIR model was developed to simulate GIR for a sufficient time window of 20 h and for higher doses. A dose-response model was then generated from the simulated GIR profiles. The resulting model provides an ED50 for TI that is 5-fold higher than for RHI, a ratio that can be used as conversion factor for equivalent doses of RHI and TI.

Chemogenomics approaches to G-protein coupled receptor lead finding.

G-protein coupled receptors (GPCRs) are promising targets for the discovery of novel drugs. In order to identify novel chemical series, high-throughput screening (HTS) is often complemented by rational chemogenomics lead finding approaches. We have compiled a GPCR directed screening set by ligand-based virtual screening of our corporate compound database. This set of compounds is supplemented with novel libraries synthesized around proprietary scaffolds. These target-directed libraries are designed using the knowledge of privileged fragments and pharmacophores to address specific GPCR subfamilies (e.g., purinergic or chemokine-binding GPCRs). Experimental testing of the GPCR collection has provided novel chemical series for several GPCR targets including the adenosine A1, the P2Y12, and the chemokine CCR1 receptor. In addition, GPCR sequence motifs linked to the recognition of GPCR ligands (termed chemoprints) are identified using homology modeling, molecular docking, and experimental profiling. These chemoprints can support the design and synthesis of compound libraries tailor-made for a novel GPCR target.

Gain of Bcl-2 is more potent than bax loss in regulating mammary epithelial cell survival in vivo.

The impact of gain of Bcl-2 function on mammary epithelial cell survival was compared with loss of Bax function during the two stages of mammary gland involution. Bcl-2 gain of function reduced apoptosis 50% during the first stage and increased cell survival 70% during the second stage. Complete loss of Bax reduced apoptosis by 20% during the first stage without second stage effect. Partial loss of Bax was ineffective but increased cell survival 2.4-fold when combined with Bcl-2 gain. Gain of Bcl-2 function is more potent than loss of Bax function in regulating mammary epithelial cell survival in vivo.

Radioimmunoscintigraphy of colorectal carcinoma using technetium-99m-labeled, totally human monoclonal antibody 88BV59H21-2.

Radioimmunoscintigraphy (RIS) using human monoclonal antibodies offers the important clinical advantage of repeated imaging over murine monoclonal antibodies by eliminating the cross-species antibody response. This article reports a Phase I-II clinical trial with Tc-99m-labeled, totally human monoclonal antibody 88BV59H21-2 in patients with colorectal carcinoma. The study population consisted of 34 patients with colorectal cancer (20 men and 14 women; age range, 44-81 years). Patients were administered 5-10 mg antibody labeled with 21-41 mCi Tc-99m by the i.v. route and imaged at 3-10 and 16-24 h after infusion using planar and single-photon emission computed tomographic (CT) techniques. Pathological confirmation was obtained in 25 patients who underwent surgery. Human antihuman antibody (HAHA) titers were checked prior to and 1 and 3 months after the infusion. RIS with Tc-99m-labeled 88BV59H21-2 revealed a better detection rate in the abdomen-pelvis region compared with axial CT. The combined use of both modalities increased the sensitivity in both the liver and abdomen-pelvis regions. Ten patients developed mild adverse reactions (chills and fever). No HAHA response was detected in this series. Tc-99m-labeled human monoclonal antibody 88BV59H21-2 RIS shows promise as a useful diagnostic modality in patients with colorectal cancer. RIS alone or in combination with CT is more sensitive than CT in detecting tumor within the abdomen and pelvis. Repeated RIS studies may be possible, due to the lack of a HAHA response.

Overexpression of Bcl-2 inhibits alveolar cell apoptosis during involution and accelerates c-myc-induced tumorigenesis of the mammary gland in transgenic mice.

Expression of the apoptosis-inhibitory protein Bcl-2 has frequently been detected in human cancer including mammary carcinoma. The functional significance of its expression has been well established in experimental tumors of the lymphoid system, however, remains to be elucidated for epithelial tumors. In order to assess the role of Bcl-2 in mammary tumorigenesis we have generated WAP-bcl-2 transgenic mice. The strong overexpression of Bcl-2 in lactating mammary glands was preserved during early postlactational involution and apoptosis of alveolar epithelial cells was prevented without influencing the dedifferentiation of the milk-producing epithelium. Although Bcl-2 overexpression was not sufficient to induce spontaneous tumors it, however, led to an accelerated development of MMTV myc transgene-induced mammary tumors. In the mammary glands of MMTV myc transgenic mice, a high proportion of apoptotic cells was detected which was significantly reduced in the mammary glands of WAP-bcl-2/ MMTV myc double transgenic mice. Taken together, these results suggest that Bcl-2 contributes to mammary tumorigenesis by inhibiting apoptosis.

Bcl-2 expression delays mammary tumor development in dimethylbenz(a)anthracene-treated transgenic mice.

Bcl-2 is known to have dual antiproliferative and antiapoptotic roles. Overexpression of Bcl-2 in the mammary gland using a whey acidic protein (WAP) promoter-driven Bcl-2 transgene inhibits apoptosis in the mammary gland during pregnancy, lactation, and involution, and also counteracts apoptosis induced by overexpression of a mutant p53 transgene (WAP-p53 172 R-L). WAP-Bcl-2 mice and nontransgenic controls were treated with the carcinogen dimethylbenz(a)anthracene (DMBA). Surprisingly, the nontransgenic mice developed mammary tumors with decreased latency. Tumors arising in WAP-Bcl-2 mice displayed substantially reduced levels of proliferation relative to those seen in nontransgenic mice (P < 0.015), perhaps resulting in the observed increase in tumor latency following carcinogen treatment. This WAP-Bcl-2 mouse tumor model reflects the situation seen in some human breast cancers overexpressing Bcl-2, where expression of Bcl-2 has been shown to correlate with a lower proliferative index in tumors.