Breaking through Barriers: Ultrafast Microbullet Based on Cavitation Bubble.
Micromotors hold great promise for extensive practical applications such as those in biomedical domains and reservoir exploration. However, insufficient propulsion of the micromotor limits its application in crossing biological barriers and breaking reservoir boundaries. In this study, an ultrafast microbullet based on laser cavitation that can utilize the energy of a cavitation bubble and realize its own hurtling motion is reported. The experiments are performed using high-speed photography. A boundary integral method is adopted to reveal the motion mechanism of a polystyrene (PS)/magnetic nanoparticle (MNP) microbullet under the action of laser cavitation. Furthermore, the influence of certain factors (including laser intensity, microbullet size, and ambient temperature) on the motion of the microbullet was explored. For the PS/MNP microbullet driven by laser cavitation, the instantaneous velocity obtained can reach 5.23 m s-1 . This strategy of driving the PS/MNP microbullet provides strong penetration ability and targeted motion. It is believed that the reported propulsion mechanism opens up new possibilities for micromotors in a wide range of engineering applications.


Surfactant protein A blocks recognition of Pseudomonas aeruginosa by CKAP4/P63 on airway epithelial cells.
We used isogenic mutant strains that were deficient or over-expressed capsule to study the function of the alginate exopolysaccharide in the interaction of Pseudomonas aeruginosa with the human airway epithelial cells (AEC) in the presence or absence of surfactant protein A (SP-A). SP-A prevented the invasion of AEC by alginate-producing P. aeruginosa strains because of a direct effect on the AEC. Monoclonal antibodies to CKAP4/P63, the principal SP-A-binding receptor on AEC, or inhibition of its expression using specific siRNA reduced the invasion of both highly encapsulated and poorly encapsulated strains, but not the invasion of the acapsular mutant. Treatment of AEC with SP-A, monoclonal antibodies to CKAP4/P63, or CKAP4/P63-specific siRNA decreased the binding of purified alginate exopolysaccharide to AEC. Alginate binding to AEC reduced SP-A release by these cells. Because the alginate exopolysaccharide is surface-exposed, levels of SP-A may be crucial to modulate the interaction of P. aeruginosa with AEC.


The impact of behavioral technology on dental caries.
Models of self-regulation of patient adherence to specific health promotion recommendations by professionals are available and have been shown effective in changing behavior. However, it is a fundamental misspecification of the caries prevention problem to look to techniques that affect the regulation of individual behavior to directly impact dental caries. Behavioral techniques are used to enhance the probability an individual will initiate, increase, or maintain the use of established caries reduction/control strategies or cease or decrease behaviors that increase caries. Behavioral techniques can also be used to affect parental behavior in a cascade of effects that can eventually lead to healthier children. Studies are needed where behaviorally oriented caries prevention actions are thought of as manipulating self-regulatory behavior and the focus of action is either on the individual or on another, such as a parent. A third category of studies should center on provider competency. Studies are recommended in each of these areas.


The evaluation of zebrafish cardiovascular and behavioral functions through microfluidics.
This study proposed a new experimental approach for the vascular and phenotype evaluation of the non-anesthetized zebrafish with representative imaging orientations for heart, pectoral fin beating, and vasculature views by means of the designed microfluidic device through inducing the optomotor response and hydrodynamic pressure control. In order to provide the visual cues for better positioning of zebrafish, computer-animated moving grids were generated by an in-house control interface which was powered by the larval optomotor response, in conjunction with the pressure suction control. The presented platform provided a comprehensive evaluation of internal circulation and the linked external behaviors of zebrafish in response to the cardiovascular parameter changes. The insights from these imaging sections was extended to identify the linkage between the cardiac parameters and behavioral endpoints. In addition, selected chemicals such as ethanol and caffeine were employed for the treatment of zebrafish. The obtained findings can be applicable for future investigation in behavioral drug screening serving as the forefront in psychopharmacological and cognition research.


Combining Autologous and Prosthetic Techniques: The Breast Reconstruction Scale Principle.
The latissimus dorsi (LD) flap remains a good option for immediate or delayed breast reconstruction. The main limitation of this flap is the small volume provided. To improve the reconstructed breast volume, the LD flap is usually combined with a breast implant. Recently, fat grafting to the LD flap was described to maximize flap volume and obtain a totally autologous breast reconstruction. We report our experience with hybrid breast reconstruction using both breast implants and fat-enriched latissimus dorsi (FELD) flaps. Between 2013 and 2016, 74 patients underwent breast reconstruction with FELD flaps only or FELD flaps combined with a breast implant. The LD flap was harvested as previously described. Donor sites for fat harvesting were chosen according to each patient's natural fat distribution. Fat was harvested, centrifuged, and injected into the LD flap. After fat grafting, breast sizers were employed to determine the final breast volume when the addition of an implant was indicated. Good cosmetic outcomes were achieved in all cases, with a mean follow-up of 2.1 years. No patients had cancer reoccurrences. Four patients experienced a seroma of the LD donor site, 1 had a breast hematoma, and 1 developed Baker grade III capsular contracture. One year postoperatively, a clinically relevant area of fat necrosis was observed in 1 patient and was surgically treated. Additional fat grafting sessions were required in 3 cases. In elected cases, a FELD flap alone or in combination with a small implant is a valuable technique for breast reconstruction surgery.


Cloud Screening Method in Complex Background Areas Containing Snow and Ice Based on Landsat 9 Images.
The first step in the application of Landsat 9 imagery is cloud screening, and the International Satellite Cloud Climatology Project (ISCCP) has made cloud screening an important part of the World Climate Research Program. The accurate identification of clouds in remote sensing satellite images containing snow and ice on the subsurface has been a challenging task in the cloud screening process. It is imperative to fully exploit the characteristic heterogeneous information of the cloud and snow subsurface, to solve the problem of cloud-snow confusion in the snow and ice environment, and to carry out research on cloud screening technology without interference from the snow and ice subsurface. In view of this, this paper will systematically carry out research on cloud screening methods in snow and ice environments. In this paper, we propose the building of a cloud screening algorithm that takes into account the difficulty of the fact that snow and ice on the subsurface can easily interfere with cloud recognition, and the influence of an empirical threshold or statistical threshold that makes its application less effective, and then establish a dynamic threshold cloud screening algorithm that is suitable for snow and ice environments. The research results will provide new ideas and perspectives to solve the problem of surface-type interference that most of the existing cloud screening algorithms contend with.


[Small cell carcinoma of the urinary bladder with synchronous esophageal cancer and incidental lung cancer: a case report].
We present a case of triple primary cancers occurring synchronously in the urinary bladder, esophagus, and incidentally in the lung. A 65-year-old man with a chief complaint of gross hematuria was admitted to our hospital. Cystoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) revealed a non-papillary broad-based bladder tumor. Histological diagnosis was transitional cell carcinoma of the urinary bladder and he underwent one course of neoadjuvant chemotherapy (M-VAC) with the preoperative diagnosis of T3bN0M0. After one course of chemotherapy, chest CT, lymph node biopsy and esophagoscopy revealed squamous cell carcinoma of the esophagus. He first underwent radiochemotherapy (total 70 Gy, CDDP 5 mg x 41, 5-FU 250 mg x 24) for esophageal cancer and achieved complete remission. Then, he underwent radiotherapy for a total of 60 Gy for bladder cancer. However, his general condition gradually became worse and he died from metastatic cancer. The autopsy proved that he died from multiple metastases of small cell carcinoma of the urinary bladder and incidentally squamous cell carcinoma of the lung was identified.


The somatosensory cortical activity in individuals with cerebral palsy displays an aberrant developmental trajectory.
Individuals with cerebral palsy (CP) have a reduced somatosensory cortical response Somatosensory cortical response strength decreases from adolescence to early adulthood Somatosensory cortical responses in youth with CP are similar to adult controls Individuals with CP may have aberrant maturation of the somatosensory system ABSTRACT: Numerous studies have documented tactile and proprioceptive deficits in children with cerebral palsy (CP) and linked these with weaker somatosensory cortical activity. However, whether such aberrations in somatosensory processing extend and/or progress into adulthood remains poorly understood. In the current study, we used magnetoencephalography (MEG) to investigate the primary somatosensory responses in a sample of individuals with CP (N = 42; age = 9-28 years) and a cohort of healthy controls (N = 23; age range = 11-23 years). Briefly, transient electrical stimulation was applied to the right tibial nerve, and standardized low-resolution brain electromagnetic tomography (sLORETA) was used to image the dynamic somatosensory cortical response. We found that the strength of somatosensory cortical activity within the 112-252 ms time window was significantly reduced in the individuals with CP compared with the healthy controls (HC = 286.53 ± 30.51, 95% CI [226.74, 346.32]; CP = 208.30 ± 19.66,CI [169.77, 246.83], P = 0.0126). These results corroborate previous findings of aberrant somatosensory cortical activity in individuals with CP. Our results also suggest that the somatosensory cortical activity tends to become weaker with age, with a similar rate of neurophysiological change in individuals with CP and healthy controls (P = 0.8790). Visualization of regression models fitted to the data imply that youth with CP may have somatosensory cortical activity similar to adult controls. These findings suggest that some individuals with CP exhibit an aberrant developmental trajectory of their somatosensory system.


The effect of head-fractioned teletherapy on pulp tissue.
To evaluate the early and delayed effects of fractioned teletherapy (radiotherapy) on the dental pulps of rats using Co(60). In group 1 - rats (n = 15) were subjected to fractioned teletherapy by 30 daily sessions fractioned in doses of 200 cGy day(-1), totaling 60 Gy and the rats were killed immediately after the final dose of irradiation; group 2 - same protocol but killed 30 days following the final irradiation dose; groups 3 (n = 7) and 4 (n = 8) - formed controls without irradiation. Following perfusion, the left mandible of each rat was dissected and processed for histopathology. Serial sections (5 microm) were obtained and stained with HE or picrosirius. Observations were recorded for the coronal pulp tissue. A blinded observer evaluated HE sections using pre-defined indices of inflammation, nuclear alterations and extracellular matrix (ECM) hyalinization. Images of sections stained with picrosirius were converted to black and white for analysis by image-pro plus; areas in black (collagen) were measured as percentage area. The pulps of mandibular incisors of the specimens prepared for transmission electron microscopy (TEM) were subjected to descriptive analysis. Magnifications of 6300 and 10000 x were used to observe 10 pulp fibroblasts from each group. No inflammatory reactions or modification of the ECM status were found (P = 0.428) in any specimens. The collagen content also displayed no significant changes (P = 0.067) as a result of treatment. Groups 1 and 2 displayed significantly more nuclear alterations than the control groups (P < 0.05). The bubble-like aspect was more pronounced in group 1, and the bubbles looked smaller in group 2. The ECM showed no differences in the hyalinization status and there were no differences in the collagen area within the pulps. Under TEM, the pulp fibroblasts in group 1 displayed nuclear alterations that resembled circular, oval or elongated perforations; perforations also appeared in the cytoplasm. Fractioned teletherapy is capable of producing nuclear alterations in the dental pulp tissue of rats.


Dual role of the RNA substrate in selectivity and catalysis by terminal uridylyl transferases.
Terminal RNA uridylyltransferases (TUTases) catalyze template-independent UMP addition to the 3' hydroxyl of RNA. TUTases belong to the DNA polymerase beta superfamily of nucleotidyltransferases that share a conserved catalytic domain bearing three metal-binding carboxylate residues. We have previously determined crystal structures of the UTP-bound and apo forms of the minimal trypanosomal TUTase, TbTUT4, which is composed solely of the N-terminal catalytic and C-terminal base-recognition domains. Here we report crystal structures of TbTUT4 with bound CTP, GTP, and ATP, demonstrating nearly perfect superposition of the triphosphate moieties with that of the UTP substrate. Consequently, at physiological nucleoside 5'-triphosphate concentrations, the protein-uracil base interactions alone are not sufficient to confer UTP selectivity. To resolve this ambiguity, we determined the crystal structure of a prereaction ternary complex composed of UTP, TbTUT4, and UMP, which mimics an RNA substrate, and the postreaction complex of TbTUT4 with UpU dinucleotide. The UMP pyrimidine ring stacks against the uracil base of the bound UTP, which on its other face also stacks with an essential tyrosine. In contrast, the different orientation of the purine bases observed in cocrystals with ATP and GTP prevents this triple stacking, precluding productive binding of the RNA. The 3' hydroxyl of the bound UMP is poised for in-line nucleophilic attack while contributing to the formation of a binding site for a second catalytic metal ion. We propose a dual role for RNA substrates in TUTase-catalyzed reactions: contribution to selective incorporation of the cognate nucleoside and shaping of the catalytic metal binding site.


[Risk factors for acute respiratory failure after liver transplantation].
To study the risk factors for acute respiratory failure during recovery after liver transplantation. We prospectively studied 340 consecutive liver transplant operations. Patient data was grouped according to whether acute respiratory failure developed (group I) or not (group II). Acute respiratory failure was defined by the need for mechanical ventilation longer than 5 days after transplantation or by the need for an inspired oxygen fraction of over 50% for 72 hours. We evaluated demographic characteristics, stage of liver disease before the transplant, comorbidity, immunosuppressant treatment administered, and complications during and after surgery. Sixty-six patients were placed in group I and 274 in group II. Univariate analysis showed significant differences between the groups for age, sex, Child-Pugh functional stage, preoperative renal failure, type of immunosuppression, and postoperative complications such as atrial fibrillation, pleural effusion, pulmonary edema, ascites, postoperative acute renal failure, brain dysfunction, early graft dysfunction, and respiratory infection. Multivariate analysis by logistic regression, taking the development or not of acute respiratory failure as the dependent variable, gave a model with 6 variables that accounted for 94% of the cases. The variables entering into the model, with their respective odds ratios (OR) were female sex (OR, 5.5), stage C liver function (OR, 3.9), pulmonary edema (OR, 16.3), postoperative acute renal failure (OR, 9), cerebral dysfunction (OR, 4.5), and respiratory infection (OR, 62). The development of acute respiratory failure after liver transplantation is affected by the following factors: female sex, Child-Pugh class, pulmonary edema, postoperative acute renal failure, cerebral dysfunction, and respiratory infection.


Platycodon grandiflorum Saponins Ameliorate Cisplatin-Induced Acute Nephrotoxicity through the NF-κB-Mediated Inflammation and PI3K/Akt/Apoptosis Signaling Pathways.
Although cisplatin is a potent chemotherapeutic agent against cancers, its clinical application is seriously limited by its severe side effects of nephrotoxicity. Previous studies reported that saponins isolated from the roots of Platycodon grandiflorum (PGS) exerted protective effects in various animal models of renal injury, with no confirmation on cisplatin-induced injury. This study was designed to investigate the protective effect of PGS (15 and 30 mg/kg) on cisplatin-induced kidney injury in mice. The levels of serum creatinine (CRE) and blood urea nitrogen (BUN), and renal histopathology demonstrated the protective effect of PGS against cisplatin-induced kidney injury. PGS exerted anti-inflammation effects via suppressing nuclear factor-kappa B (NF-κB) activation and alleviating the cisplatin-induced increase in inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in kidney tissues. The expressions of phosphorylation of phosphatidylinositol 3-kinase/protein kinase B and its downstream apoptotic factors, such as Bcl-2 and caspase families were regulated by PGS in a dose-dependent manner. In conclusion, PGS exerted kidney protection effects against cisplatin-induced kidney injury by inhibiting the activation of NF-κB and regulating PI3K/Akt/apoptosis signaling pathways in mice.


Cellular projections from sensory hair cells form polarity-specific scaffolds during synaptogenesis.
The assembly of a nervous system requires the extension of axons and dendrites to specific regions where they are matched with appropriate synaptic targets. Although the cues that guide long-range outgrowth have been characterized extensively, additional mechanisms are required to explain short-range guidance in neural development. Using a complementary combination of time-lapse imaging by fluorescence confocal microscopy and serial block-face electron microscopy, we identified a novel type of presynaptic projection that participates in the assembly of the vertebrate nervous system. Synapse formation by each hair cell of the zebrafish's lateral line occurs during a particular interval after the cell's birth. During the same period, projections emerge from the cellular soma, extending toward a specific subpopulation of mature hair cells and interacting with polarity-specific afferent nerve terminals. The terminals then extend along the projections to reach appropriately matched presynaptic sites, after which the projections recede. Our results suggest that presynaptic projections act as transient scaffolds for short-range partner matching, a mechanism that may occur elsewhere in the nervous system.


Epigenome-wide association of neonatal methylation and trimester-specific prenatal PM2.5 exposure.
Exposure to particulate matter with an aerodynamic diameter smaller than 2.5 microns (PM2.5) can affect birth outcomes through physiological pathways such as inflammation. One potential way PM2.5 affects physiology could be through altering DNA methylation (DNAm). Considering that exposures during specific windows of gestation may have unique effects on DNAm, we hypothesized a timing-specific association between PM2.5 exposure during pregnancy and DNAm in the neonatal epithelial-cell epigenome. After collecting salivary samples from a cohort of 91 neonates, DNAm was assessed at over 850,000 cytosine-guanine dinucleotide (CpG) methylation sites on the epigenome using the MethylationEPIC array. Daily ambient PM2.5 concentrations were estimated based on the mother's address of primary residence during pregnancy. PM2.5 was averaged over the first two trimesters, separately and combined, and tested for association with DNAm through an epigenome-wide association (EWA) analysis. For each EWA, false discovery rate (FDR)-corrected P < 0.05 constituted a significant finding and every CpG site with uncorrected P < 0.0001 was selected to undergo pathway and network analysis to identify molecular functions enriched by them. Our analysis showed that cg18705808 was associated with the combined average of PM2.5. Pathway and network analysis revealed little similarity between the first two trimesters. Previous studies reported that TMEM184A, the gene regulated by cg18705808, has a putative role in inflammatory pathways. The differences in pathway and network analyses could potentially indicate trimester-specific effects of PM2.5 on DNAm. Further analysis with greater temporal resolution would be valuable to fully characterize the effect of PM2.5 on DNAm and child development.


Design of self-oscillating gels and application to biomimetic actuators.
As a novel biomimetic polymer, we have developed polymer gels with an autonomous self-oscillating function. This was achieved by utilizing oscillating chemical reactions, called the Belousov-Zhabotinsky (BZ) reaction, which is recognized as a chemical model for understanding several autonomous phenomena in biological systems. Under the coexistence of the reactants, the polymer gel undergoes spontaneous swelling-deswelling changes without any on-off switching by external stimuli. In this review, our recent studies on the self-oscillating polymer gels and application to biomimetic actuators are summarized.


Availability of Recently Described Ptychadena (Anura: Ptychadenidae) Nomina from Ethiopia.
Frogs of the genus Ptychadena (Boulenger, 1917) have long been identified as harboring cryptic diversity and comprising numerous species-complexes (Largen 1997; Zimkus et al. 2017), and many authors have recognized the particularly high hidden richness in the Ethiopian highlands (Largen 1997; see Largen Spawls 2010 and refs. within). This cryptic diversity was confirmed by recent molecular studies (Freilich et al. 2014; Smith et al. 2017a, Reyes-Velasco et al. 2018). Those authors identified a congruent set of evolutionarily distinct candidate species using both mitochondrial and nuclear DNA, and described the geographic and ecological isolation of these species in detail (Freilich et al. 2014; Smith et al. 2017a).


Pigmented tumour of the eyelid with unexpected findings.
A 63-year-old patient presented with a small painless nodular tumour of his left lower eyelid which had increased in size over the last few weeks. The tumour was excised by wedge resection and submitted for ophthalmopathologic examination. Histopathologic examination revealed a cystic lesion of apocrine origin with focal proliferations. The proliferative cells appeared pleomorphic and displayed marked atypia. Staining with Ki67 revealed a significant mitotic activity supporting the diagnosis of an apocrine adenocarcinoma of Moll. As the lesion displayed in most parts characteristics of a benign apocrine hidrocystoma, a thorough and critical histopathological examination is required in such cases to avoid missing an early malignant transformation.


Comparison of the Clinical Outcomes between Echelette Extended Range of Vision and Diffractive Bifocal Intraocular Lenses.
To compare the clinical outcomes of echelette extended range of vision (ERV) and diffractive bifocal intraocular lenses (IOLs). This is a prospective, consecutive, nonrandomized clinical trial. Seventy-three eligible patients (109 eyes) received the implantation of echelette ERV IOL (Tecnis Symfony ZXR00) or diffractive bifocal IOL (Tecnis ZMB00). 1 week, 1 month, and 3 months after surgery, visual acuities at different distances were examined. At 3 months, defocus curves, contrast sensitivities (CSs) with and without glare, optic path difference (OPD) scans, and questionnaires were evaluated. Regression analyses were applied to discover influence factors on postoperative vision. ZXR00 showed better distance (P < 0.05) and intermediate (P < 0.001) visual acuities, while ZMB00 was better at distance-corrected near visual acuity (P < 0.001). Multivariate analyses indicated that worse intermediate (P < 0.001) and near vision (P=0.013) of ZMB00 might occur in patients with longer axial length. ZXR00 demonstrated smoother defocus curve and higher CSs. Superior modulation transfer function (MTF) and higher Strehl ratio (P < 0.05) were shown in ZXR00. In questionnaire evaluation, ZXR00 received better outcomes in self-reported vision, Visual Function-14 (VF-14) questionnaire, Quality of Vision (QoV) questionnaire, satisfaction, and recommendation grades. Spectacle dependence did not differ between ZXR00 and ZMB00 statistically. ZXR00 proved to be remarkable in distance and intermediate vision, defocus curve smoothness, CSs, and visual comfort, while ZMB00 achieved better near vision. ZXR00 may attain better near vision if postoperative SE remains slightly negative. Patients with relatively longer axial length might receive less favorable intermediate and near vision after ZMB00 implantation. This trial is registered with ChiCTR-ONC-17011119.


Local immune recognition of trophoblast in early human pregnancy: controversies and questions.
The role of the maternal immune system in reproductive success in humans remains controversial. Here we focus on the events that occur in the maternal decidua during the first few weeks of human pregnancy, because this is the site at which maternal leukocytes initially interact with and can recognize fetal trophoblast cells, potentially involving allorecognition by both T cells and natural killer (NK) cells. NK cells are the dominant leukocyte population in first-trimester decidua, and genetic studies point to a role of allorecognition by uterine NK cells in establishing a boundary between the mother and the fetus. By contrast, definitive evidence that allorecognition by decidual T cells occurs during the first trimester is lacking. Thus, our view is that during the crucial period when the placenta is established, damaging T cell-mediated adaptive immune responses towards placental trophoblast are minimized, whereas NK cell allorecognition contributes to successful implantation and healthy pregnancy.


[Pentax-AWS Airwayscope for awake tracheal intubation in the face-to-face sitting position in an emergency patient with acute exacerbation of aortic stenosis].
We report a successful awake tracheal intubation in an emergency patient with acute exacerbation of aortic stenosis using the Pentax-AWS Airwayscope (AWS). An 83-year-old woman was admitted to our emergency department for severe dyspnea due to exacerbation of aortic stenosis. Her Sp(O2) was 92-93% even after administration of 10 l x min(-1) oxygen through a reservoir-attached face mask. As she could not remain in the supine position, emergency tracheal intubation in the sitting position was required. After topical anesthesia with 8% lidocaine and careful administration of midazolam, the AWS was inserted into her mouth in the sitting, face-to-face position. The AWS allowed for visualization of the glottis and safe placement of the tracheal tube. Sufficient spontaneous ventilation was maintained during interventions with minimum vital sign changes. Awake intubation in the sitting position with the AWS may be helpful in resolving cardiovascular crisis in patients unable to maintain the supine position.


Safety of Anti-TNF-Alpha Therapy During Pregnancy on Long-term Outcome of Exposed Children: A Controlled, Multicenter Observation.
Evidence of the impact of in utero exposure to anti-tumor necrosis factor (TNF)-alpha on long-term childhood development is limited. The aim was to assess the impact of in utero exposure to anti-TNF-alpha due to mothers' inflammatory bowel disease (IBD) on long-term postnatal development of exposed children. We included consecutive children (≥12 months of age) born to mothers with IBD (2007-2016) treated with anti-TNF-alpha during pregnancy in 3 centers in the Czech Republic. A control group was comprised of unexposed children of non-IBD mothers undergoing mandatory check-ups at general pediatricians' offices. Data on perinatal period, psychomotor development, vaccination, infections, antibiotics, and allergy were collected by treating pediatricians using a predefined questionnaire. Seventy-two exposed and 69 unexposed children were included (median age, 35 and 50 months, respectively). Exposed children had growth and psychomotor development similar to controls. There was no significant difference in infectious complications within the first year of life (23.9% vs 17.4%; P = 0.36) or during the whole follow-up between exposed infants and controls (P = 0.32). Concomitant immunosuppressants during pregnancy and anti-TNF-alpha levels in cord blood were not associated with elevated infection rate within the first year of life (P > 0.05). Over 95% of exposed children had adequate serologic response to vaccination, except for haemophilus and mumps vaccines. Clinically manifested allergy was similar between the groups (P = 0.98). Anti-TNF-alpha exposure in utero does not seem to have a negative impact on postnatal development of children with regard to infectious complications, allergy, growth, or psychomotor development when compared with unexposed children of non-IBD women.


The spatial patterning of mouse cone opsin expression is regulated by bone morphogenetic protein signaling through downstream effector COUP-TF nuclear receptors.
Cone photopigments, known as opsins, are pivotal elements and the first detection module used in color vision. In mice, cone photoreceptors are distributed throughout the retina, and short-wavelength (S) and medium-wavelength (M) opsins have unique expression patterns in the retina with a gradient along the dorsoventral axis; however, the mechanisms regulating the spatial patterning of cone opsin expression have not been well documented. The purpose of this study was to define the mechanisms regulating the spatial patterning of cone opsin expression. By analyzing knock-outs for bone morphogenetic protein (BMP) signaling, we found an essential role for BMP in forming cone opsin expression patterns in the retina; however, BMP signaling is activated only transiently in the dorsal half of the retina during early retinal development. Thus, BMP is not likely to play a direct role in opsin gene expression, which starts at a later stage of retinal development. We identified the chicken ovalbumin upstream promoter-transcription factor (COUP-TF) nuclear receptor as a link between BMP and opsin expression. BMP signaling is essential for the correct dorsoventral spatial expression of COUP-TFI and COUP-TFII. Through gain- and loss-of-function analyses, we found that both COUP-TFI and COUP-TFII are required to suppress S-opsin expression in the dorsal retina but that only COUP-TFI plays an essential role in suppressing M-opsin expression in the ventral retina. Based on these findings, we propose a new molecular cascade involving BMP and COUP-TFs that conveys dorsoventral information to direct the expression of cone opsins during retinal development.


Cerebrospinal fluid rhinorrhea following acoustic neurinoma surgery. Technical note.
The authors describe a method of preventing cerebrospinal fluid (CSF) rhinorrhea following surgery for acoustic neurinoma. Mastoid air cells exposed during craniectomy are skeletonized and packed with bone dust, then covered with Surgicel soaked with Tisseel fibrin glue. The use of this technique has reduced the number of acoustic neurinoma cases requiring secondary mastoidectomy for CSF leakage from 16% to 5%.


Relationships among organizational family support, job autonomy, perceived control, and employee well-being.
The authors analyzed data from the 2002 National Study of the Changing Workforce (N = 3,504) to investigate relationships among availability of formal organizational family support (family benefits and alternative schedules), job autonomy, informal organizational support (work-family culture, supervisor support, and coworker support), perceived control, and employee attitudes and well-being. Using hierarchical regression, the authors found that the availability of family benefits was associated with stress, life satisfaction, and turnover intentions, and the availability of alternative schedules was not related to any of the outcomes. Job autonomy and informal organizational support were associated with almost all the outcomes, including positive spillover. Perceived control mediated most of the relationships.


[Fruits and vegetables].
Fruits and vegetables are particularly interesting for health for their content in minerals, antioxidant vitamins, phytochemicals and dietary fiber. All these substances are related to lower risk for the development of health probems, such as certain types of cancer, cardiovascular diseases, type 2 diabetes, obesity, constipation or diverticolsys. The sound basis of scientific evidence led European and American scientific organizations and societies to recommend an intake up to 150-200 g of vegetables every day; ie. 2 or more portions daily and 3 or more portions of fruit; five portions of fruit and vegetables all together. According to the consumer panel from the Spanish Ministry of Agriculture, Fisheries and Food, between the late 80s and the end of the 90s. consumption of fruit and vegetables decreased. However, in late years this trend has slow down and even reversed. Results from food consumption studies based on individual level assessment in Spain estimate an average consumption of fruit and vegetables of 154 g/per person/day in adults aged 25-60 yr. Prevalence of inadequate intake of fruit and vegetables is high among children and young people. In this age group above 70% of the population consume less than 3 portions of fruit every day on average. Reorientation of prevailing food patterns nowadays require investment in measures aimed at increasing the consumption of plant foods and estimulate healthy food habits in families.


Normal brain imaging accompanies neuroimmunologically justified, autoimmune encephalomyelitis.
To examine cases with a clinical course, signs, and symptoms mimicking MS, but without abnormalities on conventional MRI. Among 550 people with a tentative diagnosis of MS or neuromyelitis optica spectrum disorder (NMOSD), we selected patients, who met the 2010 McDonald diagnosis criteria for MS, but did not show abnormal findings on conventional brain and spinal cord MRI. After evaluating their clinical data, we analyzed fractional anisotropy (FA) values in the brain white matter on diffusion tensor MRIs and the frequencies of B-cell subsets in the peripheral blood in the corresponding cases as compared to healthy controls. Eleven patients (age: 41.1 ± 8.0 years, 9 women and 2 men) met the selection criteria. They were functionally disabled, with a median expanded disability status scale score of 6.0 (2.0-8.0). CSF oligoclonal bands were negative in all cases. IV methylprednisolone and plasmapheresis (PP) were found to be efficacious. Diffusion tensor MRI analysis revealed extensive white matter abnormalities characterized by significantly decreased FA values. The frequency of plasmablasts in the peripheral blood was significantly increased in these patients similar to NMOSD. The neurologic disabilities in these patients could be ascribed to brain white matter damage, as revealed by MRI analysis, whereas the efficacy of PP and B-cell abnormalities in the patients suggested an autoimmune-mediated pathogenesis. In the differential diagnosis of MS, we propose that this condition be referred to as, "Normal-appearing Imaging-associated, Neuroimmunologically Justified, Autoimmune encephalomyelitis."


HSP90 inhibits apoptosis and promotes growth by regulating HIF-1α abundance in hepatocellular carcinoma.
Heat shock protein (HSP)90 functions as a general oncogene by targeting several well-known oncoproteins for ubiquination and proteasomal degradation. However, the clinical significance of HSP90, as well as the mechanisms responsible for the tumor-promoting effects of HSP90 in hepatocellular carcinoma (HCC) remain unclear. In this study, HSP90 and hypoxia-inducible factor (HIF)-1α expression in 60 samples of HCC tissues and matched normal tumor-adjacent tissue were assessed using immunohistochemistry (IHC) or western blot analysis. Flow cytometry, BrdU cell proliferation assay, caspase-3/7 activity assay and MTT assay were used to detect the apoptosis and proliferation of the HCC cells. The regulatory effect of HSP90 on HIF-1α in the HCC cells was confirmed by immunofluorescence staining, western blot analysis and RT-qPCR. The interaction between HIF-1α and HSP90 was analyzed by co-immunoprecipitation. A subcutaneous tumor xenograft model in nude mice was established and TUNEL assay was performed to evaluate cancer cell apoptosis and growth in vivo. We found that HSP90 expression was higher in the HCC tissues than in the normal tissues and that a high HSP90 expression correlated with poor clinicopathological characteristics, including venous infiltration, an advanced TNM stage and high pathological grading. Furthermore, we confirmed that patients with a negative expression of HSP90 had an improved 3-year survival, and that HSP90 was an independent factor for predicting the prognosis of patients with HCC. We demonstrated that HSP90 promoted HCC by inhibiting apoptosis and promoting cancer cell growth. Pearson's correlation coefficient analysis indicated that HSP90 expression positively correlated with HIF-1α protein expression in the HCC tissues. Furthermore, we found that HSP90 regulated HIF-1α protein abundance by inhibiting the ubiquitination and proteasomal degradation of HIF-1α in HCC cells. Additionally, the upregulation of HIF-1α expression partially abrogated HSP90 siRNA-induced HCC cell growth arrest and apoptosis in vitro and in vivo. These results indicate that HSP90 may be used as a prognostic marker and that HIF-1α may be one of the potential therapeutic targets of HSP90 in HCC.


A case of extreme sexual self-mutilation.
We report on a case of extreme sexual self-mutilation in which the subject inflicted severe trauma to his genitalia and then falsely reported a sexual assault. The 30-year-old white male did not report the incident for 10 days and then checked into a hospital. The hospital called the Westminster Police Department after the subject reported that he was the victim of a sexual assault in our city. This case is unusual in that the subject's initial behavior and story did not indicate deception. It was not until the subject's computer was searched that investigators determined that the injuries were self-inflicted. Without this critical information the case might still remain open as a sexual assault. This case is reported to broaden our understanding of this behavior and inform investigators of the potential for this type of self-inflicted injury.


Plasma membrane localization of the Yck2p yeast casein kinase 1 isoform requires the C-terminal extension and secretory pathway function.
The S. cerevisiae Yck2 protein is a plasma membrane-associated member of the casein kinase 1 protein kinase family that, with its homolog Yck1p, is required for bud morphogenesis, cytokinesis, endocytosis and other cellular processes. Membrane localization of Yckp is critical for its function, since soluble mutants do not provide sufficient biological activity to sustain normal growth. Yck2p has neither a predicted signal sequence nor obvious transmembrane domain to achieve its plasma membrane localization, but has a C-terminal -Cys-Cys sequence that is likely to be palmitoylated. We demonstrate here that Yck2p is targeted through association with vesicular intermediates of the classical secretory pathway. Yck2p lacking C-terminal Cys residues fails to associate with any membrane, whereas substitution of these residues with a farnesyl transferase signal sequence allows sec-dependent plasma membrane targeting and biological function, suggesting that modification is required for interaction with early secretory membranes but that targeting does not require a particular modification. Deletion analysis within the 185 residue C-terminus indicates that the final 28 residues are critical for membrane association, and additional sequences just upstream are required for proper plasma membrane targeting.


Rhenium(VII) Compounds as Inorganic Precursors for the Synthesis of Organic Reaction Catalysts.
Rhenium is an element that exhibits a broad range of oxidation states. Synthesis paths of selected rhenium compounds in its seventh oxidation state, which are common precursors for organic reaction catalysts, were presented in this paper. Production technologies for copper perrhenate, aluminum perrhenate as well as the ammonia complex of cobalt perrhenate, are thoroughly described. An ion exchange method, based on Al or Cu metal ion sorption and subsequent elution by aqueous perrhenic acid solutions, was used to obtain perrhenates. The produced solutions were neutralized to afford the targeted aluminum perrhenate and copper perrhenate products in high purity. The developed technologies allow one to manage the wastes from the production of these perrhenates as most streams were recycled. Hexaamminecobalt(III) perrhenate was produced by a newly developed method enabling us to produce a high purity compound in a reaction of spent hexaamminecobalt(III) chloride solution with a perrhenic acid. All prepared compounds are the basis for precursor preparation in organic catalysis.


Advanced modes of mechanical ventilation: implications for practice.
Mechanical ventilation is one of the most commonly applied interventions in intensive care units. Despite its life-saving role, mechanical ventilation is associated with additional risks to the patient and additional healthcare costs if not applied appropriately. To decrease risk, new ventilator modes continue to be developed with the goal of improving patient outcomes. Advances in ventilator modes include dual control modes that enable guaranteed tidal volume and inspiratory pressure, pressure-style modes that permit spontaneous breathing at high- and low-pressure levels, and closed-loop systems that facilitate ventilator manipulation of variables based on measured respiratory parameters. Clinicians need to develop a thorough understanding of these modes including their effects on underlying respiratory physiology to be able to deliver safe and appropriate patient care.


To kill, stay or flee: the effects of lions and landscape factors on habitat and kill site selection of cheetahs in South Africa.
Understanding how animals utilize available space is important for their conservation, as it provides insight into the ecological needs of the species, including those related to habitat, prey and inter and intraspecific interactions. We used 28 months of radio telemetry data and information from 200 kill locations to assess habitat selection at the 3rd order (selection of habitats within home ranges) and 4th order (selection of kill sites within the habitats used) of a reintroduced population of cheetahs Acinonyx jubatus in Phinda Private Game Reserve, South Africa. Along with landscape characteristics, we investigated if lion Panthera leo presence affected habitat selection of cheetahs. Our results indicated that cheetah habitat selection was driven by a trade-off between resource acquisition and lion avoidance, and the balance of this trade-off varied with scale: more open habitats with high prey densities were positively selected within home ranges, whereas more closed habitats with low prey densities were positively selected for kill sites. We also showed that habitat selection, feeding ecology, and avoidance of lions differed depending on the sex and reproductive status of cheetahs. The results highlight the importance of scale when investigating a species' habitat selection. We conclude that the adaptability of cheetahs, together with the habitat heterogeneity found within Phinda, explained their success in this small fenced reserve. The results provide information for the conservation and management of this threatened species, especially with regards to reintroduction efforts in South Africa.


[Allele frequencies and species specificity of six short tandem repeat loci in Chinese population].
To develop a set of new markers for forensic application, the authors have chosen 6 short tandem repeat(STR) loci to study the allele frequencies and species specificity in Chinese Han population in Chengdu. One hundred and ten EDTA-blood samples were collected from the unrelated individuals in Chengdu city, Sichuan province. DNA was extracted by Chelex-100 and amplified by the polymerase chain reaction(PCR). Polyacrylamide gel electrophoresis (PAGE) and silver staining were used to analyze the PCR products. The polymorphisms of all 6 STR loci have been obtained in Chinese Han population in Chengdu, the alleles of D4S2366, D4S2367, D6S474, D6S1281, D2S1396 and D20S601 being 7, 7, 6, 7, 5, 7, the observed heterozygosity of them being 0.802, 0.708, 0.770, 0.627, 0.542, 0.672, the discrimination power of them being 0.887, 0.828, 0.849, 0.848, 0.794, 0.865; and the power of exclusion of them being 0.602, 0.441, 0.544, 0.325, 0.227, 0.386. Evaluated by comparison with the data from 14 different animals as controls, the 6 STR loci contain good specificity of human beings. The 6 STR loci are highly polymorphic and can play a key role in species identification. They are new candidate markers for forensic personal identification and paternity testing.


Pharmacokinetics and pharmacodynamics of mitragynine, the principle alkaloid of Mitragyna speciosa: present knowledge and future directions in perspective of pain.
Mitragyna speciosa, commonly known as Ketum or Biak in Malaysia and Kratom in Thailand, is a native plant to Southeast Asia and has various pharmacological benefits. Mitragynine (MG) is the principal alkaloid found in the leaves of Mitragyna speciosa and has been reported to be responsible for the plant's therapeutic actions. Traditionally, local communities use Kratom preparations for relief from different types of pain. The potential analgesic effects of MG using rodent models have been reported in literatures. We have reviewed the published analgesic and pharmacokinetic studies and all of these findings showed the routes of drug administration, doses employed, and type of vehicles used to solubilize the drug, varied considerably; hence this posted difficulties in predicting the drug's pharmacokinetic-response relationship. A rational approach is warranted for accurate prediction of dose-response relationship; as this is essential for the development of MG as an alternative medicinal drug for pain management. PKPD modeling would serve as a better method to understand the dose-response relationship in future MG preclinical and clinical studies.


Characterization of edible seaweed harvested on the Galician coast (northwestern Spain) using pattern recognition techniques and major and trace element data.
Major and trace elements in North Atlantic seaweed originating from Galicia (northwestern Spain) were determined by using inductively coupled plasma-optical emission spectrometry (ICP-OES) (Ba, Ca, Cu, K, Mg, Mn, Na, Sr, and Zn), inductively coupled plasma-mass spectrometry (ICP-MS) (Br and I) and hydride generation-atomic fluorescence spectrometry (HG-AFS) (As). Pattern recognition techniques were then used to classify the edible seaweed according to their type (red, brown, and green seaweed) and also their variety (Wakame, Fucus, Sea Spaghetti, Kombu, Dulse, Nori, and Sea Lettuce). Principal component analysis (PCA) and cluster analysis (CA) were used as exploratory techniques, and linear discriminant analysis (LDA) and soft independent modeling of class analogy (SIMCA) were used as classification procedures. In total, t12 elements were determined in a range of 35 edible seaweed samples (20 brown seaweed, 10 red seaweed, 4 green seaweed, and 1 canned seaweed). Natural groupings of the samples (brown, red, and green types) were observed using PCA and CA (squared Euclidean distance between objects and Ward method as clustering procedure). The application of LDA gave correct assignation percentages of 100% for brown, red, and green types at a significance level of 5%. However, a satisfactory classification (recognition and prediction) using SIMCA was obtained only for red seaweed (100% of cases correctly classified), whereas percentages of 89 and 80% were obtained for brown seaweed for recognition (training set) and prediction (testing set), respectively.


[24-hour pH monitoring of the hypopharynx in 545 patients with special regard to a critical data evaluation].
Although a number of reports exist on 24-hour pH monitoring of the hypopharynx, no consensus has been reached about evaluation standards. In particular the influence of food and beverages is still different estimated. The parameters which are used to analyze the data of pharyngeal pH monitoring are not consistent. 545 patients underwent esophagopharyngeal 24-hour pH monitoring in the Department of Otorhinolaryngology at the University of Rostock from February 1996 to December 2003. A score was calculated by excluding technical artefacts and pH drop caused by ingestion. Pharyngeal acid exposure was detected in 228 patients. The values of the reflux score ranged between 0 - 62,4 with a median value of zero. The left skewed score distribution shows a high abundance of patients with a minimum score and a limited amount of patients with high score values. The results were compared to reports of other authors. Evaluation standards are necessary for a reproducible analysis of pharyngeal pH monitoring data and for the comparison of different reports. A qualified score for the analysis and the comparison of pharyngeal pH monitoring data is suggested.


Transformation by design: nursing workforce innovation and reduction strategies in turbulent times of change.
The evolution of care delivery from an acute care and inpatient standard to the outpatient setting and health promotion model is generating the need for innovative workforce and infrastructure adjustments to meet the new paradigm of population health management. Successful transformation of the nursing workforce necessitates a positive style of thinking that addresses rational concerns during times of difficult transition. Nurse leaders are called to recognize and appreciate the strengths of the nursing workforce by involving them in the course of change through collaboration, planning, and discussion. One unique way to plan and develop new care delivery models is to adopt the framework used in health facility planning and design for new services, units, or hospitals. This framework is flexible and can be adjusted easily to meet the objectives of a small nursing workforce innovation project or expanded to encompass the needs of a large-scale hospital transformation. Structured questioning further helps the team to identify barriers to care and allows for the development of new concepts that are objective and in accord with evidence-based practice and data. This article explores the advantages and disadvantages of implementing innovative workforce redesign and workforce reduction strategies.


Mutation of CEP72 Gene May Predispose Patients to Hepatotoxicity.
Drug toxicities during treatment of acute lymphoblastic leukemia play a pivotal role in influencing the outcome as certain toxicities may impair treatment compliance. Polymorphisms in CEP72 have been linked to increased incidence of vincristine-induced toxicities, namely peripheral neuropathy. We hypothesize that polymorphisms in the same gene may increase a patient's risk of developing hepatotoxicity when receiving potentially hepatotoxic agents during chemotherapy. This report describes hepatotoxicity that first developed during consolidation in a patient homozygous for the CEP72 risk alleles. Bilirubin levels normalized following dose reduction of 6-mercaptopurine. The patient continues to tolerate maintenance therapy at a reduced dose of 6-mercaptopurine.


Head-neck rotational movements using DidRen laser test indicate children and seniors' lower performance.
Sensorimotor control strategies during cervical axial rotation movements have been previously explored in narrow age ranges but never concurrently in Children and Seniors during a well-standardized task. However, the lifespan developmental approach provides a framework for research in human sensorimotor control of the head-neck complex. A cross-sectional design was used to investigate the influence of age on head-neck dynamic performance adopted by asymptomatic Children, Adults and Seniors using a standardized task (DidRen Laser test). Participants performed 5 cycles of left/right head-neck complex fast rotational movements toward 3 targets with 30° of angular separation. Dynamic performances were computed from total execution time of the test and kinematic variables derived from rotational motion of head measured by an optoelectronic system. Eighty-one participants, aged 8-85 yrs, were stratified in four groups: Children, Younger adults, Older adults and Seniors. Children were significantly slower than Younger (p<0.001) and Older adults (p<0.004) and Seniors slower than Younger adults (p<0.017) to perform the test. Children adopted a lower average speed compared to Younger (p<0.001) and Older adults (p<0.008). Children reached the peaks speed significantly later than Younger (p<0.004) and Older adults (p<0.04) and acceleration significantly later than Younger (p<0.001) and Older adults (p<0.013). From the peak acceleration, Children reached end of the cycle significantly slower than Younger (p<0.008) and Older adults (p<0.008). Children significantly differed from all other groups for rotational kinetic energy, with smaller values compared to Younger adults (p<0.001), Older adults (p<0.005) and Seniors (p<0.012). Variability was also significantly higher for Seniors and Children. In conclusion, age influences head-neck visually elicited rotational dynamics, especially in Children. These results suggest that age should be taken into account when establishing normative data and assessing dynamic head-neck sensorimotor control of patients with neck pain.


Probing single-tumor cell interactions with different-age type I collagen networks by synchrotron-based Fourier transform infrared microspectroscopy.
We report here on a first study using synchrotron radiation-based Fourier transform infrared microspectroscopy and imaging to investigate HT1080 human fibrosarcoma cells grown onto different-aged type I collagen networks. Spectral images were analyzed with k-means and fuzzy C-means (FCM) clustering algorithms. K-means delineated tumor cells from their surrounding collagen networks and the latter as a function of age mainly due to specific changes in the sugar absorption region. The FCM analysis gave a better nuance of the spectral images. A progression of the biochemical information was observed upon going from the cellular compartments to the pericellular contact regions and to the intact collagens of the different age groups. Two spectral markers based on sugar and protein bands via the intensity ratio (I1032/I1655) and band area ratio (Asugar/Aamide II), showed an increase in advanced glycation endproducts (AGEs) with age. A clear-separation of the three age groups was obtained for spectra originating from the peripheral contact areas mainly due to changes in protein band intensities. The above-described markers decreased to constant levels for the three conditions indicating a masking of the biochemical information. These results hold promises to better understand the impact of age on tumor progression processes while highlighting new markers of the tumor cell invasion front.


Structure and function of the proline-rich region of myelin basic protein.
Myelin basic protein (MBP)--the major extrinsic membrane protein of central nervous system myelin--from several species contains a rarely encountered highly conserved triproline segment as residues 99-101 of its 170-residue sequence. Cis peptide bonds are known to arise at X-Pro junctions in proteins and may be of functional significance in protein folding, chain reversal, and/or maintenance of tertiary structure. We have examined the conformation of this proline-rich region using principally 13C nuclear magnetic resonance spectroscopy (125 MHz) both in intact bovine MBP and in several MBP fragment peptides which we synthesized, including octapeptide 97-104 (Arg-Thr-Pro-Pro-Pro-Ser-Gln-Gly). Results suggested an all-trans conformation in aqueous solution for the triproline segment in MBP hexapeptide (99-104), heptapeptide (98-104), and octapeptide. Comparison with the 13C spectrum of intact MBP (125 MHz) suggested that the proline-rich region, as well as all other X-Pro MBP peptide junctures, was also essentially all trans in aqueous solution. Although experiments in which octapeptide 97-104 was bound to a lipid preparation (4:1 dipalmitoylphosphatidylcholine/dimyristoylphosphatidic acid) demonstrated that cis-proline bonds do arise (to the extent of ca. 5%) in the membrane environment, a role of linear chain propagation is suggested for the triproline segment of myelin basic protein.


Dengue Virus Exposures Among Deployed U.S. Military Personnel.
AbstractDengue virus infections have adversely impacted U.S. military operations since the Spanish-American War. The erosion of mission capabilities and lost duty days are underestimated. Appreciating the incidence and prevalence of dengue infections in U.S. military personnel is important to inform disease prevention strategies. Banked pre- and post-deployment serum samples from 1,000 U.S. military personnel with a single deployment to a dengue-endemic region were tested using a screening microneutralization assay to detect anti-dengue-virus-neutralizing antibodies. A total of 76 (7.6%) post-deployment samples were positive and 15 of the pre-deployment samples were negative. These figures represent an infection incidence of 1.5% and total of 17.6 seroconversions per 10,000 deployment months. These data represent a deploying military population with a relatively high background rate of dengue seropositivity, a low level of infection during deployment compared with background infection rates in the local populations, and the potential for worsening clinical attack rates with increased frequency of deployment. Additional studies are required to more clearly elucidate the dengue infection and disease risk in U.S. military personnel.


[Analysis of liver pathological characteristics and exploration of noninvasive markers of liver fibrosis in children with chronic hepatitis B].
Objective: To analyze and summarize the characteristics of liver pathology and their relation to clinical markers and further explore noninvasive markers of liver fibrosis in children with chronic hepatitis B. Methods: Data of 80 hospitalized children with chronic hepatitis B who underwent liver biopsy without antiviral treatment from 2011 to 2020 were retrospectively analyzed. Inflammation and liver fibrosis characteristics were analyzed in children of different ages and genders. Variables with good correlation with liver fibrosis stage were selected to establish a non-invasive diagnostic score of liver fibrosis in children. Measurement data was used to compare the t-test or rank sum test. Mantel-Haenszel χ (2) test was used for bidirectional ordered grouping data. Spearman's rank correlation test was used for rank correlation analysis. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of the newly established diagnostic score in children with liver fibrosis. Results: The median age of the children was 6.4 years. HBV DNA level was high (P50 = 7.6 log(10) IU/ml), and serum alanine aminotransferase (ALT) in P50 was 171 U/L (< ULN: 5 cases, ULN-2ULN: 10 cases, > 2 ULN: 65 cases). Pathological analysis showed that the incidence of liver tissue inflammation was 97.5%, and the proportion of patients with G≥2 was 42.5%, while S≥2 was 36.3%. The incidence rate of liver fibrosis and liver cirrhosis was 81.3%, and 1.3%, respectively. The changes in liver tissue inflammation and fibrosis were gradually aggravated with the increase of age, and the proportion of high-grade inflammation and liver fibrosis in male children was higher than that in female children. Serum levels of glutamyl transpeptidase (GGT), γ-glutamyltransferase/platelet ratio (GPR) and HBeAg had a good correlation with fibrosis stage (r(s) = 0.397, 0.389, and - 0.311) in children with chronic hepatitis B. The combination of GGT, GPR and HBeAg can establish a non-invasive diagnostic score for evaluating liver fibrosis in children. When the score is less than 1.5, it can be diagnosed as S0, and 1.5 ≤ score < 3.5, it can be diagnosed as S1; 3.5 ≤ score < 5.5, the diagnosis of fibrosis is S2; score≥ 5.5, the diagnosis of fibrosis is S≥3. The sensitivity and specificity were 80%, 83%, 86%, and 53%, 55%, 67%, respectively. Conclusion: The incidence of liver tissue inflammation in children with chronic hepatitis B with elevated and fluctuating transaminase levels is high, and the pathological changes of liver tissue aggravate with the age of the children. GGT, GPR and HBeAg have a good correlation with liver fibrosis in children with chronic hepatitis B. Therefore, combining the above-mentioned markers to establish a new noninvasive diagnostic score has certain diagnostic value for liver fibrosis stage S0-S3 in children with chronic hepatitis B.


Assessing the Quality of Online Patient Decision Aids for Urological Conditions.
A growing number of patients use online patient decision aids (PtDAs) due to their easy accessibility. However, PtDAs found on the internet are not regulated and vary in quality and readability. The aim of this study is to assess urological PtDAs for their readability, quality as consumer health information and quality as decision aid. Searches were conducted on Google, PubMed®, Embase® and decision aid repositories for patient decision aids on pelvic organ prolapse, urinary incontinence, benign prostatic hyperplasia and overactive bladder. The decision aids were screened for relevance and patient directed nature. They were then evaluated using 4 readability formulas, the validated DISCERN quality criteria and the International Patient Decision Aids Standards v4.0 minimum standards criteria. Our search revealed 23 patient decision aids, of which 14 were ultimately included for analysis. The mean grade level readability score calculated by the 4 readability formulas was 11, far exceeding the 6th grade reading level recommended by the National Institutes of Health. The average DISCERN score was 57.6 (SD 6.7), which indicates "good" quality as online health information. The average International Patient Decision Aids Standards v4.0 minimum standards criteria score was 8.3 (SD 1.5), with none meeting all 12 minimum requirements of a patient decision aid. Online patient decision aids for pelvic organ prolapse, urinary incontinence, benign prostatic hyperplasia and overactive bladder require a higher reading level than recommended by the National Institutes of Health. While decision aids are acceptable as online health information, none meets all 12 international standards for patient decision aids.


Glaucomatous neurodegeneration and the concept of neuroprotection.
Glaucomatous neurodegeneration is a progressive pathological affair morphologically characterized by RGC death resulting in functional visual deterioration. Although a variety of primary insults ranging from mechanical trauma to ischemia to genetic susceptibility can initiate disease onset, apparently loss of trophic support and excitotoxin release remain the common themes responsible for neuronal damage and eventual cell death by apoptosis. The spread of this damage is perpetuated by secondary degeneration that allows directly injured neurons to release noxious and degenerative substances into the surrounding cells. Neuroprotection is a collective therapeutic approach the aim of which is to provide resilience to such neurons in an effort to prevent or delay progressive neuronal degeneration. At present, definitive neuroprotective therapy remains unachieved despite a variety of approaches having been defined and intensely pursued. However, the evolution in our understanding of glaucoma continues to offer reason for optimism. To this end, we remain unreservedly hopeful in the labor and committed work of dedicated investigators. We are all indebted to them.


Fluorescent immunohistochemistry and in situ hybridization analysis of mouse pancreas using low-power antigen-retrieval technique.
To facilitate the immunological reaction of antibodies with antigens in fixed tissues, it is necessary to unmask or retrieve the antigens through pretreatment of the specimens. However, adjustment of heating-induced antigen retrieval is always required for different tissues and antigens. In this study, by using a low-power antigen-retrieval technique with appropriate dilution of antibodies, we successfully immunostained key antigens in pancreas such as insulin, PDX-1, glucagon, cytokeratin, and CD31, which have previously presented a particular challenge for investigators because of the rapid autodigestion and high nonspecific antibody binding in this tissue. Satisfactory results were obtained when immunohistochemistry and fluorescence in situ hybridization analysis were combined in the same slides.


Rating Pregnancy Wheel Applications Using the APPLICATIONS Scoring System.
To identify the top-rated pregnancy wheel applications (apps) using a newly developed APPLICATIONS scoring system. A list of pregnancy wheel apps was identified. Consumer-based and inaccurate apps were excluded. The APPLICATIONS scoring system was developed to rate the remaining apps. Application comprehensiveness was evaluated. Objective rating components included price, paid subscription, literature used, in-app purchases, connectivity to the Internet, advertisements, text search field, interdevice compatibility, and other components such as images or figures, videos, and special features. Subjective rating components were ease of navigation and subjective presentation. A complete list of 55 pregnancy wheel apps was created from three sources. Thirty-nine (71%) were consumer-based, inaccurate, or both, leaving 16 (29%) for analysis using the APPLICATIONS scoring system. More than two thirds of pregnancy wheel apps were excluded from our study secondary to being consumer-based, inaccurate, or both. This highlights the importance of identifying systematically, reviewing critically, and rating the thousands of available apps to health care providers to ensure accuracy and applicability. We propose that our APPLICATIONS scoring system be used to rate apps in all specialties with the goal of improving health care provider performance and thereby patient outcomes. III.


A case of sporadic ovine mastitis caused by Listeria monocytogenes and its effect on contamination of raw milk and raw-milk cheeses produced in the on-farm dairy.
We describe a case of listerial mastitis in a flock of 130 sheep. The animals were housed at a farm where the bulk raw ewe milk was processed to produce raw milk soft cheese. List. monocytogenes was shed from the right mammary complex. Shedding was observed over a period of 99 d. A mean level of 4-56 x 10(4) cfu (colony forming units) Listeria monocytogenes/ml was recovered from the raw milk originating from the infected udder. The numbers ranged from 9 x10(1) to 2.95 x 10(5). The bulk milk was contaminated by approx. 5.7 x 10(3) cfu/ml. In the cheese product, 2.0 x 10(2) cfu List. monocytogenes/g were constantly detectable for a period of 7 d post manufacture. The starter culture used for coagulation had a pivotal influence on the behaviour of List. monocytogenes during cheesemaking. Using the same mesophilic buttermilk culture as used by the farmer allowed numbers of Listeria to increase 60-fold within 12 h owing to a delayed acidification of the bulk milk. Addition of a thermophilic yogurt culture reduced the numbers of Listeria within 8 h of incubation.


Wireless Sensor Network Congestion Control Based on Standard Particle Swarm Optimization and Single Neuron PID.
Aiming at the problem of network congestion caused by the large number of data transmissions in wireless routing nodes of wireless sensor network (WSN), this paper puts forward an algorithm based on standard particle swarm⁻neural PID congestion control (PNPID). Firstly, PID control theory was applied to the queue management of wireless sensor nodes. Then, the self-learning and self-organizing ability of neurons was used to achieve online adjustment of weights to adjust the proportion, integral and differential parameters of the PID controller. Finally, the standard particle swarm optimization to neural PID (NPID) algorithm of initial values of proportion, integral and differential parameters and neuron learning rates were used for online optimization. This paper describes experiments and simulations which show that the PNPID algorithm effectively stabilized queue length near the expected value. At the same time, network performance, such as throughput and packet loss rate, was greatly improved, which alleviated network congestion and improved network QoS.


[Effect of hemoglobin N Baltimore on HbA1c measurement in six methods].
The presence of hemoglobin variants can adversely affect the accuracy of some HbA1c methods depending on the variant. We examine the analytical interference from a rare Hb variant (Hb N Baltimore) with six different HbA1c methods using various method principles: two immunoassays methods (Tina-quant® HbA1c Gen et DCA Vantage), three high-performance liquid chromatography methods (G8 HPLC, Variant II Turbo A1c 2.0 et Variant II Dual kit), and one capillary-electrophoresis method (Capillarys Hb A1c kit). Hb N Baltimore can adversely affect determination of HbA1c levels. An underestimation of HbA1c level is observed with the chromatographic methods included in this study and no HbA1c result can be obtained with the capillary-electrophoresis method. Inversely, limited impact is observed with the immunoassays methods. The presence of an hemoglobin variant should be suspected when inconsistencies are observed between a patient's home blood glucose monitoring and laboratory-measured HbA1c. In these situations additional testing should be carried out using a test based on a different analytical method.


Attenuation of hemodynamic responses to rapid sequence induction and intubation in healthy patients with a single bolus of esmolol.
The effectiveness of a single preinduction intravenous (IV) bolus of esmolol in blunting hemodynamic responses to rapid sequence induction and tracheal intubation was evaluated. In a randomized double-blind study, 32 ASA I and II healthy patients scheduled for surgery were monitored with electrocardiography (EKG) lead V5, arterial cannulation, and impedance cardiography. After preoxygenation and a priming dose of vecuronium (0.01 mg/kg), patients received either saline (n = 12), esmolol 100 mg (n = 10), or esmolol 200 mg (n = 10) as an IV bolus (20 ml volume). This procedure was immediately followed by a 5 ml IV saline flush, cricoid pressure, thiopental sodium 5 mg/kg, and succinylcholine 1.5 mg/kg. Patients receiving 200 mg of esmolol had a 50% reduction in the usual tachycardia associated with induction and a greater decline in systolic blood pressure (SP) (by 50%) prior to intubation as compared with the placebo group (p less than 0.05). The increase in diastolic blood pressure (DP) and the reduction in stroke volume (SV) produced by induction and intubation were similar in all the groups. Plasma norepinephrine levels at 1.5 minutes after intubation increased in the esmolol groups about 130% above that measured in the placebo group. This finding was associated with a more gradual return of peripheral resistance to baseline following tracheal intubation. However, both doses of esmolol effectively attenuated heart rate (HR), SP, and rate pressure product (RPP) increases (p less than 0.05 vs placebo) produced by laryngoscopy and tracheal intubation.


A simple technique for removing a locking compression plate with a stripped locking screw.
We use a straightforward technique to remove a locking compression plate and a screw with a stripped hexagonal recess. If the hexagonal recess of the screw had been stripped during attempts at screw removal using a conical extraction device, we perform the following procedure after loosening the contact surface between the bone and the plate. Using a larger drill bit, another hole is drilled immediately adjacent to the screw through the nonlocking portion of the combination hole. The plate is struck along the line connecting the screw to the newly formed hole. Using an elevator, leverage force is then applied to the plate, which can be removed with the stripped screw attached. This technique can be used to remove plates with several stripped screws and does not require any special tools.


The necessity to develop drugs against parasitic diseases.
This review focuses on the most significant trends in the development of drugs for the treatment of malaria, African sleeping sickness and toxoplasmosis. In the case of malaria, those include new fixed-dose artemisinin combinations, antifolates and new targets in the apicoplast of Plasmodium falciparum. Targets in the treatment of trypanosomiasis are the biosynthesis of glycosylphosphatidylinositol and enzymes involved in the biosynthesis of trypanothione. Efforts to develop a vaccine against toxoplasmosis are discussed as well.


[Neurological or psychiatric symptoms in patients with systemic lupus erythematosus (SLE): terminological problems, pathogenesis, diagnosis and therapy].
The nomenclature of the American College of Rheumatology leads to misunderstandings in multidisciplinary discussions on patients with systemic lupus erythematosus (SLE) who also have neurological or psychiatric symptoms. These proposed neuropsychiatric syndromes are rarely syndromes and the symptoms are rarely neuropsychiatric. It is better first of all to determine whether the SLE patients have neurological or psychiatric symptoms, and if these symptoms are present, the first question is what is the cause. Vasculitis of the cerebral blood vessels should be considered as a possible explanation only if ischaemic lesions in the brain have been demonstrated, other causes of cerebral ischaemia in SLE are unlikely, and the clinical signs are consistent with cerebral vasculitis. These other causes of cerebral ischaemia include: antiphospholipid antibodies, atherosclerosis, heart valve disorders and thrombotic thrombocytopenic purpura.


The effects of arginine vasopressin and epinephrine on lung liquid production in fetal goats.
The effects of arginine vasopressin (AVP) and epinephrine on lung liquid secretion were investigated in 67 acute fetal goats (116 days of gestation to term) with intact umbilical cords after caesarean section. Secretion was measured by an impermeant tracer technique. AVP was infused intravenously (1.6-39.2 mU/(kg.min); 2 h) into 26 fetuses. All fetuses below 130 days of gestation, except one, showed no response. All above 133 days reduced secretion, or turned to reabsorption, except at the lowest infusion rate. The effect persisted, and usually increased postinfusion. Expansion of the lungs with saline did not change the response. The percentage reductions were linearly related to the logarithm of the infusion rate (threshold, 1.42 mU/(kg.min]. The absolute reductions were linearly related to fetal weight. Epinephrine was infused intravenously (0.30-6.72 micrograms/(kg.min); 1-2 h) into 12 fetuses. All fetuses (118 days to term) reduced secretion or reabsorbed by the second hour. At the highest infusion rate, reabsorption was immediate; at the lowest, secretion increased slightly, then fell significantly in the second hour. Epinephrine acted at levels considered physiological at delivery in the sheep. AVP appears to act at plasma levels found in most vaginal deliveries; it may augment epinephrine-induced reabsorption during stress, and help long-term removal of lung fluid.


A hierarchical approach for speech-instrumental-song classification.
Audio classification acts as the fundamental step for lots of applications like content based audio retrieval and audio indexing. In this work, we have presented a novel scheme for classifying audio signal into three categories namely, speech, music without voice (instrumental) and music with voice (song). A hierarchical approach has been adopted to classify the signals. At the first stage, signals are categorized as speech and music using audio texture derived from simple features like ZCR and STE. Proposed audio texture captures contextual information and summarizes the frame level features. At the second stage, music is further classified as instrumental/song based on Mel frequency cepstral co-efficient (MFCC). A classifier based on Random Sample and Consensus (RANSAC), capable of handling wide variety of data has been utilized. Experimental result indicates the effectiveness of the proposed scheme.


Enteral nutrient deprivation in patients leads to a loss of intestinal epithelial barrier function.
To investigate the effect of nutrient withdrawal on human intestinal epithelial barrier function (EBF). We hypothesized that unfed mucosa results in decreased EBF. This was tested in a series of surgical small intestinal resection specimens. Small bowel specifically excluding inflamed tissue, was obtained from pediatric patients (aged 2 days to 19 years) undergoing intestinal resection. EBF was assessed in Ussing chambers for transepithelial resistance (TER) and passage of fluorescein isothiocyanate (FITC)-dextran (4 kD). Tight junction and adherence junction proteins were imaged with immunofluorescence staining. Expression of Toll-like receptors (TLR) and inflammatory cytokines were measured in loop ileostomy takedowns in a second group of patients. Because TER increased with patient age (P < .01), results were stratified into infant versus teenage groups. Fed bowel had significantly greater TER versus unfed bowel (P < .05) in both age populations. Loss of EBF was also observed by an increase in FITC-dextran permeation in enteral nutrient-deprived segments (P < .05). Immunofluorescence staining showed marked declines in intensity of ZO-1, occludin, E-cadherin, and claudin-4 in unfed intestinal segments, as well as a loss of structural formation of tight junctions. Analysis of cytokine and TLR expression showed significant increases in tumor necrosis factor (TNF)-α and TLR4 in unfed segments of bowel compared with fed segments from the same individual. EBF declined in unfed segments of human small bowel. This work represents the first direct examination of EBF from small bowel derived from nutrient-deprived humans and may explain the increased incidence of infectious complications seen in patients not receiving enteral feeds.


Thymectomy in severe (Myasthenia Gravis Foundation of America classes IV-V) generalized myasthenia gravis: is the game really worth the candle?
Total thymectomy in addition to medical treatment is an accepted standard therapy for myasthenia gravis (MG). Patients with severe generalized MG present life-threatening events, poor prognosis and higher risk of postoperative myasthenic crisis. The aim of our study is to investigate neurological and surgical results in patients with Myasthenia Gravis Foundation of America (MGFA) class IV and V MG following thymectomy. Data on 76 MG patients with preoperative MGFA classes IV and V who underwent thymectomy were retrospectively collected. Primary end points included short-term surgical outcomes and long-term neurological results including the achievement of complete stable remission and any improvement as defined by MGFA Post-Intervention Status criteria. There were 27 (35.5%) males and 49 (64.5%) females; 53 (69.7%) were classified as MGFA class IV and 23 (30.3%) as class V. Thymectomy was performed through sternotomy in 25 (32.9%) patients, Video-assisted thoracic surgery (VATS) in 5 (6.6%) and Robot-assisted thoracic surgery (RATS) in 46 (60.5%). The median operative time was 120 (interquartile range: 95; 148) min. In-hospital mortality was observed in 1 (1.3%) patient and postoperative complications in 14 (18.4%) patients. The median postoperative hospital stay was 4 (interquartile range: 3; 6) days. Pathological examination revealed 31 (40.8%) thymic hyperplasia/other benign and 45 (59.2%) thymomas. Cumulative complete stable remission and improvement probabilities were 20.6% and 83.7% at 5 years and 66.9% and 97.6% at 10 years, respectively. A significant improvement rate was found in patients with age at the time of thymectomy of ≤50 years (P = 0.0236), MGFA class V (P = 0.0154) and acetylcholine receptor antibodies positivity (P = 0.0152). Thymectomy in patients with severe MG yields good perioperative outcomes and satisfactory long-term neurological improvement, especially for patients younger than 50 years, with MGFA class V and anti-AChR+ MG.


[Experimental evaluation of two-sided velour vascular prostheses of Polish production].
The experiments were performed on nine mongrel dogs. The authors used straight crenated grafts of diameters 6 and 12 mm. In 6 dogs were implanted into abdominal aorta below an origin of renal arteries and above its bifurcation. Autopsy was performed after 49, 62, 98 days. The authors evaluated the implant examining it with two methods: macroscopic and histopathologic. In addition were 6 experiments made with three dogs. The grafts were placed extracorporealy between canulated artery and femoral vein. The authors measured the volume of transudated blood, the time of transudation and degree of grafts flexibility marked by the alongation. In was stated that tested double veloured grafts of Polish production are softer and more flexible than those produced so far. The edges of the tested grafts have higher shred resistance during the sewing procedure. Their more regular texture results in smaller degree of transudation: after initial typical preclotting the grafts "sweat" evenly and quickly stops the transudation. In authors opinion the grafts should be clinically evaluated in treatment of peripheral blood vessels diseases.


Ketamine-assisted meaning-centered psychotherapy for a patient with severe suicidal behavior.
There is a current debate in society as to whether depression can be a terminal illness. Meaning-centered psychotherapy (MCP) and psychedelic medicines have both been shown to treat existential distress in palliative care settings. We are reporting the case of a patient for whom MCP combined with ketamine was an effective treatment for his recurrent and severe depressive disorder with suicidal ideation. His complex assessment and management of suicide (CAMS) scores improved significantly with this treatment modality. Ketamine is generally well tolerated and can enhance treatment outcomes in patients undergoing MCP.


[Brain stem auditory evoked potentials in "alcoholic epilepsy"].
BAEPs were studied in a group of subjects suffering from 'alcoholic epilepsy.' Results were then compared with data from normal subjects and chronic alcoholics without epilepsy. The latency for peak V and the inter-peak latencies (I-III, III-V, I-V) were significantly longer in the 'alcoholic epilepsy' group than in the control group. This increase of neural transmission time in the brain-stem auditory pathways was less important in the 'chronic alcoholics without epilepsy' group than in the alcoholic epilepsy group.


Rapid specific detection and quantification of bacteria and archaea involved in mineral sulfide bioleaching using real-time PCR.
A SybrGreen real-time PCR assay was developed to detect and quantify both total and selected 16S rDNA species of bacteria and archaea involved in the bioleaching of metals from sulfide ores. A set of specific and universal primers based on 16S rDNA sequences was designed and validated for specific detection and quantification of DNA isolated from representative strains of Acidianus brierleyi, Sulfolobus sp., Sulfobacillus thermosulfidooxidans, Sulfobacillus acidophilus, Acidithiobacillus caldus, and Leptospirillum ferrooxidans. An artificial sequence based on 16S rDNA was constructed to quantify total 16S rDNA in mixed DNA samples. The real-time PCR assay was further validated using a mixture of 16S rDNA amplicons derived from the six different species, each added at a known amount. Finally, the real-time PCR assay was used to monitor the change of 16S rDNA copies of four bioleaching strains inoculated into chalcopyrite airlift column reactors operated at different temperatures. The growth dynamics of these strains correlated well with the expected effects of temperature in the chalcopyrite-leaching environment. The suitability of this method for monitoring microbial populations in industrial bioleaching environments is discussed.


[Epidemiological characteristics of COVID-19 in Wuchang district of Wuhan].
Objective: To analyzes epidemiological characteristics of COVID-19 and provide evidence for adjustment for COVID-19 prevention and control strategies. Methods: The data of COVID-19 cases in Wuchang district reported as of 19 March, 2020 were obtained from National Notifiable Disease Report System of Chinese Disease Prevention and Control Information System. The software's of Excel 2010, SPSSS 22.0, Arc GIS10.2 and Joinpoint regression program 184.108.40.206 were used for statistical analysis. Results: A total of 7547 COVID-19 cases had been reported as of 19 March, 2020 in Wuchang district, including 5 448 confirmed cases (72.19%), 2009 clinical diagnosed cases (26.62%) and 90 asymptomatic cases case (1.19%). The age of the cases was (56.65±16.25) years and age ranged from 2 days to 105 years among confirmed cases, 2634 were males (48.35%) and 2814 were females (51.65%), 2 492 were retirees (45.74%). A total of 545 health workers were infected with SARS-CoV-2 (7.22% of all cases) including 365 confirmed cases and 5 cases have died. A total of 430 cases of death were reported with case fatality rate of 7.89% (430/5 448), case fatality rate of males (10.9%, 266/2 634) was higher than that of females (5.82%, 164/2 814). The first phase of epidemic peak was from January 24 to January 26, the second phase of epidemic peak was from February 1 to February 5 and there was no one of new confirmed case in one day for the first time on March 18. The first four Streets with the highest incidence rates of confirmed cases were Huanghelou Street (1 043.77/100 000), Ziyang Street (627.97/100 000), Yangyuan Street (503.67/100 000) and Shuiguohu Street (486.02/100 000). Compared with females, aged ≤50 years and mild cases of clinical classification respectively, males (RR=0.690, 95%CI: 0.322-1.478), aged >50 years (RR=11.745, 95%CI: 6.878-20.058), severe cases (RR=2.317, 95%CI: 1.789-3.000) and critical cases of clinical classification (RR=10.794, 95%CI: 7.997-14.569), and gender time-dependent covariate (RR=1.392, 95%CI: 1.053-1.840) were major influencing factors of prognosis of COVID-19 confirmed cases. Conclusions: The gender, ages and occupation of distribution were wide among COVID-19 cases in Wuchang district. Males, aged >50 years, severe cases and critical cases of clinical classification were influencing factors of prognosis of COVID-19 confirmed cases. The standardized management of discharged cases, asymptomatic infected cases and close contact persons were main measures to reduce incidence rates of COVID-19 cases.


[Results valuation of adhesive bridges--3-year study].
139 of 169 adhesive-bridges, incorporated from 1984 bis 1987, were reexaminated in 1988. The failure rate was 37.5% with a mean functional period of 27.3 months. The patients were in average 40.5 years old. Rate of success is discribed depending on the localization and pillar-link-relation. The peaks of loss were after 300 and 900 days incorporation period. Conclusions for indication, prognosis and methodical references are given.


Thromboprophylaxis in orthopedic surgery: how long is long enough?
Pharmacologic thromboprophylaxis with low-molecular-weight heparins, vitamin K antagonists, or fondaparinux is well tolerated and effective in preventing venous thromboembolism (VTE) in major orthopedic surgery but is often limited to in-hospital use. However, 45% to 80% of all symptomatic VTE events occur after hospital discharge. Extended-duration VTE prophylaxis for 28 to 35 days reduces risk for late VTE by up to 70%. In this article, I review the evidence supporting guideline recommendations regarding extended-duration prophylaxis after major orthopedic surgery and provide an overview of current and emerging literature regarding prevention of postoperative VTE in patients undergoing this surgery.


Factors associated with outcome and duration of therapy in outpatient parenteral antibiotic therapy (OPAT) patients with skin and soft-tissue infections.
This study was designed to identify factors associated with adverse outcomes and increased duration of parenteral therapy in patients with skin and soft-tissue infections (SSTIs) managed with outpatient parenteral antibiotic therapy (OPAT). A retrospective cohort study interrogating variables recorded prospectively in an electronic OPAT patient database was performed. 'OPAT failure' was defined as hospitalisation following initiation of OPAT, or adverse event or progression of infection necessitating a change in antibiotic therapy. Variables associated with failure or increased duration of therapy were identified via univariate and multiple logistic regression analyses. In total, 963 first patient episodes of OPAT-treated SSTIs were observed; 84% were treated with daily ceftriaxone and 15% with teicoplanin (three daily loading doses then three times per week). Progression of infection was observed in 2.8% of cases, inpatient management was required in 6% and significant adverse events occurred in 7.1%. Overall OPAT success was 87.1%. Female sex, diabetes and treatment with teicoplanin were independently associated with OPAT failure. A significant reduction in duration of OPAT therapy was observed over time. A longer duration of intravenous therapy was associated with meticillin-resistant Staphylococcus aureus (MRSA), older age, vascular disease, a diagnosis of bursitis, and treatment with teicoplanin. Non-inpatient referrals, management via a nurse-led patient group direction, and treatment with ceftriaxone were associated with reduced duration of OPAT. For selected patients with SSTIs, OPAT was generally safe and effective, but specific patient groups were identified with more complex management pathways and poorer outcomes.


Sleep apnoea syndrome and early stage cirrhosis: a pilot study.
Hepatic encephalopathy in patients with end-stage liver cirrhosis is associated with alterations in sleep patterns. Cirrhosis may also affect pulmonary function and it might be involved in the development of obstructive sleep apnoea syndrome (OSAS) in patients with ascites. We carried out a study to evaluate the presence of OSAS in cirrhotic patients without evidence of ascites (early stage cirrhosis). We investigated 20 patients with Child A or B cirrhosis (19 and one, respectively) and 10 non-cirrhotic patients with chronic viral hepatitis (disease control group). All subjects were interviewed and underwent a thorough physical examination, a full polysomnographic study and a pulmonary function testing by spirometry. Serum samples were also obtained in order to determine the liver function tests. The presence of OSAS and inverted sleep patterns was similar in cirrhotic patients and disease controls. However, significant correlations were revealed between age and hypopnoeas per hour of sleep; age and the Apneas/Hypopneas Index (AHI); age and FEV1/FVC; gamma-glutamyl transpeptidase and FEV1/FVC; and total bilirubin and total sleep time. Early stage cirrhosis is not associated with sleep disorders and OSAS. However, total bilirubin levels might be a useful laboratory marker for early assessment of disturbance in sleep patterns and therefore of subclinical hepatic encephalopathy in Child A cirrhosis.


The Implications of Regulatory Framework for Topical Semisolid Drug Products: From Critical Quality and Performance Attributes towards Establishing Bioequivalence.
Due to complex interdependent relationships affecting their microstructure, topical semisolid drug formulations face unique obstacles to the development of generics compared to other drug products. Traditionally, establishing bioequivalence is based on comparative clinical trials, which are expensive and often associated with high degrees of variability and low sensitivity in detecting formulation differences. To address this issue, leading regulatory agencies have aimed to advance guidelines relevant to topical generics, ultimately accepting different non-clinical, in vitro/in vivo surrogate methods for topical bioequivalence assessment. Unfortunately, according to both industry and academia stakeholders, these efforts are far from flawless, and often upsurge the potential for result variability and a number of other failure modes. This paper offers a comprehensive review of the literature focused on amending regulatory positions concerning the demonstration of (i) extended pharmaceutical equivalence and (ii) equivalence with respect to the efficacy of topical semisolids. The proposed corrective measures are disclosed and critically discussed, as they span from mere demands to widen the acceptance range (e.g., from ±10% to ±20%/±25% for rheology and in vitro release parameters highly prone to batch-to-batch variability) or reassess the optimal number of samples required to reach the desired statistical power, but also rely on specific data modeling or novel statistical approaches.


Bevacizumab for recurrent ependymoma.
Ependymoma is a rare type of glioma, representing 5% of all CNS malignancies. Radiotherapy (RT) is commonly administered, but there is no standard chemotherapy. At recurrence, ependymoma is notoriously refractory to therapy and the prognosis is poor. In recurrent glioblastoma, encouraging responses with bevacizumab have been observed. In this Institutional Review Board-approved study, we retrospectively analyzed the records of 8 adult patients treated for recurrent ependymoma and anaplastic ependymoma with bevacizumab containing chemotherapy regimens. We determined radiographic response (Macdonald criteria), median time to progression (TTP), and median overall survival (OS; Kaplan-Meier method). There were 4 men and 4 women with a median age of 40 years (range, 20-65). Prior treatment included surgery (n = 8), RT (8), temozolomide (5), and carboplatin (4). Bevacizumab (5-15 mg/kg every 2-3 weeks) was administered alone (2) or concurrently with cytotoxic chemotherapy including irinotecan (3), carboplatin (2), or temozolomide (1). Six patients achieved a partial response (75%) and 1 remained stable for over 8 months. Median TTP was 6.4 months (95% confidence interval 1.4-7.4) and median OS was 9.4 months (95% confidence interval 7.0-not reached), with a median follow-up of 5.2 months among 5 surviving patients (63%). The radiographic response rate to bevacizumab-containing regimens is high. A prospective study is warranted.


The role of aspirin resistance in the treatment of acute coronary syndromes.
The TIMI Risk Score recognizes prior aspirin use as an independent risk factor for adverse outcomes in subjects presenting with an acute coronary syndrome. The etiology of this increased risk awaits clarification, but prior aspirin use may be associated with altered thrombus composition which is more resistant to current treatment modalities as compared to thrombus formation in subjects without prior aspirin use. Post hoc analysis of acute coronary syndrome trials has shown that prior aspirin users treated with unfractionated heparin are at particularly high risk. The addition of glycoprotein IIb/IIIa receptor inhibitor to unfractionated heparin or substitution of low-molecular-weight heparin significantly improves outcomes in prior aspirin users. The prognostic significance of prior aspirin use in acute coronary syndromes has important implications not only in clinical practice, but also in the design and interpretation of clinical trials.