Kidney transplantation in highly sensitized recipients.
In kidney transplantation (KT), overcoming donor shortage is particularly challenging in patients with preexisting donor-specific antibodies (DSAs) against human leukocyte antigen (HLA), called HLA-incompatible KT (HLAi KT), carrying the risk of rejection and allograft loss. Thus, it is necessary to accurately evaluate the degree of sensitization before HLAi KT, and undertake appropriate pretreatment strategies. To determine the degree of sensitization, complement-dependent cytotoxicity has been the only method employed; the development of a method using flow cytometry further improved the test sensitivity. However, these tests present disadvantages, including the need for living cells, with a solid-phase assay developed to resolve this problem. Currently, the method using Luminex (Luminex Corp.) is widely used in clinical practice. As this method measures DSAs using single antigen beads, it is possible to classify immunological risks by measuring the type and amount of DSAs. Furthermore, there have been major advances in methods that involve DSA removal before HLAi KT. In the early stages of desensitization, plasmapheresis and intravenous immunoglobulins were the main treatment methods employed; however, the introduction of CD20 monoclonal antibody and proteasome inhibitors further increased the success rate of desensitization. Currently, HLAi KT has been established as an important transplant method, but an understanding of DSAs and a novel desensitization treatment are warranted.


Immune privilege extended to allogeneic tumor cells in the vitreous cavity.
Inoculation of alloantigenic P815 tumor cells into the vitreous cavity of eyes of BALB/c mice resulted in the intraocular development of progressively growing tumors. We observed by clinical and histologic examination that the tumors acquired a blood supply, lacked significant necrosis or degeneration, and gradually penetrated the globe into the orbit. Mice bearing these intraocular tumors did not develop tumor-specific delayed hypersensitivity (DH), and their spleens contained lymphocytes capable of suppressing tumor-specific DH when transferred adoptively into naive, syngeneic recipients. The authors conclude that the vitreous cavity (VC) is an immunologically privileged site for histoincompatible tumor cells and that the privilege is mediated by active suppression of DH, similar to anterior chamber (AC)-associated, immune deviation.


Rapid identification of filamentous actinomycetes to the genus level using genus-specific 16S rRNA gene restriction fragment patterns.
A rapid method for identifying filamentous actinomycete genera was developed based on 16S rRNA gene restriction fragment patterns. The patterns were generated by using specific restriction endonucleases to perform in silico digestions on the 16S rRNA gene sequences of all validly published filamentous actinomycete species. The method was applied to identifying actinomycete isolates from soil. Amplified 16S rDNA of soil actinomycetes was restricted with selected endonucleases and electrophoresed on agarose gels. The restriction fragment patterns of the unknown isolates were easily compared to the established patterns. Significantly, the genus Streptomyces could be differentiated from all other actinomycete genera by using only four restriction endonucleases, Sau3AI, AsnI, KpnI and SphI. This could be achieved in a time period of as little as a week, following PCR-template DNA isolation by a simple method. The identification method allowed unknown, non-Streptomyces soil isolates to be identified to a genus or small subgroup of genera. The genera in these subgroups could, in some cases, be distinguished by virtue of colony-morphology differences.


Comments on the New International Criteria for Electrocardiographic Interpretation in Athletes.
Sudden cardiac death is the most common medical cause of death during the practice of sports. Several structural and electrical cardiac conditions are associated with sudden cardiac death in athletes, most of them showing abnormal findings on resting electrocardiogram (ECG). However, because of the similarity between some ECG findings associated with physiological adaptations to exercise training and those of certain cardiac conditions, ECG interpretation in athletes is often challenging. Other factors related to ECG findings are race, age, sex, sports discipline, training intensity, and athletic background. Specific training and experience in ECG interpretation in athletes are therefore necessary. Since 2005, when the first recommendations of the European Society of Cardiology were published, growing scientific evidence has increased the specificity of ECG standards, thus lowering the false-positive rate while maintaining sensitivity. New international consensus guidelines have recently been published on ECG interpretation in athletes, which are the result of consensus among a group of experts in cardiology and sports medicine who gathered for the first time in February 2015 in Seattle, in the United States. The document is an important milestone because, in addition to updating the standards for ECG interpretation, it includes recommendations on appropriate assessment of athletes with abnormal ECG findings. The present article reports and discusses the most novel and relevant aspects of the new standards. Nevertheless, a complete reading of the original consensus document is highly recommended.


A pilot trial of deferiprone in pantothenate kinase-associated neurodegeneration patients.
Pantothenate kinase-associated neurodegeneration (PKAN) is the most common form of neurodegeneration with brain iron accumulation, it is an autosomal recessive disease due to mutation in PANK 2 on chromosome 20, which causes the accumulation of iron in basal ganglia and production of free radicals that cause degeneration of the cells. Deferiprone is an iron chelator that was used in treatment of thalassemia patients, it can cross the blood-brain barrier and reverse the iron deposition in the brain. Five patients with genetically confirmed PKAN received 15 mg/kg deferiprone twice daily. All patients were examined at baseline, 12 and 18 months and magnetic resonance imaging (MRI) was done at the baseline and after 18 months. In our study qualitative evaluation of MRI showed that deferiprone was able to reduce the iron load in globus pallidus of all the patients and the results of clinical rating scales show that in four patients, there is an improvement in the first 12 months. The results of our paper show that deferiprone can prevent the progression of the disease.


[Lymphocyte receptors for trophoblastic beta 1-glycoprotein].
The authors have devised a method for rosette-formation to determine TBG receptors on the surface of T lymphocytes. It has been established that among woman peripheral blood lymphocytes, 7.1% of the cells carry TBG receptors, with this percentage increasing maximally up to 50.2% (the first trimester). Among T gamma lymphocytes, 1.2% carry TBG receptors. The amount of such lymphocytes rises 10-fold by the end of pregnancy.


Effect of Various Edge Configurations on the Accuracy of the Modelling Shape of Shell Structures Using Spline Functions.
Spline functions are a useful tool for modelling the shape of shell structures. They have curvature continuity that allows good approximation accuracy for various objects, including hyperboloid cooling towers, spherical domes, paraboloid bowls of radio telescopes, or many other types of smooth free surfaces. Spline models can be used to determine the displacement of structures based on point clouds from laser scanning or photogrammetry. The curvature continuity of splines may, however, cause local distortions in models that have edges. Edges may appear in point clouds where surface patches are joined, on surfaces equipped with additional technical infrastructure or with cracks and shifts in the structure. Taking the properties of spline functions into account, several characteristic types of edge configurations can be distinguished, which may, to a different extent, affect the values of modelling errors. The research conducted below was aimed at identifying such configurations based on theoretical considerations and then assessing their effect on the accuracy of modelling shell structures measured by laser scanning. It turned out to be possible to distinguish between edge configurations, based on the deviation values.


Numerical Analysis of the Relationship between Friction Coefficient and Repose Angle of Blast Furnace Raw Materials by Discrete Element Method.
In recent years, the discrete element method (DEM) has been widely used to study the factors affecting the repose angle and calibrate particle parameters for simulations. In this paper, DEM is used to study the effects of the coefficient of rolling and static friction of pellet, sinter and coke particles on the repose angle. By comparison of the results of simulations and physical experiments, the coefficients of rolling and static friction suitable for simulation work are determined. The results demonstrate that repose angle increases with the coefficient of rolling and static friction, but the rate of increase gradually decays, when the coefficient of rolling friction exceeds 0.4 or the coefficient of static friction exceeds 0.35. The coefficient of static friction has a greater impact on the repose angle than the coefficient of rolling friction. The rougher of the base surface, the larger the repose angle of the formed particle piled. It can be concluded that appropriate coefficient of rolling and static friction for simulations can be obtained by the outlined procedure.


Effects of insect and decapod exclusion and leaf litter species identity on breakdown rates in a tropical headwater stream.
High species richness of tropical riparian trees influences the diversity of organic detritus entering streams, creating temporal variability in litter quantity and quality. We examined the influence of species of riparian plants and macroinvertebrate exclusion on leaf-litter breakdown in a headwater stream in the Luquillo Mountains of Puerto Rico. Leaf litter of Dacryodes excelsa (Burseraceae), Guarea guidonia (Meliaceae), Cecropia scheberiana (Moraceae), Manilkara bidentata (Sapotaceae), and Prestoea acuminata (Palmae) were incubated in litter bags in a pool of Quebrada Prieta. Fine mesh bags were used to exclude macroinvertebrates during leaf breakdown, and coarse mesh bags allowed access to decapod crustaceans (juvenile shrimps and crabs) and aquatic insects (mainly mayflies, chironomids, and caddisflies). D. excelsa and G. guidonia (in coarse- and fine-mesh bags) had significantly higher breakdown rates than C. scheberiana, M. bidentata, and P. acuminata. Breakdown rates were significantly faster in coarse-mesh bag treatments for all leaf types, thus indicating a positive contribution of macroinvertebrates in leaf litter breakdown in this headwater stream. After 42 days of incubation, densities of total invertebrates, mayflies and caddisflies, were higher in bags with D. excelsa and G. guidonia, and lower in P. acuminata, C. scheberiana y M. bidentata. Decay rates were positively correlated to insect densities. Our study highlights the importance of leaf identity and macroinvertebrate exclusion on the process of leaf litter breakdown in tropical headwater streams.


Effect of pleuran (beta-glucan from Pleurotus ostreatus) in diet or drinking fluid on colitis in rats.
The effects of pleuran, beta-glucan isolated from Pleurotus ostreatus, were studied in a model of acute colitis in rats. Pleuran was given either as a 2% food component or as 0.44% pleuran hydrogel drink over 4 weeks. Colitis was induced by intraluminal instillation of 4% acetic acid and after 48 h the extent of colonic damage and several biochemical parameters were examined. Pleuran supplementation both in food and in drinking fluid significantly decreased the disposition to colitis. The macroscopic damage score was reduced by 51% or 67% by pleuran diet and pleuran hydrogel drink, respectively. Pleuran did not influence the final body weights of rats but prevented significantly colonic wet weight increase which was observed in the control diet group. The enhanced activity of myeloperoxidase in the inflamed colonic segment was reduced by pleuran diets, reflecting decreased neutrophil infiltration. The colonic damage was accompanied by decreased activities of lysosomal enzymes--acid phosphatase and cathepsin D--in the control untreated group, whereas in the pleuran groups the decrease was significantly attenuated. Both pleuran regimens reduced the content of conjugated dienes in the colon, liver and erythrocytes. In contrast to this fact, activities of antioxidant enzymes in erythrocytes and the colon were not so greatly influenced. Significant increase was found only in the case of SOD activity in sham operated rat erythrocytes under influence of both pleuran regimes and in the case of GST activity in erythrocytes of pleuran hydrogel group. The mechanism of the described protective effect of pleuran is not yet fully understood. Our results indicate that the pleuran-enhanced antioxidant defence of the colonic wall against the inflammatory attack may have come into play.


Fundamental factors affecting upper-room ultraviolet germicidal irradiation - part I. Experimental.
The objective of this research was to study the factors that relate to the effectiveness of upper-room ultraviolet germicidal irradiation for inactivating airborne microorganisms. The work was conducted in a room-sized chamber designed and furnished for investigations of this nature. Nebulized Serratia marcescens, Bacillus subtilis spores, and vaccinia virus were used as test aerosols. Most data were collected from steady-state experiments comparing the number of viable organisms in the chamber air remaining with UV lamps turned on to the number with UV lamps turned off, but some decay experiments were conducted to compare the two methods. UV power level had a strong influence but was fully effective only in the presence of air mixing that produced vigorous vertical air currents. A conclusion of the study is that an upper-room ultraviolet installation is a complex system that requires careful integration of UV luminaires, UV power, and room ventilation arrangements.


Evaluation Of Congestion Levels in Septic Patients Admitted to Critical Care Units with a Combined Venous Excess-Lung Ultrasound Score (VExLUS) - a Research Protocol.
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality rate. Septic shock is a subset of sepsis with manifest circulatory dysfunction (use of vasopressors and persistent elevation of lactic acid) . As stated in literature, in addition to the use of empiric antibiotics and control of the infectious focus, intravenous fluid therapy is an essential intervention to promote hemodynamic stabilization. However, the literature also describes harmful outcomes related to fluid overload. Hemodynamic management in critically ill patients has traditionally focused on maintaining adequate cardiac output and arterial blood pressure by relying on fluid administration and/or vasopressor/inotropic support. However, organ perfusion is affected by other important factors, such as venous pressure, which can be overlooked. The evaluation of lung congestion with point of care ultrasound (POCUS), as a signal of extravascular fluid, and, more recently, a venous excess Doppler ultrasound (VExUS) grading system, are parameters for the assessment of the fluid status of the patient and organ congestion. Our main hypothesis is that adding a modified lung ultrasound score to the VExUS protocol could provide higher sensitivity and earlier identification of fluid overload, guiding the clinician in the decision of fluid administration in patients with sepsis.


Three abietane diterpenes and two diterpenes incorporated sesquiterpenes from the bark of Cryptomeria japonica.
Three new abietane diterpenes, sugikurojins D (1), E (2), and F (3), and two new abietanes which incorporate cadinane, sugikurojins G (4) and H (5) were isolated from the bark of Cryptomeria japonica. These structures were elucidated primarily by extensive NMR experiments. The structure of sugikurojin D (1) was deduced to be 6alpha-acetoxy-7beta,11-dihydroxy-12-methoxy-8,11,13-abietatriene. Sugikurojin E (2) was deduced to be 6alpha-acetoxy-7beta,12-dihydroxy-8,11,13-abietatriene. Sugikurojin F (3) was 7alpha-methoxy-8,13-abietadien-11,12-dione. Sugikurojins G (4) and H (5) had a unique skeleton incorporating an alpha-cadinol or a 1alpha-hydroxy-T-cadinol in ferruginol, respectively. Also obtained in this investigation were the known diterpenes (6-14). An antibacterial activity of ten among these against Staphylococcus aureus and Escherichia coli was inactive at the (MIC: 125 microg/ml) level. Meanwhile, in the cytotoxic activity against HL-60, compounds 4, 8, and 11 showed moderate (IC50: 4, 35.4; 8, 28.0; 11, 52.4 microM) though weak (IC50: 4, 100; 8, 80.8; 11, 100 microM) activity against HCT-15.


The promoters of the genes for colicin production, release and immunity in the ColA plasmid: effects of convergent transcription and Lex A protein.
The initiation sites of transcription in vivo for the three genes caa, cai and cal encoding respectively colicin A (Caa), the immunity protein (Cai) and the pColA lysis protein (Cal) have been analysed by nuclease S1 mapping. This analysis demonstrates that caa and cal form an operon. cai is located between these two genes and transcribed in the opposite direction from its own promoter. The start sites for caa and cai have also been determined in vitro. For caa, the same start site was found in vivo and in vitro. In contrast, for cai the most efficient start site in vitro was not used in vivo. LexA protein strongly repressed the in vivo and in vitro transcription of the caa-cal operon. As determined by DNase 1 protection experiments, LexA protein binds with a high affinity to an approximately 40 bp long sequence just downstream of the Pribnow box. The sequence of the binding site is composed of two overlapped "SOS boxes". Two transcripts of the caa-cal operon were detected by blot hybridization. The longer mRNA can direct the synthesis of both Caa and Cal while the shorter one is terminated at the end of caa. When the transcription of the caa-cal operon is induced, there is a strong interference with cai transcription.


Experimental animal study of docetaxel combined with carboplatin in the treatment of retinoblastoma.
The synergistic effects of docetaxel (DTX) combined with carboplatin in the treatment of retinoblastoma (RB) was explored in mouse RB xenografts compared with carboplatin alone and DTX alone groups. Retinoblastoma Y-79 cells (4.0×107/ml) were injected into the vitreous body of the right eye of mice to establish the mouse model of RB xenografts. Then the mice were randomly divided into 4 groups (n=30): DTX combined with carboplatin group (group A), carboplatin group (group B), DTX group (group C) and blank control group (group D). The changes in tumors, the survival time of mice, and the synergistic effects of DTX combined with carboplatin were observed and analyzed. The diameters and weight of the right eyeballs of the Institute for Cancer Research (ICR) mice were significantly larger and higher than those of the left eyeballs in each group, respectively (P<0.05). The diameters and weight in group A were significantly shorter and lighter than those in the other three groups, respectively (P<0.05), and there was no significant difference compared with that of normal eyeballs (P>0.05). There was no difference in diameter and weight between group B and group C (P>0.05), but the diameters and weight were shorter and lighter than those in group D, respectively (P<0.05). The survival time of ICR mice in groups A, B and C was significantly longer than that in group D (P<0.05). The survival time in group A was significantly longer than that in groups B and C (P<0.05). There was no significant difference in the survival time between the group B and group C (P>0.05). DTX, carboplatin and the combination of the two have significant inhibitory effects on RB; however, DTX combined with carboplatin has a better therapeutic effect on RB.


Rare Site of Parasitic Dermoid Cyst at Uterovesical Fold of Peritoneum with Absent One-Sided Adnexa.
Teratomas are the most common type of germ cell tumour. It can be congenital or acquired and are usually found in gonads (testes and ovaries). Parasitic dermoid cysts are rare and their actual incidence is unknown. We are reporting a case of 25-year-old gravida two, para one and one living child, who underwent emergency cesarean section in view of symptomatic placenta previa. A parasitic dermoid cyst was found incidently in front of uterus which was attached to uterovasical fold of bladder. This cyst did not show any connection to uterus or adnexa. Uterus, uterine cavity, right side tube and ovary were normal. Her left sided fallopian tube and ovary was completely absent. She did not have any symptoms related to the dermoid cyst. Histopathology confirmed parasitic mature dermoid cyst.


Neurophysiological approach to central pain modulation in primary headaches.
The study of CNS pain-modulating pathways has led to important discoveries about the role of central nociceptive structures such as PAG and hypothalamus in the pathophysiology of episodic and chronic primary headaches. Functional neuroimaging studies have revealed that primary headaches are characterised by different patterns of activation of central pain modulatory structures. A future model of headache pathophysiology investigating the contribution of CNS pain-modulating pathways will probably increase our understanding of pain processing in primary headaches. Herein we review the neurophysiological approaches to assess central pain modulation in primary headaches with emphasis on the diffuse noxious inhibitory control, a form of endogenous pain inhibition. In addition, patients' data will be presented that highlights the utility of such methods for primary headache's pathophysiology and clinical monitoring.


Vancomycin continuous infusion as prophylaxis for vascular surgery.
Prosthetic graft infection is a devastating complication of vascular surgery that occurs in 3%-5% of clean prosthetic procedures. Staphylococci are the most frequently isolated pathogens, and thus surgical prophylaxis regimens often include vancomycin. However, the efficacy of these regimens in ensuring a required concentration of antibiotic is uncertain. This study aimed to determine if a continuous vancomycin infusion regimen administered perioperatively as surgical prophylaxis for vascular procedures maintained an adequate serum concentration. Thirty-four consecutive patients undergoing a vascular procedure requiring a prosthetic graft or patch were given vancomycin prophylaxis. Each patient received a loading dose calculated according to body weight 12 hours before surgery. A 24-hour continuous infusion was then started, based on calculated creatinine clearance. Serum vancomycin concentrations were checked on induction of anesthesia, 2 hours postoperatively, and at the end of the infusion. Perioperative fluid administration and blood loss were recorded. An estimated creatinine clearance was repeated on the second postoperative day. Of the 34 patients recruited, 7 did not have the anticipated procedure and 6 patients had incomplete sample collection. Twenty-one patients with complete sample collection were analyzed. The target concentration (10-25 mg/L) was achieved in 81% of all samples. All patients achieved the target concentration at 1 or more time points. The regimen employed provided appropriate concentrations at the time of intervention. No potentially toxic concentrations or adverse reactions to vancomycin were encountered. Vancomycin given as a continuous infusion delivers adequate serum concentration. Long-term graft infection rates are needed to show a clinical effect.


Home versus hospital intravenous antibiotic therapy for acute pulmonary exacerbations in children with cystic fibrosis.
To compare the effectiveness of home versus hospital intravenous (IV) antibiotic therapy for acute pulmonary exacerbations in children with cystic fibrosis (CF). A retrospective chart review was performed of 143 encounters for pulmonary exacerbations in 50 patients with CF. All encounters were categorized into two groups based on location of completion of antibiotic therapy: hospital group completed treatment in hospital (n = 64), home group completed treatment at home (n = 79). Percent change was calculated for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), forced expiratory flow rate between 25 percent and 75 percent of vital capacity (FEF(25-75%)), maximum forced expiratory flow (FEF(max)), oxygen saturation (O2 SAT), and weight. Means of percent change (PC) from the beginning to the end of IV antibiotic treatment in outcome variables were compared. Total duration of treatment was compared between the two groups. The two groups had no significant differences at baseline in all outcome variables. Treatment of exacerbations in both groups resulted in significant improvement of lung function, O2 SATS, and weight (P <or= 0.001). The percent change in FEV1 was greater in hospital group versus home group (P = 0.04). The duration of treatment was significantly shorter in the hospital group (P = 0.001). Home and hospital IV antibiotic therapy resulted in significant improvement in lung function and weight. Hospital therapy, however, resulted in significantly greater improvement in FEV-1 and required less duration of treatment as compared to home treatment in children with CF.


Crosstalk between the CBM complex/NF-κB and MAPK/P27 signaling pathways of regulatory T cells contributes to the tumor microenvironment.
Regulatory T cells (Tregs), which execute their immunosuppressive functions by multiple mechanisms, have been verified to contribute to the tumor microenvironment (TME). Numerous studies have shown that the activation of the CBM complex/NF-κB signaling pathway results in the expression of hypoxia-inducible factor-1 (HIF-1α) and interleukin-6 (IL-6), which initiate the TME formation. HIF-1α and IL-6 promote regulatory T cells (Tregs) proliferation and migration through the MAPK/CDK4/6/Rb and STAT3/SIAH2/P27 signaling pathways, respectively. IL-6 also promotes the production of HIF-1α and enhances the self-regulation of Tregs in the process of tumor microenvironment (TME) formation. In this review, we discuss how the crosstalk between the CARMA1-BCL10-MALT1 signalosome complex (CBM complex)/NF-κB and MAPK/P27 signaling pathways contributes to the formation of the TME, which may provide evidence for potential therapeutic targets in the treatment of solid tumors.


[Arthroscopic repair of combined superior labrum anterior posterior and Bankart lesions].
We retrospectively evaluated patients who underwent arthroscopic treatment for superior labrum anterior posterior (SLAP) lesions combined with antero-inferior labral detachment (Bankart lesion, Maffet type 5). The study included eight male patients (mean age 31.8 years; range 23 to 50 years) who were treated with suture anchors for type 5 SLAP lesions. In all the patients the symptoms started after trauma, and all presented with shoulder instability findings. The range of motion was measured in the sitting position by a goniometer, and muscle force was assessed manually. In addition, Speed and O'Brien tests and Jobe relocation test were performed. All the patients were examined by standard shoulder magnetic resonance scans. Functional results were evaluated according to the UCLA (University of California at Los Angeles) shoulder score, and the Rowe rating scale for Bankart repairs. The mean follow-up was 37.8 months (range 24 to 52 months). Functional results were excellent-good in five patients, fair in two patients, and poor in one patient. The mean UCLA score increased from a preoperative 15 (range 14-17) to a postoperative 30 (range 20-35), with a corresponding increase in the mean Rowe score from 25 (range 15-45) to 81 (range 50-95) (p<0.05). Arthroscopic repair of combined Bankart and SLAP lesions may present technical difficulties. Nevertheless, it is possible to get good results in selected patients in whom intraarticular pathologies are diagnosed and treated appropriately.


Clinicopathological aspects of 542 cases of pancreatic cancer: a special emphasis on small pancreatic cancer.
Small pancreatic cancers (longest diameter </=2 cm) have been regarded as preliminary to early pancreatic cancer, which was thought to be highly curable. During our experience since 1989, we evaluated 542 cases of pancreatic cancer. Among them we found 74 cases of tumors </=2 cm in diameter, small pancreatic cancer (TS1 pancreatic cancer). Well-differentiated adenocarcinomas (18.9%) and absence of symptoms (8.1%) were more frequent in patients with TS1 than in those with larger pancreatic tumors. Only 16 of the 74 patients (21.6%) with small pancreatic cancers had T1 tumors. According to the International Union Against Cancer (UICC) staging, only 11 patients (14.9%) were stage IA: their 5-yr survival rate was 23.3% and their median survival was 30.0 months. Among these 11 patients, 3 had tumors <1cm; their median survival time was 30.0 months and their 5-yr survival rate was 50.0%. These findings may indicate that 'small' pancreatic cancer is not equivalent to 'early' pancreatic cancer.


Nonparaxial propagation and the radiation forces of the chirped circular Airy derivative beams.
In this paper, we investigate the nonparaxial propagation dynamics of the chirped circular Airy derivative beams (CCADBs) based on vector angular spectrum method. In the case of nonparaxial propagation, the CCADBs still maintains excellent autofocusing performances. Derivative order and chirp factor are two important physical quantities of the CCADBs to regulate the nonparaxial propagation characteristics, such as focal length, focal depth and K-value. In the nonparaxial propagation model, the radiation force on a Rayleigh microsphere induced the CCADBs are also analyzed and discussed in detail. The results demonstrate that not all derivative order CCADBs can achieve stable microsphere trapping effect. The derivative order and chirp factor of the beam can be used to coarse and fine tune the capture effect of Rayleigh microsphere, respectively. This work will contribute to the more precise and flexible use of circular Airy derivative beams in optical manipulation, biomedical treatment and so on.


Novel Applications of Non-Invasive Intravesical Botulinum Toxin a Delivery in the Treatment of Functional Bladder Disorders.
Although intravesical botulinum toxin type A (BoNT-A) injection for functional bladder disorders is effective, the injection-related problems-such as bladder pain and urinary tract infection-make the procedure invasive and inconvenient. Several vehicles have recently been developed to deliver BoNT-A without injection, thereby making the treatment less or non-invasive. Laboratory evidence revealed that liposome can carry BoNT-A across the uroepithelium and act on sub-urothelial nerve endings. A randomized placebo controlled study revealed that intravesical administration of liposome-encapsulated BoNT-A and TC-3 hydrogel embedded BoNT-A can improve urinary frequency, urgency, and reduce incontinence in patients with overactive bladders. A single-arm prospective study also revealed that intravesical administration of TC-3 hydrogel embedded BoNT-A can relieve bladder pain in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We recently administered suprapubic energy shock wave (ESW) after BoNT-A intravesical administration in six patients with IC/BPS. Although pain reduction and symptom improvement were not significant, immunochemical staining showed cleaved synaptosome-associated protein 25 in the bladder after the procedure. This suggests that ESW can promote passage of BoNT-A across the uroepithelium. In conclusion, using vehicles to intra-vesically deliver BoNT-A for functional bladder disorders is promising. Further studies are necessary to confirm the efficacy and explore novel applications.


Effect of Curing Modes on the Mechanical Properties of Commercial Dental Resin-Based Composites: Comparison between Different LEDs and Microwave Units.
Resin-based composites (RBCs) have transformed restorative dentistry and its procedures. However, the characteristics of RBCs have been modified over the years to enhance the physical and chemical properties of the materials. This context raises the need for studies that evaluate whether the properties of the RBCs that are commercially available are clinically adequate with different curing modes. This study aimed to evaluate the mechanical behavior of commercial RBCs after undergoing different curing modes. Twenty-three RBCs of different classes were evaluated. For curing the specimens, a microwave (BMS45, Brastemp) (for 3 min at 450 W) and three LED units were used: an Emitter A Fit (Schuster (second generation)) (light-curing for 15 s with an irradiance of 1250 mW/cm2), VALO (Ultradent (third generation)) (light-curing for 15 s with an irradiance of 1100 mW/cm2), and Emitter Now Duo (Schuster (second generation)) (light-curing for 15 s with an irradiance of 1100 mW/cm2). A total of 670 RBC specimens of 8 mm in diameter and 1 mm in depth were obtained. Afterward, a biaxial flexure strength test was performed until the failure of the specimens, using a universal testing machine set at a speed of 0.5 mm/min. The same specimens were subjected to infrared spectroscopy for evaluating the degree of conversion. Tukey's test was used for multiple comparisons at a significance level of 5%. The light-curing mode did not affect the flexure strength of the RBCs (p > 0.05), but the type and shade of RBCs did so (p < 0.05). In conclusion, the type of RBC directly interferes with the mechanical behavior of the material. However, the curing modes within the same RBC did not change the mechanical properties.


Effect of electroacupuncture on opioid consumption in patients with chronic musculoskeletal pain: protocol of a randomised controlled trial.
Chronic musculoskeletal pain is common and has been increasingly managed by opioid medications, of which the long-term efficacy is unknown. Furthermore, there is evidence that long-term use of opioids is associated with reduced pain control, declining physical function and quality of life, and could hinder the goals of integrated pain management. Electroacupuncture (EA) has been shown to be effective in reducing postoperative opioid consumption. Limited evidence suggests that acupuncture could assist patients with chronic pain to reduce their requirements for opioids.The proposed research aims to assess if EA is an effective adjunct therapy to standard pain and medication management in reducing opioids use by patients with chronic musculoskeletal pain. In this multicentre, randomised, sham-acupuncture controlled, three-arm clinical trial, 316 patients regularly taking opioids for pain control and meeting the defined selection criteria will be recruited from pain management centres and clinics of primary care providers in Victoria, Australia. After a four-week run-in period, the participants are randomly assigned to one of three treatment groups to receive EA, sham EA or no-EA with a ratio of 2:1:1. All participants receive routine pain medication management delivered and supervised by the trial medical doctors. Twelve sessions of semi-structured EA or sham EA treatment are delivered over 10 weeks. Upon completion of the acupuncture treatment period, there is a 12-week follow-up. In total, participants are involved in the trial for 26 weeks. Outcome measures of opioid and non-opioid medication consumption, pain scores and opioid-related adverse events are documented throughout the study. Quality of life, depression, function, and attitude to pain medications are also assessed. This randomised controlled trial will determine whether EA is of significant clinical value in assisting the management of debilitating chronic pain by reducing opioids consumption and their associated adverse events, as well as improving the quality of life for those with chronic pain. Such an outcome will provide the rationale for including EA into multidisciplinary programmes for effective management of chronic musculoskeletal pain. Australian New Zealand Clinical Trial Registry (ACTRN12609000676213)http://www.anzctr.org.au/trial_view.aspx?ID=308008.


Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients.
The global coronavirus disease 2019 (COVID-19) pandemic was associated with multiple organ failure and comorbidities, such as type 2 diabetes mellitus (T2DM). Risk factors, such as age, gender, and obesity, were associated with COVID-19 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to use several host receptors for viral entry, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the lung and other organs. However, ACE2 could be shed from the surface to be soluble ACE2 (sACE2) in the circulation. The epigenetic factors affecting ACE2 expression include a type of small non-coding RNAs called microRNAs (miRNAs). In this study, we aimed at exploring the status of the sACE2 as well as serum levels of several upstream novel miRNAs as non-invasive biomarkers that might have a potential role in T2DM patients. Serum samples were collected from 50 T2DM patients and 50 healthy controls, and sACE2 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Also, RNA was extracted, and TaqMan miRNA reverse transcription quantitative PCR (RT-qPCR) was performed to measure serum miRNA levels. Our results revealed that sACE2 is decreased in the T2DM patients and is affected by age, gender, and obesity level. Additionally, 4 miRNAs, which are revealed by in silico analysis to be potentially upstream of ACE2 were detectable in the serum. Among them, miR-421 level was found to be decreased in the serum of diabetic patients, regardless of the presence or absence of diabetic complications, as well as being differential in various body mass index (BMI) groups. The other 3 miRNAs (miR-3909, miR-212-5p, and miR-4677-3p) showed associations with multiple factors including age, gender, BMI, and serum markers, in addition to being correlated to each other. In conclusion, our study reveals a decline in the circulating serum levels of sACE2 in T2DM patients and identified 4 novel miRNAs that were associated with T2DM, which are influenced by different clinical and demographic factors.


Invited Commentary: Observing Neighborhood Physical Disorder in an Age of Technological Innovation.
Researchers across several disciplines have argued that the characteristics of neighborhood environments can affect a variety of individual- and neighborhood-level outcomes. Physical disorder is one feature of neighborhoods that scholars have argued is important, but data that capture physical disorder have been limited because of the time and resources required for in-person audits. The advent of Google Street View, which provides publicly available street-level imagery with nearly complete coverage of the United States, opens new possibilities for researchers. In this issue of the Journal, Mooney et al. (Am J Epidemiol. 2017;186(3):265-273) compare in-person and virtual audits in Detroit, Michigan, and demonstrate that virtual audits offer key advantages to measuring neighborhood physical disorder over in-person audits, including substantial reductions in time and resources with little to no loss of measurement precision. In this invited commentary, I welcome the use of virtual audits for advancing the study of neighborhoods and outline areas in which they can advance understanding of neighborhood effects. I also describe areas of caution in their implementation and outline how new innovations can advance the use of virtual audits for furthering understanding of neighborhood environments.


Rapid Contour-based Segmentation for 18F-FDG PET Imaging of Lung Tumors by Using ITK-SNAP: Comparison to Expert-based Segmentation.
Purpose To assess the performance of the ITK-SNAP software for fluorodeoxyglucose (FDG) positron emission tomography (PET) segmentation of complex-shaped lung tumors compared with an optimized, expert-based manual reference standard. Materials and Methods Seventy-six FDG PET images of thoracic lesions were retrospectively segmented by using ITK-SNAP software. Each tumor was manually segmented by six raters to generate an optimized reference standard by using the simultaneous truth and performance level estimate algorithm. Four raters segmented 76 FDG PET images of lung tumors twice by using ITK-SNAP active contour algorithm. Accuracy of ITK-SNAP procedure was assessed by using Dice coefficient and Hausdorff metric. Interrater and intrarater reliability were estimated by using intraclass correlation coefficients of output volumes. Finally, the ITK-SNAP procedure was compared with currently recommended PET tumor delineation methods on the basis of thresholding at 41% volume of interest (VOI; VOI41) and 50% VOI (VOI50) of the tumor's maximal metabolism intensity. Results Accuracy estimates for the ITK-SNAP procedure indicated a Dice coefficient of 0.83 (95% confidence interval: 0.77, 0.89) and a Hausdorff distance of 12.6 mm (95% confidence interval: 9.82, 15.32). Interrater reliability was an intraclass correlation coefficient of 0.94 (95% confidence interval: 0.91, 0.96). The intrarater reliabilities were intraclass correlation coefficients above 0.97. Finally, VOI41 and VOI50 accuracy metrics were as follows: Dice coefficient, 0.48 (95% confidence interval: 0.44, 0.51) and 0.34 (95% confidence interval: 0.30, 0.38), respectively, and Hausdorff distance, 25.6 mm (95% confidence interval: 21.7, 31.4) and 31.3 mm (95% confidence interval: 26.8, 38.4), respectively. Conclusion ITK-SNAP is accurate and reliable for active-contour-based segmentation of heterogeneous thoracic PET tumors. ITK-SNAP surpassed the recommended PET methods compared with ground truth manual segmentation.


Validation of an ELISA for the concurrent detection of total antibodies (IgM and IgG) to Rift Valley fever virus.
Rift Valley fever virus (RVFV) infects humans and livestock, causing haemorrhaging and abortions in animals. Three major RVF epizootics have occurred in South Africa since the 1950s and the outbreak in 2010 had a mortality rate of 10.7% in humans. Accurate and early detection is therefore essential for management of this zoonotic disease. Enzyme-linked immunosorbent assays (ELISAs) have been developed for the detection of either IgM or IgG antibodies to RVFV in animal sera. In this study, data are presented on the validation of a double-antigen ELISA for the simultaneous detection of both classes of antibodies to RVFV ina single test. ELISA plates were coated with a recombinant nucleoprotein. The nucleoprotein,conjugated to horseradish peroxidase, was used as the detecting reagent. A total of 534 sera from sheep and cattle were used in the validation. The sheep sera were collected during a RVF pathogenesis study at the Agricultural Research Council (ARC) - Onderstepoort Veterinary Institute and the cattle sera were collected during an outbreak of RVF in 2008 at the ARC -Animal Production Institute in Irene, Pretoria. The ELISA had a diagnostic sensitivity of 98.4% and a specificity of 100% when compared to a commercial cELISA. This convenient and fast assay is suitable for use in serological surveys or monitoring immune responses in vaccinated animals.


The major histocompatibility complex and insulin-dependent diabetes in BB rats.
The partially inbred strain of BB-Wistar rats showed a varying incidence of the insulin-dependent diabetes-like syndrome. The serological typing of a large sample of BB rats verified the homozygosity for the RTlu haplotype, whereas its parental non-inbred Wistar stock segregated for RTlu and RTla haplotypes. The histogenetical typing of BB rats by skin grafting showed a significantly prolonged rejection of grafts from RTla donors unusual in other RTlu recipients. The presumption of some recombinational or mutational events in the RTl haplotype of BB rats was not verified by the simple F1 skin grafting test from LEW.1U/RTlu standard/donors to F1/LEW X BB/recipients. Skin grafts survived permanently. When trying to get a clear-cut answer whether the RTlu haplotype is associated with the spontaneous occurrence of diabetes in F2/LEW X BB/ X /LEW X BB/hybrids, only 7.4% of RTlu homozygotes were found among 359 weaned animals. Moreover, the partial strain of BB rats became extinct with the F1 generation mainly due to an infection by the mycoplasma. A new sample of outbred BB rats with a low incidence of spontaneous diabetes was found as homogeneous for the RTlu haplotype, too. Preliminary results of typing these rats for the secondary antibody response to pig insulin indicate the low responsiveness contrary to the results given earlier for the RTlu typing strains as high responders. All these results support the idea that the RTlu haplotype of the BB rats might be a variant carrying some mutational change(s) at the RTl.B region.


Interventions for myofascial pain syndrome in cancer pain: recent advances: why, when, where and how.
Pain is one of the most feared and most common symptoms of cancer, experienced by 38-85% of patients. Pain in terminally ill cancer patients is a multidimensional experience caused by a diverse array of factors - cancer itself, its treatment or other causes. Studies have shown a high incidence of myofascial pain syndrome (MPS) in patients with cancer and the knowledge of myofascial trigger points (MTrPs) is important to address and manage existing pain, and to prevent the recurrence of pain. This review aims to summarize recent advances in interventions for managing MPS in patients with cancer. Database searches were conducted on MEDLINE, CINAHL, and Google Scholar to locate all studies published from inception until April 2019 using the keywords cancer pain, myofascial pain, TrPs with emphasis of any methodological quality that included interventions for MPS. MPS in advanced cancer patients are more commonly observed along with other cancer pains rather than independently with a prevalence of 11.9-48% in those patients diagnosed with cancer of head and neck and breast cancer. Interventional therapies employing ultrasound guided injection of the MTrPs is gaining popularity in the management of MPS in cancer pain and may be a better alternative than the use of opioid analgesics in the multidisciplinary management.


The Arabidopsis compact inflorescence genes: phase-specific growth regulation and the determination of inflorescence architecture.
During their life cycle, higher plants pass through a series of growth phases that are characterized by the production of morphologically distinct vegetative and reproductive organs and by different growth patterns. Three major phases have been described in Arabidopsis: juvenile vegetative, adult vegetative, and reproductive. In this report we describe a novel, phase-specific mutant in Arabidopsis, compact inflorescence (cif). The most apparent aspect of the cif phenotype is a strong reduction in the elongation of internodes in the inflorescence, resulting in the formation of a floral cluster at the apical end of all reproductive shoots. Elongation and expansion of adult vegetative rosette leaves are also compromised in mutant plants. The onset of the cif trait correlates closely with morphological changes marking the phase transition from juvenile to adult, and mutant plants produce normal flowers and are fully fertile. Hence the cif phenotype appears to be adult vegetative phase-specific. Histological sections of mutant inflorescence internodes indicate normal tissue specification, but reduced cell elongation compared to wild-type. compact inflorescence is inherited as a two-gene trait involving the action of a recessive and a dominant locus. These two cif genes appear to be key components of a growth regulatory pathway that is closely linked to phase change, and specifies critical aspects of plant growth and architecture including inflorescence internode length.


Lack of the detection of XMRV or polytropic MLV-related sequences in blood cells from HIV-1-infected patients in Spain.
Xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (MLV)-related virus are recently described human gammaretroviruses that have been associated with prostate cancer and chronic fatigue syndrome. These studies have been controversial because a number of laboratories have been unable to find evidence of XMRV in similar groups of patients or controls. Because the existence of XMRV raises many questions, we decided to study its presence in a group of patients infected with HIV-1 with a high proportion of intravenous drug use and coinfection by hepatitis C virus. Forty HIV-1-infected patients under follow-up in our institution were screened for XMRV/MLV by nested polymerase chain reaction using primers targeting the gag and env region. Specific primers for mouse mitochondrial DNA were used to rule out contamination. No evidence of XMRV or polytropic MLV-related sequences was found in any sample from patients or controls. Four samples yielded polymerase chain reaction bands whose sequence corresponded to murine endogenous retroviral sequences, however, contamination with mouse cell DNA was subsequently confirmed. XMRV/MLV viruses do not seem to be associated with HIV-1 infection or intravenous drug use. Contamination of samples or reagents by genomic murine DNA or XMRV vectors could account for the sporadic detection of positive samples for XMRV and related agents.


The Dictyostelium discoideum acaA gene is transcribed from alternative promoters during aggregation and multicellular development.
Extracellular cAMP is a key extracellular signaling molecule that regulates aggregation, cell differentiation and morphogenesis during multi-cellular development of the social amoeba Dictyostelium discoideum. This molecule is produced by three different adenylyl cyclases, encoded by the genes acaA, acrA and acgA, expressed at different stages of development and in different structures. This article describes the characterization of the promoter region of the acaA gene, showing that it is transcribed from three different alternative promoters. The distal promoter, promoter 1, is active during the aggregation process while the more proximal promoters are active in tip-organiser and posterior regions of the structures. A DNA fragment containing the three promoters drove expression to these same regions and similar results were obtained by in situ hybridization. Analyses of mRNA expression by quantitative RT-PCR with specific primers for each of the three transcripts also demonstrated their different temporal patterns of expression. The existence of an aggregation-specific promoter can be associated with the use of cAMP as chemo-attractant molecule, which is specific for some Dictyostelium species. Expression at late developmental stages indicates that adenylyl cyclase A might play a more important role in post-aggregative development than previously considered.


TFIIH localization is highly dynamic during zygotic genome activation in Drosophila, and its depletion causes catastrophic mitosis.
In Drosophila, zygotic genome activation occurs in pre-blastoderm embryos during rapid mitotic divisions. How the transcription machinery is coordinated to achieve this goal in a very brief time span is still poorly understood. Transcription factor II H (TFIIH) is fundamental for transcription initiation by RNA polymerase II (RNAPII). Herein, we show the in vivo dynamics of TFIIH at the onset of transcription in Drosophila embryos. TFIIH shows an oscillatory behaviour between the nucleus and cytoplasm. TFIIH foci are observed from interphase to metaphase, and colocalize with those for RNAPII phosphorylated at serine 5 (RNAPIIS5P) at prophase, suggesting that transcription occurs during the first mitotic phases. Furthermore, embryos with defects in subunits of either the CAK or the core subcomplexes of TFIIH show catastrophic mitosis. Although, transcriptome analyses show altered expression of several maternal genes that participate in mitosis, the global level of RNAPIIS5P in TFIIH mutant embryos is similar to that in the wild type, therefore, a direct role for TFIIH in mitosis cannot be ruled out. These results provide important insights regarding the role of a basal transcription machinery component when the zygotic genome is activated.


Decreased anticoagulant response to tissue factor pathway inhibitor type 1 in plasmas from patients with lupus anticoagulants.
Inhibition of tissue factor pathway inhibitor type 1 (TFPI) is one of the mechanisms by which lupus anticoagulants (LA) may upregulate tissue factor (TF) activity. We wanted to examine whether purified immunoglobulin G (IgG) from patients with LA may interfere with the ability of TFPI to inhibit ex vivo TF-induced thrombin generation. The endogenous thrombin potential (ETP) in pooled normal plasma (PNP) supplemented with IgG from either patients with LA or controls was determined in the absence or presence of recombinant TFPI (rTFPI). In the presence of a heparin neutralizer, the ETP was also determined in plasmas from patients with LA and controls before and after heparin injection in order to quantify the anticoagulant effect of heparin-releasable TFPI in vivo. Compared with IgG from controls (n = 14), IgG from patients with LA (n = 28) induced a wide range of enhancing or inhibitory effects on the ETP in PNP. The response to rTFPI in PNP with IgG from patients with LA correlated inversely with thrombin generation (r(s) = 0.637, P = 0.0003). Correspondingly, the relative inhibition of ETP in postheparin plasmas was smaller for patients (n = 11) than for controls (n = 9) (32% vs. 68%, P = 0.007). Our findings support the hypothesis that TFPI anticoagulant activity is inhibited in some patients with LA.


Dynamics in organic ionic liquids in distinct regions using charged and uncharged orientational relaxation probes.
The temperature-dependent fluorescence anisotropy decay (orientational relaxation) of perylene and sodium 8-methoxypyrene-1,3,6-sulfonate (MPTS) were measured in a series of 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (alkyl = ethyl, butyl, hexyl, octyl) organic room temperature ionic liquids (RTIL). The two fluorescent probe molecules display markedly different rotational dynamics when analyzed using Stokes-Einstein-Debye theory, demonstrating that they are located in distinct environments within the RTILs and have very different interactions with their surroundings. Perylene rotates with subslip behavior, becoming increasingly subslip as the length of ionic liquid alkyl chain is increased. The dynamics approach those of perylene in an organic oil. In contrast, MPTS shows superstick behavior, likely reflecting very strong coordination with the RTIL cations. These results are consistent with different elements of rotational friction within the ionic liquid structure, which are available to solutes depending on their chemical functionality.


The role of diallyl thiosulfinate associated with nuciferine and diosgenin in the treatment of premature ejaculation: A pilot study.
To assess the efficacy and safety of an association of diallyl thiosulfinate with nuciferine and diosgenin in the treatment of a group of patients suffering from premature ejaculation (PE), primary or secondary to erectile dysfunction (ED). From July 2015 to October 2016, 143 patients (mean age 25.3; range 18-39) affected by PE completed the study and were finally analyzed in this phase I study. All patients, after clinical assessment and laboratory evaluation were asked to take an association of diallyl thiosulfinate with nuciferine and diosgenin as oral tablet, once a day, on alternate days, for three months. At the baseline and after three months of treatment, each patient was asked to complete the following questionnaires: International Index of Erectile Function (IIEF-5), Premature Ejaculation Diagnostic Tool (PEDT), Male Sexual Health Questionnaire (MSHQ). A statistical significant improvement in terms of erectile function, comparing the IIEF-5 value at baseline and follow- up visit was found (respectively IIEF-5: 8.7 vs 14.01; p < 0.001). Moreover, at follow-up visit, 97/143 men (67.8%) referred a subjective improvement of the erection quality and a better control of the ejaculation (PROs). The IELT improved too between the baseline evaluation and the follow-up visit (p < 0.001). In conclusion, our study, even if supported by preliminary results, showed how Diallyl Thiosulfinate, Nuciferine and Diosgenin is able to improve the control of ejaculation in patients suffering from PE, primary or secondary to ED without any significant adverse effects.


Using Physical Modeling to Optimize the Aluminium Refining Process.
Concern for the environment and rational management of resources requires the development of recoverable methods of obtaining metallic materials. This also applies to the production of aluminium and its alloys. The quality requirements of the market drive aluminium producers to use effective refining methods, and one of the most commonly used is blowing an inert gas into liquid aluminium via a rotating impeller. The efficiency and cost of this treatment depends largely on the application of the correct ratios between the basic parameters of the process, which are the flow rate of the inert gas, the speed of the rotor and the duration of the process. Determining these ratios in production conditions is expensive and difficult. This article presents the results of research aimed at determining the optimal ratio of the inert gas flow rate to the rotary impeller speed, using physical modeling techniques for the rotor as used in industrial conditions. The tests were carried out for rotary impeller speeds from 150 to 550 rpm and gas flow rates of 12, 17 and 22 dm3/min. The research was carried out on a 1:1 scale physical model, and the results, in the form of visualization of the degree of gas-bubble dispersion, were assessed on the basis of the five typical dispersion patterns. The removal of oxygen from water was carried out analogously to the process of removing hydrogen from aluminium. The curves of the rate of oxygen removal from the model liquid were determined, showing the course of oxygen reduction during refining with the same inert gas flows and rotor speeds mentioned above.


Meniscal allograft transplantation.
Meniscal allograft transplantation is a reasonable treatment option for the young patient with symptomatic meniscal deficiency. Although clinical results are promising, in most studies only mixed procedures have been performed, with short- or medium-term follow-up. Important potential prognostic factors include patient selection, severity of degenerative changes, limb stability and alignment, graft sizing and processing methods, graft placement, and graft fixation. The use of meniscal allograft transplantation should be considered a salvage operation for the difficult clinical dilemma of meniscal deficiency in young patients. Nonetheless, in carefully selected patients, this procedure can predictably relieve compartmental symptoms, and, in conjunction with anterior cruciate ligament reconstruction, restore knee stability. In addition, the partial restoration of meniscal function provided by this procedure may slow the degenerative arthritic process.


Pediatric emergency department nurses' perspectives on fever in children.
Fever is the most common complaint of children seen in a Pediatric Emergency Department (PED). Since pediatric emergency nurses commonly educate parents on fever management, this study sought to examine their knowledge base regarding fever in children. Through convenience sampling, pediatric emergency registered nurses working at one of four PEDs were surveyed using a self-administered questionnaire containing 10 open-ended questions pertaining to fever in children. Eighty-eight pediatric emergency registered nurses (median experience 8.0 years, range 3 months to 28 years) were surveyed. The median temperature considered by pediatric emergency nurses to be a fever was 38.0 degrees C (100.4 degrees F) with a range of 37.2 degrees C (99.0 degrees F) to 38.9 degrees C (102.0 degrees F), while the median temperature considered to be dangerous to a child was 40.6 degrees C (105.0 degrees F) with a range of 38.0 degrees C (100.4 degrees F) to 41.8 degrees C (107.0 degrees F). Eleven percent was not sure what temperature constituted a fever while 31% was not sure what temperature would be dangerous to a child. Fifty-seven percent considered seizures the primary danger to a febrile child while 29% stated permanent brain injury or death could occur from a high fever. Sixty percent chose acetaminophen as first line treatment while 7% stated alcohol or tepid water baths were also acceptable treatment options. Thirty-eight percent stated that a different medication should be added if a child was still febrile 1 hour after initial treatment while 31% would not use additional medication. Eighteen percent stated it was dangerous for a child to leave the PED if still febrile. Fever phobia and inconsistent treatment approaches occur among experienced pediatric emergency registered nurses. These phobias and inconsistencies subsequently could be conveyed to parents. In order to assure accurate parental education, PEDs should educate their medical team regarding the management of fever in children.


Reach Out and Eat: Food and Beverages Depicted in Books for Preschoolers.
To examine food and beverage depictions in books for preschoolers. Books for preschoolers from Reach Out and Read (ROR; n = 42), public library (n = 27), and Publisher's Weekly booklists (n = 31) were examined for nutritive and empty-calorie food and beverage depictions. It was found that 66% of books depicted at least 1 food or beverage. More books depicted nutritive items than empty-calorie items (87.5% vs 54.7%, P < .001). There was a trend toward fewer empty-calorie depictions in ROR books than in other booklists. Yet nearly half of ROR books depicted at least 1 empty-calorie item. ROR books also accounted for 5 of 10 books with the most empty-calorie item depictions and 3 of 4 books with branding. With regard to messaging, approximately a third of books with the most empty-calorie depictions promoted unhealthy foods. When selecting books for ROR, it may be important to consider food and beverage depictions and messages.


Anti-tumor effect of human endostatin mediated by retroviral gene transfer in nude mice.
To explore the inhibitory effect of human endostatin gene mediated by retroviral vector on the growth of human liver carcinoma. A recombinant retroviral plasmid containing human endostatin gene and signal peptide was engineered and transferred into PA317 cells to produce retrovirus. Human liver carcinoma cells (SMMC7721) were infected with the above retrovirus to build a stable endostatin-transfected liver carcinoma cell line (SMMC-endo). The control liver carcinoma cell line (SMMC-pLncx) was developed in a similar way except that the plasmid was replaced by an empty retroviral vector. Immunohistochemistry and Western blot were used to test the expression and secretion of human endostatin. The biological activity of the expressed human endostatin was assessed by endothelial cell proliferation assay. The growth rates of SMMC-endo and control SMMC-pLncx cells in vivo and in vitro were also observed. The expression and secretion of human endostatin by endostatin-transfected SMMC-endo cells were confirmed by immunohistochemistry and Western blot. Compared with the control group, concentrated supernatant of SMMC-endo cells remarkably inhibited the proliferation of human umbilical vein endothelial cells by 48%, significantly higher than the inhibition by the control (10.2%; P < 0.01). The endostatin-transfected SMMC-endo cells had similar in vitro growth rates to SMMC-pLncx cells. The in vivo experiment showed that the growth rate of SMMC-endo cells was slowed. Only in 3 out of 5 mice were tumors formed and flank tumors of SMMC-endo cells were 94.5% smaller than those of control cells 22 days after inoculation into nude mice (P < 0.001). Gene transfer of human endostatin mediated by retroviral vector is an effective form of cancer therapy.


Angiogenesis in human normal and pathologic adrenal cortex.
The angiogenic phenotype of 13 normal adrenal glands (N), 13 aldosterone-producing adenomas (APA), 12 cortisol-producing adenomas (CPA), 13 nonfunctioning adrenal cortical adenomas (NFA), and 13 adrenal cortical carcinomas (CA) was investigated. Intratumoral vascular density was explored by CD34, a marker of endothelial cells, and the angiogenic status was investigated by vascular endothelial growth factor (VEGF) expression, an important angiogenic factor expressed by tumoral cells. Vascular density, quantified as the number of vessels per square millimeter, was significantly lower (P < 0.0001) in CA (110.3 +/- 27.8) than in N (336.6 +/- 14.5), APA (322.8 +/- 19.1), CPA (288.5 +/- 14.3), and NFA (274.2 +/- 19.8). VEGF expression, calculated as the percentage of positive cells, was significantly greater (P < 0.0001) in CA (85.3 +/- 2.1) than in APA (56.5 +/- 7.5), CPA (38.5 +/- 7.0), N (33.1 +/- 6.1), and NFA (0.76 +/- 0.6). In APA, a negative relation between CD34 and plasma renin activity (P < 0.0002) and a positive association between CD34 and aldosterone levels (P < 0.05) was found. In conclusion, the angiogenic phenotype of CA is characterized by VEGF overexpression but low vascularization, a finding suggesting a dissociation between angiogenic potential and neoangiogenic capabilities of these tumors. The lack of VEGF expression in NFA and the close association between angiogenesis and functional status in APA also suggest a possible influence of the angiogenic phenotype on hormonal secretion of these endocrine tumors.


18FDG PET/CT Tumoral and Neurologic Therapeutic Response in a Case of Anti-GABABR Paraneoplastic Limbic Encephalitis.
A 70-year-old man with a history of small cell lung carcinoma 2 years earlier was addressed for the suspicion of a paraneoplastic limbic encephalitis. Brain 18FDG PET/CT revealed a bilateral amygdalian and hippocampal hypermetabolism, confirming a limbic encephalitis, and concurrent whole-body 18FDG PET/CT showed a small cell lung carcinoma plurifocal metastatic recurrence, consistent with a paraneoplastic limbic encephalitis. 18FDG PET/CT follow-up under chemotherapy revealed an almost complete normalization of brain metabolism and a partial metabolic response of the metastatic recurrence, consistent with the good clinical neurological evolution of the patient. This case highlights the clinical-metabolic imaging correlation in paraneoplastic limbic encephalitis.


Use of lispro insulin and quality of life in adolescents on intensive therapy.
This study examined the metabolic and quality-of-life effects of using lispro insulin in teenagers. Teenagers on multiple daily injections who had not reached metabolic treatment goals were offered the opportunity to use lispro insulin as part of a larger ongoing study of intensive management in youth. Of the 51 who were eligible, 35 used lispro and were followed for 12 months; the remaining 16 had reached treatment goals, were not offered lispro, and comprised the control group. After 12 months, the teens who received lispro insulin achieved equivalent levels of metabolic control to those achieved by teens in the control group, without differences in total daily dose, insulin regimen, or adverse events. Those who received lispro found coping with diabetes less difficult than those who continued on regular insulin, and they reported less negative impact of diabetes on quality of life and fewer worries about diabetes. Both groups were equally satisfied with their diabetes treatment. Lispro insulin is a safe alternative for youth on intensive regimens, may assist youth in coping with diabetes, and may improve their quality of life.


Bactericidal activity of amikacin and gentamicin.
Using the membrane filtration method bactericidal activity of amikacin and gentamicin as a function of time and concentrations was determined. Amikacin was bactericidal against all Pseudomonas aeruginosa (n = 7) and Klebsiella pneumoniae strains (n = 8) tested. In 5 of the 7 P. aeruginosa and 3 of the 8 K. pneumoniae strains we saw a secondary regrowth at 24h. There was no difference between amikacin and gentamicin. The experiments to determine the effect of concentration on bactericidal activity showed that higher concentrations lead to a faster kill rate.


Brain irradiation: effects on regional MAO and COMT activity in the brain of the squirrel monkey and on the incorporation of [14C]tyrosine into catecholamines.
The effects of brain irradiation on the enzyme activity of monoamine oxidase (MAO) and catecholamine O-methyltransferase (COMT), as well as on the rate of incorporation of [14C]tyrosine into catecholamines (CAs), were examined in brain regions of the squirrel monkey (Saimiri sciureus). Results indicated that proton irradiation of the striate visual cortex at either 10,000 or 20,000 rad drastically affected the MAO activity, moderately affected the COMT activity, and significantly altered the incorporation of [14C]tyrosine into CAs in several brain regions. After 10,000 rad, MAO activity was increased in caudate nucleus (by 135%) and cerebellum (by 41%); significantly decreased in putamen (by 49%), gray matter (by 19%), and hippocampus (by 18%); and unchanged in brainstem. After 20,000 rad, MAO activity was markedly increased in caudate nucleus (by 114%), but decreased in cerebellum (by 24%), putamen (by 38%), gray matter (by 30%), and hippocampus (by 36%), and unchanged in brainstem. After 10,000 rad, COMT activity was significantly decreased in putamen (by 27%) and brainstem (28%). After 20,000 rad, COMT activity was significantly decreased in putamen (by 22%) and cortical gray matter (by 37%) but unchanged in the other brain regions examined. The 10,000 rad significantly increased the rate of incorporation of [14C]tyrosine into CAs in both the cerebellum (by 68%) and hypothalamus (by 26%), but 20,000 rad increased the rate only in hypothalamus (by 17%) and decreased the rate in hippocampus (by 24%). The whole-brain weights were significantly decreased after both 10,000 or 20,000 rad, by 17% and 11%, respectively. The only significant change in regional tissue weight was observed in putamen after 20,000 rad (a decrease by 17%). The protein concentration was significantly increased in hippocampus at both 10,000 (by 13%) and 20,000 (by 30%) but not affected in other brain regions examined. These data support our previous conclusion that a sustained chemical change occurs at the irradiated site and that the effect was transmitted to nonirradiated brain regions. Results also suggest that catecholaminergic pathways may exist between striate visual cortex and other cortical or subcortical brain areas where chemical changes were observed after visual cortical lesion by proton irradiation at various doses.


Linfuranones B and C, Furanone-Containing Polyketides from a Plant-Associated Sphaerimonospora mesophila.
Two new furanone-containing polyketides, linfuranones B and C, were isolated from a plant-associated actinomycete of the genus Sphaerimonospora. Their structures were determined by NMR and MS spectroscopic analyses, and the absolute configurations were established by anisotropic methods and chemical degradation approaches. In silico analysis of biosynthetic genes suggested that linfuranone B is generated from linfuranone C by oxidative cleavage of the polyketide chain. Linfuranones B and C induced preadipocyte differentiation into matured adipocytes at 20-40 μM without showing cytotoxicity.


Novel tumor necrosis factor-related long non-coding RNAs signature for risk stratification and prognosis in glioblastoma.
Tumor necrosis factor (TNF) is an inflammatory cytokine that can coordinate tissue homeostasis by co-regulating the production of cytokines, cell survival, or death. It widely expresses in various tumor tissues and correlates with the malignant clinical features of patients. As an important inflammatory factor, the role of TNFα is involved in all steps of tumorigenesis and development, including cell transformation, survival, proliferation, invasion and metastasis. Recent research has showed that long non-coding RNAs (lncRNAs), defined as RNA transcripts >200 nucleotides that do not encode a protein, influence numerous cellular processes. However, little is known about the genomic profile of TNF pathway related-lncRNAs in GBM. This study investigated the molecular mechanism of TNF related-lncRNAs and their immune characteristics in glioblastoma multiforme (GBM) patients. To identify TNF associations in GBM patients, we performed bioinformatics analysis of public databases - The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). The ConsensusClusterPlus, CIBERSORT, Estimate, GSVA and TIDE and first-order bias correlation and so on approaches were conducted to comprehensively characterize and compare differences among TNF-related subtypes. Based on the comprehensive analysis of TNF-related lncRNAs expression profiles, we constructed six TNF-related lncRNAs (C1RL-AS1, LINC00968, MIR155HG, CPB2-AS1, LINC00906, and WDR11-AS1) risk signature to determine the role of TNF-related lncRNAs in GBM. This signature could divide GBM patients into subtypes with distinct clinical and immune characteristics and prognoses. We identified three molecular subtypes (C1, C2, and C3), with C2 showing the best prognosis; otherwise, C3 showing the worst prognosis. Moreover, we assessed the prognostic value, immune infiltration, immune checkpoints, chemokines cytokines and enrichment analysis of this signature in GBM. The TNF-related lncRNA signature was tightly associated with the regulation of tumor immune therapy and could serve as an independent prognostic biomarker in GBM. This analysis provides a comprehensive understanding of the role of TNF-related characters, which may improve the clinical outcome of GBM patients.


[Embryo donation in developing countries].
In theory there are three things that can happen to surplus embryos: cryopreservation, discarding, or donation. Embryo donation has three different aims: clinical use (generally infertility therapy), research (basic biomedical research, stem cell research, etc.) or teaching (mainly used by clinical embryologists). We present a literature review that analyzes empirical data from developed countries (Germany, Australia, Belgium, Canada, Denmark, Spain, U.S.A., Finland, France, Italy, New Zealand, United Kingdom, Sweden and Switzerland) regarding the probable fate of surplus embryos. According to the literature, embryos are most often discarded or donated for research.


Mercury-induced membranous nephropathy: clinical and pathological features.
Long-term contact with mercury may induce membranous nephropathy (MN); however, the clinical pathologic features and pathogenesis of mercury-induced MN have not been investigated. The present study retrospectively evaluated 11 cases of mercury-induced MN to analyze its causes and its clinical and pathologic features. A total of 10 women and 1 man ages 15 to 45 years were enrolled in the present study. Mercury exposure was caused by mercury-containing pills (five patients), skin lightening cream (four patients), hair-dyeing agents (one patient), and mercury vapor (one patient). The duration of contact with mercury ranged from 2 to 60 months, and the urinary mercury concentrations were 1.5 to 50 times higher than reference values. All patients presented with proteinuria and normal renal function; three had nephrotic syndrome. Light microscopy revealed thickened glomerular basement membrane and mildly proliferative mesangial cells. Acute tubulointerstitial injury occurred in three patients. The immunofluorescence findings showed granular deposits of IgG and C3 along the glomerular capillary wall, mostly accompanied by deposits of C4 and C1q. IgG1 and IgG4 (predominantly IgG1) deposits were observed along the glomerular capillary loops. Nine patients reached complete remission in follow-up after withdrawal from mercury exposure. Deposits of IgG1 subclasses in renal tissues indicated that the pathogenesis of mercury-induced MN differs from that of idiopathic MN. It is important that clinicians are aware that mercury exposure should be considered a possible cause of membranous nephropathy.


On-chip selective capture of cancer cells and ultrasensitive fluorescence detection of survivin mRNA in a single living cell.
The rapid recognition of cancer cells and detection of tumor biomarker survivin mRNA plays a critical role in the early diagnosis of many cancers. Based on the integration of specific cancer cell capture and intracellular survivin mRNA detection, this work presents a novel and sensitive on-chip approach for the bioanalysis of survivin mRNA in a single living cell. The microchannel surface was firstly modified with a prostate stem cell antigen (PSCA) monoclonal antibody as the recognition element for prostate cancer cells (PC-3). As a result of the antigen-antibody specific affinity interactions, PC-3 cells could be selectively captured on the microchannel surface. After cell capture, nano-sized graphene oxide-poly(ethylene glycol) bis(amine) (NGO-PEG) was employed as a quencher and carrier of a signal tag, fluorescein isothiocyanate (FITC)-labeled antisense oligonucleotide (F-S1), which is complementary to part of survivin mRNA (target survivin mRNA), to transfect into the captured PC-3 cells. Upon the selective binding of S1 to intracellular survivin mRNA, F-S1 will be released from the NGO-PEG, inducing the fluorescence recovery of FITC. This antibody-based microfluidic device enables simple and inexpensive monitoring of the amount of survivin mRNA in single captured cell without the need for sample pretreatment. The survivin mRNA content in each PC-3 cell was estimated to be (4.8 ± 1.8) × 10(6) copies. This strategy opens a different perspective for ultrasensitive survivin mRNA detection, which may facilitate the early screening for malignancy.


In-hospital dynamics of glucose, blood pressure and temperature predict outcome in patients with acute ischaemic stroke.
We aimed to assess alterations in glucose, blood pressure and temperature in acute ischaemic stroke and investigate their association with early all-cause mortality and functional outcome. We studied all consecutive acute ischaemic stroke patients admitted in 2001-2010 to the Acute Stroke Unit, at Alexandra University Hospital, in Athens. Serial measurements were performed in the first seven days post-stroke and different parameters have been estimated: mean daily values, variability, subject-specific baseline levels and rate of change in serial measurements. Cox-proportional-hazards-model analysis and logistic-regression analysis were applied to investigate the association between these parameters and all-cause mortality and functional outcome after adjustment for known confounders of stroke outcome. In 1271 patients (mean age 72.3 ± 11.2 years), after adjusting for confounders, baseline glucose levels (HR: 1.005, 95%CI: 1.001-1.01; p = 0.017), variability of systolic BP (SBP) as estimated by standard deviation (HR: 1.028, 95%CI: 1.01-1.048; p = 0.005), the baseline temperature (HR: 2.758, 95%CI: 2.067-3.68; p < 0.001) and the rate of temperature change (HR: 1.841, 95%CI: 1.616-2.908; p < 0.001) were independently associated with all-cause mortality within three months. Poor functional outcome was associated with subject-specific baseline values of temperature (OR: 1.743; 95%CI: 1.076-2.825; p = 0.024), the rate of SBP (OR: 1.159; 95% CI: 1.047-1.280; p = 0.004) and temperature change (OR: 1.402; 95% CI: 1.061-1.853; p = 0.018). The main strength of our study is that we analysed simultaneously three parameters and we used four different variables for each parameter of interest. Baseline glucose levels, variability of SBP and baseline temperature and its rate of change are independent predictors of all-cause mortality. Baseline values of temperature and the rate of changes in SBP and temperature are independent predictors of poor functional outcome.


Volumetric verification of multiaxis machine tool using laser tracker.
This paper aims to present a method of volumetric verification in machine tools with linear and rotary axes using a laser tracker. Beyond a method for a particular machine, it presents a methodology that can be used in any machine type. Along this paper, the schema and kinematic model of a machine with three axes of movement, two linear and one rotational axes, including the measurement system and the nominal rotation matrix of the rotational axis are presented. Using this, the machine tool volumetric error is obtained and nonlinear optimization techniques are employed to improve the accuracy of the machine tool. The verification provides a mathematical, not physical, compensation, in less time than other methods of verification by means of the indirect measurement of geometric errors of the machine from the linear and rotary axes. This paper presents an extensive study about the appropriateness and drawbacks of the regression function employed depending on the types of movement of the axes of any machine. In the same way, strengths and weaknesses of measurement methods and optimization techniques depending on the space available to place the measurement system are presented. These studies provide the most appropriate strategies to verify each machine tool taking into consideration its configuration and its available work space.


Small intestinal submucosa sandwich Zilver stent-grafts for TIPS: experimental pilot study in swine.
The aim of this study was the evaluation of preliminary suitability of the piglet small intestinal submucosa (SIS) sandwich Zilver endograft for experimental transjugular intrahepatic portosystemic shunt (TIPS) creation. TIPS was created in six swine. The five surviving animals underwent the follow-up portogram and were sacrificed at four weeks after TIPS creation. Gross and histologic examination was performed in all animals. TIPS creation was successful in all animals. One animal died four days after TIPS creation. In the five surviving animals, one shunt was occluded and four shunts were stenosed on the follow-up portogram. The mean percentage narrowing of the most advanced stenoses was 72% (range, 60%-100%). The most advanced stenosis was located in the parenchymal tract in three shunts and in the hepatic vein portion in one shunt. Gross and histologic examination showed abundant neointimal formation composed mainly of fibroblasts leading to the significant shunt stenoses. The piglet SIS sandwich Zilver stent-graft was found to offer only limited TIPS patency and should not be used for the definitive long-term TIPS study.


FBG Spectrum Regeneration by Ni-Coating and High-Temperature Treatment.
FBG sensors are used in many scientific and industrial fields for assessing the structural integrity of mechanical components and in very high (above 600 °C) or very low (cryogenic) temperature applications. The main concerns with the use of such sensors in applications involving extreme temperatures are related partly to the instability of the reflected spectrum, which tends to dissolve into the noise floor, and partly to the degradation of the mechanical properties of the optical fiber, which tends to worsen the inherent brittleness. All of this raises the need for a robust nickel protective coating to ensure the grating's integrity in high-temperature environments. In addition, the inherent brittleness of fiber-optic gratings leaves one to wonder whether it is possible to recover a broken, seemingly unusable sensor. In this way, a single-peak commercial FBG was intentionally broken in the middle of the grating length and re-spliced, inducing a strongly asymmetric chirped-like spectrum; then, a nickel coating was electrodeposited on its surface. The most important outcome achieved by this work is the regeneration of a highly distorted reflected spectrum through three thermal cycles performed from room temperature up to 500, 750, and 800 °C, respectively. After reaching a temperature of at least 700 °C, the spectrum, which has been drastically altered by splicing, becomes stable and restores its single peak shape. A further stabilization cycle carried out at 800 °C for 80 min led to an estimation of the stabilizing time of the new single-peak reflected spectrum.


F18, a novel small-molecule nonnucleoside reverse transcriptase inhibitor, inhibits HIV-1 replication using distinct binding motifs as demonstrated by resistance selection and docking analysis.
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are one of the key components of antiretroviral therapy drug regimen against human immunodeficiency virus type 1 (HIV-1) replication. We previously described a newly synthesized small molecule, 10-chloromethyl-11-demethyl-12-oxo-calanolide A (F18), a (+)-calanolide A analog, as a novel anti-HIV-1 NNRTI (H. Xue et al., J. Med. Chem. 53:1397-1401, 2010). Here, we further investigated its antiviral range, drug resistance profile, and underlying mechanism of action. F18 consistently displayed potent activity against primary HIV-1 isolates, including various subtypes of group M, circulating recombinant form (CRF) 01_AE, and laboratory-adapted drug-resistant viruses. Moreover, F18 displayed distinct profiles against 17 NNRTI-resistant pseudoviruses, with an excellent potency especially against one of the most prevalent strains with the Y181C mutation (50% effective concentration, 1.0 nM), which was in stark contrast to the extensively used NNRTIs nevirapine and efavirenz. Moreover, we induced F18-resistant viruses by in vitro serial passages and found that the mutation L100I appeared to be the dominant contributor to F18 resistance, further suggesting a binding motif different from that of nevirapine and efavirenz. F18 was nonantagonistic when used in combination with other antiretrovirals against both wild-type and drug-resistant viruses in infected peripheral blood mononuclear cells. Interestingly, F18 displayed a highly synergistic antiviral effect with nevirapine against nevirapine-resistant virus (Y181C). Furthermore, in silico docking analysis suggested that F18 may bind to the HIV-1 reverse transcriptase differently from other NNRTIs. This study presents F18 as a new potential drug for clinical use and also presents a new mechanism-based design for future NNRTI.


Treatment of benign bone tumours using external fixation.
We present a retrospective study of patients suffering from a variety of benign tumours in whom external fixators were used to treat deformity and limb-length discrepancy, and for the reconstruction of bone defects. A total of 43 limbs in 31 patients (12 male and 19 female) with a mean age of 14 years (2 to 54) were treated. The diagnosis was Ollier's disease in 12 limbs, fibrous dysplasia in 11, osteochondroma in eight, giant cell tumour in five, osteofibrous dysplasia in five and non-ossifying fibroma in two. The lesions were treated in the tibia in 19 limbs, in the femur in 16, and in the forearm in eight. The Ilizarov frame was used in 25 limbs, the Taylor Spatial Frame in seven, the Orthofix fixator in six, the Monotube in four and the Heidelberg fixator in one. The mean follow-up was 72 months (22 to 221). The mean external fixation period was 168 days (71 to 352). The mean external fixation index was 42 days/cm (22.2 to 102.0) in the 22 patients who required limb lengthening. The mean correction angle for those with angular deformity was 23 degrees (7 degrees to 45 degrees ). At final follow-up all patients had returned to normal activities. Four patients required a second operation for recurrent deformity of further limb lengthening. Local recurrence occurred in one patient, requiring further surgery.


Breast Milk as a Potential Source of Epstein-Barr Virus Transmission Among Infants Living in a Malaria-Endemic Region of Kenya.
We previously reported that infants in Kenya were infected with Epstein-Barr virus (EBV) at <6 months of age, suggesting that mothers were the likely source of transmissible virus to the infant. In this study, we investigated whether breast milk contained infectious EBV and the role of malaria in EBV shedding in breast milk. Breast milk samples were obtained from Kenyan mothers at postpartum weeks 6, 10, 14, and 18 and analyzed for presence of infectious EBV. We found that the prevalence of EBV DNA and the mean EBV load were significantly higher at 6 weeks and decreased through postpartum week 18 (P < .0001). High EBV load in breast milk correlated with mothers who had Plasmodium falciparum malaria at delivery. To determine whether viral DNA was encapsidated, breast milk samples were treated with DNAse before DNA extraction. Sixty percent of samples were DNAse resistant, suggesting that the viral DNA in breast milk was encapsidated. Next, we exposed peripheral blood mononuclear cells to breast milk supernatant, which resulted in the generation of EBV-positive lymphoblastoid cell lines, indicating that the virus in breast milk was infectious. Our data suggest that breast milk contains infectious EBV and is a potential source of viral transmission to infants living in malaria-endemic regions.


The treatment of endocarditis by vancomycin.
The narrow spectrum of vancomycin includes the common causal bacteria of endocarditis. This agent has been used since the 1960s for therapy and prophylaxis of infections when first-line drugs are inappropriate because of antibiotic resistance or drug allergy. Some personal experiences of vancomycin usage and a literature survey are presented in this paper which is based on the subdivision of endocarditis into medical, surgical (early--less than 60 days after operation--or late), and addict-related. The commonest bacterial causes of medical or late surgical infections are streptococci, and of the early surgical and addict-related infections are staphylococci. Vancomycin is bactericidal for Gram-positive cocci, except enterococci, but for optimal action it is arguable that combinations with gentamicin, fusidic acid, rifampicin or erythromycin should be used for staphylococcal endocarditis. The attainment of bactericidal blood levels may still be accompanied by failure of monotherapy and the need for early surgery is stressed. The prophylaxis of endocarditis is primarily required for tooth extraction and for cardiac surgery. The streptococci and staphylococci involved are normally vancomycin-susceptible, and the rabbit model shows that it is a suitable alternative to a beta-lactam and aminoglycoside combination. The combination is therefore suitable for patients already in hospital, especially those with prosthetic valves or undergoing cardiac surgery.


Complement Factor H Inhibits Anti-Neutrophil Cytoplasmic Autoantibody-Induced Neutrophil Activation by Interacting With Neutrophils.
Our previous study demonstrated that plasma levels of complement factor H (FH) were inversely associated with the disease activity of patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). In addition to serving as an inhibitor of the alternative complement pathway, there is increasing evidence demonstrating direct regulatory roles of FH on several cell types. Here, we investigated the role of FH in the process of ANCA-mediated activation of neutrophils and neutrophil-endothelium interaction. We demonstrated that FH bound to neutrophils by immunostaining and flow cytometry. Interestingly, ANCA-induced activation of neutrophils, including respiratory burst and degranulation, was inhibited by FH. Although FH enhanced neutrophils adhesion and migration toward human glomerular endothelial cells (hGEnCs), it inhibited ANCA-induced activation of neutrophils in the coculture system of hGEnCs and neutrophils. Moreover, the activation and injury of hGEnCs, reflected by the level of endothelin-1 in the supernatant of cocultures, was markedly reduced by FH. However, we found that FH from patients with active AAV exhibited a deficient ability in binding neutrophils and inhibiting ANCA-induced neutrophil activation in fluid phase and on endothelial cells, as compared with that from healthy controls. Therefore, our findings indicate a novel role of FH in inhibiting ANCA-induced neutrophil activation and protecting against glomerular endothelial injury. However, FH from patients with active AAV are deficient in their ability to bind neutrophils and inhibit neutrophil activation by ANCA. It further extends the current understanding of the pathogenesis of AAV, thus providing potential clues for intervention strategies.


Infection prevention as "a show": a qualitative study of nurses' infection prevention behaviours.
Control of infection and prevention of healthcare associated infections is an ongoing issue worldwide. Yet despite initiatives and strategies to reduce the burden that these infections cause, healthcare workers' practice is still reported as suboptimal and these infections persist. Much of the research to date has primarily focused on predicting infection prevention behaviours and factors associated with guideline compliance. While this has given valuable insight, an investigation aiming to understand and explain behaviours that occur in everyday practice from the perspective of the actors themselves may hold the key to the challenges of effecting behaviour change. This study questioned "How can nurses' infection prevention behaviour be explained?" This paper presents one of three identified themes 'Rationalising dirt-related behaviour'. This interpretative qualitative study uses vignettes, developed from nurses' accounts of practice, to explore nurses' reported infection prevention behaviours. Registered nurses working in an acute hospital setting and had been qualified for over a year. They were recruited while studying part-time at a London University. Twenty semi-structured interviews were undertaken using a topic guide and vignettes. Interviews were transcribed verbatim and analysed using the framework method. The findings demonstrate that participants were keen to give a good impression and present themselves as knowledgeable practitioners, although it was evident that they did not always follow procedure and policy. They rationalised their own behaviour and logically justified any deviations from policy. Deviations in others were criticised as irrational and explained as superficial and part of a 'show' or display. However, participants also gave a presentation of themselves: a show or display that was influenced by the desire to protect self and satisfy patient scrutiny. This study contributes to the identification and explanation of nurses' infection prevention behaviours which are considered inappropriate or harmful. Behaviour is multifaceted and complex, stemming from a response to factors that are outside a purely 'scientific' understanding of infection and not simply understood as a deficit in knowledge. This calls for educational interventions that consider beliefs, values and social understanding of dirt and infection.


A systematic review of the efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia.
Vascular dementia (VaD) is a comprehensive syndrome related to the damage of cognitive function and various cerebral vascular illnesses. VaD is also generally recognized as the second most common type of dementia after Alzheimer disease, contributing to 30% of the dementia population in Asia and developing countries. The ability of donepezil hydrochloride and nimodipine had been respectively proven in improving cognitive function in vascular dementia. However, whether the combined application of both drugs contribute to better efficacy remains as a research hotspot. Studies had shown definite satisfactory result with such combination, however evidence-based evaluation of the efficacy is still lacking. Therefore, meta-analysis is employed in this study to evaluate the efficacy and safety of using donepezil hydrochloride combined with nimodipine in treating VaD to provide references for clinical treatments. The efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia is systematically reviewed to provide evidence-based references for clinical applications. Both Chinese and English databases were searched from the start till August, 2020 for any RCT regarding the combined use of the 2 drugs in treating vascular dementia. Two investigators would later evaluate and screened out research and data based on an improved Jaded scale. Software Rev Man 5.3.0 was employed to carry out meta-analysis on clinical effificacy, mini-mental state examination (MMSE) ratings, activity of daily living (ADL) ratings, and clinical dementia scale (CDR) ratings. Donepezil hydrochloride combined with nimodipine had demonstrated satisfactory efficacy on the treatment of vascular dementia. Improvements were namely spotted on MMSE scale, ADL scale, and CDR scale, with the utmost efficacy by 12 weeks after intervention. Donepezil hydrochloride combined with nimodipine had good efficacy in the treatment of patients with vascular dementia, mainly in terms of improving the Simple MMSE scores, the ability to use daily living scale (ADL) scores and the CDR, and the best results were obtained after 12 weeks of intervention. Such conclusion should be cautiously evaluated.