Biotics: An emerging food supplement for health improvement in the era of immune modulation.
The involvement of the commensal microbiota in immune function is a multifold process. Biotics, such as probiotics, prebiotics, synbiotics, and paraprobiotics, have been subjected to animal and human trials demonstrating the association between gut microbes and immunity biomarkers leading to improvement in overall health. In recent years, studies on human microbiome interaction have established the multifarious role of biotics in maintaining overall health. The consumption of biotics has been extensively reported to help in maintaining microbial diversity, enhancing gut-associated mucosal immune homeostasis, and providing protection against a wide range of lifestyle disorders. However, the establishment of biotics as an alternative therapy for a range of health conditions is yet to be ascertained. Despite the fact that scientific literature has demonstrated the correlation between biotics and immune modulation, most in vivo and in vitro reports are inconclusive on the dosage required. This review provides valuable insights into the immunomodulatory effects of biotics consumption based on evidence obtained from animal models and clinical trials. Furthermore, we highlight the optimal dosages of biotics that have been reported to deliver maximum health benefits. By identifying critical research gaps, we have suggested a roadmap for future investigations to advance our understanding of the intricate crosstalk between biotics and immune homeostasis.


Impact of visual, olfactory, and auditory cues on circulating concentrations of ghrelin in wethers.
Ghrelin is a hormone that stimulates feed intake and regulates energy homeostasis. A link has been observed in sheep, in which simulated feedings at scheduled meal times resulted in an increase in ghrelin concentrations. The present study sought to characterize the effect of feeding cues outside of scheduled meal times on circulating ghrelin concentrations in sheep. Katahdin wethers (age 201 ± 4.9 d; weight 35 ± 1.2 kg) were not offered feed (CONT; = 5), offered 275 g of feed (FED; = 5), or fitted with a muzzle and offered 275 g of feed (SHAM; = 5) during the sampling period, which began 2.5 h after normally scheduled daily feeding time. Blood samples were collected via jugular catheter every 15 min for 2.5 h. Feed was offered for 15 min 0.5 h after the start of blood sampling. The CONT samples were collected on d 1, and FED and SHAM samples were collected on d 2. The active ghrelin present in the plasma was then analyzed by RIA. After the Shapiro-Wilk W goodness of fit test demonstrated that 1 SHAM wether was an outlier and it was removed, data were tested for effect of treatment (FED, SHAM, or CONT), time, and treatment × time interaction using procedures for repeated measures with JMP Software (SAS Inst. Inc., Cary, NC). There was no treatment or time effect ( > 0.05); however, there was a treatment × time interaction on plasma ghrelin concentrations ( = 0.0028) such that ghrelin concentrations in SHAM wethers were greater than in CONT wethers 15, 60, and 90 min after feeding, whereas ghrelin concentrations in SHAM wethers were greater than those in FED wethers 30, 60, 90, and 120 min after feeding ( < 0.05). Within the SHAM treatment, ghrelin concentrations were greater at 15 min than at -30 min. Moreover, ghrelin concentrations within the FED treatment were greater at -30 min than at 30, 45, 60, 90, 105, and 120 min and at -15 min than at 15 through 120 min. The area under the curve representing circulating concentrations of ghrelin in CONT, FED, and SHAM treatments, determined using the trapezoidal method, yielded a treatment effect with a tendency toward significance ( = 0.0866). These results indicate plasma ghrelin concentrations in scheduled meal-fed wethers are elevated following visual, olfactory, and auditory feeding cues outside of scheduled feeding times.


Woeseia oceani gen. nov., sp. nov., a chemoheterotrophic member of the order Chromatiales, and proposal of Woeseiaceae fam. nov.
A novel Gram-stain-negative, rods or bent rods, facultatively anaerobic, oxidase-negative and catalase-positive bacterium, designated XK5T, was isolated from coastal sediment from Xiaoshi Island, Weihai, China. Optimal growth occurred at 28-35 °C (range 8-42 °C) and pH 7.0-8.0 (range pH 6.0-9.0) with 1-3 % (w/v) NaCl (range 0.5-8 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain XK5T was 92.1 % similar to the type strain of Thioalkalivibrio thiocyanodenitrificans, 91.9 % to the type strain of Thioalkalivibrio sulfidiphilus and 91.8 % to the type strain of Thioalkalivibrio denitrificans; similarity to other species was less than 91 %. The isolate and closely related environmental clones formed a novel family level clade in the order Chromatiales. The polar lipid profile of the novel isolate consisted of phosphatidylethanolamine, phosphatidylglycerol and some other unknown phospholipids, aminolipids and lipids. Major cellular fatty acids were iso-C17 : 1ω9c and iso-C15 : 0 and the main respiratory lipoquinone was Q-8. The DNA G+C content of strain XK5T was 59.3 mol%. Comparative analysis of 16S rRNA gene sequences and characterization indicated that strain XK5T represents a novel species of a new genus within a novel family of the order Chromatiales, for which the name Woeseia oceani gen. nov., sp. nov. is proposed. The type strain of Woeseia oceani is XK5T ( = ATCC BAA-2615T = CICC 10905T). In addition, a novel family name, Woeseiaceae fam. nov., is proposed to accommodate the genus Woeseia.


Stuck in the moment: cognitive inflexibility in preschoolers following an extended time period.
Preschoolers display surprising inflexibility in problem solving, but seem to approach new challenges with a fresh slate. We provide evidence that while the former is true the latter is not. Here, we examined whether brief exposure to stimuli can influence children's problem solving following several weeks after first exposure to the stimuli. We administered a common executive function task, the Dimensional Change Card Sort, which requires children to sort picture cards by one dimension (e.g., color) and then switch to sort the same cards by a conflicting dimension (e.g., shape). After a week or after a month delay, we administered the second rule again. We found that 70% of preschoolers continued to sort by the initial sorting rule, even after a month delay, and even though they are explicitly told what to do. We discuss implications for theories of executive function development, and for classroom learning.


[Analgesic effects of chemical lumbar sympathectomy on refractory pain in the lower limbs].
To evaluate the effect of chemical lumbar sympathectomy (CLS) on relieving refractory pain in the lower limbs. Twenty-four patients with refractory pain in the lower limbs underwent CLS under X-ray guidance, and 2 ml contrast agent was injected at 1/3 of the second L2 vertebrae (the L2 sympathetic ganglion). Lidocaine was then injected followed by injection of 7% phenol for performing CLS. The visual analog scale was used to assess the pain severity before and after CLS. The effect of CLS on relieving lower limb pain was compared with that of oral pain-relieving medication. The lower limb pain was obviously relieved as shown by significantly decreased VAS scores in these patients after CLS. CLS exhibited a much more potent effect of pain relief in the lower limbs than the oral medication. CLS produces significant analgesic effects to relieve refractory pain in the lower limbs.


Hay fever holiday: health, leisure, and place in Gilded-Age America.
By the 1880s hay fever (also called June Cold, Rose Cold, hay asthma, hay cold, or autumnal catarrh) had become the pride of America's leisure class. In mid-August each year, thousands of sufferers fled to the White Mountains of New Hampshire, to the Adirondacks in upper New York State, to the shores of the Great Lakes, or to the Colorado plateau, hoping to escape the dreaded seasonal symptoms of watery eyes, flowing nose, sneezing fits, and attacks of asthma, which many regarded as the price of urban wealth and education. Through a focus on the White Mountains as America's most fashionable hay fever resort in the late nineteenth century, this essay explores the embodied local geography of hay fever as a disease. The sufferers found in the White Mountains physical relief, but also a place whose history affirmed their social identity and shaped their relationship to the natural environment. And, they, in turn, became active agents in shaping the geography of place: in the very material relationships of daily life, in the social contours of the region, and in the symbolic space that nature inhabited. In the consumption of nature for health and pleasure, this article suggests, lies an important, yet relatively unexplored, source for understanding changing perceptions of environment and place and the impact of health on the local and regional transformation of the North American landscape.


[Radiomodifying effect of serotonin on the cells of the hematopoietic system].
Mice were injected with serotonin (0.5 and 2.0 mg/mouse) 15 min before and immediately after irradiation (4.5 and 7.0 Gy). With the preparation administered prior to irradiation one could observe an increase in the quantity of CFUc survived (endo- and exo-test), acceleration of restoration of cellularity (in the bone marrow) and growth of the spleen weight. The acceleration of restoration of the bone-marrow cellularity was also noted when serotonin was administered after irradiation. The post-irradiation effect of serotonin was also detected in cells in vitro. It is concluded that the radiomodifying effect of serotonin on the haemopoietic system is due to a decrease in the number of damaged cells and increase in the rate of reproduction of intact cells.


Prognosis of colorectal cancer varies in different high-risk conditions.
Variation in prognosis between different colorectal cancer (CRC) patient groups was studied by comparing the survival rates of patients belonging to three cancer predisposition groups with those with sporadic CRC. The high-risk groups included 43 members of hereditary nonpolyposis colorectal cancer (HNPCC) families, 25 patients with familial adenomatous polyposis (FAP) and 33 patients with underlying ulcerative colitis (UC). The control group included 122 consecutive sporadic CRC patients. Cumulative 5-year survival was highest in HNPCC (86%), which is significantly better than in sporadic colorectal cancer (59%, hazard ratio 0.41, P = 0.02). Cancer associated with UC had a 5-year survival rate of 39%, which is significantly less than in sporadic cancer (hazard ratio 1.83, P = 0.03). There was no significant difference in the survival between patients with FAP and patients with sporadic CRC (hazard ratio 1.27, P = 0.5). Exclusion of cases detected by screening examinations slightly reduced the survival rates; 85% for HNPCC, 53% for FAP and 28% for UC. However, the differences between the groups remained significant. The survival of patients with HNPCC was found to be better than that among other groups in this study, which probably relates to the specific tumourigenesis involving DNA mismatch repair dysfunction.


Paraneoplastic Anti-3-hydroxy-3-methylglutary-coenzyme A Reductase Antibody-positive Immune-mediated Necrotizing Myopathy in a Patient with Uterine Cancer.
We report the case of a 69-year-old woman with proximal limb muscle weakness, who received post-operative chemotherapy for uterine cancer. Her serum creatinine kinase level was high (10,779 mg/dL) and a muscle biopsy from her left biceps revealed various sizes of muscle fibers accompanied by necrotic and regenerating fibers. She was positive for anti-3 hydroxy-3-methylglutary-coenzyme A reductase (anti-HMGCR) antibodies, but negative for anti-signal recognition particle (anti-SRP) antibodies. She was diagnosed with immune-mediated necrotizing myopathy (IMNM) and treated with prednisolone. Our findings indicate that not only drug-induced myopathy but also paraneoplastic myopathy can be involved in the pathogenesis of IMNM.


Retrograde intra-vesical reconstructive surgery (RIVRS): A novel technique.
Management of distal ureter by en block resection during radical nephrectomy for upper urinary tract transitional cell carcinoma (TCC) is considered as standard of care. In this report, we describe our technique for management of lower ureter which utilizes both the endoscopic and laparoscopic approach. The nephrectomy including the dissection of the lower ureter was completed laproscopically. The ureteral orifice was scored using a hook passed through a 24 Fr nephroscope and secured .Transurethral suturing of the defect with SewRight SR5 device passed through the working channel of the 24 Fr nephroscope was done. Our report highlights the fact that management of lower ureter in TCC pelvis can be done endoscopically/laproscopically without compromising the oncological principles. Our novel technique demonstrates feasibility of intra mural resection of the ureter and primary closure of the bladder endoscopically.


Generalized morphea as the first sign of breast carcinoma: a case report.
Generalized morphea is a rare idiopathic form of scleroderma that literally means "hard skin." Morphea is usually considered an isolated event that is not associated with malignancy. However, case reports of lung, hematologic, and breast cancer occurring simultaneously with large plaque morphea have caused dermatologists to question whether a work-up for malignancy is appropriate. We highlight a case of generalized morphea that preceded invasive ductal carcinoma of the breast and provide a discussion about the possible paraneoplastic origin of generalized morphea and systemic sclerosis (SSc).


Administration of 2.5 mg of estradiol followed by 1,500 mg of progesterone to anovulatory mares promote similar uterine morphology, hormone concentrations and molecular dynamics to those observed in cyclic mares.
To test the hypothesis that the administration of 2.5 mg of estradiol benzoate (EB) followed by 1500 mg of long acting progesterone (LA P4) causes similar uterine changes and molecular dynamics in anovulatory mares to those observed in cyclic ones, we evaluated the changes of estrogen (ERα and ERβ) and progesterone receptors (PR) in anestrous, transitional and cyclic mares by RT-qPCR and immunohistochemistry. In addition, we evaluated uterine edema, tonus and estrogens and progesterone plasma profile. Endometrial biopsies were taken from anestrous and transitional mares immediately before EB injection, 48 h after EB administration and five days after LA P4 was given. In cyclic mares, biopsies were collected at estrus and at five days after ovulation. Similar estrogen peaks were achieved after the injection of the single EB dose between treated and cyclic groups, as well as maximum uterine edema. Uterine tone was increased to diestrus levels after administration of 1500 mg of LA P4. Changes in relative abundance of transcripts for PR, ERα and ERβ when progesterone stimulated endometrium was compared to estrogen stimulated endometrium were similar between cyclic and non-cyclic treated mares. However, apparent decreased PR in the endometrial glandular epithelium was not observed in non-cyclic mares five days after LA P4 administration as observed at five days after ovulation in cyclic mares. The protocol produced similar endometrial edema, uterine tonus and changes in relative abundance of PR, ERα and ERβ transcripts to those observed in cyclic mares during late estrus and early diestrus, as well as similar estradiol and estrogen conjugate plasma concentrations.


The American South: Explorations on southern attachments and personal values.
Group membership is central to understanding political behavior and political psychology. However, regional group membership is rarely examined, despite its relevance to political psychology and personal values. To address this, we investigated the relationships among southern identity, southern nationalism, southern pride, and southern constructive patriotism for the U.S. South, as well as the connections between personal values and southern attachments. Results from the structural equation modeling (N = 268) revealed that stronger southern identity predicted more southern nationalism, southern pride, and southern constructive patriotism. Additionally, greater endorsement of conservation values predicted stronger southern identity and southern pride; those favoring self-transcendence values exhibited less southern nationalism and more southern constructive patriotism; and those with higher self-enhancement values expressed more southern nationalism. This study confirms the predictive role of southern identity on other southern attachments and provides support for how different southern attachments are related to but distinctive from each other.


Studies on the removal of Pb(II) from wastewater by activated carbon developed from Tamarind wood activated with sulphuric acid.
The low-cost activated carbon were prepared from Tamarind wood material by chemical activation with sulphuric acid for the adsorption of Pb(II) from dilute aqueous solution. The activated carbon developed shows substantial capacity to adsorb Pb(II) from dilute aqueous solutions. The parameters studied include physical and chemical properties of adsorbent, pH, adsorbent dose, contact time and initial concentrations. The kinetic data were best fitted to the Lagergren pseudo-first-order and pseudo-second order models. The isotherm equilibrium data were well fitted by the Langmuir and Freundlich models. The maximum removal of lead(II) was obtained 97.95% (experimental) and 134.22 mg/g (from Langmuir isotherm model) at initial concentration 40 mg/l, adsorbent dose 3g/l and pH 6.5. This high uptake showed Tamarind wood activated carbon as among the best adsorbents for Pb(II).


In vitro antioxidant properties of calcium dobesilate.
Calcium dobesilate, a vascular protective agent, was tested in vitro for its scavenging action against oxygen free radicals. Calcium dobesilate was as potent as rutin to scavenge hydroxyl radicals (IC50 = 1.1 vs 0.7 microM, respectively). It was also able to scavenge superoxide radicals, but with 23 times less potency than rutin (IC50 = 682 vs 30 microM, respectively). Calcium dobesilate significantly reduced platelet activating factor (PAF)-induced chemiluminescence in human PMN cells and lipid peroxidation by oxygen free radicals in human erythrocyte membranes, although these actions required calcium dobesilate concentrations > or = 50 microM. Finally, in cultured bovine aortic endothelial cells, magnesium dobesilate reduced the increase in cytosolic free calcium induced by hydrogen peroxide and inhibited phenazine methosulfate-induced cell potassium loss. In conclusion, calcium dobesilate was effective in scavenging hydroxyl radicals in vitro, at therapeutically relevant concentrations. Conversely, higher concentrations of the compound were required to scavenge superoxide radicals or to protect the cells against the deleterious effects of intracellular reactive oxygen species. Further studies in vivo are required to determine if these antioxidant properties of calcium dobesilate can play a role in its vascular protective mechanisms.


[Sentinel surveillance for viral hepatitis C in China, 2016-2017].
Objective: To understand the prevalence of hepatitis C virus (HCV) infection in 5 populations in China during 2016-2017 and provide evidence for the estimation of prevalence trend of hepatitis C and evaluation on the prevention and control effect. Methods: A total of 87 national sentinel surveillance sites for hepatitis C were set up in 31 provinces (autonomous regions and municipalities) of China to obtain the information about HCV infection prevalence in 5 populations, including volunteer blood donors, people receiving physical examination, patients receiving invasive diagnosis and treatment, patients receiving hemodialysis, and clients visiting family planning outpatient clinics. From April to June, 2016 and 2017, cross-sectional surveys were repeatedly conducted in the 5 populations and blood samples were collected from them for HCV antibody detection. Results: In 2016, 86 sentinel sites completed the surveillance (one sentinel site was not investigated), and 115 841 persons were surveyed. The overall HCV positive rate was 0.38% (442/115 841, 95%CI: 0.23%-0.53%). In 2017, all the 87 sentinel sites completed the surveillance, and 120 486 persons were surveyed. The overall HCV positive rate was 0.37% (449/120 486, 95%CI: 0.23%-0.52%). In 2016 and 2017, the anti-HCV positive rates were 4.46% (223/5 005, 95%CI: 2.18%-6.73%) and 4.39% (216/4 919, 95%CI: 2.29%-6.50%) respectively in hemodialysis patients, 0.85% (44/5 200, 95%CI: 0.27%-1.42%) and 0.70% (36/5 150, 95%CI: 0.15%-1.24%) respectively in patients receiving invasive diagnosis and treatment and remained to be ≤0.25% in volunteer blood donors, people receiving physical examination and clients visiting family planning outpatient clinics. Results for the comparison of the anti-HCV positive rates in the 5 populations indicated that the differences were significant (F=23.091, P<0.001 in 2016 and F=20.181, P<0.001 in 2017). Conclusions: Data from the sentinel surveillance of HCV infection on prevalence in China showed that the anti-HCV positive rates varied in the 5 populations during 2016-2017. The anti-HCV positive rate appeared the highest in the hemodialysis patients, followed by that in the patients receiving invasive diagnosis and treatment, and the prevalence of HCV infection in other 3 populations were at low levels.


Impact of different antiseptics on umbilical cord colonization and cord separation time.
There is still some uncertainty on cord care practices all around the world, especially in developing countries. The aim of our study was to investigate the effects of six different umbilical cord care practices on the rate of colonization and cord separation time. A total of 516 newborns were randomly allocated to the following six umbilical cord care groups: group 1 received dry care; groups 2-4 received a single application of 70% alcohol, 4% chlorhexidine, or povidon-iodine in the delivery room, respectively, which were discontinued thereafter; groups 5 and 6 received a single application of 70% alcohol or 4% chlorhexidine, respectively, starting in the delivery room and continuing every six hours until discharge. Umbilical cords were examined on the second and third days and between the fifth and seventh day for signs of omphalitis. Swab cultures were taken on the second or third day from all cases. Cord separation time (median [interquartile range]) was the shortest for group 1 (7 [6-7] days) and the longest for group 3 (10 [7-12] days) and group 6 (10 [8-12] days) (p < 0.001). The cord colonization in the swab cultures was significantly lower in groups 3 and 6 (p < 0.001). Omphalitis was detected in eight (1.5%) patients among the study population, and there was no significant difference between the groups. Our study showed that chlorhexidine application was the most effective agent in decreasing colonization, though it increased cord separation time significantly in both groups.


Role of hormonal and reproductive factors in the etiology and treatment of uterine leiomyoma.
Uterine leiomyomas are the most common gynecologic neoplasm in reproductive-age women. While it is clear that hormonal factors play a prominent role in this disease, how steroid hormones contribute to disease etiology or may be utilized as targets for intervention are currently areas of active scientific investigation. To study the impact of hormones on uterine leiomyomas, the Eker rat has been developed as an in vivolin vitro animal model system for these tumors. Spontaneous leiomyomas arise in intact Eker rats with a high frequency and leiomyoma-derived cell lines from these animals maintain the biochemical and physiological characteristics of the tumors from which they were obtained. Using this animal model system, it has been established that tumor development is absolutely dependent on steroid hormones and that sensitivity/responsiveness to estrogen is enhanced in tumors and tumor-derived cell lines. Modulation of hormonal milieu, such as that which naturally occurs during pregnancy, can effectively inhibit tumor development. The hormone responsiveness of these tumors makes them good candidates for hormonal therapy. Selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene hold promise as potential therapeutic agents for this disease. SERMs inhibit proliferation of leiomyoma-derived cell lines in vitro, repress the growth of these lines in nude mice, and, when administered over a 2- to 4-month course of treatment to Eker rats, reduce tumor incidence by more than 50%. In addition to endogenous hormones, xenoestrogens in our environment (e.g., phytoestrogens, organochlorine pesticides, pharmacologic compounds) are of potential concern with regards to their impact on this disease. These environmental estrogens have been shown to promote the growth of leiomyoma cells in vitro and in vivo. Further elucidation of the role of these and other hormonal and reproductive factors in the development of uterine leiomyoma will be invaluable for increasing our understanding of the etiology of this disease and developing new therapeutic strategies to help to reduce the negative impact of uterine leiomyomas on women's health.


Plasma aldosterone concentration and plasma renin activity decrease during the third trimester in women with twin pregnancies.
Changes in the plasma aldosterone concentration (PAC) and the plasma renin activity (PRA) have not been extensively studied in women with twin pregnancies. The PAC and PRA levels were determined during the second and third trimesters and on postpartum day 3 in 14 normotensive women with twin pregnancies and 80 normotensive and 7 preeclamptic women with singleton pregnancies. In women with twin pregnancies, elevated PAC and PRA levels (598 ± 248 pg/mL and 10.0 ± 4.7 ng/mL/h, respectively) in the second trimester decreased significantly during the third trimester (to 396 ± 210 pg/mL and 3.5 ± 2.9 ng/mL/h, respectively), whereas the corresponding PAC increased significantly (from 421 ± 207 to 667 ± 371 pg/mL) and the PRA did not change significantly (from 7.3 ± 3.4 to 6.9 ± 4.2 ng/mL/h) in women with normal singleton pregnancies. These changes in the PAC and PRA levels in women with twin pregnancies resembled those in hypertensive women with singleton pregnancies. In women with twin pregnancies, both the PAC and PRA levels were significantly enhanced during the second trimester, whereas those in the third trimester were significantly reduced compared with those in women with normal singleton pregnancies.


Cell transplantation for diabetes.
For 30 years there has been experimental work aimed at transplanting islets for the treatment of diabetes with a view to curing the disease and preventing the secondary complications. Many technical difficulties were experienced, first in isolating the islets without damaging them, and second in finding a suitable place to inject them, but until recently the results of a vascularized pancreas transplant have been superior to islet transplantation. In 2000, the group in Edmonton, headed by Shapiro, published encouraging results using a different immunosuppression in transplanting patients earlier in the course of their disease than had been attempted previously. The results were excellent at a year and good at 2 years in patients with Type I diabetes, however there was the rather worrying attrition at five years. Nevertheless, the Edmonton observations were proof of concept and have intensified interest in treating diabetes and other diseases where a specific protein synthesis was required by cell transplantation and/or genetic engineering. The recent interest in embryonic stem cells extenuated these efforts and progress is being made in defining the difficulties, which are greater than most workers would have predicted. In this review, the subject is discussed explaining where progress needs to be made in order to provide treatment that would be of value to patients.


Variable Nanoelectrode at the Air/Water Interface by Hydrogel-Integrated Atomic Force Microscopy Electrochemical Platform.
A nanoelectrode with a controllable area was developed using commercial atomic force microscopy and a hydrogel. Although tremendous advantages of small electrodes from micrometer scale down to nanometer scale have been previously reported for a wide range of applications, precise and high-throughput fabrication remains an obstacle. In this work, the set-point feedback current in a modified scanning ionic conductance microscopy system controlled the formation of electrodes with a nanometer-sized area by contact between the boron-doped diamond (BDD) tip and the agarose hydrogel. The modulation of the electroactive area of the BDD-coated nanoelectrode in the hydrogel was successively investigated by the finite element method and cyclic voltammetry with the use of a redox-contained hydrogel. Moreover, this nanoelectrode enables the simultaneous imaging of both the topography and electrochemical activity of a polymeric microparticle embedded in a hydrogel.


[Fracture of the triquetrum. Pathomechanics, classification, treatment and results within the scope of follow-up].
In 231 patients, 65 underwent a follow-up control after a mean interval of 46.8 months. Fractures of the triquetrum are classified, considerations on the pathomechanism are explained, and the clinical and radiological outcome are evaluated. In case of a fall to the extended and ulnar deviated wrist, chip fractures of the triquetrum are caused by the chisel-like effect of the dorsoproximal edge of the hamate. Our mode of conservative treatment with immobilisation for three weeks has proven successful. Healing of the bony fragment occurs not before six to eight weeks. Surgical treatment was never indicated. A posttraumatic instability of the wrist was not observed. On the basis of good vascularisation, avascular necrosis of the triquetrum is not to be feared. All fractures of the body of the triquetrum resulted in osseous consolidation.


Biophysical Characterization of Cationic Antibacterial Oligothioetheramides.
Biophysical analysis into the mechanism of action of membrane-disrupting antibiotics such as antimicrobial peptides (AMPs) and AMP mimetics is necessary to improve our understanding of this promising but relatively untapped class of antibiotics. We evaluate the impact of cationic nature, specifically the presence of guanidine versus amine functional groups using sequence-defined oligothioetheramides (oligoTEAs). Relative to amines, guanidine groups demonstrated improved antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). To understand the mechanism of action, we evaluated membrane interactions by performing a propidium iodide assay and fluorescence microscopy of supported MRSA mimetic bilayers treated with oligoTEAs. Both studies demonstrated membrane disruption, while fluorescence microscopy showed the formation of lipid aggregates. We further analyzed the mechanism using surface plasmon resonance with a recently developed two-state binding model with loss. Our biophysical analysis points to the importance of lipid aggregation for antibacterial activity and suggests that guanidine groups improve antibacterial activity by increasing the extent of lipid aggregation. Altogether, these results verify and rationalize the importance of guanidines for enhanced antibacterial activity of oligoTEAs, and present biophysical phenomena for the design and analysis of additional membrane-active antibiotics.


Intracellular trafficking pathways of Cx43 gap junction channels.
Gap Junction (GJ) channels, including the most common Connexin 43 (Cx43), have fundamental roles in excitable tissues by facilitating rapid transmission of action potentials between adjacent cells. For instance, synchronization during each heartbeat is regulated by these ion channels at the cardiomyocyte cell-cell border. Cx43 protein has a short half-life, and rapid synthesis and timely delivery of those proteins to particular subdomains are crucial for the cellular organization of gap junctions and maintenance of intracellular coupling. Impairment in gap junction trafficking contributes to dangerous complications in diseased hearts such as the arrhythmias of sudden cardiac death. Of recent interest are the protein-protein interactions with the Cx43 carboxy-terminus. These interactions have significant impact on the full length Cx43 lifecycle and also contribute to trafficking of Cx43 as well as possibly other functions. We are learning that many of the known non-canonical roles of Cx43 can be attributed to the recently identified six endogenous Cx43 truncated isoforms which are produced by internal translation. In general, alternative translation is a new leading edge for proteome expansion and therapeutic drug development. This review highlights recent mechanisms identified in the trafficking of gap junction channels, involvement of other proteins contributing to the delivery of channels to the cell-cell border, and understanding of possible roles of the newly discovered alternatively translated isoforms in Cx43 biology. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve.


Growth Retardation Of Chick Embryo Exposed To A Low Dose Of Electromagnetic Waves.
The objectives of this study were to explore the effects of low dose of the nonionizing (REW) emitted by a mobile phone on the development of chick embryo. one hundred and twenty chick fertilized eggs were equally divided into a control and an exposed group. Sixty fertilized eggs were placed in an egg incubator with a mobile phone (SAR US: 1.10W/kg (head) 0.47 W/kg body) in silent mode having vibration disable mode. Mobile was called for a total of 20 minutes in 24 hours. Twenty embryos each were sacrificed at day 5, 10 and 15, mortality, wet body weight, head to rump length, eye diameter and morphological changes were noted. The control group, 60 eggs were incubated in the same conditions, having removed the phone. No mortality was noted. The experimental group exposed to REW showed subcutaneous haemorrhagic areas and significant growth retardation at day 10 as evidence by smaller eye diameter, wet weight and CR length than the control group. There were no significant growth differences at either day 5 or at day 15. Electromagnetic waves emitted from mobile phones even though for a very short duration of 20 minutes per day have affected the growth of the chick embryo at day 10 of incubation, Hence exposure of these waves are not 100% safe.


[Comparative study of biological effect of purified gonadotropins of sturgeon (Acepenser stellatus) and carp (Cyprinus carpio)].
A comparison was made of the biological effect of purified gonadotropins of the sevryuga and the carp on the activation of adenyl cyclase in the homogenate of the goldfish ovary, the reaction of spermiation in two species of frogs, and the in vitro maturation of oocytes of two amphibian species and sevryuga. The ratio of specific activities of the preparations under study was shown to vary markedly with respect to test-subject and test-reaction. The data obtained suggest, thus, qualitative differences in the effect of the gonadotropins under study and the response of organs-targets. It is proposed to use the system of in vitro maturation of amphibian oocytes for studying the phenomenon of species specificity of gonadotropins of lower vertebrates.


Efficacy of Deltamethrin Against Stored-Product Beetles at Short Exposure Intervals or on a Partially Treated Rice Mass.
Stored-product insects can potentially be exposed to grain protectants for variable time periods. Adults of three species, the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae), the granary weevil Sitophilus granarius (L.) (Coleoptera: Curculionidae), and the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) were exposed for 1, 4, 8, and 24 h on brown rice treated with the pyrethroid deltamethrin at the label rate of 0.5 ppm, then removed and placed on untreated rice. Adults of these same species plus the rice weevil, Sitophilus oryzae (L.) (Coleoptera: Curculionidae), the maize weevil, Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae), and the warehouse beetle, Trogoderma variabile Ballion (Coleoptera: Dermestidae) were exposed on treated brown rice mixed with varying amounts of untreated rice to assess progeny production. Immediate and delayed mortality of exposed adults did not exceed 7% for any exposure interval, but progeny production for T. castaneum was generally lower in comparison with that for the other species. Increasing the amount of treated rice decreased progeny production of R. dominica but not for any Sitophilus species. Mixed results were obtained for T. castaneum and T. variabile. Results show that long exposure times and treatment of an entire rice mass may be necessary to give complete control of stored-product beetles.


The Biomechanical Role of the Deltoid Ligament on Ankle Stability: Injury, Repair, and Augmentation.
Deltoid ligament injuries occur in isolation as well as with ankle fractures and other ligament injuries. Both operative treatment and nonoperative treatment are used, but debate on optimal treatment continues. Likewise, the best method of surgical repair of the deltoid ligament remains unclear. To determine the biomechanical role of native anterior and posterior components of the deltoid ligament in ankle stability and to determine the efficacy of simple suture versus augmented repair. Controlled laboratory study. Ten cadaveric ankles (mean age, 51 years; age range, 34-64 years; all male specimens) were mounted on a 6 degrees of freedom robotic arm. Each specimen underwent biomechanical testing in 8 states: (1) intact, (2) anterior deltoid cut, (3) anterior repair, (4) tibiocalcaneal augmentation, (5) deep anterior tibiotalar augmentation, (6) posterior deltoid cut, (7) posterior repair, and (8) complete deltoid cut. Testing consisted of anterior drawer, eversion, and external rotation (ER), each performed at neutral and 25° of plantarflexion. A 1-factor, random-intercepts, linear mixed-effect model was created, and all pairwise comparisons were made between testing states. Cutting the anterior deltoid introduced ER (+2.1°; P = .009) and eversion laxity (+6.2° of eversion; P < .001) at 25 degrees of plantarflexion. Anterior deltoid repair restored native ER but not eversion. Tibiocalcaneal augmentation reduced eversion laxity, but tibiotalar augmentation provided no additional benefit. The posterior deltoid tear showed no increase in laxity. Complete tear introduced significant anterior translation, ER, and eversion laxity (+7.6 mm of anterior translation, +13.8° ER and +33.6° of eversion; P < .001). A complete deltoid tear caused severe instability of the ankle joint. Augmented anterior repair was sufficient to stabilize the complete tear, and no additional benefit was provided by posterior repair. For isolated anterior tear, repair with tibiocalcaneal augmentation was the optimal treatment. Deltoid repair with augmentation may reduce or avoid the need for prolonged postoperative immobilization and encourage accelerated rehabilitation, preventing stiffness and promoting earlier return to preinjury activity.


[Comorbidity and polymorbidity - a modern interpretation and urgent tasks facing the therapeutic community].
The article presents an overview of data on polymorbidity. It is shown that polymorbidity is associated with higher mortality, disability, side effects of treatment, increased use of health system resources, and also with a lower quality of life. The issues of effective treatment of people with multiple chronic diseases are discussed. The necessity of clinical trials, including patients with multiple chronic diseases, and the development of new clinical recommendations, which could be based on practical doctors in the treatment of polymorbid patients, are substantiated.


Increased donor CD86+CD14+ cells in the bone marrow and peripheral blood of patients with chronic graft-versus-host disease.
Based on experimental models, chronic graft-versus-host disease (cGVHD) may depend on activated donor antigen-presenting cells presenting host antigens to donor T cells. Peripheral blood (PB) and marrow samples from 24 patients with cGVHD and 17 patients without GVHD after an allogeneic hematopoietic stem-cell transplant were analyzed by flow cytometry. The absolute number of myeloid dendritic cells (mDC) (BDCA1+CD19-), plasmacytoid DC (pDC) (BDCA2+CD123+) and monocytes (CD45+CD14+), and mean fluorescence intensity of costimulatory molecules and chemokine receptors were assessed in each antigen-presenting cell population. Patients with cGVHD showed increased numbers of marrow monocytes when compared with patients without cGVHD (P=0.006). Moreover, monocytes of cGVHD patients had greater CD86 mean fluorescence intensity in marrow (P=0.02) and PB (P=0.04). Treatment with prednisone resulted in decreased CD86 expression in marrow (P=0.02) and PB (P=0.04) monocytes. The number and phenotype of mDC and pDC were similar in patients with or without cGVHD. Full-donor chimerism was detected in the PB of all patients, and in purified CD14+ monocytes from three cGVHD patients. Our results show an increased activation of donor-derived marrow and blood monocytes in patients with cGVHD, possibly suggesting the need to target monocytes in the treatment of cGVHD.


Development of a large-item environmental sound test and the effects of short-term training with spectrally-degraded stimuli.
Accurate identification of environmental sounds plays an important role in maintaining listeners' awareness of their environment, and is a major concern for cochlear implant patients. Although research indicates that decreased spectral resolution has a negative effect on environmental sound identification, little is known about the processes underlying perceptual adaptation to spectrally-degraded input. The goals of this study were (1) to develop a test of environmental sound perception containing a large variety of easily identifiable and familiar sound sources, represented by multiple exemplars, and (2) to examine whether auditory training improves listeners' identification of spectrally-degraded environmental sounds. In experiment 1, familiarity ratings and identification accuracy were obtained for 21 normal-hearing subjects for 48 environmental sound sources; there were 4 exemplars of each sound source, for a total of 192 stimuli. A second test was developed using a subset of 40 sound sources (4 exemplars each, for a total of 160 stimuli). In experiment 2, seven normal-hearing subjects (who did not participate in experiment 1) were asked to identify spectrally-degraded environmental sounds processed by a four-channel noise-band vocoder. The second stimulus set developed in experiment 1 (40 sound sources, 4 exemplars each) was used in experiment 2. The subjects were tested in a pretest-posttest design with five training sessions between the pretest and the posttest. The training sounds were selected individually for each subject, and comprised one half of the sound sources that were misidentified in the pretest. Each sound source used in training was represented by two exemplars. During training, subjects received trial and block feedback. For each incorrect response, subjects were allowed to replay the stimulus up to five times after being shown the correct response. In experiment 1, listeners' average identification accuracy was 95% correct, with 178 of all sounds identified with an accuracy of 80% or more. The average identification accuracy of the 160 sounds selected for experiment 2 was 98% correct, and their average familiarity rating was 6.39 (on a 7-point scale). In experiment 2, the average identification accuracy of spectrally-degraded sounds was 33% correct on the pretest. However, after training, average identification accuracy across all sounds improved to 63% correct on the posttest. The largest improvement (86 percentage points) was obtained for the sound exemplars used during training. The identification accuracy for alternative exemplars of the training sounds (that referenced the same sources) improved by 36 percentage points. Finally, the identification of sound sources not included in the training, but perceived with equal difficulty on the pretest, improved by 18 percentage points. These results demonstrate positive effects of training on the identification of spectrally-degraded environmental sounds and suggest that training effects can generalize to other sound exemplars and sources, although with a reduced magnitude of improvement. The findings also indicate a timeline for initial perceptual adaptation to spectrally-degraded environmental sounds, and provide a preliminary basis for incorporating environmental sounds into auditory rehabilitation programs for cochlear implant patients.


Characteristics of patients with C1 esterase inhibitor deficiency: a single center study.
Hereditary angioedema (HAE) is a primary complement factor deficiency, characterized by recurrent submucosal/subcutaneous swelling episodes. SERPING1 gene defects encoding C1 esterase inhibitor (C1INH) are responsible from the disease. Fifteen patients with HAE are retrospectively evaluated in this study. All patients (n = 15) had HAE type I, 13 were from the same family, other two from two different families. Median age at onset of symptoms was 7 years (2-20); median age on diagnosis, 12 (0,5-41) and median delay in diagnosis, 3 years (0-33). Clinical symptoms were extremity edema(92,3%), facial edema(46%), abdominal pain (46%), genital edema (46%), and laryngeal edema (23%). Some patients suffered from recurrent abdominal pain, had been empirically given colchicine with familial mediterranean fever (FMF) when they admitted. One presented with bullous skin eruption, soon after developed extremity edema. Both resolved spontaneously after C1INH concentrate therapy. Two females suffered from recurrent genital edema after sexual activity. One patient experienced compartment syndrome-like swelling of extremity after playing football. One patient diagnosed with panic attack due to fear of death by asphyxiation, and was diagnosed with HAE disease. A nonsense mutation in exon 8, a missense mutation in exon 2 in SERPING1 gene was present in Family 1 and another patient (P14) from the other family, respectively. Sporadic/autosomal dominant inheritance ratio was 2/3 in the families present in our series. Patients with HAE presents with a large spectrum of symptoms. In mediterranean countries, patients with abdominal attacks may be misdiagnosed with FMF. Thus, health-care professionals should be alert, and put HAE in the first line of differential diagnoses when the disease symptoms are present. Consequently, morbidity/mortality will decrease with effective treatment options.


A swelling-suppressed Si/SiOx nanosphere lithium storage material fabricated by graphene envelopment.
A swelling-suppressed, Si nanocrystals-embedded SiOx nanospheres lithium storage material was prepared by graphene envelopment. The free void spaces formed between the graphene envelope and Si/SiOx nanospheres effectively accommodated the volume changes of Si/SiOx nanospheres during cycling, which significantly suppresses the swelling behavior and improves the capacity retention up to 200 cycles.


[Protective effect of wenfei huayin recipe on lung of rats with chronic obstructive pulmonary diseases].
To explore the mechanism of Wenfei Huayin Recipe (WHR) in treating chronic obstructive pulmonary diseases (COPD). The COPD model was induced by modified fumigating method and intra-tracheal instillation of lipopolysaccharide. Then reformed COPD model of cold-phlegm retention in Fei syndrome type. All the model rats were randomly divided into two groups, the model group and the treated group, treated respectively with WHR and saline for 14 successive days. Besides, a blank group without any intervention was set up for control. The general condition, weight growth rate, pathological changes of lung tissue under light microscope, ultrastructure under electron microscope, arterial blood gas analysis and levels of interleukin 4 (IL-4), interleukin 8 (IL-8), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in lung homogenate by radio-immunity assay were observed. In the treated group, as compared with the control group, the symptoms of aversion to cold, swarming, wheezing, the degree of epithelial cell degeneration and necrosis, the inflammatory cell infiltration and the volume of cilia lodging, sloughing, and bullae of lung were lessened and weight growth rate was higher (P<0.01). Moreover, the treated group was superior to the control group in decreasing levels of PaCO2, IL-4, IL-8, TNF-alpha and increasing PaO2, IFN-gamma and IFN-gamma/IL-4 ratio (P<0.01 or P<0.05). WHR can correct the Th1/Th2 imbalance and inhibit the inflammatory reaction, displaying an important role in improving the airway function and structure in COPD rats.


Dynamics of Lewis b binding and sequence variation of the babA adhesin gene during chronic Helicobacter pylori infection in humans.
Helicobacter pylori undergoes rapid microevolution during chronic infection, but very little is known about how this affects host interaction factors. The best-studied adhesin of H. pylori is BabA, which mediates binding to the blood group antigen Lewis b [Le(b)]. To study the dynamics of Le(b) adherence during human infection, we analyzed paired H. pylori isolates obtained sequentially from chronically infected individuals. A complete loss or significant reduction of Le(b) binding was observed in strains from 5 out of 23 individuals, indicating that the Le(b) binding phenotype is quite stable during chronic human infection. Sequence comparisons of babA identified differences due to mutation and/or recombination in 12 out of 16 strain pairs analyzed. Most amino acid changes were found in the putative N-terminal extracellular adhesion domain. One strain pair that had changed from a Le(b) binding to a nonbinding phenotype was used to study the role of distinct sequence changes in Le(b) binding. By transformations of the nonbinding strain with a babA gene amplified from the binding strain, H. pylori strains with mosaic babA genes were generated. Recombinants were enriched for a gain of Le(b) binding by biopanning or for BabA expression on the bacterial surface by pulldown assay. With this approach, we identified several amino acid residues affecting the strength of Le(b) binding. Additionally, the data showed that the C terminus of BabA, which is predicted to encode an outer membrane β-barrel domain, plays an essential role in the biogenesis of this protein. Helicobacter pylori causes a chronic infection of the human stomach that can lead to ulcers and cancer. The bacterium can bind to gastric epithelial cells with specialized outer membrane proteins. The best-studied protein is the BabA adhesin which binds to the Lewis b blood group antigen. Since H. pylori is a bacterium with very high genetic variability, we asked whether babA evolves during chronic infection and how mutations or recombination in babA affect binding. We found that BabA-mediated adherence was stable in most individuals but observed a complete loss of binding or reduced binding in 22% of individuals. One strain pair in which binding was lost was used to generate babA sequences that were mosaics of a functional allele and a nonfunctional allele, and the mosaic sequences were used to identify amino acids critically involved in binding of BabA to Lewis b.


RZRs, a new family of retinoid-related orphan receptors that function as both monomers and homodimers.
Members of the superfamily of nuclear receptors share the greatest homology in their DNA-binding domains. We have used reverse transcription-polymerase chain reaction and highly degenerate primers based on the amino acid sequence of the zinc finger motif of known nuclear receptors to identify novel members of the family. Starting with rat brain RNA, we have isolated an orphan receptor that we call RZR beta. The sequence of its nearly full-length complementary DNA shows great similarity to RZR alpha, a receptor we recently identified from human umbilical vein endothelial cells. These RZR subtypes represent members of a new family of orphan nuclear receptors that most likely regulate specific gene expression. Sequence comparison with other known nuclear receptors reveals great similarity for both RZR subtypes to retinoic acid and retinoid-X receptors. By Northern blot analyses, we found RZR beta messenger RNA only in brain, whereas RZR alpha is expressed in many tissues. We show here that the RZRs bind as monomers to natural retinoid response elements formed by (A/G)GGTCA half-sites. However, a T-residue in the -1 position of this motif greatly enhances the DNA binding affinity of RZRs, whereas the -2 position has no influence. We show that RZRs can bind as homodimers on response elements formed by palindromes, inverted palindromes, or direct repeats of two TAGGTCA half-sites. Interestingly, these response elements display dramatically reduced affinity for retinoic acid receptor-retinoid-X receptor heterodimers. Thus, the 5'-flanking sequence of hexameric half-sites appears to be crucial to direct the activity of several nuclear receptors. On monomeric as well as dimeric binding sites, RZRs show constitutive transactivational activity that can be enhanced by unidentified components of fetal calf serum.


[A case of hepatocellular carcinoma with bone metastasis which responded to oral administration of UFT].
A 61-year-old male was referred to our hospital for evaluation of right upper arm pain. He was diagnosed as having primary hepatocellular carcinoma with bone metastasis by his high titer (111,683 ng/ml) of serum alpha-fetoprotein, computed tomography and abdominal angiography, and so UFT therapy, 400 mg daily, was instituted. After 2 months of this therapy, the titer of serum alpha-fetoprotein gradually decreased. Seven months later, the titer was 3,997 ng/ml and reduction of the hepatic tumor size was shown by computed tomography and ultrasonography. Furthermore, the right upper arm pain diminished and X-ray examination revealed remarkable improvement. During chemotherapy, there was no severe side effect apart from mild anemia and the patient is presently still alive. This case suggests the efficacy of UFT for the treatment of primary hepatocellular carcinoma.


Primary pancreatic lymphoma presenting as acute pancreatitis.
Primary pancreatic lymphoma is a rare disease and usually presents with nonspecific symptoms like abdominal pain, weight loss, or jaundice. Here we report a case of primary pancreatic lymphoma presenting as acute pancreatitis.


Rhythmicity, recurrence, and recovery of flagellar beating.
The eukaryotic flagellum beats with apparently unfailing periodicity, yet responds rapidly to stimuli. Like the human heartbeat, flagellar oscillations are now known to be noisy. Using the alga C. reinhardtii, we explore three aspects of nonuniform flagellar beating. We report the existence of rhythmicity, waveform noise peaking at transitions between power and recovery strokes, and fluctuations of interbeat intervals that are correlated and even recurrent, with memory extending to hundreds of beats. These features are altered qualitatively by physiological perturbations. Further, we quantify the recovery of periodic breaststroke beating from transient hydrodynamic forcing. These results will help constrain microscopic theories on the origins and regulation of flagellar beating.


Radiotherapy for hypoglycaemia associated with large leiomyosarcomas.
A patient with recurrent severe hypoglycaemia attacks due to a large, irresectable retroperitoneal leiomyosarcoma was treated with radiotherapy (60 Gy). The blood glucose level gradually and steadily improved as the cumulative radiation dose was increased. Weaning of hyperalimentation was started when the cumulative dose reached 21.6 Gy. The patient became completely free from hypoglycaemic attacks despite no significant diminishment of local tumour size and untreated multiple lung metastases. The patient was discharged and the attacks did not recur until expiration as a result of tumour bleeding. This case report supports the clinical usefulness of radiation therapy in treating hypoglycaemia induced by non-islet cell tumour.


Outcome of periacetabular osteotomy: joint contact pressure calculation using standing AP radiographs, 12 patients followed for average 2 years.
Due to wide variations in acetabular structure of individuals with hip dysplasia, the measurement of the acetabular orientation may not be sufficient to predict the joint loading and pressure distribution across the joint. Addition of mechanical analysis to preoperative planning, therefore, has the potential to improve the clinical outcome. We analyzed the effect of periacetabular osteotomy on hip dysplasia using computer-aided simulation of joint contact pressure on regular AP radiographs. The results were compared with the results of surgery based on realignment of acetabular angles to the normal hip. We studied 12 consecutive periacetabular osteotomies with no femoral head deformity. The median age of patients, all females, was 35 (20-50) years. The median follow-up was 2 years (1.3-2.2). Patient outcome was measured with the total score of a self-administered questionnaire (q-score) and with the Harris hip score. The pre- and postoperative orientation of the acetabulum was defined using reconstructed 3D CT-slices to measure angles in the three anatomical planes. Peak contact pressure, weight-bearing area, and the centroid of the contact pressure distribution (CP-ratio) were calculated. While 9 of 12 cases showed decreased peak pressure after surgery, the mean changes in weight-bearing area and peak contact pressure were not statistically significant. However, CP-ratio changed (p < 0.001, paired t-test) with surgery. For the optimal range of CP-ratio (within its mid-range 40-60%), the mechanical outcome improved significantly. Verifying the correlation between the optimal CP-ratio and the outcome of the surgery requires additional studies on more patients. Moreover, the anatomically measured angles were not correlated with the ranges of CP-ratio, suggesting that they do not always associate with objective mechanical goals of realignment osteotomy. Mechanical analysis, therefore, can be a valuable tool in assessing two-dimensional radiographs in hip dysplasia.


High quality stealth dicing of sapphire with a picosecond Bessel beam by controlling the polarization direction.
Sapphire is an important substrate material in optoelectronic devices, and it is also widely used as a touch screen panel. In order to achieve high quality cutting of sapphire, the stealth dicing of 500 µm thick sapphire by a picosecond Bessel beam is studied in this paper. The influences of laser polarization direction and process parameters on cutting section roughness were studied. By controlling the laser polarization direction, different crack propagation morphologies were obtained. When the polarization direction was vertical to the cutting path, the crack propagation path was straighter, and the sapphire had better cutting quality. The laser processing parameters, including burst mode, hole spacing, and pulse energy, had a significant impact on the cutting section roughness. When the polarization direction was vertical to the cutting path under the optimal process parameters, the cutting section was uniform and flat, with no recondensable particles, no ripples, and no chamfer, and an 89.7 nm average roughness of the cutting section could be obtained.


Survival of Trichomonas vaginalis in human semen.
Although exposure of Trichomonas vaginalis to human semen is of short duration, any effect that this fluid may have on the urogenital protozoon could affect its transmission, especially if only few trichomonads are present. Small numbers of parasites (about 2500/ml semen) incubated in semen from different donors at 37 degrees C, were found to survive or grow for up to 12 hours in all samples and for up to 24 hours in most. Survival and growth of T vaginalis in semen most resembled that found in Diamond's trypticase, yeast extract, and maltose (TYM) medium without serum supplement, rather than in complete TYM medium and phosphate buffered saline. Contrary to previous reports, semen did not inhibit the survival of T vaginalis, and the presence of trichomonads did not alter motility or numbers of spermatozoa up to 24 hours. The data suggest that semen provides a favourable milieu for transmitting trichomonads.


Information and communication processes in the microbiology laboratory--implications for computerised provider order entry.
The aim of this multi-method study based at a microbiology department in a major Sydney metropolitan teaching hospital was to: i) identify the role that information and communication processes play in a paper-based test request system, and ii) examine how these processes may affect the implementation and design of Computerised Provider Order Entry (CPOE) systems. Participants in this study reported that clinical information can impact on the urgency and type of tests undertaken and affect the interpretation of test results. An audit of 1051 microbiology test request forms collected over a three-day period showed that 47% of request forms included clinical notes which provide a variety of information often vital to the test analysis and reporting process. This transfer of information plays an important role in the communication relationship between the ward and the laboratory. The introduction of new CPOE systems can help to increase the efficiency of this process but for that to be achieved research attention needs to be given to enhancing the provision and communication of clinical information.


Coevolutionary Neural Solution for Nonconvex Optimization With Noise Tolerance.
The existing solutions for nonconvex optimization problems show satisfactory performance in noise-free scenarios. However, they are prone to yield inaccurate results in the presence of noise in real-world problems, which may lead to failures in optimizing nonconvex problems. To this end, in this article, we propose a coevolutionary neural solution (CNS) by combining a simplified neurodynamics (SND) model with the particle swarm optimization (PSO) algorithm. Specifically, the proposed SND model does not leverage the time-derivative information, exhibiting greater stability compared to existing models. Furthermore, due to the noise tolerance capacity and rapid convergence property exhibited by the SND model, the CNS can rapidly achieve the optimal solution even in the presence of various perturbations. Theoretical analyses ensure that the proposed CNS is globally convergent with robustness and probability. In addition, the effectiveness of the CNS is compared with those of the existing solutions by a class of illustrative examples. We further apply the proposed solution to design a finite impulse response (FIR) filter and a pressure vessel to demonstrate its performance.


Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non-protein-bound concentrations.
Given that only the free non-protein-bound concentration of an antiepileptic drug (AED) crosses the blood-brain barrier, entering the brain and producing an antiepileptic effect, knowledge and measurement of the free drug fraction is important. Such data are sparse, particularly for newer AEDs, and have arisen from the use of disparate methodologies and settings over the past six decades. We report on the protein binding of 25 AEDs that are available for clinical use, along with two pharmacologically active metabolites (carbamazepine-epoxide and N-desmethyl clobazam), using standardized methodology and under set conditions. The protein binding of the various AEDs was undertaken in sera of 278 patients with epilepsy. Separation of the free non-protein-bound component was achieved by using ultracentrifugation (Amicon Centrifree Micropartition System) under set conditions: 500 μl serum volume; centrifugation at 1,000 g for 15 min, and at 25°C. Free and total AED concentrations were measured by use of fully validated liquid chromatography/mass spectroscopy (LC/MS) techniques. Gabapentin and pregabalin are non-protein-bound, whereas highly bound AEDs (≥88%) include clobazam, clonazepam, perampanel, retigabine, stiripentol, tiagabine, and valproic acid as well as the N-desmethyl-clobazam (89%) metabolite. The minimally bound drugs (<22%) include ethosuximide (21.8%), lacosamide (14.0%), levetiracetam (3.4%), topiramate, (19.5%) and vigabatrin (17.1%). Ten of the 25 AEDs exhibit moderate protein binding (mean range 27.7-74.8%). These data provide a comprehensive comparison of serum protein binding of all available AEDs including the metabolites, carbamazepine-epoxide and N-desmethyl-clobazam. Knowledge of the free fraction of these AEDs can be used to optimize epilepsy treatment.


The best method of detecting prior Helicobacter pylori infection.
Prior Helicobacter pylori (H pylori) infection has often been underestimated. These underestimations have misled physicians attempting to determine the significance between H pylori and certain gastrointestinal lesions such as intestinal metaplasia, atrophic gastritis, and gastric cancer. Our study endeavored to detect past H pylori infections accurately, easily, and rapidly with the newly developed immunoblot kit, Helico Blot 2.1. Thirty-three patients, including 25 H pylori infected and 8 uninfected cases, were enrolled in our study. All patients received consecutive gastroendoscopic examinations and (13)C-urea breath test (UBT) tests at 6- or 12-mo intervals for up to 4 years. Serum samples were obtained from each patient at the same time. Intragastric H pylori infection was confirmed in accordance with the gold standard. Twenty-five H pylori-infected patients received triple therapies after initial bacterial confirmation, and were successful in eradicating their infections. Serially obtained sera were tested by means of Helico Blot 2.1. Current infection marker detected by Helico Blot 2.1 was unreliable for representing ongoing H pylori infection. Only 35 and 37 ku antibodies of H pylori had significant seroconversion rates 1 year after having been cured. The seropositive rates of 116 ku (cytotoxin-associated antigen (CagA)) and Helico Blot 2.1 were nearly 100% during 4-year follow-up period. Both CagA antigen and Helico blot 2.1 could serve as indicators of long-term H pylori infection. Helico Blot 2.1 can detect past H pylori infections for up to 4 years, and is the best method to date for detecting previous long-term H pylori infection.


Desquamative stomatitis associated with routine use of oral health care products.
Oral mucosal desquamation is a common manifestation of a number of pathologic conditions. The differential diagnoses may range from chemical and electrical burns to conditions such as allergic reactions, hormonal disorders, and mucocutaneous conditions. This article reports two cases of oral mucosal reactions that became a diagnostic challenge at the time of examination. Both subjects had chronic extensive desquamative stomatitis and gingival ulcerations. Following a careful review of their medical and dental history, the use of oral health care products was projected as a possible cause of their mucosal condition.


Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs.
Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC50s), and in particular, two FDA-approved drugs-niclosamide and ciclesonide-were notable in some respects.


Water uptake coefficients and deliquescence of NaCl nanoparticles at atmospheric relative humidities from molecular dynamics simulations.
Deliquescence properties of sodium chloride are size dependent for particles smaller than 100 nm. Molecular dynamics (MD) simulations are used to determine deliquescence relative humidity (DRH) for particles in this size range by modeling idealized particles in contact with humid air. Constant humidity conditions are simulated by inclusion of a liquid reservoir of NaCl solution in contact with the vapor phase, which acts as a source of water molecules as uptake by the nanoparticle proceeds. DRH is bounded between the minimum humidity at which sustained water accumulation is observed at the particle surface and the maximum humidity at which water accumulation is not observed. Complete formation of a liquid layer is not observed due to computational limitations. The DRH determined increases with decreasing particle diameter, rising to between 91% and 93% for a 2.2 nm particle and between 81% and 85% for an 11 nm particle, higher than the 75% expected for particles larger than 100 nm. The simulated size dependence of DRH agrees well with predictions from bulk thermodynamic models and appears to converge with measurements for sizes larger than 10 nm. Complete deliquescence of nanoparticles in the 2-11 nm size range requires between 1 and 100 mus, exceeding the available computational resources for this study. Water uptake coefficients are near 0.1 with a negligible contribution from diffusion effects. Planar uptake coefficients decrease from 0.41 to 0.09 with increasing fractional water coverage from 0.002 to 1, showing a linear dependence on the logarithm of the coverage fraction with a slope of -0.08+/-0.01 (representing the effect of solvation). Particle uptake coefficients increase from 0.13 at 11 nm to 0.65 at 2.2 nm, showing a linear dependence on the logarithm of the edge fraction (which is a function of diameter) with a slope of 0.74+/-0.04 (representing larger edge effects in smaller particles).


Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review.
Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.


How the Physical Environment Shapes the Microbiota.
Living systems, from micro- to macro-scales, are strongly impacted by physical factors such as temperature, pH, and the concentration of compounds in their surrounding environment. In the macro-world, it is obvious that small changes in these parameters can have profound, and even devastating, impacts on an ecosystem. For example, in the case of global warming, a change in climate, and specifically a few degrees in temperature, has taken one million species of animals to the brink of extinction. Scale things down 6 orders of magnitude, our gut microbiota also experiences similar changes in temperature due to disease. In this highly competitive environment, physical perturbations inflict long-term consequences on the microbiota ecosystem and, in turn, on the host organism. My laboratory is exploring the feedback between the gut's physical environment, the microbiota, and disease. Our research highlights the importance of measuring physical parameters for the prediction of microbial dynamics and microbiota therapies.


Massive lymphorrhoea after fine needle biopsy of the cystic haemolymphangioma of the liver.
Trauma to a hepatic haemangioma from a fine needle biopsy has not yet been reported and the theoretical high risk with 22-23 g needles in patients with this lesion tends to be minimised. Through misdiagnosis biopsy was ordered in one case of cystic haemolymphangioma of the liver in a patient being checked by ultrasonography for possible metastases. Aspiration was complicated by a massive peritoneal lymphorrhoea, which regressed completely in 15 days. The mechanics of the event and its possible effect on the pre-existing liver failure, held to be the direct cause of death three months later, is a matter of hypothesis.


[Therapeutic and physiopathological contribution of electric stimulation of deep brain structures in Parkinson's disease].
Ablative functional neurosurgery constituted during the first half of the 20th century the main treatment of advanced forms of Parkinson's disease. The surgical procedure was spectacularly efficient on tremor, but sometimes complications were not totally regressive and even more severe when surgery was bilateral, this leading to neurocognitive deficits or to speech problems. This, associated to the efficiency of levodopa, was at the origin of the almost total disappearance of this type of surgery during the '60s until the eighties. The rebirth of functional neurosurgery, necessitated by the appearance of dyskinesias, was possible in most part because of the development of techniques with a lower morbidity, such as high frequency stimulation (HFS). This was initially applied to the thalamic ventral intermedius nucleus VIM, and the low morbidity of the method has been demonstrated by the possibility to operate a large number of patients bilaterally without complication. The demonstration that the pallidal target, which had been abandoned during the '50s because of its low efficiency on the triad of symptoms of Parkinson's disease, was selectively efficient on dyskinesias, led naturally to apply HFS to this target. In 1990, the demonstration in the field of fundamental research of the role of the subthalamic nucleus as a key element of regulation of movement, suggested to register this nucleus into the list of targets, despite the risk of hemiballism that this structure presents when it is lesioned by haemorrhage, because of the good tolerance of HFS as a surgical method. This target quickly showed its remarkable efficiency on all symptoms of Parkinson's disease. Because of the reduction of the doses of dopaminergic treatments which were allowed, this target had also the capacity to reduce, indirectly, the intensity of dyskinesias. If the efficiency of the method is nowadays demonstrated as well as the stability on the long term of its results, the mechanism is still mostly not understood. Moreover the physiopathogenic hypothesis suggests the possibility of a neuroprotective effect of the stimulation, which still needs to be clearly established at the experimental level as well as at the level of clinical applications.


Carcinoembryonic antigen, carbohydrate antigen 199 and carbohydrate antigen 724 in gastric cancer and their relationship with clinical prognosis.
Gastric cancer (GC) is a common malignant tumor of the digestive system with a high degree of malignancy. It usually develops insidiously without any specific symptoms in the early stages. As one of the diseases caused by abnormal gene changes, GC has abnormal expression of various oncogenes and products during its development. Tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and carbohydrate antigen 724 (CA724) are not expressed or lowly expressed in normal people, but significantly increased after carcinogenesis. Monitoring the changes in the levels of tumor markers such as CEA, CA199 and CA724 is conducive to early diagnosis and evaluation of the occurrence of some solid tumors. To investigate the expression of CEA, CA199 and CA724 in GC and their correlation with clinical features, hoping to provide more effective markers for the early preventive diagnosis of GC. Of 87 patients with GC admitted to our hospital from September 2020 to December 2021 were included in the GC group, and another 80 healthy people who came to our hospital for physical examination with normal results during the same period were selected as the control group. The serum CEA, CA199, and CA724 levels were compared between the two groups, and the serum CEA, CA199, and CA724 levels were compared in patients with GC at different TNM stages, and the differences in the positive rates of CEA, CA199, and CA724 alone and in combination in detecting TNM stages of GC and GC were compared. In addition, the relationship between the levels of tumor markers CEA, CA199 and CA724 and the clinicopathological characteristics of GC patients was also analyzed. The relationship between the serum levels of CEA, CA199 and CA724 and the survival period of GC patients was analyzed by Pearson. The serum levels of CEA, CA199 and CA724 in GC group were significantly higher than those in control group (P < 0.05). With the increase of TNM stage, the serum CEA, CA199 and CA724 expression levels in GC patients increased significantly, and the differences between groups were statistically significant (P < 0.05). The positive rate of the CA724 single test was higher than that of CEA and CA199 single test (P < 0.05). The positive rate of the three combined tests was 95.40% (83/87), which was higher than that of CEA, CA199 and CA724 single tests. The difference was statistically significant (P < 0.05). The combined detection positive rates of CEA, CA199, and CA724 in stages I, II, III, and IV of GC were 89.66%, 93.10%, 98.85%, and 100.00% respectively, all of which were higher than the individual detection rates of CEA, CA199, and CA724. The differences were statistically significant (P < 0.05). There was no significant difference in serum CEA, CA199 and CA724 levels between GC patients with different genders, smoking history and alcohol history (P > 0.05). However, the serum CEA, CA199 and CA724 levels were significantly higher in GC patients aged ≥ 45 years, TNM stage III-IV, with lymph node metastasis and tumor diameter ≥ 5 cm than in GC patients aged < 45 years, TNM stage I-II, without lymph node metastasis and tumor diameter < 5 cm (P < 0.05). The expression levels of serum tumor markers CEA, CA199 and CA724 in patients with GC are high and rise with the increase of TNM stage. The levels of CEA, CA199 and CA724 are related to age, TNM stage, lymph node metastasis and tumor diameter. The combined detection of CEA, CA199 and CA724 is helpful to improve the diagnostic accuracy of GC with high clinical guidance value.


Bioinformatics Analysis of Prognostic miRNA Signature and Potential Critical Genes in Colon Cancer.
This study aims to lay a foundation for studying the regulation of microRNAs (miRNAs) in colon cancer by applying bioinformatics methods to identify miRNAs and their potential critical target genes associated with colon cancer and prognosis. Data of differentially expressed miRNAs (DEMs) and genes (DEGs) downloaded from two independent databases (TCGA and GEO) and analyzed by R software resulted in 472 DEMs and 565 DEGs in colon cancers, respectively. Next, we developed an 8-miRNA (hsa-mir-6854, hsa-mir-4437, hsa-mir-216a, hsa-mir-3677, hsa-mir-887, hsa-mir-4999, hsa-mir-34b, and hsa-mir-3189) prognostic signature for patients with colon cancer by Cox proportional hazards regression analysis. To predict the target genes of these miRNAs, we used TargetScan and miRDB. The intersection of DEGs with the target genes predicted for these eight miRNAs retrieved 112 consensus genes. GO and KEGG pathway enrichment analyses showed these 112 genes were mainly involved in protein binding, one-carbon metabolic process, nitrogen metabolism, proteoglycans in cancer, and chemokine signaling pathways. The protein-protein interaction network of the consensus genes, constructed using the STRING database and imported into Cytoscape, identified 14 critical genes in the pathogenesis of colon cancer (CEP55, DTL, FANCI, HMMR, KIF15, MCM6, MKI67, NCAPG2, NEK2, RACGAP1, RRM2, TOP2A, UBE2C, and ZWILCH). Finally, we verified the critical genes by weighted gene co-expression network analysis (WGCNA) of the GEO data, and further mined the core genes involved in colon cancer. In summary, this study identified an 8-miRNA model that can effectively predict the prognosis of colon cancer patients and 14 critical genes with vital roles in colon cancer carcinogenesis. Our findings contribute new ideas for elucidating the molecular mechanisms of colon cancer carcinogenesis and provide new therapeutic targets and biomarkers for future treatment and prognosis.


[Expression and purification of recombinant Trail protein in E.coli and the optimal conditions for Trail purification].
To construct the expression vector pET-28α-Trail(114-281); and find the optimal conditions for target gene expression, host bacteria lysis, and protein purification, and to detect the apoptosis function of the recombinant protein. The functional domain of Trail(114-281); was amplified by PCR and cloned into the expression vector pET-28α(+). After confirmed by DNA sequencing, the Trail(114-281); was expressed in E.coli BL21 under the condition of different A(600);, IPTG concentration and temperature. Host bacteria were lysed using three different ways, including ultrasonication, osmotic shock and IP lysis, and the target protein was purified using Ni-NTA affinity chromatography or cutting-gel purification. The advantages and shortcomings of these methods were compared to find the most efficient ways for expression and purification of the recombinant protein. The immunocompetence of Trail protein from cutting-gel purification was analyzed by Western blotting, A549 cell apoptosis induced by purified protein from Ni-NTA chromatography was detected by flow cytometry. The 516 bp Trail(114-281); gene was cloned, and expressed in E.coli BL21. When A(600);=0.6, recombinant host bacteria were induced by 1.0 mmol/L IPTG at 37 DegreesCelsius for 4 h, which was the optimal condition for the expression of inclusion body, and the soluble protein was expressed stably on the condition of 25 DegreesCelsius, A(600);=1.0, IPTG1.0 mmol/L. Ultrasonication could get maximal protein compared to the other methods. The two purification ways both could purify taget protein successfully. Western blot analysis showed that the protein purified by cutting-gel has a good immunologic activity. Protein from Ni-NTA affinity chromatography caused cell apoptosis. The expression vector pET-28α-Trail(114-281); can be constructed and expressed in E.coli BL21 successfully. Temperature is a more important effect factor of Trail(114-281); expression in host bacteria compared with other factors. Cutting-gel protein has immunogenicity, and Ni-NTA protein could keep its function. These results provide a basis for the further functional research and application of Trail.


Differential adrenergic response to extrinsic denervation in canine longitudinal jejunal and ileal smooth muscle.
Early postoperative complications after small bowel transplantation (SBT) are likely mediated, at least in part, by dysmotility caused by the obligate disruption of extrinsic and enteric nerves in the graft. Adrenergic hypersensitivity of gut smooth muscle has been observed in some (but not all) segments of intestine in various experimental models of SBT, highlighting regional and species variability in response to denervation. Little is known about changes in canine longitudinal muscle after extrinsic denervation. Six dogs each underwent either complete extrinsic denervation of the jejunoileum or a control operation (transection and reanastomosis of the proximal jejunum and distal ileum). In vitro contractile response of longitudinal muscle strips to norepinephrine was evaluated at the time of the operation, and 2 weeks and 8 weeks later. After extrinsic denervation, the jejunal response to norepinephrine was preserved at all time points; however, the ileum displayed a decreased sensitivity to norepinephrine, an effect unmasked after intramural neural blockade with tetrodotoxin. These data support a potential for neurally mediated dysmotility after SBT and reinforce the differences in responses to extrinsic denervation between species, as well as differences within different regions and between anatomic segments of small intestine in the same species.


Verification of poultry carcass composting research through application during actual avian influenza outbreaks.
An avian influenza outbreak in 2002 affected 197 poultry farms in Virginia and cost an estimated $130 million in losses and cleanup. In 2004-2005, researchers initiated a project to investigate the feasibility and practicality of in-house composting of turkey mortalities (heavy hens and toms) as a method of disposal and disease containment. Occurrences of low pathogenic avian influenza (LPAI) in West Virginia and Virginia in 2007 provided an opportunity for first responders to verify composting as an effective carcass disposal method. Many lessons learned from these experiences have led to improvements in the application of this technology. Market-weight turkeys, once thought too large for effective composting, were composted sufficiently for land application within 4 to 6 weeks. Additionally, fire-fighting foam, a new method of mass depopulation, proved to be compatible with composting. Knowledge gained from these incidents will be valuable not only for future responses to LPAI but also for outbreaks of highly pathogenic avian influenza such as the H5N1 virus, which currently causes disease in both animals and humans in many parts of the world. Since three-quarters of all recent emerging infectious diseases (EIDs) have arisen from animals, control of disease in animals is the principal way to reduce human exposure and prevent EIDs. Many of the general approaches and specific techniques used to eradicate the avian influenza virus can also be used to control other EIDs such as H1N1, Nipah virus, Rift Valley Fever, and plague.


Bacteriologic epidemiology of Hemophilus influenzae type b strains causing invasive infections in Finland.
Consecutive Hemophilus influenzae type b (Hib) isolates (333 total) from children with invasive disease in Finland in 1985-1986 were analyzed. All belonged to the common genetic clusters described in the USA and Europe. However, detailed typing demonstrated some characteristics unique to Hib strains in Finland. Of the isolates, 86% belonged to one of four distinct patterns according to the combination of outer membrane protein subtype, biotype, and lipopolysaccharide serotype: 1-I-1 (25%), 1-II-9 (8%), and 1c-I-1 (18%). Pattern 1-II-9 has not been previously reported; it was most commonly found in the most densely populated area of Finland and among children cared for outside the home. Multilocus enzyme electrophoresis revealed that 87% of isolates with the pattern 1c-I-1 belonged to the electrophoretic type 21.8, which is seldom recovered from patients with invasive Hib disease in other countries.


High-level expression and characterization of fully active recombinant conger eel galectins in Eschericia coli.
An expression system for recombinant conger eel galectins, congerins I and II, were constructed using the pTV 118N plasmid vector and Escherichia coli. Recombinant congerins I and II could be obtained in the soluble active form with high quantitative yield. Mutation of codons for Val and Leu located in the N-terminal region of Con I increased the expression efficiency. Purification of recombinant proteins were done by only two chromatographical steps from E. coli extract. The purified recombinant congerins were found to be almost the same as the native ones except for the acetyl group at the N-terminus; that is, they showed the same structures and carbohydrate binding activities, suggesting that N-terminal acetyl groups of congerins were not significant for activity.


Bouncing a ball: tuning into dynamic stability.
Rhythmically bouncing a ball with a racket was investigated and modeled with a nonlinear map. Model analyses provided a variable defining a dynamically stable solution that obviates computationally expensive corrections. Three experiments evaluated whether dynamic stability is optimized and what perceptual support is necessary for stable behavior. Two hypotheses were tested: (a) Performance is stable if racket acceleration is negative at impact, and (b) variability is lowest at an impact acceleration between -4 and -1 m/s2. In Experiment 1 participants performed the task, eyes open or closed, bouncing a ball confined to a 1-dimensional trajectory. Experiment 2 eliminated constraints on racket and ball trajectory. Experiment 3 excluded visual or haptic information. Movements were performed with negative racket accelerations in the range of highest stability. Performance with eyes closed was more variable, leaving acceleration unaffected. With haptic information, performance was more stable than with visual information alone.


Treatment of rats with the Pelargonium sidoides extract EPs 7630 has no effect on blood coagulation parameters or on the pharmacokinetics of warfarin.
Umckaloabo is a herbal drug for the treatment of respiratory tract infections. It contains an aqueous ethanolic extract from roots of Pelargonium sidoides DC (EPs) 7630) as the active ingredient. Polymeric polyphenols and coumarins have been identified as the principal ingredients of EPs 7630. In view of the coumarin content, it has been suggested that the administration of Umckaloabo could possibly be associated with an increased risk of bleeding. This study, therefore, investigated whether a change in blood coagulation parameters or an interaction with coumarin-type anticoagulants occurred after administration of EPs 7630 to rats. No effect on thromboplastin time (TPT), partial TPT (PTPT) or thrombin time (TT) was observed after oral administration of EPs 7630 (10, 75, 500 mg/kg) for 2 weeks, while treatment with warfarin (0.05 mg/kg) for the same period resulted in significant changes in TPT and PTPT. If EPs 7630 (500 mg/kg) and warfarin (0.05 mg/kg) were given concomitantly, the anticoagulant action of warfarin was not influenced. Similarly, the pharmacokinetics of warfarin were unchanged after pre-treatment with EPs 7630 for 2 weeks. Coumarin-type anticoagulants inhibit the synthesis of vitamin K-dependent coagulation factors via an identical mechanism in rat and man, and have a similar pattern of metabolism in both species. Moreover, as the coumarins so far identified in EPs 7630 do not posses the structural characteristics needed for anticoagulant activity, it appears unlikely that an increased tendency to haemorrhage arises in patients after intake of Umckaloabo.


Twist1 Enhances Hypoxia Induced Radioresistance in Cervical Cancer Cells by Promoting Nuclear EGFR Localization.
Twist1 is a crucial transcription factor that regulates epithelial mesenchymal transition and involves in metastasis. Recent evidence suggests that Twist1 plays important role in hypoxia-induced radioresistance, but the underlying mechanism remains elusive. Here we investigated the change of Twist1 expression in human cervical squamous cancer cell line SiHa after hypoxia treatment. We also explored the role of Twist1 in radioresistance by manipulating the expression level of Twist1. We observed that hypoxia treatment elevated the expression of Twist1 in SiHa cells. Knockdown of Twist1 with siRNA increased the radiosensitivity of SiHa cells under hypoxia condition, accompanied by reduced levels of nuclear Epidermal Growth Factor Receptor (EGFR) and DNA-dependent protein kinase (DNA-PK). Conversely, overexpression of Twist1 led to increased radioresistance of SiHa cells, which in turn increased nuclear EGFR localization and expression levels of nuclear DNA-PK. Moreover, concomitant high expression of hypoxia-inducible factor-1α (HIF-1α) and Twist1 in primary tumors of cervical cancer patients correlated with the worse prognosis after irradiation treatment. Taken together, these data provide new insights into molecular mechanism underlying hypoxia-induced radioresistance in cervical cancer cells, and suggest that Twist1 is a promising molecular target to improve the efficacy of cancer radiotherapy.


[Drugs involved in toxic epidermal necrolysis (Lyell's syndrome)].
Drug-induced toxic epidermal necrolysis (Lyell's syndrome) is a rare, potentially lethal disease that is characterized by the sudden necrosis of the epidermis and frequently associated with mucous and systemic involvement. Even though the etiology of the disease is probably multifactorial (including viral infections and anomalies of drug metabolism), its iatrogenic origin is the principally recognized cause. We have drawn up a substantial list of the culprit drugs showing their frequency of involvement in the syndrome.


Influence of acetaminophen and trichloroethylene on liver cytochrome P450-dependent monooxygenase system.
The aim of the study was to evaluate the effect of acetaminophen (APAP) and/or trichloroethylene (TRI) on the liver cytochrome P450-dependent monooxygenase system, CYP2E1 and CYP1A2 (two important P450 isoforms), and liver glutathione (GSH) content in rats. Rats were given three different doses of APAP (250, 500 and 1000 mg/kg b...) and then the above-mentioned parameters were measured for 48 h. The lowest APAP dose produced small changes in the cytochrome P450 content of liver. At 500 mg/kg APAP increased the cytochrome P450 content to 230% of the control. The inductive effect was seen at 1000 mg/kg dose but at 24 h and later. NADPH-cytochrome P450 reductase activity was the highest after the lowest dose of APAP, while after the highest dose it was equal to the control value. TRI increased both the cytochrome P450 content and the NADPH-cytochrome P450 reductase activity. When TRI was combined with APAP, both these parameters increased in the first hours of observation, but they returned to the control values at 24 h. When APAP was given at 250 mg/kg, GSH levels decreased to 55% of the control at 8 h and returned to the control values at 24 h. The higher doses of APAP decreased GSH levels more than the lowest dose, but after 24 h GSH levels did not differ from those of the control. When TRI was given at 250 mg/kg, the GSH levels decreased to 68% of the control at 2 h and then they increased gradually and tended to exceed the control values at 48 h. The effect of TRI combined with APAP on the level of GSH was virtually the same as that of APAP alone given at 500 mg/kg.


HLA Genotypes in Turkish Hematopoietic Cell Recipients and Likelihood of Finding a Matched Donor Through Family Searches.
Allogeneic hematopoietic stem cell transplant is a life-saving treatment, but donor numbers in Turkey do not meet the increasing demand for this procedure. Here, our objectives were (1) to assess the frequency of HLA-matched related donors in the Turkish population and (2) to identify the HLA antigens and haplotypes that are most frequent in Turkey. The HLA genotypes of 841 consecutive recipients and 3071 family members were retrospectively reviewed. Matched related donors were identified for 368/841 recipients (44%). Extended family donor searches were performed for 111/181 pediatric recipients (61%), with nonsibling matched related donors found for 23 patients (21%). Matched related donors were found for a significantly higher proportion of pediatric patients (52%) than adult patients (41%) (odds ratio of 2.5; 95% confidence interval, 1.9-4.1; P = .02). The percentage of pediatric versus adult patients with 3 or more siblings was 13% versus 46% (odds ratio of 5.6; 95% confidence interval, 3.6-8.5; P = .001). The most frequent HLA class I antigens at each locus were HLA-A*02 (20.2%), HLA-B*35 (19.5%), and HLA-C*07 (19.8%). The most frequent HLA class II antigens at each locus were HLA-DRB1*11 (21.6%) and HLA-DQB1*03 (40.2%). The most common 3-locus haplotypes were HLA-A*24 B*35 DRB1*11 (F:0.020) and HLA-A*01 B*08 DRB1*03 (F:0.015). When adult and pediatric groups were combined, the most common locus haplotypes were found in 43/345 sibling donors (12%) and in 7/23 nonsibling pediatric donors (30%) (odds ratio of 2.7; 95% confidence interval, 1.2-6.4; P = .02). The results indicate that, in Turkey, it can be beneficial to revise donor search algorithms to include an extended family donor search before an unrelated donor search. This type of search can be effective because of the HLA haplotype diversity in Turkey, the frequency of consanguinity, and the country's limited donor pool.