Novel immunosuppressive agents in kidney transplantation.
Excellent outcomes have been achieved in the field of renal transplantation. A significant reduction in acute rejection has been attained at many renal transplant centers using contemporary immunosuppressive, consisting of an induction agent, a calcineurin inhibitor, an antiproliferative agent plus or minus a corticosteroid. Despite improvements with these regimens, chronic allograft injury and adverse events still persist. The perfect immunosuppressive regimen would limit or eliminate calcineurin inhibitors and/or corticosteroid toxicity while providing enhanced allograft outcomes. Potential improvements to the calcineurin inhibitor class include a prolonged release tacrolimus formulation and voclosporin, a cyclosporine analog. Belatacept has shown promise as an agent to replace calcineurin inhibitors. A novel, fully-human anti-CD40 monoclonal antibody, ASKP1240, is currently enrolling patients in phase 2 trials with calcineurin minimization and avoidance regimens. Another future goal of transplant immunosuppression is effective and safe treatment of allograft rejection. Novel treatments for antibody mediated rejection include bortezomib and eculizumab. Several investigational agents are no longer being pursed in transplantation including the induction agents, efalizumab and alefacept, and maintenance agents, sotrastaurin and tofacitinib. The purpose of this review is to consolidate the published evidence of the effectiveness and safety of investigational immunosuppressive agents in renal transplant recipients.


Structural basis of molecular recognition of helical histone H3 tail by PHD finger domains.
The plant homeodomain (PHD) fingers are among the largest family of epigenetic domains, first characterized as readers of methylated H3K4. Readout of histone post-translational modifications by PHDs has been the subject of intense investigation; however, less is known about the recognition of secondary structure features within the histone tail itself. We solved the crystal structure of the PHD finger of the bromodomain adjacent to zinc finger 2A [BAZ2A, also known as TIP5 (TTF-I/interacting protein 5)] in complex with unmodified N-terminal histone H3 tail. The peptide is bound in a helical folded-back conformation after K4, induced by an acidic patch on the protein surface that prevents peptide binding in an extended conformation. Structural bioinformatics analyses identify a conserved Asp/Glu residue that we name 'acidic wall', found to be mutually exclusive with the conserved Trp for K4Me recognition. Neutralization or inversion of the charges at the acidic wall patch in BAZ2A, and homologous BAZ2B, weakened H3 binding. We identify simple mutations on H3 that strikingly enhance or reduce binding, as a result of their stabilization or destabilization of H3 helicity. Our work unravels the structural basis for binding of the helical H3 tail by PHD fingers and suggests that molecular recognition of secondary structure motifs within histone tails could represent an additional layer of regulation in epigenetic processes.


Increase in neurotensin-like immunoreactivity in rat plasma after administration of calcium, bombesin and fat and its inhibition by somatostatin.
Neurotensin-like immunoreactivity (NTLI) is released from the small intestine into the blood after enteral administration of fat and systemic administration of bombesin. The purpose of the present investigation in the rat was to study the effect of intravenously (i.v.) administered CaCl2 on the plasma concentration of NTLI (p-NTLI) and to investigate the effect of i.v. infusion of somatostatin on basal NTLI release, as well as that stimulated by fat, bombesin and CaCl2. Administration of CaCl2 (5-25 mg X kg-1) increased p-NTLI levels in a significant and dose-dependent manner. In contrast, somatostatin 25-200 ng X min-1) reduced the basal p-NTLI levels, as well as the increase in p-NTLI levels induced by CaCl2 (10 and 25 mg X kg-1), fat (oleic acid, 0.5 ml) and bombesin (25 and 125 pmol X kg-1), in a dose-related manner. Injection of bombesin released immunoreactive material that was indistinguishable from synthetic bovine neurotensin (1-13) upon gel-filtration. This material seemed to be rapidly converted to the more stable metabolite neurotensin (1-8).


Auditory Brainstem Implantation in Chinese Patients With Neurofibromatosis Type II: The Hong Kong Experience.
To describe our experience and outcomes of auditory brainstem implantation (ABI) in Chinese patients with Neurofibromatosis Type II (NF2). Retrospective case review. Tertiary referral center. Patients with NF2 who received ABIs. Between 1997 and 2014, eight patients with NF2 received 9 ABIs after translabyrinthine removal of their vestibular schwannomas. One patient did not have auditory response using the ABI after activation. Environmental sounds could be differentiated by six (75%) patients after 6 months of ABI use (mean score 46% [range 28-60%]), and by five (63%) patients after 1 year (mean score 57% [range 36-76%]) and 2 years of ABI use (mean score 48% [range 24-76%]). Closed-set word identification was possible in four (50%) patients after 6 months (mean score 39% [range 12-72%]), 1 year (mean score 68% [range 48-92%]), and 2 years of ABI use (mean score 62% [range 28-100%]). No patient demonstrated open-set sentence recognition in quiet in the ABI-only condition. However, the use of ABI together with lip-reading conferred an improvement over lip-reading alone in open-set sentence recognition scores in two (25%) patients after 6 months of ABI use (mean improvement 46%), and five (63%) patients after 1 year (mean improvement 25%) and 2 years of ABI use (mean improvement 28%). At 2 years postoperatively, three (38%) patients remained ABI users. This is the only published study to date examining ABI outcomes in Cantonese-speaking Chinese NF2 patients and the data seems to show poorer outcomes compared with English-speaking and other nontonal language-speaking NF2 patients. Environmental sound awareness and lip-reading enhancement are the main benefits observed in our patients. More work is needed to improve auditory implant speech-processing strategies for tonal languages and these advancements may yield better speech perception outcomes in the future.


Safety and Efficacy of Flow Diverters for Treatment of Unruptured Anterior Communicating Artery Aneurysms: Retrospective Multicenter Study.
The anterior communicating artery (AComm) region is the most common site of intracranial aneurysms, with increased rupture risk compared with other locations. Overall, flow diverters present as a safe and efficacious treatment for intracranial aneurysms, but there is paucity of data for their use in the treatment of unruptured AComm aneurysms. We present the largest multicentric analysis evaluating the outcomes of flow diverters in AComm aneurysm treatment. Databases from 10 centers were retrospectively reviewed for unruptured AComm aneurysms treated with flow diverters. Demographics, clinical presentation, radiographic characteristics, procedural complications, and outcomes were assessed. A total of 144 patients harboring 147 AComm aneurysms were treated between January 2012 and December 2021. Seventy-four were women (51.4%) and median age was 60 (IQR 50-67) years. All were unruptured AComm aneurysms. Half of the cohort had similar anterior cerebral artery sizes (51.4%). The most common morphology was saccular (94.6%), with a branch involvement in 32.7% of cases. Median vessel diameter was 2.4 mm, and the Pipeline Flex was the most prevalent device (32.7%). Median follow-up time was 17 months, with complete occlusion in 86.4% at the last follow-up. Functional independence (modified Rankin Scale score 0-2) was reported in 95.1%. Intraprocedural complications occurred in 5.6%, and postoperative complications were noted in 9.7% of cases. Combined major complication and mortality rate was 2.1%. Our study suggests that flow diverters are a useful treatment for AComm aneurysms. Mid-term results indicated favorable aneurysm occlusion with a good safety profile. Additional prospective studies with longer follow-up periods and independent adjudication are warranted to better assess these results.


Development of a fermented quinoa-based beverage.
Quinoa is a crop that originated from the Andes. It has high nutritional value, outstanding agro-ecological adaptability, and low water requirements. Quinoa is an excellent crop alternative to help overcome food shortages, and it can also have a role in the prevention of developed world lifestyle diseases, such as type-2 diabetes, cardiovascular diseases, osteoporosis, inflammatory and autoimmune diseases, etc. In order to expand the traditional uses of quinoa and to provide new, healthier and more nutritious food products, a fermented quinoa-based beverage was developed. Two quinoa varieties (Rosada de Huancayo and Pasankalla) were studied. The fermentation process, viscosity, acidity, and metabolic activity during the preparation and storage of the drink were monitored, as well as the preliminary organoleptic acceptability of the product. The drink had viable and stable microbiota during the storage time and the fermentation proved to be mostly homolactic. Both quinoa varieties were suitable as base for fermented products; Pasankalla, however, has the advantage due to higher protein content, lower saponin concentration, and lower loss of viscosity during the fermentation process. These results suggest that the differences between quinoa varieties may have substantial effects on food processes and on the properties of final products. This is a factor that should be taken into account when planning novel products based on this grain.


[Mortality and hospital discharges in the population of Biancavilla (Sicily) contaminated by natural fibres].
The volcanic area of Biancavilla (Sicily Italy) has been included by the Italian national law among the areas of "environmental reclamation" due to the presence of amphibole fluoro-edenitic fibres in the environment. The aim of the study was to evaluate the health of residents in the area, through the analysis of the mortality registry and the hospital discharge records. Age, cause and gender specific indirect standardized mortality ratios SMR (1995-2000) and morbidity ratios SHR (2001-2003) were computed with 95% confidence intervals, using the population of surrounding municipalities as reference. statistically significant increases in mortality and morbidity were observed, both in men and women, for malignant pleural neoplasms (mortality: men SMR= 700, 6 observed; women SMR= 840, 3 observed; hospital admissions: women SHR= 1210, 5 observed), cardiovascular diseases (mortality: men SMR= 115, 267 observed, women SMR= 115, 278 observed; hospital admissions: men SHR= 109, 631 observed; women SHR= 114, 528 observed) and respiratory diseases (mortality: men SMR= 164, 68 observed; women: SMR= 215, 44 observed; hospital admissions: men SHR= 139, 558 observed, women SHR= 125, 374 observed). the excesses observed in this study are consistent with previous findings and suggest the need for further investigations aimed at improving the knowledge of the mineralogical aspects of the fibres, the assessment of human exposure and at estimating the prevalence of pleural plaques and lung fibrosis.


Effects of acute and chronic nicotine administration on probability discounting.
Nicotine use is a continuing public health concern. Smokers are more likely to make risky or maladaptive decisions compared to nonsmokers, so the relation between nicotine and risky choice warrants further investigation. Risky choice can be operationally defined as the choice for a larger, uncertain reinforcer over a smaller, certain reinforcer and can be assessed through a probability-discounting procedure. Acute nicotine administration has been shown to alter risky choice, but because the everyday smoker uses nicotine repeatedly, more research on chronic administration is needed and would allow for assessment of tolerance or sensitization of any effects. The present study examined effects of acute and repeated nicotine administration on probability discounting. Sprague-Dawley rats were used as subjects and the probability-discounting task involved discrete-trial choices between a small, certain reinforcer and a larger, uncertain reinforcer. The probability of larger-reinforcer delivery decreased across blocks within each session. Acute nicotine (0.1-1.0 mg/kg) administration dose-dependently increased risky choice, increased lose-stay ratios (a measure of response perseveration), and decreased reinforcement frequency. Tolerance to nicotine's effects on larger-reinforcer choice was observed after repeated 1.0 mg/kg nicotine administration. The results of the present study add to the existing literature that acute nicotine administration increases risky choice and demonstrates that tolerance to this effect develops after chronic exposure to the drug. Possible behavioral mechanisms behind this effect are discussed, as are suggestions for future research on nicotine and risky choice.


Chitinase-Like Protein PpCTL1 Contributes to Maintaining Fruit Firmness by Affecting Cellulose Biosynthesis during Peach Development.
The firmness of the flesh fruit is a very important feature in the eating process. Peach fruit is very hard during development, but its firmness slightly decreases in the later stages of development. While there has been extensive research on changes in cell wall polysaccharides during fruit ripening, little is known about the changes that occur during growth and development. In this study, we investigated the modifications in cell wall components throughout the development and ripening of peach fruit, as well as its impact on firmness. Our findings revealed a significant positive correlation between fruit firmness and cellulose content at development stage. However, the correlation was lost during the softening process, suggesting that cellulose might be responsible for the fruit firmness during development. Members of the chitinase-like protein (CTL) group are of interest because of their possible role in plant cell wall biosynthesis. Here, two CTL homologous genes, PpCTL1 and PpCTL2, were identified in peach. Spatial and temporal expression patterns of PpCTLs revealed that PpCTL1 exhibited high expression abundance in the fruit and followed a similar trend to cellulose during fruit growth. Furthermore, silencing PpCTL1 expression resulted in reduced cellulose content at 5 DAI (days after injection), this change that would have a negative effect on fruit firmness. Our results indicate that PpCTL1 plays an important role in cellulose biosynthesis and the maintenance of peach firmness during development.


Selected Flavonols in Breast and Gynecological Cancer: A Systematic Review.
The consumption of foods that are rich in phenolic compounds has chemopreventive effects on many cancers, including breast cancer, ovarian cancer, and endometrial cancer. A wide spectrum of their health-promoting properties such as antioxidant, anti-inflammatory, and anticancer activities, has been demonstrated. This paper analyzes the mechanisms of the anticancer action of selected common flavonols, including kemferol, myricetin, quercetin, fisetin, galangin, isorhamnetin, and morin, in preclinical studies, with particular emphasis on in vitro studies in gynecological cancers and breast cancer. In the future, these compounds may find applications in the prevention and treatment of gynecological cancers and breast cancer, but this requires further, more advanced research.


Impact of prone versus supine positioning on small bowel dose with pelvic intensity modulated radiation therapy.
To report the results of a prospective study that compares small bowel doses during prone and supine pelvic intensity modulated radiation therapy. Ten patients receiving pelvic radiation therapy each had 2 intensity modulated radiation therapy plans generated: supine and prone on a belly board (PBB). Computed tomography on rails was performed weekly throughout treatment in both positions (10 scans per patient). After image fusion, doses to small bowel (SB) loops and clinical target volume were calculated for each scan. Changes between the planned and received doses were analyzed and compared between positions. The impact of bladder filling on SB dose was also assessed. Prone treatment was associated with significantly lower volumes of SB receiving ≥20 Gy. On average, prone on a belly board positioning reduced the volume of SB receiving a given dose of radiation by 28% compared with supine positioning. Target coverage throughout the treatment course was similar in both positions with an average minimum clinical target volume dose of 88% of the prescribed prone dose and 89% of the supine (P = .54). For supine treatment, SB dose was inversely correlated with bladder filling (P = .001-.013; P > .15 for prone). For 96% of treatments, the volume of SB that received a given dose deviated >10% from the plan. The deviation between the planned and delivered doses to SB did not differ significantly between the positions. Prone positioning on a belly board during pelvic IMRT consistently reduces the volume of SB that receives a broad range of radiation doses. Prone IMRT is associated with interfraction dose variation to SB that is similar to that of supine positioning. These findings suggest that prone positioning with daily image guided radiation therapy is an effective method for maximizing SB sparing during pelvic IMRT.


Glucagon regulates hepatic inducible nitric oxide synthesis in vivo.
The inducible nitric oxide synthase (iNOS) is stimulated to produce large quantities of nitric oxide (NO) by proinflammatory stimuli, hemorrhagic shock, and a variety of cytokines. We have previously shown that cAMP profoundly inhibits hepatocyte iNOS expression in vitro. In this study, we tested whether glucagon, a hormone that increases cAMP in hepatocytes, could regulate hepatic iNOS expression and activity in vivo. Rats were injected intraperitoneally with lipopolysaccharide (LPS, 10 mg/kg) and treated with either saline or glucagon (500 microg/kg i.p.). Plasma and liver tissue were obtained 6 and 24 h after LPS. LPS induced increased iNOS mRNA, iNOS protein, and plasma levels of nitrite/nitrate that were all significantly decreased by glucagon treatment. The reduction in iNOS expression produced by glucagon was associated with a reduction in plasma AST and LDH levels, suggesting decreased LPS-induced hepatic injury. These data suggest that glucagon may participate in the in vivo regulation of hepatic iNOS expression after proinflammatory stimuli.


Core-Cone Structured Monodispersed Mesoporous Silica Nanoparticles with Ultra-large Cavity for Protein Delivery.
A new type of monodispersed mesoporous silica nanoparticles with a core-cone structure (MSN-CC) has been synthesized. The large cone-shaped pores are formed by silica lamellae closely packed encircling a spherical core, showing a structure similar to the flower dahlia. MSN-CC has a large pore size of 45 nm and a high pore volume of 2.59 cm(3) g(-1). MSN-CC demonstrates a high loading capacity of large proteins and successfully delivers active β-galactosidase into cells, showing their potential as efficient nanocarriers for the cellular delivery of proteins with large molecular weights.


PCR-based DNA typing of saliva stains recovered from human skin.
Human bites in cases of homicide, sexual assault, and abuse are often distorted due to the elasticity and curvature of the skin. Physical comparison of a bite mark to a suspect's teeth is sometimes difficult. Saliva, which is usually deposited during biting, can be collected and analyzed to identify the perpetrator. Using simulated bite mark situations in two experimental series, three samples of 40 microL of whole saliva were deposited on the skin of 27 cadavers (at 33 sites) and three samples of 100 microL of whole saliva were deposited on the skin of 5 cadavers (at 12 sites). Saliva was collected using the double swab technique at t = 5 min, t = 24 h, and t = 48 h. DNA was extracted using the modified Chelex method and submitted to PCR-based typing at two short tandem repeat loci. Results indicate that the concentration of DNA in saliva recovered from skin varies as a function of time since deposition. There is a significant decrease in concentration in the first 24 h but the concentration remains stable from 24 to 48 h. The success of PCR amplification is independent of the time since deposition or the concentration of DNA in the saliva sample. Contamination from the DNA of the cadaver was not found in any of the cases studied.


Validity of combined cytology and human papillomavirus (HPV) genotyping with adjuvant DNA-cytometry in routine cervical screening: results from 31031 women from the Bonn-region in West Germany.
Our aim was to improve the accuracy of routine cervical screening by a risk-adapted multimodal protocol with special focus on possible reduction and prognostic assessment of false positive results. A cohort of 31031 women from the Bonn-region in West Germany, median age 36 years, were screened by cytology (conventional or liquid-based), followed by PCR-based HVP detection with genotyping and adjuvant DNA image cytometry, if indicated, in a sequential manner. The true prevalence of high-grade cervical intraepithelial neoplasia and carcinoma (>/=CIN2) was 0.32% in the population as projected from cervical biopsies of 123 women (0.4%), of whom 100 showed >/=CIN2. Sensitivity of the cytology screening program at PapIIID/HSIL threshold for detecting histologically confirmed >/=CIN2 cases was 81%, with specificity, positive predictive value (PPV) and negative predictive value (NPV) of 99, 20.9 and 99.9%, respectively. Of 38 women receiving the complete screening protocol, all the 31 >/=CIN2 cases were correctly detected by cytology alone, 30 by positive high-risk HPV genotype and 30 by aneuploid DNA profile. The combination of the three methods resulted in an up to 6.9% increase in PPV for >/=CIN2 at practically unchanged detection rate with the additional benefit of being able to predict the probable outcome of CIN1 lesions detected as false positives with any single test. Multimodal cervical screening might permit identification of those women with low-grade squamous intraepithelial lesions likely to progress at an earlier and curable stage of disease and lengthen the screening interval in those with transient minor lesions caused by productive HPV infection.


Impact of Exposure to Environmental Enrichment on the Anxiety-Like Behavior of Ovariectomized Mice.
Objective: The aim of this study was to explore the influence of short-term (2-week) exposure to social (SE) and/or physical enrichment (PE) on the anxiety-like behavior of ovariectomized (OVX) NIH Swiss mice. Method : One week after surgery, each OVX mouse was housed under one of 4 social conditions: (1) isolated, (2) accompanied by an intact female, (3) accompanied by an intact male, or (4) in a community of 10 OVX individuals. The animals in each of these environments were divided into 2 subgroups, consisting of the presence and absence of PE. Following a 2-week exposure to the respective conditions, each OVX mouse was subjected to either the light/dark exploration test (LDT) or the elevated plus maze (EPM) to examine anxiety-like behavior. Results: The LDT and EPM showed very similar patterns. Compared to an impoverished environment, PE elicited a significant anxiolytic effect for OVX mice housed alone or in companion of an intact female (F [1, 54] = 16.11, P = 0.001). By contrast, mice living in community but without PE displayed anxiogenic-like behavior, perhaps due to crowding, compared to the animals living in isolation (F [1, 36] = 5.64, P = 0.023). Conclusion: This study emphasized the importance of taking housing conditions into account during the screening of new anxiolytic agents and the critical role of OVX in the regulation of anxiety.


Comparison of calcium import as a function of contraction in the aortic smooth muscle of Sprague-Dawley, Wistar Kyoto and spontaneously hypertensive rats.
Genetic variations of far-reaching consequences have been established between spontaneously hypertensive rats (SHR) and their controls, Wistar Kyoto rats (WKY). The SHR strain is the most widely used model for the study of genetic hypertension. Calcium homeostasis in the vascular smooth muscle (VSM) is controlled by calcium channels and calcium pumps located in both VSM and the overlying endothelial cells that line the large blood vessels and the heart. Hypertension adversely affects calcium homeostasis. Investigations on the import of calcium from extracellular spaces with alpha1-adrenergic stimulation as a function of contractility of VSM cells in SHR and WKY were made and compared with the contractility observed in VSM cells of Sprague-Dawley (CD) rats. Experiments were performed on rings from thoracic aortas of three strains with endothelial lining intact or removed to discern the paracrine control of endothelium on contractility in response to calcium import. The internal stores of Ca2+ were depleted by repeated alpha 1-adrenergic stimulation with phenylephrine (PE) and refilling of these stores was prevented by cyclopiazonic acid (CPA) and/or thapsigargin (TG), two known inhibitors of Ca2+ATPase, the enzyme that drives sarcoplasmic calcium pumps. The two components of tonic muscular contraction, T I and T II, which are known to be due to the flow of Ca2+ from the extracellular gradient controlled via the poly-phosphoinositide cascade and nifedipine sensitive Ca2+ channels were found to be variable among these strains. Implications of these variations are discussed in this report


An Unusual Pathogen Causing Native Valve Endocarditis.
We present the case of a gentleman who was being evaluated for restrictive lung disease and was incidentally found to have mitral valve stenosis on an HRCT. During the surgical procedure for valve replacement, he was found to have an abscess around the native mitral valve which was drained. Pus from the abscess as well as the valve tissue grew Propionibacterium acnes after holding the cultures long. The patient was treated with IV ceftriaxone with good response to therapy. While Propionibacterium acnes is known to cause prosthetic valve infections there are rare case reports with native valves. This is the first case to be reported from our country.


Dapsone for the treatment of doxorubicin extravasation injury in the rat.
Doxorubicin is the most common antitumor drug implicated in serious extravasation injuries. Progressive tissue necrosis may lead to intense pain, chronic ulceration, and disfiguring tissue loss. This progressive necrosis is analogous to that seen with brown recluse spider bites, where dapsone is an established mode of therapy, minimizing the area of tissue loss by a proposed antiinflammatory mechanism. The backs of 50 Lewis rats were injected intradermally with 1 mg of doxorubicin in 1 cc of saline to simulate an extravasation injury. The rats were divided into five groups for treatment with oral dapsone 50 mg/kg/day: 10 were controls (no treatment), 10 were started the day before injury, 10 were started the day of injury, 10 were started the day after injury, and 10 were started 1 week after injury. The area of ulceration was calculated by planimetry. The data suggest that dapsone has little positive effect on healing extravasation ulcers.


Day 0 protocol: superstimulatory treatment initiated in the absence of a large follicle improves ovarian response and embryo yield in goats.
A new superstimulatory protocol (Day 0 Protocol) to initiate FSH treatment in the absence of a large follicle was compared to a traditional protocol in goats. The Day 0 Protocol (n=44) consisted of pre-treatment with progesterone and eCG to synchronize ovulation and the emergence of Wave 1, with FSH starting 84 h after the end of progesterone exposure (i.e., soon after ovulation). The traditional protocol (n=46) consisted of 11 d of progesterone exposure, with FSH treatment beginning 2 d before the end of progesterone exposure. Treatment with FSH was initiated in the absence of a large follicle in 37/44 and in 6/46 goats in the Day 0 Protocol and traditional protocol, respectively (P<0.01). There was more CL in the Day 0 Protocol than in the traditional protocol (breeding season: 9.6+/-0.6 and 6.3+/-0.8, P<0.05; non-breeding season: 14.3+/-1.5 and 10.7+/-1.5; P<0.05). More Grades 1 and 2 embryos were recovered in the Day 0 Protocol than in the traditional protocol (breeding season: 4.8+/-0.7 and 1.8+/-0.5, P<0.05; non-breeding season: 5.6+/-1.1 and 3.5+/-0.7, P=0.07). Similarly, the proportion of embryos that were Grades 1 and 2 was higher for the Day 0 Protocol than for the traditional protocol (breeding season: 81/114, 71%, versus 16/43, 37%, P<0.05; non-breeding season: 118/203, 58% versus 95/205, 46%, P<0.05). In summary, the Day 0 Protocol, was effective in initiating superstimulatory treatment in the absence of a large follicle, and compared to the traditional protocol, induced a higher ovulation rate and better embryo yield in goats.


The identification of mixed granulocytic-erythrocytic colonies in vitro.
The identification of mixed granulocytic-erythrocytic colonies in culture poses special problems. First, methods based on the detection of peroxidase-like activity of red-cell hemoglobin using benzidine can give false-positive results with eosinophilic cells in colonies. Secondly, the use of the color of hemoglobin itself to identify mixed colonies prevents the detection of those colonies where the erythrocytic component is small or contains relatively little hemoglobin. We present here a new method using O-Dianisidine (O-D) to detect red-cell peroxidase activity. Subsequent staining with Luxol fast blue showed that eosinophils did not give a positive reaction with O-D. The technique also has the advantage that the whole culture gel is processed and that there is no need to pick off individual clones for identification. Using the combined stain O-D and Luxol fast blue most lineages within clones can be discriminated.


Cyclic AMP mediates ovine cumulus-oocyte gap junctional function via balancing connexin 43 expression and phosphorylation.
Gap junction channels in cumulus-oocyte complexes (COCs) enable the transmission and communication of small molecular signals between adjacent cells, such as cAMP. However, the regulation of gap junction function (GJF) by cAMP and the underlying mechanisms involved are not fully clarified. This study investigated the effect of cAMP on connexin 43 (CX43) expression and GJF in ovine COCs using immunofluorescence, quantitative real-time PCR (qRT-PCR), western blotting, and GJF detection. The CX43 was only found in the cumulus cells (CCs) side of ovine COC. The intra-oocyte cAMP showed a significant increase at 30 min, while the intra-CC cAMP exhibited two peaks at 10 min and 1 h during in vitro maturation (IVM). Phosphorylated CX43 protein exhibited an immediate increase at 10 min, and CX43 protein displayed two peaks at 10 min and 1 h during IVM. The duration of pre-IVM exposure to forskolin and IBMX significantly enhanced phosphorylated and total CX43, as well as Gja1 and Creb genes, for 10 min; these effects were counteracted by Rp-cAMP. Both pre-IVM with forskolin and IBMX for 1 h and the GJF and CX43/p-CX43 ratio were elevated. The closure of gap junction channels caused by phosphorylated CX43 to prevent cAMP outflow from oocytes in early IVM of COC. Cyclic AMP upregulated phosphorylated and total CX43 via genomic and non-genomic pathways, but its functional regulation was dependent on the balance of the two proteins. This study provides a new insight into the regulatory mechanism between cAMP and GJF, which would improve IVM in animal and clinical research.


The effects of learning American Sign Language on co-speech gesture().
Given that the linguistic articulators for sign language are also used to produce co-speech gesture, we examined whether one year of academic instruction in American Sign Language (ASL) impacts the rate and nature of gestures produced when speaking English. A survey study revealed that 75% of ASL learners (N = 95), but only 14% of Romance language learners (N = 203), felt that they gestured more after one year of language instruction. A longitudinal study confirmed this perception. Twenty-one ASL learners and 20 Romance language learners (French, Italian, Spanish) were filmed re-telling a cartoon story before and after one academic year of language instruction. Only the ASL learners exhibited an increase in gesture rate, an increase in the production of iconic gestures, and an increase in the number of handshape types exploited in co-speech gesture. Five ASL students also produced at least one ASL sign when re-telling the cartoon. We suggest that learning ASL may (i) lower the neural threshold for co-speech gesture production, (ii) pose a unique challenge for language control, and (iii) have the potential to improve cognitive processes that are linked to gesture.


Posterior lumbar interbody fusion (PLIF) with cages and local bone graft in the treatment of spinal stenosis.
Posterior lumbar interbody fusion (PLIF) implants are increasingly being used for 360 degrees fusion after decompression of lumbar spinal stenosis combined with degenerative instability. Both titanium and PEEK (PolyEtherEtherKetone) implants are commonly used. Assessing the clinical and radiological results as well as typical complications, such as migration of the cages, is important. In addition, questions such as which radiological parameters can be used to assess successful fusion, and whether the exclusive use of local bone graft is sufficient, are frequently debated. We prospectively evaluated 30 patients after PLIF instrumentation for degenerative lumbar spinal canal stenosis, over a course of 42 months. In all cases, titanium cages and local bone graft were used for spondylodesis. The follow-up protocol of these 30 cases included standardised clinical and radiological evaluation at 3, 6, 12 and 42 months after surgery. Overall satisfactory results were achieved. With one exception, a stable result was achieved with restoration of the intervertebral space in the anterior column. After 42 months of follow-up in most cases, a radiologically visible loss of disc space height can be demonstrated. Clinically relevant migration of the cage in the dorsal direction was detected in one case. Based on our experience, posterior lumbar interbody fusion (PLIF) can be recommended for the treatment of monosegmental and bisegmental spinal stenosis, with or without segmental instability. Postoperative evaluation is mainly based on clinical parameters since the titanium implant affects the diagnostic value of imaging studies and is responsible for artefacts. The results observed in our group of patients suggest that local autologous bone graft procured from the posterior elements after decompression is an adequate material for bone grafting in this procedure.


Evaluation of Columbia, USMARC-Composite, Suffolk, and Texel rams as terminal sires in an extensive rangeland production system: IV. Postfabrication carcass component weights.
Postfabrication carcass component weights of 517 crossbred wether lambs were analyzed to evaluate 4 terminal-sire breeds. Wethers were produced over 3 yr from single-sire matings of 22 Columbia, 22 USMARC-Composite (Composite), 21 Suffolk, and 17 Texel rams to adult Rambouillet ewes. Lambs were reared to weaning in an extensive western rangeland production system and finished in a feedlot on a high-energy finishing diet. When wethers reached a mean BW of 54.4, 61.2, or 68.0 kg, they were transported to The Ohio State University abattoir for harvest. After refrigeration for approximately 24 h, chilled carcass weight (CCW) was measured, carcasses were fabricated according to Style A of Institutional Meat Purchase Specifications, and postfabrication weights were recorded. At comparable numbers of days on feed, Suffolk-sired lambs had heavier (P < 0.04) neck, breast, shoulder, foreshank, rack, loin, leg, sirloin, roast-ready rack, trimmed loin, and boneless leg cuts than progeny of the other sire breeds. Boneless sirloins were heavier (P < 0.01) for Suffolk-sired than Composite-sired lambs but did not differ from those for Columbia- or Texel-sired lambs. Columbia- and Suffolk-sired lambs had heavier (P < 0.01) hindshanks than Texel-sired lambs. Suffolk-sired lambs had heavier (P < 0.01) high-value cuts (rack, loin, leg, and sirloin) and trimmed high-value cuts than progeny of the other sire breeds. Cutting loss (CCW - wholesale cut weights) and high-value trimming loss were greatest (P < 0.02) for Suffolk-sired lambs and least for Texel- and Composite-sired lambs. Sire breed did not affect (P > 0.06) flank weight. Data adjusted to comparable CCW reduced the number of significant sire-breed effects and changed sire-breed rankings of carcass component weights, for which sire breeds differed. After adjusting, Suffolk-sired lambs had lighter (P < 0.05) loins than Columbia- and Composite-sired lambs, Composite-sired lambs had heavier (P < 0.05) high-value cuts than Suffolk-sired lambs, and Suffolk- and Columbia-sired lambs had heavier (P < 0.05) necks than Texel-sired lambs. At predicted backfat thickness of 6.6 mm, Composite-sired lambs had a greater (P < 0.05) percentage of high-value cuts than Suffolk-sired lambs before but not after trimming. Producers can use these results to select terminal-sire breeds that will complement their production system and improve lamb value.


Pruning and loss of excitatory synapses by the parkin ubiquitin ligase.
Mutations in the PARK2 gene cause hereditary Parkinson disease (PD). The PARK2 gene product, termed parkin, is an E3 ubiquitin ligase that mediates the transfer of ubiquitin onto diverse substrate proteins. Despite progress in defining the molecular properties and substrates of parkin, little is known about its physiological function. Here, we show that parkin regulates the function and stability of excitatory glutamatergic synapses. Postsynaptic expression of parkin dampens excitatory synaptic transmission and causes a marked loss of excitatory synapses onto hippocampal neurons. Conversely, knockdown of endogenous parkin or expression of PD-linked parkin mutants profoundly enhances synaptic efficacy and triggers a proliferation of glutamatergic synapses. This proliferation is associated with increased vulnerability to synaptic excitotoxicity. Thus, parkin negatively regulates the number and strength of excitatory synapses. Increased excitatory drive produced by disruption of parkin may contribute to the pathophysiology of PD.


The Relationship between Intrinsic Couplings of the Visual Word Form Area with Spoken Language Network and Reading Ability in Children and Adults.
Reading plays a key role in education and communication in modern society. Learning to read establishes the connections between the visual word form area (VWFA) and language areas responsible for speech processing. Using resting-state functional connectivity (RSFC) and Granger Causality Analysis (GCA) methods, the current developmental study aimed to identify the difference in the relationship between the connections of VWFA-language areas and reading performance in both adults and children. The results showed that: (1) the spontaneous connectivity between VWFA and the spoken language areas, i.e., the left inferior frontal gyrus/supramarginal gyrus (LIFG/LSMG), was stronger in adults compared with children; (2) the spontaneous functional patterns of connectivity between VWFA and language network were negatively correlated with reading ability in adults but not in children; (3) the causal influence from LIFG to VWFA was negatively correlated with reading ability only in adults but not in children; (4) the RSFCs between left posterior middle frontal gyrus (LpMFG) and VWFA/LIFG were positively correlated with reading ability in both adults and children; and (5) the causal influence from LIFG to LSMG was positively correlated with reading ability in both groups. These findings provide insights into the relationship between VWFA and the language network for reading, and the role of the unique features of Chinese in the neural circuits of reading.


Chemical Vapor Deposition Growth and Applications of Two-Dimensional Materials and Their Heterostructures.
Two-dimensional (2D) materials have attracted increasing research interest because of the abundant choice of materials with diverse and tunable electronic, optical, and chemical properties. Moreover, 2D material based heterostructures combining several individual 2D materials provide unique platforms to create an almost infinite number of materials and show exotic physical phenomena as well as new properties and applications. To achieve these high expectations, methods for the scalable preparation of 2D materials and 2D heterostructures of high quality and low cost must be developed. Chemical vapor deposition (CVD) is a powerful method which may meet the above requirements, and has been extensively used to grow 2D materials and their heterostructures in recent years, despite several challenges remaining. In this review of the challenges in the CVD growth of 2D materials, we highlight recent advances in the controlled growth of single crystal 2D materials, with an emphasis on semiconducting transition metal dichalcogenides. We provide insight into the growth mechanisms of single crystal 2D domains and the key technologies used to realize wafer-scale growth of continuous and homogeneous 2D films which are important for practical applications. Meanwhile, strategies to design and grow various kinds of 2D material based heterostructures are thoroughly discussed. The applications of CVD-grown 2D materials and their heterostructures in electronics, optoelectronics, sensors, flexible devices, and electrocatalysis are also discussed. Finally, we suggest solutions to these challenges and ideas concerning future developments in this emerging field.


Dynamic changes during evacuation of a left temporal abscess in open MRI: technical case report.
We demonstrate the usefulness of "near real-time" neuro-navigation by open MRI systems for guidance of stereotactic evacuation of intracranial abscesses. A 70-year-old patient was referred to our institution with an intracranial left temporal abscess. He presented with headache, senso-motor aphasia and mild right hemiparesis. The abscess (35 x 25 mm) was stereotactically evacuated under MRI guidance, and a recurrence of a daughter abscess was again evacuated on the 9th postoperative day. "Near real-time" imaging showed an indentation of the abscess wall of 11 mm along the trajectory. A thermosensitive MRI protocol demonstrated a higher temperature around the abscess capsule than in the brain tissue more distant to the capsule, demonstrating the inflammatory process. The patient had 6 weeks of antibiotic therapy for gram-negative bacteria and was discharged with improved clinical symptoms 5 weeks after admission. Follow-up CT 2 months postoperatively showed a complete resolution of the abscess. Open MRI-guided interventions with "near real-time" imaging demonstrate the anatomical changes during an ongoing procedure and can be accommodated for enhancing the overall precision of stereotactic procedures. Thermosensitive MRI protocols are capable of revealing temperature gradients around inflammatory processes.


Advancing Diagnostics to Address Antibacterial Resistance: The Diagnostics and Devices Committee of the Antibacterial Resistance Leadership Group.
Diagnostics are a cornerstone of the practice of infectious diseases. However, various limitations frequently lead to unmet clinical needs. In most other domains, diagnostics focus on narrowly defined questions, provide readily interpretable answers, and use true gold standards for development. In contrast, infectious diseases diagnostics must contend with scores of potential pathogens, dozens of clinical syndromes, emerging pathogens, rapid evolution of existing pathogens and their associated resistance mechanisms, and the absence of gold standards in many situations. In spite of these challenges, the importance and value of diagnostics cannot be underestimated. Therefore, the Antibacterial Resistance Leadership Group has identified diagnostics as 1 of 4 major areas of emphasis. Herein, we provide an overview of that development, highlighting several examples where innovation in study design, content, and execution is advancing the field of infectious diseases diagnostics.


A flexible parylene probe for in vivo recordings from multiple subregions of the rat hippocampus.
The hippocampus is crucial to the formation of long-term memory and declarative memory. It is divided into three sub-fields the CA1, the CA3 and the DG. To understand the neuronal circuitry within the hippocampus and to study the role of the hippocampus in memory function requires the collection of neural activities from multiple subregions of the hippocampus simultaneously. Micro-wire electrode arrays are commonly used as an interface with neural systems. However, recording from multiple deep brain regions with curved anatomical structures such as the thin cell body layers of the hippocampus requires the micro-wires to be arranged into a highly accurate, complex layout that is difficult to fabricated manually. In this work, we designed and developed a flexible parylene-C based neural probe which can be easily micro-machined to the desired dimensions. Sixty-four electrical recording sites are micromachined on to 8 parylene shanks and spaced according to the distribution of hippocampal principal neurons in different hippocampus subregions. Together with our collaborators, we developed and optimized the implantation procedure of the flexible parylene probe and tested the insertion method both in brain tissue phantom and in vivo with a sham device. Immunohistochemistry (IHC) staining post-implantation of the sham probe was used to verify the location of the probe and to evaluate immune responses to the probe. Fully functional devices were fabricated and, in future studies, functional probes will be chronically implanted into the rat hippocampus, and neural activities will be recorded and compared with signals obtained with micro-wire arrays.


Exploring the multiplicity of childhood sexual abuse with a focus on polyincestuous contexts of abuse.
This study explored the prevalence of multiple abusers and polyincest in a clinical sample of 88 adult women, focusing on interviews with a subset of 30. For the sample as a whole, 43% reported three or more abusers and 23% reported polyincest. The narrative data was divided into three categories defined as Single-Abuser (N=8), Multiple Abuser (N=8), and Polyincestuous (N=14). These were compared to determine how survivors perceived family members' and others' reactions to disclosure of CSA. All three groups experienced various forms of silencing. The most negative responses were linked to polyincestuous abuse. Three themes were identified as denial/ minimization/normalization, fear/reprisal, and negative/inadequate. Results suggest the need for further research on the frequency of multiple abusers among victims of sexual abuse, as well as the ways in which family and social contexts serve as collusive environments for the practice of CSA.


Is obesity a risk factor for deep tissue injury in patients with spinal cord injury?
Deep tissue injury (DTI) is a severe form of pressure ulcers that occur in subcutaneous tissue under intact skin by the prolonged compression of soft tissues overlying bony prominences. Pressure ulcers and DTI in particular are common in patients with impaired motosensory capacities, such as those with a spinal cord injury (SCI). Obesity is also common among subjects with SCI, yet there are contradicting indications regarding its potential influence as a risk factor for DTI in conditions where these patients sit in a wheelchair without changing posture for prolonged times. It has been argued that high body mass may lead to a greater risk for DTI due to increase in compressive forces from the bones on overlying deep soft tissues, whereas conversely, it has been argued that the extra body fat associated with obesity may reduce the risk by providing enhanced subcutaneous cushioning that redistributes high interface pressures. No biomechanical evaluation of this situation has been reported to date. In order to elucidate whether obesity can be considered a risk factor for DTI, we developed computational finite element (FE) models of the seated buttocks with 4 degrees of obesity, quantified by body mass index (BMI) values of 25.5, 30, 35 and 40kg/m(2). We found that peak principal strains, strain energy densities (SED) and von Mises stresses in internal soft tissues (muscle, fat) overlying the ischial tuberosities (ITs) all increased with BMI. With a rise in BMI from 25.5 to 40kg/m(2), values of these parameters increased 1.5 times on average. Moreover, the FE simulations indicated that the bodyweight load transferred through the ITs has a greater effect in increasing internal tissue strains/stresses than the counteracting effect of thickening of the adipose layer which is concurrently associated with obesity. We saw that inducing some muscle atrophy (30% reduction in muscle volume, applied to the BMI=40kg/m(2) model) which is also characteristic of chronic SCI resulted in further substantial increase in all biomechanical measures reflecting geometrical distortion of muscle tissue, that is, SED, tensile stress, shear stress and von Mises stress. This result highlights that obesity and muscle atrophy, which are both typical of the chronic phase of SCI, contribute together to the state of elevated tissue loads, which consequently increases the likelihood of DTI in this population.


A proteome signature of umbilical cord serum associated with congenital diaphragmatic hernia.
Congenital diaphragmatic hernia (CDH) is a congenital anomaly characterized by a defect in the diaphragm. Despite the recent improvements in its treatment, CDH is associated with a high rate of neonatal mortality, which is often related to pulmonary hypoplasia (PH) as well as pulmonary hypertension. A better understanding of the underlying pathological mechanisms of PH in CDH could help establish a new treatment to improve its prognosis. In this study, we investigated serum biological profiles in neonates with CDH. For comprehensive investigation, umbilical cord serum samples were collected from isolated CDH cases (n = 4) and matched healthy controls (n = 4). Samples were analyzed using liquid chromatography-tandem mass spectrometry. A total of 697 proteins were detected; of them, 98 were identified as differentially expressed proteins. Among these differentially expressed proteins, complement C1q subcomponent showed the largest fold change, followed by complement C5. In the pathway enrichment analysis, the complement and coagulation cascades expressed the most significant enrichment (p = 2.4 × 10-26). Thus, the complement pathway might play some role in the pathophysiology of CDH.


Evolving therapies for Fuchs' endothelial dystrophy.
Fuchs' endothelial dystrophy (FED) is characterized by corneal endothelial dysfunction and guttate excrescences on the posterior corneal surface, and is the leading indication for corneal transplantation in developed countries. In severe cases, keratoplasty is considered as the gold standard of treatment. However, there have been significant developments in our understanding of FED over the past decade. Attempts have been made to treat this disease with regenerative therapy techniques such as primary descemetorhexis without an endothelial graft or with a tissue-engineering approach. The discovery of a strong association between the CTG18.1 trinucleotide repeat expansion sequence and FED may pave the way for gene therapy strategies in the future. In this review, we evaluate these novel therapeutic modalities as possible alternatives to keratoplasty as the standard of care for FED.


Aortic tumor or mobile thrombus?
Isolated large mobile mass in the thoracic aorta can be due to thrombus or, rarely, aortic tumor. We report the case of a 61-year-old man with no history of medical problems presenting with neurologic deficits and in whom a large mobile echogenic mass in the distal aortic arch was found with transesophageal echocardiography. Given his few cardiovascular risk factors and absence of other systemic symptoms, he received anticoagulant therapy. Subsequent resolution of the aortic mass suggested a diagnosis of thrombus. This case illustrates an unusual manifestation of aortic arch atherosclerosis and underscores the utility of transesophogeal echocardiography for patients with ischemic stroke.


The Molecular Mechanisms of Plant-Derived Compounds Targeting Brain Cancer.
Glioblastoma multiforme (GBM) is one of the most aggressive and malignant forms of brain tumors. Despite recent advances in operative and postoperative treatments, it is almost impossible to perform complete resection of these tumors owing to their invasive and diffuse nature. Several natural plant-derived products, however, have been demonstrated to have promising therapeutic effects, such that they may serve as resources for anticancer drug discovery. The therapeutic effects of one such plant product, n-butylidenephthalide (BP), are wide-ranging in nature, including impacts on cancer cell apoptosis, cell cycle arrest, and cancer cell senescence. The compound also exhibits a relatively high level of penetration through the blood-brain barrier (BBB). Taken together, its actions have been shown to have anti-proliferative, anti-chemoresistance, anti-invasion, anti-migration, and anti-dissemination effects against GBM. In addition, a local drug delivery system for the subcutaneous and intracranial implantation of BP wafers that significantly reduce tumor size in xenograft models, as well as orthotopic and spontaneous brain tumors in animal models, has been developed. Isochaihulactone (ICL), another kind of plant product, possesses a broad spectrum of pharmacological activities, including impacts on cancer cell apoptosis and cell cycle arrest, as well as anti-proliferative and anti-chemoresistance effects. Furthermore, these actions have been specifically shown to have cancer-fighting effects on GBM. In short, the results of various studies reviewed herein have provided substantial evidence indicating that BP and ICH are promising novel anticancer compounds with good potential for clinical applications.


Analysis of the Motional Stark Effect (MSE) diagnostic to measure the rotational transform and current profile in the Large Helical Device.
The analysis method of the Motional Stark Effect (MSE) diagnostic to measure the rotational transform and current profiles in the Large Helical Device has been improved. This was done by using the Variational Moments Equilibrium Code to calculate an equilibrium database for various pressure profiles and current profiles. This method looks for the radial profile of the rotational transform in the equilibrium database that gives the best fit to the polarization angle profiles measured with the MSE diagnostic. This analysis improves the measurements of rotational transform, especially near the magnetic axis, where the sensitivity of the polarization angle measurements becomes low and the uncertainty due to error in the estimation of the Pfirsch-Schlüter current becomes large. The radial profiles of the rotational transform and current profiles for Electron Cyclotron Current Drive and Neutral Beam Current Drive are obtained in the new analysis method with a sufficiently high accuracy to discuss the discrepancy of the current density profiles between the measurements and the calculations.


Generation of [Ala1,Thr6]bradykinin in the plasma of a snake, the reticulated python.
Incubation of heat-denatured plasma from the reticulated python, Python reticulatus with trypsin generated bradykinin-like immunoreactivity which was detected by radioimmunoassay using an antiserum raised against mammalian bradykinin. The primary structure of python bradykinin was established as Ala-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg. This amino acid sequence contains two substitutions (Arg1-->Ala and Ser6-->Thr) compared with mammalian bradykinin. Treatment of python plasma with glass beads under conditions previously shown to generate [Thr6]bradykinin in the plasma of a turtle and an alligator did not generate bradykinin-like immunoreactivity. The data indicate that the plasma of a lepidosaur contains a kininogen but, unlike the plasma of chelonians and crocodilians, does not contain a prekallikrein activator related to Factor XII.


Generation and characterisation of bovine antigen-specific T cell lines.
15 antigen-specific T cell lines have been generated from eight individual cattle immunised with ovalbumin. Several sources of interleukin-2 (IL-2) were used, including a supernatant from a gibbon cell line (MLA-Sup), human recombinant IL-2 (hrIL-2) and bovine recombinant IL-2 (brIL-2). These IL-2 sources were used alternately with autologous peripheral blood mononuclear cells (PBM) together with ovalbumin to generate the lines. They grew least well in MLA-Sup and best in brIL-2. FACS analysis indicated that the lines generated with the recombinant IL-2s were extremely homogeneous in that the majority of cells were BoCD4+ (bovine CD4 equivalent) and therefore of TH phenotype. The lines were antigen specific and responded to antigen only in the presence of autologous PBM and not allogeneic (MHC class I nonidentical) PBM. However, allogeneic PBM did support their proliferation to ConA. No MLR response was observed by the cell lines to allogeneic PBM. The response to antigen was inhibited by anti bovine class II mAbs but not an anti bovine class I mAb. The subpopulation of PBM which acted as antigen presenting cells for these bovine TH cell lines had typical macrophage characteristics.


Association of Serum Manganese Levels with Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.
Manganese (Mn) is one of the most studied environmental heavy metals linked to Alzheimer's disease (AD). However, it remains unclear whether serum Mn levels are associated with AD and mild cognition impairment (MCI, a prodromal stage of AD). We conducted a metaanalysis to analyze the serum Mn levels in patients with AD and MCI. A systematic database search of PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) identified 17 studies, including 836 cases and 1254 health controls (HC). Random-effects meta-analysis showed that patients with AD had significantly reduced serum Mn levels compared with HC subjects (SMD = -0.39; 95% CI (-0.71, -0.08); p = 0.015). MCI individuals had a tendency toward reduced serum Mn levels compared with HC subjects (SMD = -0.31; 95% CI (-0.70, 0.08); p = 0.117). A significant decrease in serum Mn levels was found in patients with cognitive impairment (including both AD patients and MCI patients) (SMD = -0.37, 95% CI (-0.60; -0.13); p = 0.002). Finally, no significant differences were observed between AD and MCI patients in serum levels (SMD = 0.24; 95% CI (-0.23, 0.72); p = 0.310). Our findings show that the serum Mn levels are lower in AD patients, and Mn deficiency may be a risk factor for AD.


The impact of cognitive load on delayed recall.
Recent studies have suggested that long-term retention of items studied in a working memory span task depends on the refreshing of memory items-more specifically, on the number of refreshing opportunities. However, it was previously shown that refreshing depends on the cognitive load of the concurrent task introduced in the working memory span task. Thus, cognitive load should determine the long-term retention of items assessed in a delayed-recall test if such retention relies on refreshing. In two experiments, while the amount of refreshing opportunities remained constant, we varied the cognitive load of the concurrent task by either introducing tasks differing in their attentional demands or varying the pace of the concurrent task. To verify that this effect was related to refreshing and not to any maintenance mechanism, we also manipulated the availability of subvocal rehearsal. Replicating previous results, increasing cognitive load reduced immediate recall. This increase also had a detrimental effect on delayed recall. Conversely, the addition of concurrent articulation reduced immediate but not delayed recall. This study shows that both working and episodic memory traces depend on the cognitive load of the concurrent task, whereas the use of rehearsal affects only working memory performance. These findings add further evidence of the dissociation between subvocal rehearsal and attentional refreshing.


Changes in cerebrospinal fluid biomarkers in human herpesvirus-6-associated acute encephalopathy/febrile seizures.
To determine the involvement of oxidative stress in the pathogenesis of acute encephalopathy associated with human herpesvirus-6 (HHV-6) infection, we measured the levels of oxidative stress markers 8-hydroxy-2'-deoxyguanosine (8-OHdG) and hexanoyl-lysine adduct (HEL), tau protein, and cytokines in cerebrospinal fluid (CSF) obtained from patients with HHV-6-associated acute encephalopathy (HHV-6 encephalopathy) (n = 16) and complex febrile seizures associated with HHV-6 (HHV-6 complex FS) (n = 10). We also examined changes in CSF-8OHdG and CSF-HEL levels in patients with HHV-6 encephalopathy before and after treatment with edaravone, a free radical scavenger. CSF-8-OHdG levels in HHV-6 encephalopathy and HHV-6 complex FS were significantly higher than in control subjects. In contrast, CSF-HEL levels showed no significant difference between groups. The levels of total tau protein in HHV-6 encephalopathy were significantly higher than in control subjects. In six patients with HHV-6 infection (5 encephalopathy and 1 febrile seizure), the CSF-8-OHdG levels of five patients decreased after edaravone treatment. Our results suggest that oxidative DNA damage is involved in acute encephalopathy associated with HHV-6 infection.


Serum thyrotropin, prolactin, and growth hormone levels during the early neonatal period in the human infant.
Normal term newborn infants have been studied during the first four hours after birth. Cord blood and brachial venous blood samples were collected for measurement of serum prolactin (n = 15; 11 vaginal delivery; four cesarean section delivery), thyrotropin (n=8), growth hormone (n=7), tri-iodothyronine (n=7) and thyroxine (n=7). The mean cord serum TSH concentration was 12 +/- 2 muU/ml and peaked in all infants 30 minutes after birth (67 +/- 7 muU/ml). Blood PRL also increased in all of the 15 infants studied; the mean cord blood value of 165 +/- 15 ng/ml increased significantly to a mean of 214 +/- 22 ng/ml at 30 minutes and 204 +/- 17 ng/ml at 60 minutes. The peak blood PRL concentration was observed at 30 minutes in eight newborn infants, at 60 minutes in three, and at 120 minutes in four. Mean serum GH concentrations were statistically similar during the first four hours but there was a tendency for serum levels to fall somewhat during the first hour after birth. The mean cord serum T3 concentration (47 +/- 5 mug/ml) increased significantly to a peak value of 227 +/- 38 ng/dl at 120 minutes. The increase in T4 from a mean of 15.3 +/- 1.2 mug/dl to a mean of 17.9 +/- 2.6 mug/dl at four hours was less dramatic. These data are consistent with the possibility that the same mechanism responsible for the neonatal TSH surge may be responsible for a significant but lesser PRL surge during the early minutes after birth.


Synthesis of Enantioenriched β-Aryl-β-aryloxy Esters via Sequential Photoisomerization and Enantioselective Hydrogenation.
A general method to prepare valuable chiral synthon β-aryl-β-aryloxy esters from enantioselective hydrogenation of (E)-β-aryl-β-aryloxy-α,β-unsaturated esters is described. The E-isomer was prepared via isomerization of the mixture of E- and Z-isomers using photocatalyst [Ir(ppy)2(dtbbpy)]PF6. A laser as the light source facilitated isomerization with only 0.05 mol % catalyst. The enantioselective hydrogenation was conducted with (NBD)2Rh(BF4) and a commercially available Josiphos ligand to provide the synthons in up to 95% yield with 97% ee.


Cytokines in various molecular subtypes of breast cancer.
Breast cancer is a heterogeneous disease that has multiple molecular and morphological subtypes. Nonetheless, the relation between various molecular subtypes and functional characteristics of a tumor in terms of cytokine secretion remains unknown. We studied spontaneous and mitogen-induced cytokine secretion by invasive breast carcinoma of no special type (IBC NST; cultured tumors and cultured peripheral blood cells), depending on a molecular tumor subtype (where "mitogens" means "polyclonal activators" (PA): phytohemagglutinin p, phytohemagglutinin M, concanavalin A, and Escherichia coli lipopolysaccharide). Enzyme-linked immunosorbent assays were used to determine concentrations of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 in culture supernatants of the tumors and peripheral blood cells. The luminal B HER2-positive molecular subtype of IBC NST was found to feature the highest spontaneous secretion of IL-6 and IL-8 and the highest mitogen-induced secretion of IL-6, IL-8, IL-1Ra, and TNF-α by tumors; the highest mitogen-induced secretion of IL-2, IL-6, IL-8, IL-1β, TNF-α, IFN-γ, and G-CSF by peripheral blood cells; and the highest cytokine-producing potential (the ratio of mitogen-induced to spontaneous secretion) of peripheral blood cells for the secretion of IL-6, IL-8, and IL-1Ra as compared to other molecular subtypes. The triple-negative subtype of IBC NST was characterized by the lowest cytokine-producing potential of tumors for the secretion of IL-6 and IL-8 as compared to other molecular subtypes as well as a lower "stimulation index of polyclonal activators" (calculated as (cytokine secretion after incubation with PA)/(spontaneous cytokine secretion)) for IL-18 secretion as compared to luminal subtypes. The XYZ correlated with a suppressive effect of PA on cytokine secretion by tumors of the triple-negative molecular subtype. Therefore, our findings indicate that in IBC NST of luminal B HER2-positive and triple-negative molecular subtypes, the cytokine network has distinctive functional features.


Association of endogenous viral genes with quantitative traits in chickens selected for high egg production and susceptibility or resistance to Marek's disease.
1. The association of endogenous viral (ev) genes with quantitative traits in 2 genetically distinct sets of White Leghorn strains were investigated. Strain S had been selected for susceptibility to Marek's disease (MD) whereas strain K had been selected for resistance to MD and high egg production and egg weight. 2. In all, 8 ev genes were typed. Ev10, ev19 and 'newB' occurred exclusively in strain S, 'newA' occurred only in strain K, and ev1, ev3, ev6 and ev8 occurred in both strains. 3. Whereas ev6 and ev8 were associated with reduction in egg production rate in strain S, in strain K, the presence of ev3 was associated with increased group specific antigen. 4. The genetic background of the chicken strain may play a role in the way certain ev genes affect traits. 5. It was thought that the position of ev genes on the chromosome may be important and their association with traits of economic importance make them potential genetic markers for uncovering quantitative trait loci.


Restoration of in situ fiber degradation and the role of fibrolytic microbes and ruminal pH in cows fed grain-rich diets transiently or continuously.
In this study, we used two different grain-rich feeding models (continuous or transient) to determine their effects on in situ fiber degradation and abundances of important rumen fibrolytic microbes in the rumen. The role of the magnitude of ruminal pH drop during grain feeding in the fiber degradation was also determined. The study was performed in eight rumen-fistulated dry cows. They were fed forage-only diet (baseline), and then challenged with a 60% concentrate diet for 4 weeks, either continuously (n=4 cows) or transiently (n=4 cows). The cows of transient feeding had 1 week off concentrate in between. Ruminal degradation of grass silage and fiber-rich hay was determined by the in situ technique, and microbial abundances attached to incubated samples were analyzed by quantitative PCR. The in situ trials were performed at the baseline and in the 1st and the last week of concentrate feeding in the continuous model. The in situ trials were done in cows of the transient model at the baseline and in the 1st week of the re-challenge with concentrate. In situ degradation of NDF and ADF of the forage samples, and microbial abundances were determined at 0, 4, 8, 24 and 48 h of the incubation. Ruminal pH and temperature during the incubation were recorded using indwelling pH sensors. Compared with the respective baseline, both grain-rich feeding models lowered ruminal pH and increased the duration of pH below 5.5 and 5.8. Results of the grass silage incubation showed that in the continuous model the extent of NDF and ADF degradation was lower in the 1st, but not in the last week compared with the baseline. For the transient model, degradation of NDF of the silage was lower during the re-challenge compared with the baseline. Degradation of NDF and ADF of the hay was suppressed by both feeding models compared with the respective baseline. Changes in fiber degradation of either grass silage or hay were not related to the magnitude of ruminal pH depression during grain-rich feeding. In both feeding models total fungal numbers and relative abundance of Butyrivibrio fibrisolvens attached to the incubated forages were decreased by the challenge. Overall, Fibrobacter succinogenes was more sensitive to the grain challenge compared with Ruminococcus albus and Ruminococcus flavefaciens. The study provided evidence for a restored ruminal fiber degradation after prolonged time of grain-rich feeding, however depending on physical and chemical characteristics of forages.


A research approach to simplifying the accrediting process of allied health programs.
The operationalization and quantification of selected measures of effectiveness and their application to 25 allied health departments in junior and community colleges is described. Principal results are that the 34 measures of effectiveness suggested by experts' opinions could be reduced to 14 criteria. These could be combined into two indices of effectiveness, one of instructional effectiveness and one of administrative effectiveness. The results hold promise for simplification of the accrediting process. Part I of this article appeared in the February 1984 issue of JAH.


Clinician perspectives on decision-making capacity after acquired brain injury.
Acquired brain injury frequently alters an individual's ability to make health care decisions based on a clear understanding of the situation and options. This exploratory study investigated the ways health care providers address issues of decisionmaking capacity (DMC) on a daily, functional basis. 33 clinicians providing rehabilitation services to persons with acquired brain injury participated in 1 of 5 semi-structured focus groups. All 33 participants, representing 8 different occupations, agreed that DMC determinations affected their practice every day. Participants underscored a multidimensional rather than a unitary definition of DMC, with an emphasis on fluctuating capacities due to the injury. Important concerns were for the safety of the person with brain injury, the health care provider, and community members. Other themes included rehabilitation team involvement, family context, and professional socialization. Clinical determinations of DMC are context dependent and are affected by the abilities of the individual and the substance and consequences of the decision being made and include the concepts of regaining trust and reclaiming capacity.


Pectin/zein beads for potential colon-specific drug delivery: synthesis and in vitro evaluation.
Novel complex hydrogel beads were prepared from two edible polymers: pectin, a carbohydrate from citrus fruits, and zein, a protein from corn. The pectin/zein complex hydrogels did not swell in physiological environments, but hydrolyzed in the presence of pectinases. An in vitro study showed the capacity of the hydrogels to endure protease attack and residence time variation. The physical and biological properties of the new hydrogels were attributed to molecular entanglement of the two polymers. The pectin networks were stabilized by the bound zein molecules. In turn, the pectin networks shielded the bound zein from protease digestion.


TERT Expression in Pituitary Adenomas.
Although pituitary adenomas have benign histomorphological features, some of them may present in an aggressive manner. To predict the behaviour of these tumours, telomerase reverse transcriptase (TERT) activity in pituitary adenomas has been the subject of a few studies with contradictory results. This study aims to investigate whether immunohistochemical expression of TERT differs in neoplastic and nonneoplastic pituitary tissues and aims to investigate whether TERT expression is related to clinicopathological features of pituitary adenomas. The study included 48 patients who had been diagnosed with pituitary adenomas and had clinical follow-ups. Nonneoplastic pituitary tissues were obtained from autopsy specimens (n=20). Immunohistochemistry for TERT antibody was performed. Both the nuclear and cytoplasmic expression of TERT antibody was noted, and total combined TERT staining was evaluated according to nuclear and cytoplasmic stainings. TERT expression did not differ between neoplastic and nonneoplastic pituitary tissues. Neither total (combined nuclear and cytoplasmic) TERT nor nuclear TERT expression revealed any statistically significant relationship with any of the clinicopathological features. Higher cytoplasmic TERT expression was observed in adenomas with recurrence than adenomas without recurrence (p=0.035). This study introduces the notion that immunohistochemical expression of TERT does not differ in neoplastic and nonneoplastic pituitary tissues. Pituitary adenomas with cytoplasmic immunohistochemical expression of TERT have significantly higher rates of recurrence. Further studies, including combined methods of immunohistochemistry and molecular analyses in larger groups, may reveal applicable results for the clinical significance of TERT in pituitary adenomas.


Fasting plasma glucose and HbA1c as risk factors for Type 2 diabetes.
We examined the value of combining fasting plasma glucose (FPG) and glycated haemoglobin (HbA(1c)) as a predictor of diabetes, using the new American Diabetes Association (ADA) criteria of FPG and lower cut-off point of HbA(1c). A retrospective cohort study was conducted from 1998 to 2006, inclusive, in 10 042 persons (55 884 person-years), with a mean age of 53.0 years at baseline. The cumulative incidence of diabetes (defined either as an FPG > or = 7.0 mmol/l or as clinically diagnosed diabetes) was measured. The cumulative incidence and incidence density of diabetes were 3.7% (368 cases) and 6.6/1000 person-years over a mean follow-up period of 5.5 years. The cumulative incidence of diabetes in subjects with impaired fasting glucose (IFG) and HbA(1c) 5.5-6.4% was 24.8% (172/694 persons) compared with 0.4% (25/6698 persons), 2.5% (15/605 persons), 7.6% (156/2045 persons) in those with normal fasting glucose (NFG) and HbA(1c) < 5.5%, NFG and HbA(1c) 5.5-6.4% and IFG and HbA(1c) < 5.5%, respectively. The hazard ratio for diabetes, adjusted for possible confounders, was 7.4 (95% confidence interval, 4.70 to 11.74) for those with NFG and HbA(1c) 5.5-6.4%, 14.4 (11.93 to 27.79) for those with IFG and HbA(1c) < 5.5% and 38.4 (24.63 to 59.88) for those with IFG and HbA(1c) 5.5-6.4%. The combination of FPG and HbA(1c) identifies individuals who are at risk of progression to Type 2 diabetes at the new ADA criteria of FPG and a lower cut-off point of HbA(1c) than previous studies.


Synthetic peptides derived from the Listeria monocytogenes p60 protein as antigens for the generation of polyclonal antibodies specific for secreted cell-free L. monocytogenes p60 proteins.
All species of the genus Listeria secrete a major extracellular protein called p60. A comparison of the deduced amino acid sequences of all listerial p60 proteins previously indicated there were only a few regions which were unique to the pathogenic, food-borne species Listeria monocytogenes. Two of these p60 regions were chosen for the development of antibodies specific for the facultative intracellular species L. monocytogenes. Initially, these regions were characterized via epitope mapping, and this led to the development of two different synthetic peptides. Rabbits immunized with these synthetic peptides generated polyclonal antibodies that were then used in Western blot (immunoblot) analyses. Antiserum against peptide A (PepA) recognized the p60 protein in the supernatants collected from most L. monocytogenes serotypes except for several strains belonging to serotypes 4a and 4c. No p60-related protein was detected in the supernatants from other Listeria species with this anti-PepA antiserum. Antibodies raised against peptide D (PepD) reacted with p60 from all L. monocytogenes serotypes, including all 4a and 4c strains that were tested, and also showed no cross-reactivity with supernatant proteins from other Listeria species. Both antisera also detected p60 in supernatants of a large number of environmental isolates of L. monocytogenes. Besides Western blot analyses, these antisera to PepA and PepD reacted with secreted p60 in an enzyme-linked immunosorbent assay, indicating recognition of the native antigen in addition to the denatured form. These data suggest that synthetic peptides derived from the variable region of the L. monocytogenes p60 protein may be useful for the development of an immunological diagnostic assay.


Action of a novel nonsteroidal antiandrogen, AA560.
The antiandrogenic properties of a new nonsteroidal antiandrogens, AA560 (N-2-chloromethyl-2-hydroxypropionyl)-3, 4, 5-trichloroaniline) were investigated. The ventral prostate, dorselateral prostate and coagulating gland weights in rats given AA560 at 1-9 mg/head were significantly less than those in the intact rats. The seminal vesicle weights in rats given 3-9 mg/head were significantly less than those of the intact group. In intact animals given daily 3 or 9 mg of AA560 there were significantly increases of serum FSH, LH and testosterone concentrations. In the in vivo experiment, the pretreatment with AA560 decreased the uptake of 3H-androgens in the nuclear fraction of the ventral prostate. On the other hand, a significant increase in the uptake of 3H-radioactivity in the cytosol fraction was observed. It was proved by the in vitro displacement study that AA560 inhibited the binding of 5 alpha-dihydrotestosterone with a receptor protein in the prostatic cytosol.


Tid1 is a Smad-binding protein that can modulate Smad7 activity in developing embryos.
In a search for binding partners to Smad8, we identified the chicken homologue of the mammalian Tid1 protein (cTid1), which is a regulator of apoptosis related to the Drosophila tumour suppressor Tid56. The cTid1 coding sequence is highly conserved with mammalian Tid1, including the DnaJ domain that interacts with Hsp70 (heat-shock protein 70). The cTid1 gene is widely expressed with transcripts enriched in the developing blood islands of the embryonic-yolk sac. We show that cTid1 can bind to other members of the Smad family and that highest binding activity occurs with the negative regulatory Smad7, through the conserved MH2 domain. This interaction can have functional relevance in vivo, since co-expression of Tid1 blocks the dorsalizing and BMP (bone morphogenetic protein)-dependent regulatory activity of Smad7 in developing Xenopus embryos. The finding that these proteins can interact suggests the potential for linking two important cell survival/apoptosis pathways.


Intellectual Disability and Assistive Technology: Opening the GATE Wider.
The World Health Organization has launched a program to promote Global Cooperation on Assistive Technology (GATE). The objective of the GATE program is to improve access to high quality, affordable assistive technology for people with varying disabilities, diseases, and age-related conditions. As a first step, GATE has developed the assistive products list, a list of priority assistive products based on addressing the greatest need at population level. A specific group of people who can benefit from user appropriate assistive technology are people with intellectual disabilities. However, the use of assistive products by people with intellectual disabilities is a neglected area of research and practice, and offers considerable opportunities for the advancement of population health and the realization of basic human rights. It is unknown how many people with intellectual disabilities globally have access to appropriate assistive products and which factors influence their access. We call for a much greater focus on people with intellectual disabilities within the GATE program. We present a framework for understanding the complex interaction between intellectual disability, health and wellbeing, and assistive technology.


Aversive Learning of Colored Lights in Walking Honeybees.
The honeybee has been established as an important model organism in studies on visual learning. So far the emphasis has been on appetitive conditioning, simulating floral discrimination, and homing behavior, where bees perform exceptionally well in visual discrimination tasks. However, bees in the wild also face dangers, and recent findings suggest that what is learned about visual percepts is highly context dependent. A stimulus that follows an unpleasant period, is associated with the feeling of relief- or safety in humans and animals, thus acquiring a positive meaning. Whether this is also the case in honeybees is still an open question. Here, we conditioned bees aversively in a walking arena where each half was illuminated by light of a specific wavelength and intensity, one of which was combined with electric shocks. In this paradigm, the bees' preferences to the different lights were modified through nine conditioning trials, forming robust escape, and avoidance behaviors. Strikingly, we found that while 465 nm (human blue) and 590 nm (human yellow) lights both could acquire negative valences (inducing avoidance response), 525 nm (human green) light could not. This indicates that green light holds an innate meaning of safety which is difficult to overrule even through intensive aversive conditioning. The bees had slight initial preferences to green over the blue and the yellow lights, which could be compensated by adjusting light intensity. However, this initial bias played a minor role while the chromatic properties were the most salient characteristics of the light stimuli during aversive conditioning. Moreover, bees could learn the light signaling safety, revealing the existence of a relief component in aversive operant conditioning, similar to what has been observed in other animals.


Thermal and mechanical properties of aluminized fabrics for use in ferrous metal handling operations.
Protective garments are normally worn in molten handling operations to provide some protection against molten metal splashes. These garments are also intended to provide protection against radiant heat, and they should be as heat resistant and comfortable as possible. Asbestos-based fabrics have been employed for many years, but recently some concern has been expressed over possible asbestos exposure. This program was undertaken to explore the ability of several types of fabrics to resist heat transfer during molten metal impact. A molten metal splash test, along with standard methods for determining tensile strength, flame resistance, and abrasion-flexing resistance were used to evaluate several classes of protective fabrics. The results indicate that there are materials available that offer equal or better mechanical properties and thermal protection compared to aluminized asbestos.


Modular Synthesis of Tetrasubstituted Pyrroles via an Annulative Migration Reaction of Allenyl Ketones and p-Toluenesulfonylmethyl Isocyanide.
The metal-free cyclization of allenyl ketones and p-toluenesulfonylmethyl isocyanide (TosMIC), promoted by Cs2CO3, provides a convenient access to tetrasubstituted pyrroles in which an acyl group undergoes 1,2-migration. This tandem Michael addition/annulative migration synthetic strategy is general and high-yielding for various substituted allenyl ketones. Moreover, a phosphoryl or ester moiety is also a suitable functionality to enable such migration.


Application of structural equation modeling to develop a conceptual model for entrepreneurship for psychological service workers during the COVID-19 pandemic.
This study aimed to investigate entrepreneurship predictors among psychological service workers during the COVID-19 pandemic and detect the difference in entrepreneurship among psychological service workers due to sex and experience in work. A random sample of 321 workers in the field of psychological Services answered an online questionnaire that contained six scales (mental traits, psychological traits, success in work, effectiveness, creativity, and innovation, responsible decision). The data collected from the study participants were analyzed quantitatively by using a t-test, One-way ANOVA, Exploratory Factor Analysis EFA, Confirmatory Factor Analysis CFA, and Structural Equation Model (IBM SPSS statistics 21, and Amos v.25). The findings showed the validity of the conceptual proposed model of entrepreneurship among the psychological service workers. The default model has goodness-of-fit indicators to predict the workers' psychological services' entrepreneurship in their professional practice. The results also indicated significant differences due to the years of work experience in work and responsible decision dimensions in favor of the sample members belonging to the experiences group with more than ten years. Simultaneously, there are no differences in entrepreneurship's total score, mental traits, psychological, effectiveness, and creativity and innovation. The results also showed that there are statistically significant differences between males and females in the success in work dimension in favor of males (males mean = 21.359, females mean = 19.461, t = 2.797, P < 0.05), also in responsible decisions in favor of males (males mean = 9.734, females mean = 6.927, t = 8.853, P < 0.05). Mental traits, psychological traits, success in work, effectiveness, creativity and innovation, creativity, and innovation make responsible decisions significant predictors of entrepreneurship among the workers in psychological services. Thus, we recommend adopting the six criteria for entrepreneurship in professional practice when evaluating the workers in psychological services' performance. These results indicate the need for plaining training programs to increase the entrepreneurship among workers in psychological services whose experience is less than ten years, especially female workers in psychological services.


Paediatric road accidents in two health districts.
For a 1-year period from 1 January 1990 all children seen, as a result of road traffic accidents (RTAs), in two accident and emergency departments (A&E), one in Liverpool and one in Chester were studied. Simple data were collected and injury severity scores (ISS) were used to assess injuries. Progress was monitored at 3 months post-injury by a review of hospital case notes. A total of 710 children fulfilled the study criteria in the year with a male:female ratio of 1.7:1. Only 37% of children were accompanied by an adult at the time of their accident. Overall 29% of children in vehicles were restrained and only three of 75 cyclists wore cycle helmets. Most injuries were minor with ISS of less than 9 in 96% of cases. Two children died after admission as a result of severe head injuries. The results were similar to those from other centres but highlight a need for continuing public education on child supervision, safe driving habits and the need for environmental changes.


[A study of green tea for a positive gastrointestinal MR imaging enhancing agent].
Green tea has been incidentally found to produce a high signal on T1-weighted MR images. This study was therefore designed to investigate what substance in the green tea produced this T1-shortening effect and whether a green tea solution could be used as a positive enhancing agent in MR studies. As a result of the chemical analysis and measurement of T1 relaxation times in various solutions originating from green tea, it was found that the T1-shortening effect was produced not only by free manganese, but also by a high molecular weight substance (molecular weight 1.2 x 10(4) or more) united with manganese. In clinical MR studies, the gastrointestinal tract was markedly enhanced after oral administration of a green tea solution. The pancreatic head was clearly delineated with visualization of both the gastric wall and descending portion of the duodenum. However, visualization of the jejunum and ileum was not improved, suggesting that the green tea solution was diluted by intestinal fluid in the small bowel. Since only a small amount of manganese (1500 ppm) united with a high molecular weight compound such as pectin was sufficient to produce excellent enhancement of the gastrointestinal tract, it would be better to develop a purely synthetic chemical compound, for example, one consisting of a polysaccharide and manganese, rather than to use a green tea solution as a gastrointestinal enhancing agent in MR studies.


Lung transplantation for advanced bronchiectasis.
Lung transplant (LT) can be successfully performed on patients with advanced bronchiectatic lung disease with subsequent good posttransplant quality of life and long-term outcome. Most of the data are derived from patients with cystic fibrosis (CF), but LT can be effective in patients with non-CF bronchiectasis as well. Despite the presence of chronic lower respiratory tract infection with bacterial pathogens in these patients pretransplant, posttransplant infections do not generally have significant impact on survival, although infection with antibiotic-resistant bacteria may complicate posttransplant management. Although benefit of LT for young children with CF is somewhat controversial, LT can clearly benefit older children and adults with advanced lung disease due to bronchiectasis. This article reviews indications (and contraindications) for LT, discusses particular problems that may arise posttransplant, and provides a rationale for referring patients with bronchiectasis for LT.


MUTAROTASE INHIBITION BY 1-DEOXYGLUCOSE.
The Michaelis-Menten constant for glucose and the inhibitor constant of 1-deoxyglucose for the intestinal mutarotase, glucose, 1-deoxyglucose system are consistent with the properties of the glucose transport system of intestine. The alleged sharing of the intestinal glucose transport system by 1-deoxyglucose does not contradict the mutarotase theory.


Reduced miR-300 expression predicts poor prognosis in patients with laryngeal squamous cell carcinoma.
miR-300 has been demonstrated to play an important role in the progression of several tumors, but its role in tumorigenesis of laryngeal squamous cell carcinoma (LSCC) is still unclear. The purpose of this study was to explore miR-300 expression in LSCC patients and analyze its association with clinicopathological factors and prognosis. In the present study, we measured the expression level of miR-300 in LSCC tissues by RT-PCR. Associations between miRNA-300 expressions and various clinicopathological characteristics were analyzed. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. The univariate and multivariate analysis were performed using the Cox proportional hazard analysis. miR-300 expression was significantly increased in LSCC tissues compared with that in adjacent non-cancerous tissues (p < 0.01). In addition, lymph node metastasis (p = 0.004) and TNM stage (p = 0.001) were obvious influence factors for the expression of miR-300. More importantly, Kaplan-Meier analysis showed that LSCC patients with low miR-300 expression tended to have shorter overall survival (p < 0.001). Finally, multivariate analysis revealed that miR-300 expression was an independent prognostic factor for LSCC patients. Our results pointed to miR-300 as a powerful prognostic marker in LSCC and as a novel target for tumor-suppressive therapy.


Arthroscopic ACL reconstruction with reverse "Y"-plasty grafts and fixation in the femur with either a bioabsorbable interference screw or an Endobutton.
We propose a new reverse "Y"-plasty graft for use in anterior cruciate ligament (ACL) reconstruction that involves double tibial tunnels and a single femoral tunnel. With this technique, the hamstrings were used as autografts and fixed separately with bioabsorbable interference screws (group A) or Endobuttons (group B) in femurs. A prospective series of 63 patients underwent primary reconstruction of the ACL; all procedures were performed by the same surgeon. Group A included 35 patients (22 male, 13 female), with a mean age of 25.5 (17-40) years, who were followed up for 28.5 (12-48) months. Group B included 28 patients (17 male, 11 female), with a mean age of 24.3 (18-38) years, who were followed up for 29.5 (12-46) months. Lysholm, International Knee Documentation Committee (IKDC) and Larson scoring were used to compare the therapeutic effects experienced at the knee. Lysholm scores were 93.26±2.67 (group A) and 93.81±2.42 (group B); Larson scores were 91.91±2.29 (group A) and 92.81±2.39 (group B); IKDC scores were 93.89±1.88 (group A) and 94.15±1.77 (group B). None of the scoring differences between groups were statistically significant (T(1)=0.849, P(1)=0.399, T(2)=1.506, P(2)=0.137, T(3)=0.560, P(3)=0.578). The Lachman test was negative in 46 patients (90.2%) and 51 knees, including 25 (89.3%) of the 28 knees in group A and 21 (91.3%) of the 23 knees in group B. Negative Pivot shift was present postoperatively in 49 knees of 51 patients (96.1%), including 27 (96.4%) of the 28 knees in group A and 22 (95.7%) of the 23 knees in group B. All of the patients in both groups achieved full extension and at least 135° of knee flexion. This novel technique involves the creation of double tibial tunnels and a single femoral tunnel. In the tibia, there was a bone bridge, ranging from 2 to 3mm, between the two bundles, which are tensioned at different degrees of flexion to maintain the stability of the knee. In the femur, the grafts were fixed with bioabsorbable interference screws or Endobuttons. The outcomes show that normal function and joint stability were achieved in both groups, as compared with preoperative measurements. Although the outcomes in group A (grafts fixed with the bioabsorbable interference screws in the femur) was better than those observed in group B (grafts fixed with Endobuttons), there was no statistical difference between the groups.


A bifunctional archaeal protein that is a component of 30S ribosomal subunits and interacts with C/D box small RNAs.
We have identified a novel archaeal protein that apparently plays two distinct roles in ribosome metabolism. It is a polypeptide of about 18 kDa (termed Rbp18) that binds free cytosolic C/D box sRNAs in vivo and in vitro and behaves as a structural ribosomal protein, specifically a component of the 30S ribosomal subunit. As Rbp18 is selectively present in Crenarcheota and highly thermophilic Euryarchaeota, we propose that it serves to protect C/D box sRNAs from degradation and perhaps to stabilize thermophilic 30S subunits.


The Voluntariat: A Frieirean framework to understand the nature of undergraduate international (medical) experiences.
Despite literature documenting limited and asymmetrical benefits along with ethical issues, short-term international volunteering is increasingly popular among North American university students as a perceived advantage when applying to professional healthcare schools or the job market. Academic institutions are also encouraging students to pursue international experiences in order to cultivate values as global citizens. These experiences are most typically limited to economically privileged students. Furthermore, international activities in developing countries often lack a pedagogy of social justice and may confirm a simplistic understanding of development. Brazilian educator Paulo Freire's "liberation pedagogy" provides a framework for understanding the limitations of international volunteering, whereby the presence of privileged volunteers implementing Western models of development may hinder aspects of local movements. Regardless, university students face intense competition in accessing opportunities, such as medical school, and pay large sums to participate in volunteering to strengthen their academic credentials. We propose that these students form "the voluntariat." They simultaneously play two roles by, first, contributing to the conditions that oppress the very communities in which they volunteer and, second, by playing a role as objects of oppression by the liberal institutions of learning and employment to which they are attempting to gain access.