Emergency surgery for obstructing and perforated colon cancer: patterns of recurrence and prognostic factors.
The aim of this study was to analyze the incidence, patterns and prognostic factors of recurrence in patients with complicated colon cancer who had emergency surgery within 24 h of admission. A retrospective observational study was performed on patients with obstructing or perforated colon cancer having resection with curative intent between 1996 and 2014 at a single center. Data were obtained from a prospectively maintained database. Patients who had rectal cancer, iatrogenic endoscopic perforation, stage IV disease, palliative surgery, a colonic stent or decompressive colostomy were excluded. The study included 393 patients. Obstruction was observed in 320 patients (81.4%) and perforation in 73 (18.6%). Hartmann's procedure was more frequently performed by general surgeons (7.5% vs 23.3%; p = 0.023). 30-day postoperative mortality was 13.5% (53/393), including 47 (14.7%) obstructed and 6 (8.2%) perforated patients. Postoperative complications (Clavien-Dindo III-IV) occurred in 87 patients (22.1%), including 68 (21.2%) of obstructed and 19 (26.0%) of perforated patients. Anastomotic dehiscence was diagnosed in 52 of 329 (15.8%) patients with primary anastomosis and was higher in the obstructing group than in the perforated group (17.4% vs 7.6%). There was a significantly higher anastomotic dehiscence rate after procedures performed by general surgeons when compared with those performed by colorectal surgeons (10.3% vs 21.3%; p = 0.005; OR 2.81, 95% CI 1.4-5.9). With a median follow-up of 6 years, the recurrence rate was 30.1% (67.4% distant, 22.8% local, 9.8% both). Overall and cancer-related survivals were 68.7% and 77.8%, respectively. The presence of positive nodes, male gender, anastomotic dehiscence and diffuse peritonitis were independent predictors for local recurrence while type of surgeon (general) was an independent factor for distant recurrence. Male gender, diffuse peritonitis, positive lymph nodes, type of surgeon and postoperative anastomotic dehiscence significantly influence recurrence of colorectal cancer in this series.


[Peripheral vertigo classification. Consensus document. Otoneurology committee of the Spanish otorhinolaryngology society (2003-2006)].
There are many different vertigo classifications and different denominations are frequently used for the same clinical processes. The Otoneurology Committee of the Spanish Society for Otorhinolaryngology and Head and Neck Pathology proposes an eminently practical classification of peripheral vertigo to facilitate a common terminology that can be easily used by the general ENT practitioners. The methodology used has been by consensus within our Society and especially among the most outstanding work groups in the area of otoneurology in Spain. Initially vertigo is divided into single-episode vertigo and recurring attacks of vertigo, and these are then sub-divided into 2 groups, depending on whether or not hearing loss is present. Acute vertigo without hearing loss corresponds to vestibular neuritis and if it is associated with hearing loss, it is due to labyrinthitis of different aetiologies and cochleo-vestibular neuritis. Recurrent vertigos without hearing loss are classified as induced, either by posture (BPPV) or pressure (perilymphatic fistula), or as spontaneous, including migraine-associated vertigo, metabolic vertigo, childhood paroxysmal vertigo and vertigo of vascular causes (AITs, vertebral-basilar failure). Finally, recurrent vertigo with hearing loss includes Ménière's disease and others such as vertigo-migraine (with hearing loss), autoimmune pathology of the inner ear, syphilitic infection, and perilymphatic fistula (with hearing loss).


Reference gene validation for qPCR on normoxia- and hypoxia-cultured human dermal fibroblasts exposed to UVA: is β-actin a reliable normalizer for photoaging studies?
Data normalization of gene expression on human dermal fibroblasts (HDF) exposed to UVA has commonly been done using either GAPDH or β-actin as reference genes without any validation of their expression stability. Since this aspect, important for accurate normalization, has been overlooked, we aimed to establish a suitable set of reference genes for studies on UVA-treated HDF cultured under both standard atmospheric oxygen tension (normoxia, 21%) and under a physiological, low oxygen tension for these cells (hypoxia, 5%). The stability of six commonly used reference genes was assessed using the geNorm and NormFinder softwares subsequent to reverse-transcription quantitative real-time PCR (RT-qPCR). GAPDH/SDHA were found to be the most stable genes under normoxia, while SDHA/TBP or HPRT1/β2M were the most stable ones under hypoxia in HDF exposed to 18 J/cm(2) UVA. β-Actin was always the most unstable reference gene. To emphasize the importance of selecting the most stably expressed reference genes for obtaining reliable results, mRNA expression levels of MMP-1 and COL1A1 were analyzed vs the best reference genes and the worst one. These reference genes are hence recommended for future qPCR analyses in studies concerning photo-damage on UVA-treated HDF.


High resolution computed tomography of the cadaveric sternoclavicular joint: findings in degenerative joint disease.
High resolution, narrow collimation, axial computed tomography of the sternoclavicular joint was used to describe changes secondary to degenerative joint disease in 32 cadaveric specimens. The distribution and pattern of sclerosis, cystic changes, and osteophyte formation in the axial plane were well demonstrated using this technique. Joint space narrowing was sometimes difficult to assess. Subtle joint space calcification was exquisitely demonstrated using computed tomography. Clavicular head cupping, an anatomic variant, may predispose to more severe degenerative change. Computed tomography is an excellent means to analyze the sternoclavicular joint for the presence of degenerative joint disease and may be the imaging modality of choice in assessing articular disorders of the sternoclavicular joint.


PMA-SiO2 catalyzed synthesis of indolo[2,3-c]quinolines as potent anti cancer agents.
PMA-SiO2 catalyzed Pictet-Spengler reaction of aryl amine linked to C-3 of the indole and the aryl aldehydes was achieved. In the series of the synthesized compounds, 6b, 10b and 12b were found to be cytotoxic against prostate, lung, breast and cervical cancer cell lines selectively with no significant effect on the growth of the control fibroblast cell line NIH3T3. Further determining their cytotoxic potential we found that 10b and 12b show cell cycle arrest in DU145 prostate cancer cells indicating a role in cell cycle progression. Both the molecules showed effect on decreased phosphorylation of NF-κB on serine 536 residue which is strongly implicated in many different types of cancers. Taken together, the series of indoloquinolines elicit potent anti-cancer potential providing a mean for developing novel indoloquinoline based anti-cancer agents.


Toxicity of methyl testosterone in the beagle dog.
When methyl testosterone was administered orally to beagle dogs at dosage levels of 2, 4 and 6 mg/kg per day for 27 weeks, hepatotoxicity was induced. The change induced was characterized by enlargement of periportal hepatocytes and the presence of haemosiderin within macrophages. There was some evidence of recovery over a 13-week period.


Sustainable electrification planning of rural microgrid using renewable resources and its environmental impact assessment.
The global population continually increases, and providing power and ensuring sustainable development is becoming increasingly challenging. As a result of increased industrialization and mobility, population growth produces changes in land usage and greenhouse gas emissions. Air quality is influenced by the amount of energy used. The release of carbon dioxide and other pollutants into the atmosphere harms the ecosystem. Although renewable energy sources can help reduce carbon emissions, their unreliability means that energy output is unpredictable, necessitating the development of battery storage to bridge the demand-supply gap. Much attention has been paid to combining renewable energy sources with batteries into rural electrification. The designing and operation of a rural standalone microgrid with electrical loads modeled for the electrification energy deficient village of Uttarakhand (India). The proposed work optimized the component size, cost of energy, net present cost, and pollutant emission reduction in the environment. The optimization is carried out using the gray wolf optimization algorithm. Four different microgrid systems are investigated for the feasibility evaluation of cost-effective rural power. A comparative evaluation of models is provided based on environmental and economic factors. The optimum design has an energy cost of 0.313 $/kWh and a net present cost of $ 65,241.32. The second arrangement, which has the most significant level of renewable energy penetration (90%), has provided a reliable power supply to the region. On the other hand, the proposed design satisfied all constraints while retaining a competitive energy cost.


Impacts of renewable energy on climate vulnerability: A global perspective for energy transition in a climate adaptation framework.
The transition to renewable energy can disproportionately impact the effectiveness of climate change adaptation, due to regional heterogeneity. Many countries attempt to promote renewable energy to reduce the impact of climate change, but the impacts of national energy policy in the climate vulnerability framework remain little understood. Here, we exploit variations in renewable energy uses to test the effectiveness of climate adaptation policy across the dimensions of climate impact and vulnerability. Using the Fuzzy Analytic Hierarchy Process and panel data regression, we analyze the spatiotemporal correlation between renewable energy transition and climate vulnerability across the world. We find that while renewable energy increases proportionally with climate exposure and sensitivity, many countries exhibit discrepancies between the variation in renewable energy transition and climate vulnerability. The promotion of renewable energy funnels into nations with a higher level of adaptive capacity while bypassing more vulnerable countries. The results signify that existing renewable energy policies can exacerbate climate inequality and undermine the benefits of the transition to renewable energy by neglecting the spatial heterogeneity in climate vulnerability. Our findings provide empirical evidence for the ways in which renewable energy policy can generate spatial inequalities in climate adaptation.


Outcome for children with group III rhabdomyosarcoma treated with or without radiotherapy.
To analyze the sites of relapse, relapse-free survival, and overall survival in children with Group III rhabdomyosarcoma treated with or without radiotherapy (RT). The outcomes of 48 children with Group III rhabdomyosarcoma treated between 1980 and 1997 were evaluated. The median overall survival follow-up was 7.3 years. Of the 48 patients, 65% had embryonal histology. Local treatment after induction chemotherapy included complete surgical resection (CSR) alone in 9 (19%), CSR plus RT in 13 (27%), partial resection or rebiopsy plus RT in 10 (21%), and RT alone in 15 patients (31%). One child developed distant disease before completing local therapy. Of the 48 patients, 12 developed relapse at local (n = 3), regional (n = 4), or distant (n = 5) sites. All 9 patients treated with CSR after induction chemotherapy had embryonal/botryoid histology. Only 1 of these 9 patients developed relapse. No statistically significant difference was found in overall survival (p = 0.95) or relapse-free survival (p = 0.67) between patients treated with or without RT. The Kaplan-Meier estimate of 5-year overall survival and relapse-free survival was 76% +/- 7% and 74% +/- 7%, respectively. Significant predictors of relapse-free survival on univariate analysis included CSR (p = 0.03), nodal positivity (p = 0.001), and embryonal histology (p = 0.0003). On multivariate analysis, embryonal histology was the most significant predictor of relapse-free (p = 0.001) and overall (p = 0.01) survival. The overall survival for children with Group III rhabdomyosarcoma in this series was favorable. Embryonal/botryoid histology was the most significant predictor of both overall and relapse-free survival. We found that for a selected subgroup of children with embryonal histology, induction chemotherapy followed by complete surgical resection alone may be adequate local therapy.


Downregulation of protein kinase C gamma reduces epithelial property and enhances malignant phenotypes in colorectal cancer cells.
Loss of epithelial integrity is associated with colorectal cancer (CRC) aggressiveness. Protein kinase C (PKC) is frequently implicated in human cancers, but the role of PKCγ in CRC remains poorly understood. Here, we show that PKCγ, a conventional PKC, is expressed in normal colonic epithelium, but this is lower in dedifferentiated CRC. PKCγ expression was downregulated by SNAI1 overexpression, and low PKCγ expression was associated with poor prognosis in patients with CRC. Transient or stable knockdown of PKCγ reduced E-cadherin expression in CRC cells. PKCγ knockdown enhanced proliferation, anchorage-independent cell growth, resistance to anti-cancer drugs, and in vivo tumor growth of DLD-1 cells. We have also identified phosphorylation substrates for PKCγ. Among them, ARHGEF18, a RhoA activator that stabilizes cell-cell junctions, was phosphorylated and stabilized by PKCγ. Thus, these results suggest that the downregulation of PKCγ decreases the epithelial property of CRC cells and enhances its malignant phenotypes.


Altered Ca2+ sensitivity of tension in single skeletal muscle fibres from MyoD gene-inactivated mice.
1. Single, fast glycolytic skeletal muscle fibres were isolated from wild-type (MyoD+/+) and MyoD mutant mice (MyoD-/-), which lack a functional copy of the MyoD gene. Fibres were chemically permeabilized to permit manipulation and control of the ionic environment of the otherwise intact myofilament apparatus. 2. Results show a fivefold greater variability in the [Ca2+] required for half-maximum tension generation among individual MyoD-/- fibres in comparison with controls (p < 0.05). 3. Consistent with this finding, Western blot analysis showed a sevenfold greater variability in the isoform expression pattern of the thin filament regulatory protein troponin T in Myod-/- compared with control fibres (p < 0.05). 4. Electrophoretic analysis of single-fibre segments indicated no apparent alteration in the isoform expression pattern of other regulatory and contractile proteins. In addition, other parameters of contractile function, including velocity of unloaded shortening, and maximum force production, were not significantly different between MyoD-/- and MyoD ø fibres. 5. These findings indicate that the thin filament structure- function relationship is altered due to the MyoD mutation and suggest that MyoD plays a role in establishing and/or maintaining the differentiated phenotype of adult fast skeletal muscle fibres.


Killer-sensitive relationships in yeasts from natural habitats.
Yeast strains (157) belonging to at least 9 genera were isolated from natural habitats and screened for killer-sensitive relationships. Killer and sensitive characteristics were exhibited by 17 and 11% of the isolates, respectively. The strains belong to either one of two mutually exclusive killer-sensitive groups.


Using simple models to review the application and implications of different approaches used to simulate transmission of pathogens among aquatic animals.
Disease is an important issue affecting aquatic animal populations. Aquatic pathogens may be transmitted in ways that could result in qualitatively different impacts to those of terrestrial diseases. I analyse simple SIR epidemic models with different functions to describe transmission. Four forms of transmission are applied: density-dependent, density-independent, non-linear density-dependent and constant infection pressure; the first two are similar to terrestrial systems, the second two are based on specifically aquatic modes of transmission. Observed diseases and existing models are reviewed in terms of these simple forms. The significance of mode of transmission to host populations, to strategies to prevent or control diseases, and to wild-farm interactions are analysed. Different diseases are simulated by different transmission models, for example furunculosis depends on host density, while spread of phocine distemper virus is density-independent, and sea lice infestation pressure may result from open transmission processes that are not dependent on local infested hosts. Appropriate transmission model may also depend on the scale of interest (inter- or intra-population). These different models result in very different responses to intervention strategies, for example culling may be effective for controlling density-dependent disease but may be counter-productive when pathogens depend on open recruitment. It is therefore important for management that appropriate models (whether existing or novel) be selected and this paper aims to provide a basic framework for cataloguing and management of aquatic diseases.


Plasma testosterone and dihydrotestosterone in male rats during sexual maturation and following orchidectomy and experimental bilateral cryptorchidism.
Plasma concentration of testosterone and dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) were measured at frequent intervals (daily between day 20 and 40) in intact male rats from early pre-pubertal stage to full maturity. Effect of orchidectomy and experimental bilateral cryptorchidism on these two blood-born compounds at different stages of sexual maturation was also studied. A distinct spurt in testosterone level was noted on day 26, and in 3 days a leval of 2600pg/ml was reached, which was about 90% of the highest peak value (2940 pg/ml) seen at day 70. In the same animals dihydrotestosterone spurt was noted at the same time, but the peak value (163 pg/ml) was reached later (day 33). Within 4 days after orchidectomy plasma testosterone level showed no significant change in 20-day old animals, but dropped to 15% of the intact value in 40-day old ones, while remaining at a steady level of about 23% in older animals. Plasma dihydrotestosterone was undetectable after orchidectomy at each stage of sexual maturation. With bilateral cryptorchid animals plasma testosterone was higher than seen in the intact 20-day old control, but remained similar at other stages of sexual maturation. Plasma dihydrotesterone in the same animals was significantly less (p less 0.01) than those seen in the intact controls at all stages of sexual development except in 20-day old ones, where it was essentially similar.


Role of serial quantitative gallium-67 tumor uptake in assessing response rates for chemotherapy in lymphoma patients.
To evaluate in serial gallium-67 scans (GS) the role of semiquantitative tumor-to-background (Tm/Bg) and tumor-to-liver ratios in assessing response rates to chemotherapy, in Hodgkin's disease and non-Hodgkin's lymphoma. Twenty-seven consecutive patients (15 Hodgkin's disease and 12 non-Hodgkin's lymphoma patients) with an average age of 30 (range, 5-60) years underwent GS at prechemotherapy, early chemotherapy (after first cycle), and postchemotherapy. Average tumor, background, and liver region of interest counts obtained and Tm/Bg, tumor-to-liver, and liver region to background ratios were derived for each patient on serial GS. All patients were assessed by visual and quantitative GS and followed up clinically for more than 7 years. At early visual GS, 70% (19 of 27) of the patients showed rapid response, 15% (four of 27) showed delayed response (negative at post-GS), and 15% showed no response. Mean early-GS Tm/Bg ratio of disease-free patients (1+/-0.04) was significantly different from relapsed (1.4+/-0.2) (P<0.025) and progressive disease (1.8+/-0.7) patients. A significant difference was noted (P<0.01) in serial paired comparisons of Tm/Bg ratios between pretherapy and early-therapy scans in relapsed patients, whereas progressive disease patients showed no significant change during the same time. At early-GS, 15 patients showed quantitative rapid response (Tm/Bg ratio 1.04), nine patients showed quantitative delayed response (Tm/Bg ratio >1.04 with significant serial change between pretherapy and early-therapy GS), and three patients showed quantitative no response (Tm/Bg ratio >1.04 with nonsignificant serial change between pretherapy and posttherapy GS). Quantitative GS is an effective tool in the detection of early response to chemotherapy. Quantitative response rates after the first cycle can more reliably identify patients who are most likely to be disease-free or relapse after first-line therapy or those that will show no response to therapy as compared with visual analysis alone.


Organic aciduria in hypoxic premature newborns simulating an inborn error of metabolism.
A very unusual pattern of organic acid excretion was established in the urine of two premature newborns with severe respiratory distress and cerebral haemorrhages. By combined gas chromatography/mass spectrometry the following acids were identified: lactic acid, alpha-hydroxy-butyric acid, beta-hydroxy-butyric acid, alpha-hydroxy-isovaleric acid, and p-hydroxy-phenyllactic acid. Calculation of the concentration revealed an excessive excretion of lactic acid and also very high excretion of the other acids. A postmortem blood sample from one of the patients revealed a comparable pattern. The abnormal urinary organic acid excretion pattern was most probably caused by severe tissue hypoxia.


Venous malformations treated with dual wavelength 595 and 1064 nm laser system.
Venous malformations (VM) represent a localized error in the embryological development of the venous branch of the circulation. The management of VM is complex and challenging. The aim of this study was to assess the efficacy and safety of combined sequential pulsed dye laser (PDL)-Nd:YAG laser in patients with cutaneous or mucosal VM. Thirty patients (age from 8 to 65 years) with cutaneous or mucosal VM treated with dual wavelength PDL-Nd:YAG laser were retrospectively analyzed. Laser parameters were 10 mm spot size with 10 ms pulse and 8-10 J/cm(2) of PDL, followed with a second delay by Nd:YAG with 15 or 20 ms at 35-70 J/cm(2); or 7 mm spot size with 10 ms pulse and 5-10.5 J/cm(2) of PDL, followed with a second delay by Nd:YAG with 15 or 20 ms at 50-100 J/cm(2). Laser sessions were repeated approximately every 2-6 months. Air cooling was applied during treatment. Three dermatologists evaluated treatment effectiveness by means of photographs of the patients before and after laser treatment (scale from 0 to 4). Differences in the degree of clinical improvement between patients with cutaneous or mucosal VM were also assessed. Adverse events were registered. Patient satisfaction was also assessed in 19 cases (scale from 0 to 10). Mean global improvement was rated as 3.37. Mean improvement in patients with cutaneous VM was 3.35 and 3.38 in patients with mucosal VM. No significant difference between both groups was observed (P = 0.53). Long-lasting side effects included partial epilation of the eyelashes in one patient, ulceration in two patients and permanent scarring in three patients. Mean patient satisfaction was 8.55. Our study concludes that dual wavelength PDL-Nd:YAG laser was effective for treatment of the superficial component of cutaneous and mucosal VM.


Role of FoxO transcription factors in aging and age-related metabolic and neurodegenerative diseases.
Aging happens to all of us as we live. Thanks to the improved living standard and discovery of life-saving medicines, our life expectancy has increased substantially across the world in the past century. However, the rise in lifespan leads to unprecedented increases in both the number and the percentage of individuals 65 years and older, accompanied by the increased incidences of age-related diseases such as type 2 diabetes mellitus and Alzheimer's disease. FoxO transcription factors are evolutionarily conserved molecules that play critical roles in diverse biological processes, in particular aging and metabolism. Their dysfunction is often found in the pathogenesis of many age-related diseases. Here, we summarize the signaling pathways and cellular functions of FoxO proteins. We also review the complex role of FoxO in aging and age-related diseases, with focus on type 2 diabetes and Alzheimer's disease and discuss the possibility of FoxO as a molecular link between aging and disease risks.


African Trypanosomes Find a Fat Haven.
The African trypanosome was thought to primarily develop in the bloodstream and interstitial spaces of its mammalian host. In this issue of Cell Host & Microbe, Trindade et al. (2016) report the surprising finding that during ongoing persistent infections in mice, a major fraction of the parasites reside within fatty tissues.


Binding to histone of an anomalous IgG from patients with SLE and drug-induced lupus.
The mechanism of attachment of circulating immune complexes (CIC) to glomerular basement membranes (GBM) in systemic lupus erythematosus (SLE) has not yet been elucidated. One difficulty is that CIC must be strongly cationic for such deposition to occur, which is opposite to the anionic nature of putative DNA-anti-DNA immune complexes (DNA-IC). The strongly cationic histone has been proposed as a potential "planted antigen"; it would decorate the GBM to function as a ligand for DNA in the DNA-IC. However, DNA-IC, aggregated IgG and most of the IgG "anti-histone antibodies" in SLE patient sera bind to histone on a solid phase not through DNA, but through the Fcgamma. Here, we investigated the nature of the anti-histone "antibody" in sera of 18 patients with SLE and 57 with drug-induced lupus (DIL). The binding to nucleosomes of IgG from these patients was mainly pepsin-resistant and F(ab')(2)-dependent, whereas the binding to histone was mainly pepsin-sensitive and Fcgamma-dependent. Surprisingly, after molecular sieving of 12 of these sera, the pepsin-sensitive histone-binding IgG was located mainly in the 150-kDa monomeric IgG peak. The binding to nucleosomes was only in the 150-kDa peak. These findings are consistent with the existence of an anomalous IgG in SLE and DIL sera, capable, like aggregated IgG, DNA-IC and other CIC, of binding to histone-decorated structures. We propose that this anomalous IgG plays an essential role in the pathogenesis of lupus nephritis and other related inflammatory conditions. These observations also explain the large discrepancies in the reports on anti-histone autoantibodies in autoimmune conditions.


Efficacy and safety of lemborexant in midlife women with insomnia disorder.
Insomnia is common in midlife women. The efficacy and safety of lemborexant (LEM), a competitive dual orexin receptor antagonist, was assessed for 12 months in a subgroup of midlife women (age, 40-58 y) from Study E2006-G000-303 (Study 303; SUNRISE-2). This was a randomized, double-blind, placebo (PBO)-controlled (first 6 mo) study of adults with insomnia disorder ( N = 949). During treatment period 1 (TP1), participants received PBO or LEM 5 mg (LEM5) or 10 mg (LEM10). During TP2 (second 6 mo), LEM participants continued their assigned dose; PBO participants were rerandomized to LEM5 or LEM10. Assessments included patient-reported sleep- and fatigue-related measures and treatment-emergent adverse events. The midlife female subgroup comprised 280 of 949 participants (TP1: PBO, n = 90 of 318 [28.3%]; LEM5, n = 82 of 316 [25.9%]; LEM10, n = 108 of 315 [34.3%]). At 6 months, median changes from baseline in subjective sleep-onset latency (in minutes) were -17.9, -20.7, and - 30.4 for PBO, LEM5, and LEM10 (vs PBO: LEM5, P = not significant; LEM10, P = 0.0310). At 6 months, mean changes from baseline in subjective wake after sleep onset (in minutes) were -37.0 (59.6), -50.1 (74.5), and -54.5 (65.4) for PBO, LEM5, and LEM10 (vs PBO: LEM5 and LEM10, P = not significant), with benefits sustained through 12 months. Greater decreases from baseline (improvement) in Insomnia Severity Index total score and Fatigue Severity Scale total score were seen with LEM versus PBO at 6 months; benefits continued through 12 months. Most treatment-emergent adverse events were mild to moderate in severity. Consistent with the total population, subjective sleep parameters improved, and improvement was sustained over time in midlife women. LEM was well tolerated, suggesting that LEM may be a potential treatment option for midlife women with insomnia.


Degrees of saturation with respect to apatites in fruit juices and acidic drinks.
Some fruit juices and carbonated acidic drinks, recognized as agents causing dental erosions, were analyzed for calcium, phosphate, fluoride and pH. Ionic activity/concentration products for hydroxyapatite and fluorapatite were calculated. It was found that all liquids analyzed were unsaturated with respect to both apatites, which explains their erosive effect.


[Diabetes education of Turkish people with low literacy skills: Results of an online survey of training practices].
For patients with diabetes mellitus, training is an essential part of therapy. There is a lack of empirical data regarding training experiences for people with a (Turkish) migration background and low literacy skills concerning the established training programmes. The objective of this research was to collect data from general practices based on their experiences in training these particular groups of patients. In a quantitative cross-sectional study design, 795 general practices throughout Germany with the additional designation of diabetology were invited via e-mail to participate in a fully structured, standardised online survey. An exploratory data analysis was performed using the statistics software IBM SPSS. Out of 146 participating practices (response rate 18%), 66 (45%) estimated the proportion of patients with migration background in their practice to be more than 20%. Approximately 76% of the practices providing diabetes training (n=119) trained patients of Turkish origin. Forty six percent of these practices estimated the ratio of patients of Turkish origin with low literacy skills to be 10 to 50%. Less than 36% of the practices were aware of suitable training programmes for this target group. Existing programmes were modified to special needs and new materials creatively developed. Additional culturally sensitive and visually enriched materials are needed. Forty two percent of the interviewed practices reported billing difficulties concerning frequently needed individual trainings. Training was carried out in different ways due to individual addition or deletion of content elements. There is a lack of evaluated materials that are adapted to the users' cultural background and level of education. In the face of a significantly changed immigration structure, information and materials as well as interpreters for additional languages are increasingly required. Further development of evidence-based, multi-lingual, image-based, culturally sensitive and educationally diverse materials and training units and their scientific evaluation is needed. Learning contents adapted to the level of education and promoting cultural sensitivity in the provision of healthcare should be implemented increasingly in the training and continuous professional development of health professionals.


[Sonography of the neck and superior mediastinum].
Sonography of the neck and superior mediastinum is a very instructive method of investigation. However, the topographical anatomy of the region makes major demands on the investigator. In many diseases in this area, ultrasonography may be used as the first and also only imaging method (thyroid, salivary glands, lymph nodes). Pathological findings are detected with high sensitivity. The dynamic investigation with palpation, compression and observation of deglutition is especially helpful in appraising the consistency, displace-ability and topographical identification of structures. The specificity can be substantially improved by use of color Doppler sonography and ultrasound-guided biopsy. The pharyngeal and retropharyngeal space, the base of the brain and the posterior mediastinum are difficult to access by sonography. The investigator must therefore arrange for supplementary imaging procedures such as CT, MRI or thyroid scintigraphy in unclear cases, e.g. in diagnosis and staging of tumors. Mediastinal space occupations are most frequent in the anterior upper mediastinum. They can be appraised almost as reliably by transthoracic sonography as by computer tomography.


Chloropentafluorobenzene: short-term inhalation toxicity, genotoxicity and physiologically-based pharmacokinetic model development.
Ten Fischer 344 rats and six B6C3F1 mice of each sex were exposed to air, 0.25, 0.80, or 2.50 mg chloropentafluorobenzene (CPFB)/liter of air for three weeks, excluding weekends. Exposure to 2.50 mg/liter caused a reduction in the growth rate of rats but did not affect the growth rate of mice. Following the exposure there was reduced SGOT activity in the blood serum of exposed rats and a dose related increase in liver weights. Increased liver weights were observed in mice as well; the response in the female groups was clearly dose dependent. Histologically the livers of both rats and mice presented single cell necrosis. In exposed mice hepatocytes exhibited mild hepatocytomegaly with increased granular eosinophilic cytoplasm. In evaluations for its potential to induce chromosomal damage following this exposure regimen, CPFB did not alter the rate of bone marrow cellular proliferation. Assessment of the micronucleated polychromatic erythrocytes and normochromatic erythrocyte populations during the inhalation exposures indicated a general absence of genotoxic activity.


Downregulation of microRNA-6125 promotes colorectal cancer growth through YTHDF2-dependent recognition of N6-methyladenosine-modified GSK3β.
MicroRNAs (miRNAs), the key regulator of gene expression, and N6-methyladenosine (m6A) RNA modification play a significant role in tumour progression. However, regulation of m6A-modified mRNAs by miRNAs in colorectal cancer (CRC), and its effect on progression of CRC, remains to be investigated. Expression of miR-6125 and YTH Domain-Containing Family Protein 2 (YTHDF2) was detected by western blotting and immunohistochemistry. The effects of miR-6125 and YTHDF2 on proliferative capacity of CRC cells were analysed using soft agar, ATP, CCK8 and EdU assays, and in animal experiments. MiR-6125 expression was downregulated markedly in CRC, and expression correlated negatively with tumour size and prognosis. MiR-6125 targeted the 3'-UTR of YTHDF2 and downregulated the YTHDF2 protein, thereby increasing the stability of m6A-modified glycogen synthase kinase 3 beta (GSK3β) mRNA. Increased GSK3β protein levels inhibited the expression of Wnt/β-catenin/Cyclin D1 pathway-related proteins, leading to G0-G1 phase arrest and ultimately inhibiting the proliferation of CRC cells. MiR-6125 regulates YTHDF2 and thus plays a critical role in regulating the Wnt/β-catenin pathway, thereby affecting the growth of CRC. Collectively, these results suggest that miR-6125 and YTHDF2 are potential targets for treatment of CRC.


Mutational drivers of cancer cell migration and invasion.
Genomic instability and mutations underlie the hallmarks of cancer-genetic alterations determine cancer cell fate by affecting cell proliferation, apoptosis and immune response, and increasing data show that mutations are involved in metastasis, a crucial event in cancer progression and a life-threatening problem in cancer patients. Invasion is the first step in the metastatic cascade, when tumour cells acquire the ability to move, penetrate into the surrounding tissue and enter lymphatic and blood vessels in order to disseminate. A role for genetic alterations in invasion is not universally accepted, with sceptics arguing that cellular motility is related only to external factors such as hypoxia, chemoattractants and the rigidity of the extracellular matrix. However, increasing evidence shows that mutations might trigger and accelerate the migration and invasion of different types of cancer cells. In this review, we summarise data from published literature on the effect of chromosomal instability and genetic mutations on cancer cell migration and invasion.


Palliation of gastroesophageal carcinoma with endoscopic insertion of a new antireflux prosthesis.
Noninvasive insertion of an antireflux prosthesis by means of endoscopy was accomplished in 20 patients with nonoperable cardioesophageal carcinoma. There were no perforations in 23 successful intubations. The new antireflux prosthesis avoids the morbidity and mortality associated with gastroesophageal reflux, thus allowing a much improved quality of life in patients with nonresectable cancer of the esophagus or gastric cardia.


Clonal replacement among 19A Streptococcus pneumoniae in Massachusetts, prior to 13 valent conjugate vaccination.
As part of an ongoing study of the response of the Streptococcus pneumoniae population to conjugate vaccination, we applied multi-locus sequence typing (MLST) to 291 isolates sampled from nasopharyngeal carriage in Massachusetts children. We found 94 distinct sequence types (STs), including 19 that had not been previously recorded, and a xpt allele containing a large insertion. Comparison with a similar sample collected in 2007 revealed no significant overall difference in the ST composition (p=0.51) suggesting that the population has reached a new equilibrium following the introduction of 7 valent vaccination in 2000. Within serotypes, a large and statistically significant increase (p=0.014 Fisher's Exact test) was noted in the prevalence of the major multiresistant clone ST 320, which is apparently outcompeting ST 199 among serotype 19A strains. This sample will be used as a baseline to study the future evolution of the pneumococcal population in Massachusetts following introduction of vaccines with higher valency.


The expression of soluble intercellular adhesion molecule-1 in endometriosis.
To investigate the association between concentrations of soluble intercellular adhesion molecule-1 (ICAM-1) and interferon-gamma (IFN-gamma) with regard to the severity of endometriosis. Cross-sectional study. Infertility unit in a university hospital. Seventy-one infertile patients who underwent laparoscopic evaluation were divided into two groups: 36 patients with endometriosis served as cases, and 35 patients without endometriosis served as control subjects. Peripheral blood and peritoneal fluid (PF) were collected from these patients during laparoscopic examination. Quantitative determination of levels of human ICAM-1 and IFN-gamma was performed with the use of an ELISA. The data were evaluated by Student's t-test, analysis of variance, and regression analysis. Significantly elevated levels of soluble ICAM-1 were found in the sera of patients with endometriosis, especially those with advanced stages of the disease. Decreased IFN-gamma levels, which were negatively correlated with serum levels of soluble ICAM-1, also were noted in the PF of patients with endometriosis. The increased serum levels of ICAM-1 found in patients with endometriosis may indicate the presence of an active disease process. Further, the increased levels of soluble ICAM-1 in peripheral blood were inversely correlated with the concentrations of IFN-gamma in PF. The increased levels of soluble ICAM-1 in plasma may be associated with an immunologic feedback response that blocks further infiltration of immune cells. These findings may be of value in the diagnosis and evaluation of endometriosis.


[Semantic Segmentation of Eight Regions of Upper and Lower Limb Bones Using 3D U-Net in Whole-body CT Images].
Automated analysis of skeletal muscle in whole-body computed tomography (CT) images uses bone information, but bone segmentation including the epiphysis is not achieved. The purpose of this research was the semantic segmentation of eight regions of upper and lower limb bones including the epiphysis in whole-body CT images. Our targets were left and right upper arms, forearms, thighs, and lower legs. We connected two 3D U-Nets in cascade for segmentation of eight upper and lower limb bones in whole-body CT images. The first 3D U-Net was used for skeleton segmentation in whole-body CT images, and the second 3D U-Net was used for eight upper and lower limb bones' segmentation in skeleton segmentation results. Thirty cases of whole-body CT images were used in the experiment, and the segmentation results were evaluated using Dice coefficient with 3-fold cross-validation. The mean Dice coefficient was 93% in the left and right upper arms, 89% in the left and right forearms, 95% in the left and right thighs, and 94% in the left and right lower legs. Although the accuracy of the segmentation results of relatively small bones remains a challenge, the semantic segmentation of eight regions of upper and lower limb bones including the epiphysis in whole-body CT images has been achieved.


[COMPARISON OF BIOLOGICAL DIFFERENCE BETWEEN BONE MARROW AND PLACENTA-DERIVED MESENCHIMAL STEM CELLS IN HYPOXIA].
To comprehensively analyze and compare the biological difference between bone marrow mesenchymal stem cells (BMSCs) and placenta-derived MSCs (PMSCs) in hypoxia and to extend the knowledge for seed cells selection. The domestic and foreign related literature about the effects of hypoxia microenvironment on proliferation, apoptosis, differentiation, paracrine secretion, migration, and homing ability of BMSCs and PMSCs were summarized and analysed. PMSCs proliferated much faster and more sensitive to the hypoxia than BMSCs; in addition, PMSCs showed stronger survivability. Similar to BMSCs, PMSCs can home to hypoxic-ischemic tissues efficiently, secrete a lot of growth factors and differentiate into tissue-specific cells to stimulate tissue regeneration. PMSCs as the seed cells will have broad application prospects in the regenerative medicine.


A cysteine proteinase inhibitor ALLN alleviates bleomycin-induced skin and lung fibrosis.
Systemic sclerosis (SSc) is a connective tissue disease that is characterized by fibrosis in the skin and internal organs, such as the lungs. Activated differentiation of progenitor cells, which are mainly resident fibroblasts, into myofibroblasts is considered a key mechanism underlying the overproduction of extracellular matrix and the resultant tissue fibrosis in SSc. Calpains are members of the Ca2+-dependent cysteine protease family, whose enzymatic activities participate in signal transduction and tissue remodeling, potentially contributing to fibrosis in various organs. However, the roles of calpain in the pathogenesis of SSc remain unknown. This study aimed to examine the anti-fibrotic properties of N-acetyl-Leu-Leu-norleucinal (ALLN), one of the cysteine proteinase inhibitors that primarily inhibit calpain, in vitro and in vivo, to optimally translate into the therapeutic utility in human SSc. Normal human dermal and lung fibroblasts pretreated with ALLN were stimulated with recombinant transforming growth factor beta 1 (TGF-β1), followed by assessment of TGF-β1/Smad signaling and fibrogenic molecules. ALLN treatment significantly inhibited TGF-β1-induced phosphorylation and nuclear transport of Smad2/3 in skin and lung fibroblasts. TGF-β1-dependent increases in α-smooth muscle actin (αSMA), collagen type I, fibronectin 1, and some mesenchymal transcription markers were attenuated by ALLN. Moreover, our findings suggest that ALLN inhibits TGF-β1-induced mesenchymal transition in human lung epithelial cells. Consistent with these in vitro findings, administering ALLN (3 mg/kg/day) three times a week intraperitoneally remarkably suppressed the development of skin and lung fibrosis in a SSc mouse model induced by daily subcutaneous bleomycin injection. The number of skin- and lung-infiltrating CD3+ T cells decreased in ALLN-treated mice compared with that in control-treated mice. Phosphorylation of Smad3 and/or an increase in αSMA-positive myofibroblasts was significantly inhibited by ALLN treatment on the skin and lungs. However, no adverse effects were observed. Our results prove that calpains can be a novel therapeutic target for skin and lung fibrosis in SSc, considering its inhibitor ALLN.


To Evaluate the Pre and Post Shunt Sensorineural Hearing Loss in Hydrocephalus Patients.
Hydrocephalus means watery head and defined as disturbance of formation, flow, or absorption of cerebrospinal fluid. The clinical presentation of hydrocephalus includes hearing loss especially sensorineural hearing loss (SNHL). Ventriculoperitoneal (VP) shunting is the most commonly performed procedure in these patients. Pure tone audiogram, impedence and BAEPs, were done for preoperative hearing assessment in 20 hydrocephalus patients. Out of 20 patients, 12 cases (60%) had SNHL while, rest 8 (40%) patients had mixed hearing loss. Post VP shunting hearing improvement was observed in 14 patients (70%) whereas it worsened in 30% of patients. The result is even better if shunt is placed at early age.


Sensor-based evaluation and treatment of nocturnal hypokinesia in Parkinson's disease: An evidence-based review.
The manifestations of nocturnal movements in Parkinson's disease (PD) are protean, with major disabilities related to nocturnal hypokinesia. While it can be assessed by clinical interviews and screening instruments, these are often inaccurate and prone to recall bias. In light of advances in sensor technology, we explored the use of sensors in the study of nocturnal hypokinesia, by performing a systematic review of the professional literature on this topic. Evidence suggests that nocturnal hypokinesia exists even in patients in the early stages, and PD patients turned significantly less and with much slower speed and acceleration than controls, partly related to low nocturnal dopamine level. We conducted another systematic review to evaluate the evidence of the efficacy of dopaminergic agents in the treatment of nocturnal hypokinesia. Several lines of evidence support the use of long-acting drugs or by continuous administration of short-acting agents to control symptoms. Sensor parameters could be considered as one of the important objective outcomes in future clinical trials investigating potential drugs to treat nocturnal hypokinesia. Physicians should be aware of this technology as it can aid the clinical assessment of nocturnal hypokinesia and enhance the quality of patient care. In addition, the use of sensors currently is being considered for various aspects of research on early diagnosis, treatment, and rehabilitation of PD patients.


5-Methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid (folinic acid), and folic acid requirements of normal and Rous sarcoma virus-infected chicken fibroblasts.
Normal and Rous sarcoma virus-infected chicken fibroblasts proliferate maximally in a culture medium containing a physiological (10 ng/ml) concentration of 5-methyltetrahydrofolic acid or folinic acid (5-formyltetrahydrofolic acid), while their maximal proliferation requires a hyperphysiological (1000 ng/ml) concentration of folic acid. The normal and Rous-infected fibroblasts do not differ in their requirements for 5-methyltetrahydrofolate, folinic acid, or folic acid.


Origin of the structure-directing effect resulting in identical topological open-framework materials.
In the synthesis of zeolites and related crystalline materials with open-frameworks, a single structure is obtained in the presence of many different templates, known as the "one-structure/multiple-templates" phenomenon. However, the reasons behind this phenomenon have yet to be elucidated. By analyzing the possible starting point of crystallization in several "one-structure/multiple-templates" systems and applying the molecular dynamics simulation to such systems, we found that the template-framework binding free energy level or charge transfer (exchange) degree was the key to the structure-directing effect of a template. This discovery explains why the structure-directing effect of a template can be affected by many variables, such as the nature of the source materials, molar composition of the initial reaction mixture (recipe), mineralizers, type of solvent, and heating temperature. In the synthesis of zeolites and related crystalline materials with open-frameworks, the template or organic additive played a topological structure-directing role instead of a structure-directing role.


Use of carbapenems in the combined treatment of emerging ceftazidime/avibactam-resistant and carbapenem-susceptible KPC-producing Klebsiella pneumoniae infections: Report of a case and review of the literature.
To describe the case of a patient with infection due to a KPC-producing Klebsiella pneumoniae (K. pneumoniae) isolate developing ceftazidime-avibactam resistance with restored carbapenem susceptibility during ceftazidime-avibactam therapy. To review the clinical/microbiological cure and survival rates using carbapenems in other similar case reports and case series. A patient with an intra-abdominal infection due to K. pneumoniae producing the KPC-48 variant (L169P-A172T) (resistant to ceftazidime/avibactam and susceptible to carbapenems) who was treated with imipenem-cilastatin in combination with tigecycline and gentamicin. The literature was reviewed in order to summarise the in vivo (clinical/microbiological cure and survival rate) use of carbapenems in this emerging scenario. The patient was successfully treated with the indicated regimen. In other reported cases (mostly with pneumonia) all-cause mortality was 50% and clinical cure was 62.5%. Meropenem-vaborbactam has been successful used in an additional case. A carbapenem-based regimen of combination therapy seems to be an option for treating patients infected with K. pneumoniae resistant to ceftazidime/avibactam and susceptible to carbapenems, at least when the risk of mortality is low.


The effect of pentoxifylline on oxidative stress in CO2 pneumoperitoneum.
Carbon dioxide (CO(2)) pneumoperitoneum induces peritoneal oxidative stress. This experimental, randomized, controlled study was designed to investigate the effect of pentoxifylline on oxidative stress induced by CO(2 )pneumoperitoneum. For this study, 36 Swiss albino rats were randomized into three groups. Arteria, vena femoralis, and peritoneal cavity were cannulated after anesthesia. The arterial pH, partial arterial oxygen pressure (PaO(2)), venous PO(2), arterial and venous PO(2) difference (P((a-v))O(2)), serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and thiobarbituric acid-reactive substances (TBARS) were studied at the end of the first and second hours in group 1 (control). In group 2, 1 cc isotonic NaCl was injected into peritoneal cavity and then CO(2) pneumoperitoneum was established. At the end of the first hour of insufflation and one hour after desufflation, the same parameters as in group 1 were studied. In group 3, the CO(2) pneumoperitoneum plus pentoxifylline group, all procedures as in group 2 were repeated, with the exception of pentoxifylline (50 mg/kg) injected in place of saline. At the end of the first hour, P((a-v))O(2 )value in group 2 was significantly less than in the control group (group 1) and group 3 (p \ 0.05). There were no significant differences in PaO(2, )pH, AST, and ALT values between groups (p [ 0.05). TBARS level in group 1 was significantly lower than in the other groups, but there was no significant difference in TBARS level between groups 2 and 3. At the end of the second hour, TBARS level in group 3 was significantly lower than in group 2 (p \ 0.05). Pentoxifylline may reduce the oxidative injury following laparoscopic procedures.


Immunization of elderly people with high doses of influenza vaccine.
Healthy ambulatory elderly were immunized with increasing doses of the 1984-1985 influenza vaccine formulation. Two types of vaccines, split-product vaccine (SPV) and whole virus vaccine (WVV), were used. Three different doses, 0.5 mL (the standard volume, 1X), or 1.0 mL (2X), and 1.5 mL (3X) of each of the two vaccines were compared. The size of each of the six groups was between 23 and 26 subjects. The mean ages in each of the groups ranged from 71 to 74 years. No difference in local or systemic reaction was noted among the six groups. A dose-response effect was observed for the SPV recipients to the influenza A/Chile/83 (H1N1) strain. The geometric mean hemagglutination inhibition (HI)titer (GMT) was 1:76 after the 3X dose vs 1:38 after the 1X dose (P less than 0.025). To the influenza A/Philippines/82 (H3N2) strain the GMT was 1:70 after the 3X dose vs 1:43 after the 1X dose. A similar trend was noted for the influenza B/USSR/83 strain. A (HI) titer of greater than or equal to 1:40 for all the strains was seen in greater than 70% of the split product vaccine recipients only after the 3X dose. For the WVV recipients, increasing doses did not result in increasing GMT for any of the three vaccine strains. In addition, HI titers greater than or equal to 1:40 were not uniformly seen in greater than 70% of the vaccine recipients at any of the three whole virus vaccine doses.(ABSTRACT TRUNCATED AT 250 WORDS)


Tuning the Carrier Transfer Behavior of Coaxial ZnO/ZnS/ZnIn2 S4 Nanorods with a Coherent Lattice Heterojunction Structure for Photoelectrochemical Water Oxidation.
Invited for this month's cover is the group of Feng Li at the Ningxia University. The image shows how the coherent lattice heterojunction interface can play a role in the efficient separation of photogenerated carriers of ZnO-based photoanode for photoelectrochemical water splitting. The Research Article itself is available at 10.1002/cssc.202201469.


Opacification of Middlebrook agar as an aid in identification of Nocardia farcinica.
One hundred twenty seven human isolates of Nocardia asteroides complex were identified to the species level by drug susceptibility testing, acetamide utilization, thermotolerance studies, studies of arylsulfatase activity, and studies of acid production from rhamnose. N. asteroides complex organisms which were not identifiable as N. farcinica or N. nova were designated N. asteroides sensu stricto. All of the N. farcinica isolates and none of the other isolates produced a milky-white opacity surrounding colonies on Middlebrook 7H10 agar. This finding may facilitate the identification of N. farcinica.


Ubiquitin‑specific protease 8 ameliorates lipopolysaccharide‑induced spleen injury via suppression of NF‑κB and MAPK signaling pathways.
In human immunity, the spleen is a major organ, being central to humoral and cellular immunity. In vitro and in vivo, inflammation is regulated by ubiquitin‑specific protease 8 (USP8); however, to the best of our knowledge, the effect of USP8 on spleen injury remains unknown. The present study aimed to investigate the protection offered by USP8 against spleen injury in lipopolysaccharide (LPS)‑induced mice via attenuation of inflammation. A total of 119 C57BL/6J mice were placed into the following groups: Control group, saline group, LPS group, USP8 group, USP8 + LPS group and negative control (NC) + LPS group. A USP8 lentivirus was injected into mice at 1x108 TU/ml intracerebroventricularly for 7 days before LPS was administered via intraperitoneal injection at 750 µg/kg. From each group, serum and spleen samples were collected for analysis. Histological imaging was used to examine the spleen structure. Western blotting was used to detect the expression levels of proteins associated with the mitogen‑activated protein kinase (MAPK) and nuclear factor (NF)‑κB signaling pathways. Pro‑inflammatory cytokines were detected using enzyme‑linked immunosorbent assays. Compared with that in the saline, control and USP8 + LPS groups, the spleen volume in the LPS group was markedly increased, and the width of the splenic cord and sinus exhibited morphological damage in the LPS group. Compared with that in the saline, control and USP8 + LPS groups, the protein expression levels of USP8 in the spleen were decreased in the LPS group. Furthermore, the production of LPS‑induced pro‑inflammatory cytokines (e.g., interleukin‑1β and tumor necrosis factor‑α) was reduced in serum and spleen homogenates by USP8. Related inflammatory pathways, including the NF‑κB and MAPK pathways, were downregulated in the USP8 + LPS group compared with those in the LPS group. In conclusion, the anti‑inflammatory effect of USP8 on LPS‑induced spleen injury may be mediated by the inhibition of MAPK and NF‑κB signaling pathways.


Gender-Affirmation Hair Transplantation Techniques.
Hair restoration can play an important role for transgender patients seeking gender-affirmation procedures. In our clinic, we have seen an increase in transgender patients seeking hair restoration. The most common hair restoration procedures performed in our clinic for the transgender patient are hairline lowering procedures, facial hair restoration procedures including eyebrow and beard transplantation, and body hair transplantation.


Depth-Resolved Localization Microangiography in the NIR-II Window.
Detailed characterization of microvascular alterations requires high-resolution 3D imaging methods capable of providing both morphological and functional information. Existing optical microscopy tools are routinely used for microangiography, yet offer suboptimal trade-offs between the achievable field of view and spatial resolution with the intense light scattering in biological tissues further limiting the achievable penetration depth. Herein, a new approach for volumetric deep-tissue microangiography based on stereovision combined with super-resolution localization imaging is introduced that overcomes the spatial resolution limits imposed by light diffusion and optical diffraction in wide-field imaging configurations. The method capitalizes on localization and tracking of flowing fluorescent particles in the second near-infrared window (NIR-II, ≈1000-1700 nm), with the third (depth) dimension added by triangulation and stereo-matching of images acquired with two short-wave infrared cameras operating in a dual-view mode. The 3D imaging capability enabled with the proposed method facilitates a detailed visualization of microvascular networks and an accurate blood flow quantification. Experiments performed in tissue-mimicking phantoms demonstrate that high resolution is preserved up to a depth of 4 mm in a turbid medium. Transcranial microangiography of the entire murine cortex and penetrating vessels is further demonstrated at capillary level resolution.


Antifungal activity of gallic acid purified from Terminalia nigrovenulosa bark against Fusarium solani.
The antifungal activities of methanolic extracts from Terminalia nigrovenulosa bark (TNB) was investigated for effects on the initial growth of mycelia against Fusarium solani. The ethyl acetate fraction separated from TNB demonstrated the highest antifungal activity against F. solani. The antifungal compound was isolated from TNB using silica gel column and Sephadex LH-20 chromatography combined with thin-layer chromatography and high performance liquid chromatography. Structural identification of the antifungal compound was conducted using (1)H NMR, (13)C NMR, and liquid chromatography-tandem mass spectrometry. The purified antifungal compound was gallic acid (GA) or 3,4,5-trihydroxy benzoic acid. Purified-GA possesses the high antifungal activity against F. solani, and that antifungal activity was dosage-dependent. The hyphae became collapsed and shrunken after 24 h incubation with GA (500 ppm). In pot experiments, the application of TNB crude extract was found to be effective in controlling the cucumber Fusarium root rot disease by enhancing activities of chitinase, peroxidase thereby promoting the growth of plants. The applied TNB extract significantly suppressed root rot disease compared to control. It resulted in 33, 75 and 81% disease suppression with 100, 500 and 1000 ppm of TNB crude extract, respectively. The study effectively demonstrated biological activities of the TNB extract, therefore suggesting the application of TNB for the control of soil-borne diseases of cucumber plants.


Nanoscale engineering of catalytic materials for sustainable technologies.
Nanostructured materials of diverse architecture are ubiquitous in industrial catalysis. They offer exciting prospects to tackle various sustainability challenges faced by society. Since the introduction of the concept a century ago, researchers aspire to control the chemical identity, local environment and electronic properties of active sites on catalytic surfaces to optimize their reactivity in given applications. Nowadays, numerous strategies exist to tailor these characteristics with varying levels of atomic precision. Making headway relies upon the existence of analytical approaches able to resolve relevant structural features and remains challenging due to the inherent complexity even of the simplest heterogeneous catalysts, and to dynamic effects often occurring under reaction conditions. Computational methods play a complementary and ever-increasing role in pushing forward the design. Here, we examine how nanoscale engineering can enhance the selectivity and stability of catalysts. We highlight breakthroughs towards their commercialization and identify directions to guide future research and innovation.


Deletion of SHATI/NAT8L decreases the N-acetylaspartate content in the brain and induces behavioral deficits, which can be ameliorated by administering N-acetylaspartate.
We previously identified a novel molecule "SHATI/NAT8L" that exerts an inhibitory effect on methamphetamine (METH)-induced behavioral deficits. Recently, it has been reported that SHATI might function as an aspartate N-acetyltransferase, which synthesizes N-acetylaspartate (NAA) in vitro. However, whether SHATI actually synthesizes NAA in vivo in the brain is still unclear. In this study, we found that both Shati-deleted mice showed significantly lower NAA levels in all brain areas than wild-type (Shati(+/+)) mice using HPLC and fluorescence detection, suggesting that SHATI regulates NAA content in the brain. Next, we measured the levels of monoamines and their metabolites in the adult mouse brain and found that the activities of monoaminergic systems were altered in Shati(-/-) mice. In particular, dopaminergic turnover increased in the nucleus accumbens (NAc) in Shati(-/-) mice, suggesting activation of the dopaminergic system. In fact, basal level of extracellular dopamine, and METH-induced dopamine release in the NAc of Shati(-/-) mice was significantly higher than that of Shati(+/+) and Shati(+/-) mice, which is consistent with findings that Shati(-/-) mice showed enhanced hyperlocomotion induced by METH. Moreover, in the forced swimming test, Shati-deleted mice showed a shortened immobility time, which was improved by intracerebroventricular (i.c.v.) administration of NAA prior to the test in Shati(+/-) but not in Shati(-/-) mice. The i.c.v. preinjection of NAA inhibited dopamine release after high K(+) stimulation in the NAc of Shati(+/+) and Shati(+/-) mice, but not Shati(-/-) mice. These results suggested that the behavioral deficits in Shati-deleted mice were caused by dopaminergic abnormality via deprivation of NAA.


Ectopic Vas Deferens in a Male Infant.
Vas deferens ectopia is a rare congenital anomaly associated with urinary tract and anorectal anomalies. It is important to recognize the complex embryology of the reproductive, urinary, and lower enteric systems to understand how these processes can go awry.1 As the ureteric bud arises from the mesonephric duct, a failure of the channel that connects the two to obliterate can produce an ectopic vas deferens connected to the ureter or bladder.2 We present a 2-month-old male with vas deferens ectopia. Our patient uniquely did not present with associated anorectal anomalies or urinary tract symptoms.


ALSUntangled #68: ozone therapy.
ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review ozone therapy. Ozone therapy has possible mechanisms for slowing ALS progression based on its antioxidant, anti-inflammatory, and mitochondrial effects. A non-peer-reviewed report suggests that ozone treatment may slow progression in a mTDP-43 mouse model of ALS. One verified "ALS reversal" occurred on a cocktail of alternative treatments including ozone. There are no ALS trials using ozone to treat PALS. There can be potentially serious side effects associated with ozone therapy, depending on the dose. Based on the above information, we support an investigation of ozone therapy in ALS cell or animal models but cannot yet recommend it as a treatment in PALS.


Depression predicts repeated heart failure hospitalizations.
Management of depression, if it is independently associated with repeated hospitalizations for heart failure (HF), offers promise as a viable and cost-effective strategy to improve health outcomes and reduce health care costs for HF. The objective of this study was to assess the association between depression and the number of HF-related hospitalizations in patients with low-to-moderate systolic or diastolic dysfunction, after controlling for illness severity, socioeconomic factors, physician adherence to evidence-based medications, patient adherence to HF drug therapy, and patient adherence to salt restrictions. The Heart Failure Adherence and Retention Trial (HART) was a randomized behavioral trial to evaluate whether patient self-management skills coupled with HF education improved patient outcomes. Depression was measured at baseline with the Geriatric Depression Scale (GDS). The number of hospitalizations was analyzed with a negative binomial regression model that included an offset term to account for the differential duration of follow-up for individual subjects. The average unadjusted number of hospitalizations per year was 0.40 in the depressed group (GDS ≥10) and 0.33 in the nondepressed group (GDS <10). Depression was a strong predictor (incident rate ratio 1.45; P = .006) after adjusting for physician adherence to evidence-based medication use, patient adherence to HF drug therapy, patient adherence to salt restriction, illness severity, HF severity (6-minute walk <620 feet), and socioeconomic factors. Depression is a strong psychosocial predictor of repeated hospitalizations for HF. Compared with nondepressed individuals, those with depression were hospitalized for HF 1.45 times more often, even after controlling for physician adherence to evidence-based medications and patient adherence to HF drug therapy and salt restrictions. This finding suggests that clinicians should screen for depression early in the course of HF management.


Recurrent ventricular tachycardia induced by an atrial synchronous ventricular-inhibited pacemaker.
Atrial synchronous pacemakers have been known to cause a variety of cardiac arrhythmias. Of particular concern are those arrhythmias involving a pacemaker stimulus occurring on a T wave, because these may lead to ventricular tachycardia. The Medtronic 2409 ASVIP pacemaker is an atrial synchronous pacemaker with several features designed to decrease the likelihood of such arrhythmias. We report a patient in whom a normally functioning Medtronic 2409 ASVIP pacemaker, despite these features, induced recurrent ventricular tachycardia. Conditions which predisposed this patient to pacemaker-induced re-entrant arrhythmias are discussed.


Metabolic design for selective production of nicotinamide mononucleotide from glucose and nicotinamide.
β-Nicotinamide mononucleotide (NMN) is, one of the nucleotide compounds, a precursor of NAD+ and has recently attracted attention as a nutraceutical. Here, we develop a whole-cell biocatalyst using Escherichia coli, which enabled selective and effective high production of NMN from the inexpensive feedstock substrates glucose and nicotinamide (Nam). Notably, we identify two actively functional transporters (NiaP and PnuC) and a high-activity key enzyme (Nampt), permitting intracellular Nam uptake, efficient conversion of phosphoribosyl pyrophosphate (PRPP; supplied from glucose) and Nam to NMN, and NMN excretion extracellularly. Further, enhancement of the PRPP biosynthetic pathway and optimization of individual gene expression enable drastically higher NMN production than reported thus far. The strain extracellularly produces 6.79 g l-1 of NMN from glucose and Nam, and the reaction selectivity from Nam to NMN is 86%. Our approach will be promising for low-cost, high-quality industrial production of NMN and other nucleotide compounds using microorganisms.


Fastigial modulation of brainstem behavioral mechanisms.
Stimulation of the rostral, but not caudal, half of the cerebellar fastigial nucleus was found to induce coordinated eating and grooming behaviors in the cat. These behaviors persisted, unchanged, after lesions of the ascending fastigial projections in the superior cerebellar peduncle, suggesting that such behaviors are produced by direct fastigio-bulbar pathways. These results support the suggestion that there is a close anatomical association between fastigial systems mediating elicited behaviors and those mediating fastigial pressor responses. The present results are also consistent with the growing view that cerebellar systems can exert important modulatory influences on neurobehavioral mechanisms.


Lateral column lengthening osteotomies.
Lateral column lengthening procedures, either an Evans-type procedure or a calcaneocuboid distraction arthrodesis, clearly have a role to play in the management of a pes planovalgus foot deformity, as is evident from clinical outcome studies. Despite an abundance of literature intricately detailing the biomechanical effects of different operative procedures on the hindfoot, there is no clear consensus as to the best procedure or procedures to perform for a flexible pes planovalgus foot deformity. There is, therefore, no single solution to this problem; the surgeon must treat each patient as an individual and choose the procedure that will work best in their hands for any given foot pathology they are presented with. The surgeon must also be aware that to improve the kinematics of a planovalgus foot deformity, one may often have to perform multiple procedures and not a lateral column lengthening in isolation.


Staining of interphase nuclei and mitotic figures in cultured cells with alcian blue 8GX.
Cultured endothelial cells derived from bovine calf pulmonary artery were subjected to a variety of fixatives and stained with 1% Alcian blue 8GX at pH 2.59 to 3.26. Within this range of pH, interphase nuclei and especially mitotic figures were (a) strongly stained in cells fixed with 10% formalin (phosphate buffered or unbuffered) or 2.5% buffered glutaraldehyde, (b) weakly stained or unstained in cells fixed in formaldehyde containing divalent cations, and (c) unstained in cells fixed in acetic acid-containing fluids. However, optimal nuclear staining with Alcian blue under the conditions of this study was judged to be achieved after fixation with neutral phosphate buffered 10% formalin. Endothelial cell cytoplasm exhibited a similar fixative-dependent staining. At pH 2.59 the cytoplasm of interphase cells fixed in formaldehyde (containing no divalent cations) or glutaraldehyde remained unstained; however, at higher pH cytoplasmic staining did occur and it increased as pH increased. In contrast, when these latter fixatives were employed the cytoplasm of mitotic cells stained at all pH levels tested. In cultured endothelial cells after appropriate fixation, 1% Alcian blue 8GX (pH 2.59) was found to possess the ability to stain nuclei with a selectivity and intensity that compared favorably to those of the Feulgen reaction of Heidenhain iron hematoxylin but without the latters' length and complexity. Therefore, this procedure may provide a rapid, simple, and selective method for visualizing interphase nuclei or mitotic figures, or both in the majority of cultured cells.


Event-oriented data integration: a qualitative strategy in studying professional practice.
The purpose of this article is to present a qualitative mixed-method strategy that uncovers the compound reality in professional practice and the inner aspects of actions, feelings, values, and thoughts embedded therein. The authors developed a systematic strategy for collecting and handling data from different sources. This strategy, called event-oriented data integration represents within-method triangulation as well as triangulation during data analysis. The analysis involves 2 distinctive new steps for structuring of data--the braiding of data threads and the braiding of data ropes. We found that the process of weaving together different data created an inclusive text that allowed the researcher to undertake a holistic, coherent, and consistent analysis and to attain a more complete picture of professional practice.


RNA-PAIRS: RNA probabilistic assignment of imino resonance shifts.
The significant biological role of RNA has further highlighted the need for improving the accuracy, efficiency and the reach of methods for investigating RNA structure and function. Nuclear magnetic resonance (NMR) spectroscopy is vital to furthering the goals of RNA structural biology because of its distinctive capabilities. However, the dispersion pattern in the NMR spectra of RNA makes automated resonance assignment, a key step in NMR investigation of biomolecules, remarkably challenging. Herein we present RNA Probabilistic Assignment of Imino Resonance Shifts (RNA-PAIRS), a method for the automated assignment of RNA imino resonances with synchronized verification and correction of predicted secondary structure. RNA-PAIRS represents an advance in modeling the assignment paradigm because it seeds the probabilistic network for assignment with experimental NMR data, and predicted RNA secondary structure, simultaneously and from the start. Subsequently, RNA-PAIRS sets in motion a dynamic network that reverberates between predictions and experimental evidence in order to reconcile and rectify resonance assignments and secondary structure information. The procedure is halted when assignments and base-parings are deemed to be most consistent with observed crosspeaks. The current implementation of RNA-PAIRS uses an initial peak list derived from proton-nitrogen heteronuclear multiple quantum correlation ((1)H-(15)N 2D HMQC) and proton-proton nuclear Overhauser enhancement spectroscopy ((1)H-(1)H 2D NOESY) experiments. We have evaluated the performance of RNA-PAIRS by using it to analyze NMR datasets from 26 previously studied RNAs, including a 111-nucleotide complex. For moderately sized RNA molecules, and over a range of comparatively complex structural motifs, the average assignment accuracy exceeds 90%, while the average base pair prediction accuracy exceeded 93%. RNA-PAIRS yielded accurate assignments and base pairings consistent with imino resonances for a majority of the NMR resonances, even when the initial predictions are only modestly accurate. RNA-PAIRS is available as a public web-server at http://pine.nmrfam.wisc.edu/RNA/.


Preoperative Masseter Muscle Sarcopenia Predicts Mortality in Patients With Oesophageal Cancer.
The impact of masseter muscle sarcopenia on the prognosis of patients with oesophageal cancer after oesophagectomy remains unclear. We retrospectively analysed data from 70 patients with oesophageal cancer who underwent oesophagectomy between 2013 and 2019. Overall survival and disease-free survival rates were analysed using Cox proportional hazards models and Kaplan-Meier curves with the log-rank test. Masseter muscle sarcopenia was diagnosed in 36 patients. Multivariate analysis identified cytokeratin 19 fragment >1.1 (p=0.04); stage II, III, and IV cancer (p=0.01); and masseter muscle sarcopenia (p<0.01) as significant independent predictors of disease-free survival. Stage II, III, and IV cancer (p<0.01); masseter muscle sarcopenia (p<0.01); and postoperative pneumonia (p<0.01) were significant independent predictors of overall survival. Preoperative masseter muscle sarcopenia could be a strong predictor of long-term outcomes in patients who undergo oesophagectomy for oesophageal cancer.


Evaluation of Vitronectin Expression in Prostate Cancer and the Clinical Significance of the Association of Vitronectin Expression with Prostate Specific Antigen in Detecting Prostate Cancer.
To detect the expression of vitronectin (VTN) in the tissues and blood serum of prostate cancer (PCa) patients, and evaluate its clinical significance and to evaluate the significance of the combined assay of VTN and prostate specific antigens (PSA) in PCa diagnosis. To detect the expression of VTN as a potential marker for PCa diagnosis and prognosis, immunohistochemistry was performed on the tissues of 32 patients with metastatic PCa (PCaM), 34 patients with PCa without metastasis (PCa), and 41 patients with benign prostatic hyperplasia (BPH). The sera were then subjected to Western blot analysis. All cases were subsequently examined to determine the concentrations of PSA and VTN in the sera. The collected data were collated and analyzed. The positive expression rates of VTN in the tissues of the BPH and PCa groups (including PCa and PCaM groups) were 75.61% and 45.45%, respectively (P = .005). VTN was more highly expressed in the sera of the BPH patients (0.83 ± 0.07) than in the sera of the PCa patients (0.65 ± 0.06) (P < .05). It was also more highly expressed in the sera of the PCa patients than in the sera of the PCaM patients (0.35 ± 0.08) (P < .05). In the diagnosis of BPH and PCa, the Youden indexes of PSA detection, VTN detection, and combined detection were 0.2620, 0.3468, and 0.5635; the kappa values were 0.338, 0.304, and 0.448, respectively, and the areas under the receiver operating characteristic curve were 0.625, 0.673, and 0.703 (P < .05), respectively. VTN levels in sera may be used as a potential marker of PCa for the diagnosis and assessment of disease progression and metastasis. The combined detection of VTN and PSA in sera can be clinically applied in PCa diagnosis.&nbsp.


Characterization of Liver CD8 T Cell Subsets that are Associated with Protection Against Pre-erythrocytic Plasmodium Parasites.
Murine models of malaria, such as Plasmodium berghei (Pb) and Plasmodium yoelii (Py), have been used for decades to identify correlates of protection associated with immunization using radiation-attenuated sporozoites (RAS). To date, RAS is the only known immunization regimen to consistently deliver 100 % sterilizing immunity and is considered the "gold standard" of protection against malaria. The ability to isolate lymphocytes directly from the liver of immune mice has facilitated the identification of correlates of protection at the site of infection. Liver CD8 T cells have been identified as a key factor in mediating protection against challenge with infectious Plasmodium sporozoites. Liver CD3 + CD8 T cells can further be divided into subsets based on the expression of specific surface molecules and the increase of CD8 effector memory (TEM) cells (identified by the phenotype CD44(+)CD62L(-)) has been shown to mediate protection by releasing of IFN-γ while CD8 central memory (TCM) cells (CD44(+)CD62L(+)) are important for maintaining long-term protection.Identification of multiple CD8 T cell subsets present in the liver relies on the ability to detect multiple surface markers simultaneously. Polychromatic flow cytometry affords the user with the ability to distinguish multiple lymphocyte populations as well as subsets defined within each population. In this chapter we present a basic 9-color surface staining panel that can be used to identify CD8 TEM, CD8 TCM, short-lived effector cells (SLECs), and memory precursor cells (MPECs) as well as identify those cells which have recently undergone degranulation (surface expression of CD107a). This panel has been designed to allow for the addition of intracellular staining for IFN-γ on other available channels (such as PE) as is discussed in another chapter for analysis of functional CD8 T cell responses.


Analysis of methylene blue in human urine by capillary electrophoresis.
A capillary electrophoresis method for the determination of the dye methylene blue (tetramethylthionine, MB) in human urine depending on liquid/liquid-extraction and diode array detection has been developed, validated, and applied to samples of healthy individuals, who had been dosed with methylene blue within clinical studies. After extraction with dichloromethane and sodium hexanesulfonate, sample extracts were measured on an extended light path capillary. The dye was detected simultaneously at 292 and 592 nm using methylene violet 3 RAX as internal standard. The limit of quantification was 1.0 microg/ml. The accuracy of the method varied between -15.2 and +0.8% and the precision ranged from 2.0 to 12.0%. The method was linear at least within 1.0 and 60 microg/ml. In contrast to earlier indirect determinations no leuco methylene blue (LMB) was directly detected in urine, whereas in aqueous test solutions containing surplus amounts of ascorbic acid leuco methylene blue was well separated from MB in a single run.


Comparison of molecular analysis and touch imprint cytology for the intraoperative evaluation of sentinel lymph nodes in primary breast cancer: results of the China Breast Cancer Clinical Study Group (CBCSG) 001c trial.
To validate the clinical value of the One-Step Nucleic Acid Amplification (OSNA) Breast Cancer System for the intraoperative detection of sentinel lymph node (SLN) metastases in early-stage breast cancer patients in a Chinese population, a prospective, multicenter trial, the China Breast Cancer Clinical Study Group (CBCSG)-001c trial, was conducted. The present study focused on the prospective comparison of the performance between OSNA and touch imprint cytology (TIC). The retrieved SLNs were divided into sections. Alternate slices from the tissue blocks were subjected either to OSNA analysis or to postoperative histopathology evaluation through serial sectioning. TIC was performed on every sample surface of each tissue block and was used by the surgeon to determine whether to perform an immediate ALND. A total of 552 patients qualified for the analysis. The sensitivity, specificity, and overall accuracy of OSNA were 87.8%, 89.6%, and 88.4%, respectively, on a per-patient basis compared with those of TIC, which were 81.3%, 96.9%, and 92.0%, respectively. OSNA detected more micrometastasis-involved nodes than TIC (52.8% vs. 25.0%; p = 0.029) on a per-node basis. Tissue allocation bias (TAB) was the main cause of discordant results. The performance of TIC varied significantly among the institutes, while the performance of OSNA was steady. Both OSNA and TIC can serve as qualified intraoperative assessments of SLNs. For institutes lacking the support of experienced cytopathologists, OSNA can be the first choice for the intraoperative assessment. In addition, OSNA can be applied as a complement to histopathology assessment. However, the results of the present study do not support the routine application of OSNA in the entire SLNs in place of pathology with serial sectioning.


Quorum sensing of Streptococcus mutans is activated by Aggregatibacter actinomycetemcomitans and by the periodontal microbiome.
The oral cavity is inhabited by complex microbial communities forming biofilms that can cause caries and periodontitis. Cell-cell communication might play an important role in modulating the physiologies of individual species, but evidence so far is limited. Here we demonstrate that a pathogen of the oral cavity, Aggregatibacter actinomycetemcomitans (A. act.), triggers expression of the quorum sensing (QS) regulon of Streptococcus mutans, a well-studied model organism for cariogenic streptococci, in dual-species biofilms grown on artificial saliva. The gene for the synthesis of the QS signal XIP is essential for this interaction. Transcriptome sequencing of biofilms revealed that S. mutans up-regulated the complete QS regulon (transformasome and mutacins) in the presence of A. act. and down-regulated oxidative stress related genes. A.act. required the presence of S. mutans for growth. Fimbriae and toxins were its most highly expressed genes and up-regulation of anaerobic metabolism, chaperones and iron acquisition genes was observed in co-culture. Metatranscriptomes from periodontal pockets showed highly variable levels of S. mutans and low levels of A. act.. Transcripts of the alternative sigma-factor SigX, the key regulator of QS in S. mutans, were significantly enriched in periodontal pockets compared to single cultures (log2 4.159, FDR ≤0.001, and expression of mutacin related genes and transformasome components could be detected. The data show that the complete QS regulon of S. mutans can be induced by an unrelated oral pathogen and S. mutans may be competent in oral biofilms in vivo.


Atypical antipsychotic properties of AD-6048, a primary metabolite of blonanserin.
Blonanserin is a new atypical antipsychotic drug that shows high affinities to dopamine D2 and 5-HT2 receptors; however, the mechanisms underlying its atypicality are not fully understood. In this study, we evaluated the antipsychotic properties of AD-6048, a primary metabolite of blonanserin, to determine if it contributes to the atypicality of blonanserin. Subcutaneous administration of AD-6048 (0.3-1mg/kg) significantly inhibited apomorphine (APO)-induced climbing behavior with an ED50 value of 0.200mg/kg, the potency being 1/3-1/5 times that of haloperidol (HAL). AD-6048 did not cause extrapyramidal side effects (EPS) even at high doses (up to 10mg/kg, s.c.), whereas HAL at doses of 0.1-3mg/kg (s.c.) significantly induced bradykinesia and catalepsy in a dose-dependent manner. Thus, the therapeutic index (potency ratios of anti-APO action to that of EPS induction) of AD-6048 was much higher than that of haloperidol, illustrating that AD-6048 per se possesses atypical antipsychotic properties. In addition, immunohistochemical analysis of Fos protein expression revealed that both AD-6048 and HAL significantly increased Fos expression in the shell part of the nucleus accumbens and the striatum. However, in contrast to HAL which preferentially enhanced striatal Fos expression, AD-6048 showed a preferential action to the nucleus accumbens. These results indicate that AD-6048 acts as an atypical antipsychotic, which seems to at least partly contribute to the atypicality of blonanserin.


Human and bovine serotype G8 rotaviruses may be derived by reassortment.
The origin of, and relationship between human and bovine serotype G8 rotaviruses were investigated by genomic hybridisation. Radiolabelled mRNAs of human G8 rotaviruses 69M (isolated in Indonesia) and HAL1271 (isolated in Finland), and bovine rotaviruses KK3 (G10) and NCDV (G6), were used as probes. The products of liquid hybridisation between the probes and the genomic RNA of human and bovine rotaviruses, including bovine G8 rotavirus 678 (isolated in Scotland) and two other Finnish human G8 rotaviruses HAL1166 and HAL8590, were examined by separation in polyacrylamide gels. The genomes of Finnish human G8 rotaviruses were similar to those of bovine G6 and G10 rotaviruses. Neither Indonesian human G8 nor bovine G8 viruses had high levels of similarity to each other or to other bovine and human rotaviruses. Thus these three epidemiologically distinct G8 rotaviruses have different origins and may be derived by reassortment with rotaviruses of a third, as yet unknown, host species. The similarity between the Finnish isolates and the bovine isolate NCDV suggests that they have diverged recently and that these human G8 rotaviruses may be derived from a zoonotic infection, or alternatively, from the live rotavirus vaccine of bovine origin which has been used to vaccinate Finnish children.


A photoactivated prodrug.
A photolabile derivative (1) of the anticancer drug, 5-fluorodeoxyuridine (2), was designed and synthesized as a model prodrug. Photolysis of 1 with long-wavelength UV light rapidly released 2 in solution. While compound 1 alone is nontoxic to cells, the presence of both 1 and UV irradiation (lambda = 350 nm) resulted in potent inhibition of cell growth.


ATP-dependent potassium channel mediates neuroprotection by chemical preconditioning with 3-nitropropionic acid in gerbil hippocampus.
Chemical preconditioning with low dose of 3-nitropropionic acid (3-NPA) prolongs the latency to hypoxic depolarization (HD), which triggers cell death, and also restores the synaptic transmission which disappears during hypoxia in gerbil hippocampal slices. Here we show that these neuroprotective effects are mediated by the activation of K(ATP) channels. Diazoxide, a K(ATP) channel opener, prolonged the latency to HD dose-dependently to the same extent as that of the chemical preconditioning with 3-NPA. Glibenclamide, a K(ATP) channel blocker, abrogated the prolongation of HD with 3-NPA. The hypoxic tolerance of synaptic transmission with 3-NPA was also abolished by glibenclamide. Diazoxide also induced the hypoxic tolerance of synaptic transmission. Theses results suggest that K(ATP) channel is involved in the neuroprotection afforded by the chemical preconditioning.


[Urticaria … and treatment fails].
According to the guidelines the treatment goal for all types of urticaria is to achieve complete symptom relief. Therefore the available literature for urticaria treatment was reviewed regarding this aim and treatment failure, respectively. Systematic studies are not available. Standard doses of H1-antihistamines are the only approved therapy. Review of the limited data where statements are made about complete alleviation of symptoms shows that standard doses of H1-antihistamines rarely achieve this. Even when the dosage is increased up to four-fold, the failure rate is high. Additional therapy with montelukast, dapsone, and cyclosporine A also often fails to produce complete control. For severe chronic spontaneous urticaria, controlled studies using omalizumab have shown low failure rates over long time periods. It has not been investigated whether up-dosing or reduced injection intervals could further improve this rate. Taken together, the small amount of available data on complete symptom relief in urticaria treatment is astonishing. Moreover, the studies can not be compared due to different inclusion criteria (severity of urticaria, allowed basic treatment) and evaluated parameters. Further controlled studies are vitally needed to achieve the goal of complete symptom relief in urticaria.


[Research advances of the influence factors of high level expression of recombinant protein in Pichia pastoris].
Pichia pastoris is one of the most important systems used in the field of molecular biology for the expression of recombinant proteins. The system has advantages of high expression, high stability, high secretion, easy high-density fermentation and low cost. Many factors affect the expression of recombinant protein, such as gene copy number, codon usage preference, type of promoter, molecular chaperones, glycosylation, signal peptide and fermentation process. In this review, research advances of the above aspects are summarized, which lay a foundation for improving the expression of recombinant proteins in P. pastoris.


The G-Protein-Coupled Estrogen Receptor Agonist Prevents Cardiac Lipid Accumulation by Stimulating Cardiac Peroxisome Proliferator-Activated Receptor α: A Preclinical Study in Ovariectomized-Diabetic Rat Model.
Type 2 diabetes mellitus (T2DM) is associated with cardiometabolic changes, and menopause exacerbates these conditions, leading to a greater risk of cardiovascular diseases (CVDs). The G protein-coupled estrogen receptor (GPER), which mediates the rapid effects of estrogen, has beneficial cardiac effects in both T2DM and menopause, but its mechanism of action is not well understood. This study aimed to determine whether G1 as a selective GPER-agonist has beneficial effects on cardiac lipid metabolism in ovariectomized rats with T2DM. Female Wistar rats were divided into 5 groups (n = 7 in each group): Sham-control (Sh-Ctl), T2DM, ovariectomized-T2DM (OVX-T2DM), OVX-T2DM-G1 (GPER-agonist), and OVX-T2DM-vehicle (OVX-T2DM-Veh). After stabilization of T2DM, G1 (200 μg/Kg) was administrated for 6 weeks. Then, the levels of free fatty acids (FFAs), CD36, peroxisome proliferator-activated receptor α (PPARα), and lipid accumulation in the cardiac tissue were determined. Compared with the Sh-Ctl group, cardiac FFAs (P < 0.001), CD36 (P < 0.05), and lipid accumulation (P < 0.001) increased, and cardiac PPARα (P < 0.01) decreased in T2DM animals; ovariectomy intensified these changes. Also, cardiac FFAs, PPARα, and lipid accumulation (P < 0.05) significantly decreased in the OVX-T2DM-G1 group compared to the OVX-T2DM-Veh group. However, cardiac CD36 levels did not change. G1 as a selective GPER-agonist affects lipid metabolism in T2DM animals. It also plays a vital role in improving cardiac metabolism during postmenopausal diabetic conditions.


Stereotactic biopsy complicated by pneumocephalus and acute pulmonary edema.
The aim of this study was to describe pneumocephalus as a rare complication of stereotactic biopsy and as a possible cause of acute neurogenic pulmonary edema. A case of frameless stereotactic biopsy complicated by pneumocephalus presenting with acute lung injury 48 hours after the procedure. A frameless stereotactic procedure was performed in the standard fashion. Immediate postoperative CT showed no intracranial air except for a gas inclusion at the biopsy site within the lesion. The skin staple placed at the end of surgery on the skin incision was removed 36 hours later. A CT scan performed 48 hours postoperatively showed new pneumocephalus. The patient exhibited acute respiratory distress but no new neurologic symptoms. There was no detectable systemic cause for the pulmonary edema. The patient received supportive respiratory treatment and fully recovered. Pneumocephalus is apparently a rare complication of stereotactic brain biopsy and one that may result from early removal of the skin staple or suture. The occurrence of acute neurogenic pulmonary edema may be attributed to the pneumocephalus.


Non-traumatic cerebrospinal-fluid rhinorrhoea in cases of primary empty-sella syndrome.
Non-traumatic cerebrospinal-fluid rhinorrhoea is a rare condition. Its insidious onset may occur with a sneezing or coughing episode which may lead to an incorrect diagnosis of allergic rhinitis or vasomotor rhinorrhoea. Two cases that occurred in association with primary empty-sella syndrome are described--in the second case, the fistula arose from the pituitary fossa. The history, incidence, clinical profile, investigation and management of this condition are reviewed.


The effect of ultraviolet (UVB and PUVA) radiation on the expression of epidermal keratins.
Using a panel of monoclonal antibodies directed against keratins (PKK2, CK8.12 and KL1), the effects of ultraviolet B (UVB) and psoralen plus ultraviolet A (PUVA) irradiation on keratin expression in guinea-pig skin were examined immunohistochemically. Following irradiation, whether by UVB or PUVA, rapid alterations in the distribution pattern of keratins were observed in the epidermis. The alterations included the induction of basal cell-type keratins (PKK2 and CK8.12 staining) in the suprabasal layers, with concomitant reduction of the suprabasal-type keratins (KL1 staining). These alterations in keratin expression were observed during the period when DNA synthesis appears to be accelerated by ultraviolet light exposure (5 h-5 days after UVB, and 2-10 days after PUVA irradiation). Therefore, these changes are probably reflections of a proliferative or regenerative state of keratinocytes. This explanation was supported by the result of an experiment involving tape stripping of the epidermal horny layers, which also accelerates DNA synthesis by keratinocytes. Immunohistochemistry appears to be a useful and sensitive method of detecting the effect of ultraviolet light on keratinization.


Medication safety problems priorities in community pharmacy in Saudi Arabia: a multi-stakeholder Delphi study using the human factors framework.
To achieve multi-stakeholder consensus and prioritisation of medication safety problems in community pharmacies in Saudi Arabia. A theoretically-underpinned, three-round Delphi study. Saudi Arabia. Patients and public (pharmacy users), pharmacy-related professionals (policymakers, academics, medication safety officers and pharmacy owners) and community pharmacists. Round 1 comprised 84 statements derived from a qualitative study. The items were grouped according to the Human Factors Framework (HFF). Rounds 1 and 2 aimed to achieve consensus, 6-point Likert response scale (agreement/disagreement) was used. Round 3 aimed to prioritise the items for which consensus was achieved in Rounds 1 and 2 indicated on a 5-point scale (very important to unimportant). Consensus was predefined as any item that achieved ≥70%. The number of respondents in Rounds 1, 2 and 3 was 161, 120 and 112, respectively. In all three rounds, the majority of respondents were pharmacy users (Round 1 77% (n=124), Round 2 74% (n=89), Round 3 72% (n=81)). Consensus was achieved with 28/84 items. The top five medication safety priorities were: lack of pharmacy facilities such as counselling area, lack of communication between pharmacists and physicians, lack of patient databases, lack of post-registration pharmacist education and pharmacists' long working hours. The professional and pharmacy user groups achieved consensus on similar items through different categories of the HFFs. Community pharmacists had the highest percentage of consensus among the three groups for factors related to work, such as high workload and low salaries. This multi-stakeholder study used the HFF to identify and prioritise the main medication safety challenges facing community pharmacy in Saudi Arabia. It indicates the need for changes to practice and policy and further research to address these priorities and promote medication safety at an individual, pharmacy and population level.