Pelle Modulates dFoxO-Mediated Cell Death in Drosophila.
Interleukin-1 receptor-associated kinases (IRAKs) are crucial mediators of the IL-1R/TLR signaling pathways that regulate the immune and inflammation response in mammals. Recent studies also suggest a critical role of IRAKs in tumor development, though the underlying mechanism remains elusive. Pelle is the sole Drosophila IRAK homolog implicated in the conserved Toll pathway that regulates Dorsal/Ventral patterning, innate immune response, muscle development and axon guidance. Here we report a novel function of pll in modulating apoptotic cell death, which is independent of the Toll pathway. We found that loss of pll results in reduced size in wing tissue, which is caused by a reduction in cell number but not cell size. Depletion of pll up-regulates the transcription of pro-apoptotic genes, and triggers caspase activation and cell death. The transcription factor dFoxO is required for loss-of-pll induced cell death. Furthermore, loss of pll activates dFoxO, promotes its translocation from cytoplasm to nucleus, and up-regulates the transcription of its target gene Thor/4E-BP. Finally, Pll physically interacts with dFoxO and phosphorylates dFoxO directly. This study not only identifies a previously unknown physiological function of pll in cell death, but also shed light on the mechanism of IRAKs in cell survival/death during tumorigenesis.


Is the Antioxidant Capacity of Stored Human Milk Preserved?
Background: In the neonatal intensive care unit (NICU) expressed mothers' milk usually is stored frozen until used. We found that when human milk was stored at -20°C for up to 9 months there were reduced bacterial counts and pH, increased free fatty acids, but unchanged immune proteins. Antioxidant protection is an important benefit of human milk. Few studies have evaluated long-term effects of cold storage on the antioxidant capacity of human milk. We hypothesized that the antioxidant capacity of human milk is affected adversely by long-term storage at -20°C. Objective: To study the impact of long-term cold storage on the oxidative capacity of human milk and the biological impact of these changes on macromolecular constituents of human milk. Methods: Freshly expressed milk was obtained from mothers in the NICU, stored at -20°C for 6 months, and compared with the baseline. Paired samples were analyzed for glutathione, hydrogen peroxide (H2O2), 8-isoprostane, catalase, and superoxide dismutase. Results: There was no change in H2O2 concentration between baseline and 6 months. Significant reductions from baseline in both catalase and superoxide dismutase concentrations and activities, total glutathione, oxidized glutathione, reduced glutathione, and the ratio of reduced to oxidized glutathione were observed (p < 0.05). There was a significant increase in 8-isoprostane concentrations (p < 0.001). Conclusion: These data indicate significant changes in antioxidant capacity of human milk, including oxidation of macromolecules, after storage at -20°C for 6 months. The clinical implication of these findings may explain the nonuniform protection against oxidant disease in preterm infants fed human milk.


Smoked marijuana attenuates performance and mood disruptions during simulated night shift work.
Individuals who work nonstandard schedules, such as rotating or night shifts, are more susceptible to workplace injuries, performance decrements, and reduced productivity. This population is also almost twice as likely to use illicit drugs as individuals working a standard day shift. The purpose of this study was to examine the effects of smoked marijuana on performance, mood, and sleep during simulated shift work. Ten experienced marijuana smokers completed this 23-day, within-participant residential study. They smoked a single marijuana cigarette (0, 1.9, 3.56% Δ9-THC) one hour after waking for three consecutive days under two shift conditions: day shift and night shift. Shifts alternated three times during the study, and shift conditions were separated by an 'off' day. When participants smoked placebo cigarettes, psychomotor performance and subjective-effect ratings were altered during the night shift compared to the day shift: performance (e.g., vigilance) and a few subjective ratings were decreased (e.g., "Self-Confident"), whereas other ratings were increased (e.g., "Tired"). Objective and subjective measures of sleep were also disrupted, but to a lesser extent. Marijuana attenuated some performance, mood, and sleep disruptions: participants performed better on vigilance tasks, reported being less miserable and tired and sleep a greater number of minutes. Limited negative effects of marijuana were noted. These data demonstrate that abrupt shift changes produce performance, mood, and sleep decrements during night shift work and that smoked marijuana containing low to moderate Δ9-THC concentrations can offset some of these effects in frequent marijuana smokers.


Using magnetic resonance imaging to accurately assess injury to the posterior ligamentous complex of the spine: a prospective comparison of the surgeon and radiologist.
Magnetic resonance imaging has been proposed as a powerful technique for assessing the integrity of the posterior ligamentous complex (PLC) in spinal trauma. Because MR imaging is often used to determine appropriate treatment, it is important to determine the accuracy and reliability of MR imaging in diagnosing PLC disruption. The purpose of this study is to compare the ability of the radiologist and surgeon to assess disruption of the PLC in the setting of acute cervical and thoracolumbar trauma using MR imaging. The components of the PLC in 89 consecutive patients with cervical or thoracolumbar fractures following acute spinal trauma were evaluated using MR imaging by both a musculoskeletal radiologist and an independent spine surgeon and assessed intraoperatively under direct visualization by the treating surgeon. The MR imaging interpretations of the musculoskeletal radiologist and surgeon were compared with the intraoperative report for accuracy, sensitivity, specificity, and positive and negative predictive values. A comparison between the radiologist's and spine surgeon's accuracy of MR imaging interpretation was performed. The agreement between both the spine surgeon's and radiologist's MR imaging interpretation and the actual intraoperative findings was moderate for most components of the PLC. Overall, the MR imaging interpretation of the surgeon was more accurate than that of the radiologist. The interpretation of MR imaging by the surgeon had negative predictive value and sensitivity of up to 100%. However, the specificity of MR imaging for both the surgeon and radiologist was lower, ranging from 51.5 to 80.5%. Comparison of the MR imaging interpretations between surgeon and radiologist indicates that the surgeon was more accurate for some PLC components. The relatively low positive predictive value and specificity for MR imaging in assessing PLC integrity suggests that both the surgeon and radiologist tend to overdiagnose PLC injury using MR imaging. This can lead to unnecessary surgeries if only MR imaging is used for treatment decision making.


Detection of shared H-2Kk and H-2Dk antigens that function as self determinants for cell-mediated lympholysis to trinitrophenyl-self.
Spleen cells from C3H/He mice immunized in vivo to trinitrophenyl (TNP)-self were sensitized in vitro to TNP-self. These spleen cells displayed strong lysis on TNP-modified H-2D end-matched (Kd-Dk) targets as well as enhanced cytotoxicity against H-2 matched (Kk-Dk) or H-2K end-matched (Kk-Dd) target cells. Cold target-blocking studies showed that the lysis of TNP-Kd-Dk targets could be blocked by the addition of TNP-modified Kk-Dk, Kk-Dd Kk-Db, or Kd-Dk, but not by TNP-modified Kd-Dd, Kb-Db and Kq-Kq spleen cells. These results demonstrate that the lysis of TNP-Kd-Dk targets is not due to cross-reactive clones against TNP-Kd-Dd, Kb-Db or Kq-Dq antigens. Inhibition of the TNP-Kd-Dk target lysis by TNP-Kk-matched (Kk-Dd or Kk-Db) as well as TNP-Dk-matched (Kd-Dk) blockers also reveals that this target is lysed by clones directed against shared antigens between Kk-TNP and Dk-TNP, indicating that no cytotoxic response restricted for Dk-TNP only could be detected even after in vivo priming.


Expression of the adhesion molecules L1, N-CAM and J1/tenascin during development of the murine small intestine.
We have previously studied the immunohistological localization of the three adhesion molecules L1, N-CAM and J1/tenascin in adult mouse small intestine and shown that L1 expression in epithelial crypt cells underlies the adhesion of these cells to one another [63]. To obtain further insight into the functional roles of L1, N-CAM and J1/tenascin in this organ we studied their expression starting at embryonic day 14 during embryonic and early postnatal morphogenesis and during epithelial cell migration in the adult. Expression of L1 was restricted to neural cells until approximately postnatal day 5, when L1 started to be detectable on crypt but not on villus cells, predominantly on the basolateral membrane infoldings. As in brain, L1-specific mRNA was approximately 6 kb in size. L1 from intestine appears to differ from the brain-derived equivalent in possessing a higher level of glycosylation. N-CAM was detectable from embryonic day 14 onward in neural and also in mesenchymal cells. Expression by smooth muscle cells decreased during development. In the villus core, N-CAM was strongly detectable at contact sites between smooth muscle cells forming the cellular scaffold of the villus. From embryonic day 14 onward, N-CAM appeared in both 180- and 140-kDa forms. J1/tenascin was present in both neural and mesenchymal cells from embryonic day 14 onward. Starting at embryonic day 17, J1/tenascin appeared concentrated at the boundary between mesenchyme and epithelium in an increasing gradient from the crypt base to the villus top. From embryonic day 14 onward J1/tenascin consisted of the 190- and 220-kDa components. J1/tenascin from intestine differed from brain-derived J1 in its carbohydrate composition. These observations show that the three adhesion molecules are expressed by distinct cell populations and may serve as cell-type-specific markers in pathologically altered intestinal tissue.


Sphingosine 1-Phosphate Receptor 2 Regulates the Migration, Proliferation, and Differentiation of Mesenchymal Stem Cells.
Mesenchymal stem cells (MSCs) are a multipotent cell population acquired most prominently from bone marrow with the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, and others. MSCs demonstrate the capacity to home to sites of injury and contribute to tissue repair. Sphingosine 1-phosphate (S1P) is a biologically active sphingolipid impacting proliferation, apoptosis, inflammation, and angiogenesis with changes in S1P concentration providing significant implications for various disease conditions including cancer, diabetes, and cardiac disease. These functions are primarily mediated by interactions with 5 G-protein coupled S1P receptors (S1PR1-5). In this paper, we demonstrate that inhibition of S1PR2 results in increased MSC clonogenicity, migration, and proliferation; features dependent on Erk phosphorylation. Furthermore, decreased S1PR2 expression decreases the differentiation of MSCs into adipocytes and mature osteoblasts that may be the result of increased expression of MSC pluripotency factors including Nanog, Sox-9, and Oct-4. Inhibition of S1PR1 and S1PR3 in contrast does not impact MSC migration or Erk activation although increased proliferation is observed. In the study, we describe the essential role of S1PR2 in MSC differentiation pathways through modification of pluripotency factors. We propose a MAPK dependent mechanism through S1PR2 inhibition that promotes equally multipotent MSC proliferation.


How do cancer patients manage unattainable personal goals and regulate their emotions?
This article addressed the role of goal adjustment (i.e. disengagement from unattainable goals and reengagement in alternative goals) and cognitive emotion-regulation strategies (i.e. rumination, catastrophizing, positive refocusing) in cancer patients' psychological well-being. We expected that patients who are better able to disengage from unattainable goals, identify alternative goals, and regulate their emotions by positive refocusing and not engaging in rumination and catastrophizing would experience less negative and more positive affect. In this cross-sectional study, data were collected using a self-report questionnaire. Cancer patients (N=108) were recruited on a psychoeducational meeting aimed to inform them about the illness and its consequences. To examine the relationships between goal adjustment, cognitive emotion-regulation strategies, and affect, Pearson correlations were calculated and regression analyses were performed. Regression analyses showed that reengaging in meaningful goals and focusing on pleasant issues were significantly associated with more positive affect. Focusing on pleasant issues was also significantly associated with less negative affect, whereas rumination and catastrophizing were significantly associated with more negative affect. Goal reengagement as well as cognitive emotion-regulation strategies seems to play an important role in cancer patients' psychological well-being. Health care professionals may assist patients in paying more attention to positive experiences in their daily life and in finding new meaningful goals. Techniques based on mindfulness may be used to assist cancer patients in decreasing the repetitive negative thinking about causes, meanings, and consequences of the illness and helping them to focus attention on the present moment.


Enhancing the sensitivity of Dengue virus serotype detection by RT-PCR among infected children in India.
Dengue surveillance relies on reverse transcription-polymerase chain reaction (RT-PCR), for confirmation of dengue virus (DENV) serotypes. We compared efficacies of published and modified primer sets targeting envelope (Env) and capsid-premembrane (C-prM) genes for detection of circulating DENV serotypes in southern India. Acute samples from children with clinically-diagnosed dengue were used for RT-PCR testing. All samples were also subjected to dengue serology (NS1 antigen and anti-dengue-IgM/IgG rapid immunochromatographic assay). Nested RT-PCR was performed on viral RNA using three methods targeting 654bp C-prM, 511bp C-prM and 641bp Env regions, respectively. RT-PCR-positive samples were validated by population sequencing. Among 171 children with suspected dengue, 121 were dengue serology-positive and 50 were dengue serology-negative. Among 121 serology-positives, RT-PCR detected 91 (75.2%) by CprM654, 72 (59.5%) by CprM511, and 74 (61.1%) by Env641. Among 50 serology-negatives, 10 (20.0%) were detected by CprM654, 12 (24.0%) by CprM511, and 11 (22.0%) by Env641. Overall detection rate using three methods sequentially was 82.6% (100/121) among serology-positive and 40.0% (20/50) among serology-negative samples; 6.6% (8/120) had co-infection with multiple DENV serotypes. We conclude that detection of acute dengue was enhanced by a modified RT-PCR method targeting the 654bp C-prM region, and further improved by using all three methods sequentially.


Long-term use of oral poliovirus vaccine from Sabin strains in the Soviet Union.
Success in control of poliomyelitis in the USSR has been achieved after mass immunization with oral polio vaccine ( OPV ) manufactured from attenuated Sabin strains. Procedures for large-scale production of the OPV have been developed by Soviet researchers with the leadership of Chumakov and Smorodintsev , and the safety and efficacy of the vaccine have since been demonstrated. A mass immunization program was initiated in the USSR in 1959 and completed in 1960, covering 77.5 million people or 36.7% of the entire population. This immunization campaign resulted in a sharp decrease in the incidence of poliomyelitis: from 10.6 per 100,000 population in 1958 to 0.43 in 1963. Beginning in 1964 the incidence remained at a level of 0.01-0.1 per 100,000 population. At present the vaccination schedule consists of three basic vaccinations given to infants. Over 20 years of experience with OPV in the USSR has shown that this vaccine is a safe and efficient preparation.


Skin, muscle and joint disease from the 17th century: scurvy.
We report three cases of scurvy, with differing musculoskeletal presentations, from a tertiary teaching hospital in Sydney, Australia. Case 1 was a man with cerebral palsy who presented with knee swelling following a minor injury. In Case 2, a patient with thalassaemia major presented with purpuric rash, difficulty walking and distal thigh swelling and ecchymosis. Case 3 was a man with Down's syndrome who presented with acute ankle arthritis. Scurvy in Cases 1 and 3 were related to abnormal dietary preferences, whereas in Case 2, scurvy was thought to be related to thalassaemia. All three cases responded rapidly to vitamin C replacement. The subjects did not appear malnourished as they had adequate carbohydrate and protein intake.


SOX2 and ALDH1 as Predictors of Operable Breast Cancer.
Sex-determining region Y-box binding protein-2 (SOX2) and aldehyde dehydrogenase-1 (ALDH1) are known cancer stem-cell markers, and represent candidate predictors for breast cancer prognosis. In this study we investigated the relationships between SOX2/ALDH1 expression and prognosis. One hunred and two breast cancer surgical specimens were immunohistochemically analyzed for SOX2 and ALDH1 expression. Disease-free survival (DFS) and overall survival (OS) were significantly poorer for SOX2-positive patients than SOX2-negative (p=0.0024 and p=0.0021, respectively), and for ALDH1-positive patients than ALDH1-negative (p=0.0049 and p=0.0083). DFS and OS were worse for SOX2- or ALDH1-positive patients than double-negative (p=0.0053 and p=0.0166). While an obvious tendency toward worse DFS was seen for estrogen receptor (ER)-negative patients, and attenuated for ER-positive, only SOX2/ALDH1 any-positive patients showed significantly poorer DFS (p=0.0258). SOX2 and ALDH1 can be considered markers of poor prognosis, particularly in ER-negative patients. SOX2/ALDH1 any-positivity might also offer a reliable predictor of poor prognosis.


American psychoanalysis today: a plurality of orthodoxies.
American psychoanalysis, Freudian in origin, has recently developed in multiple directions among different groups in the current theoretical and clinical pluralistic atmosphere. The history of the effort to exclude new ideas is briefly reviewed. A survey of a group of leading analysts representing a variety of schools reveals a plethora of newer ideas, some areas of consensus, and broad areas of disagreement concerning the meaning and value of the ideas that dominate our current discourse. While we welcome the "pluralism" that has partially replaced the "rejectionist" policy of only a few decades ago, our contemporary pluralism is, to a surprising degree, a multiplicity of authoritarian orthodoxies, each derived from a particular thinker, rather than a scientific discourse. After a discussion of some aspects of the philosophy of science, the author suggests a controversial, but possible consensus view of American psychoanalysis today. The need for the creation of a psychoanalytic research effort, focused on efficacy, is emphasized.


Intraocular lens power calculation in eyes with keratoconus.
The purpose was to review and document the methods used to calculate the power of the intraocular lens (IOL) to be implanted in cataract surgery in the specific scenario of eyes with keratoconus. This review included all scientific articles published in English that focused on the parameters and formulas used to calculate the power of the IOL to be implanted in eyes with keratoconus undergoing cataract surgery. There are few publications that show in detail how IOL power is calculated in these particular cases. If the keratometric value used was based on the standard refractive index (1.3375), it resulted in a postoperative refractive error with a tendency to hyperopia. The SRK/T formula yielded the best outcomes. The greater the severity of keratoconus the greater was the deviation of the postoperative refractive status from the target outcome.


Factors That Influence Breastfeeding Initiation Among African American Women.
To examine cultural and socioenvironmental factors that affect breastfeeding initiation among African American women. Qualitative descriptive design and conventional content analysis. A large, inner-city, primary care center affiliated with a 500-bed children's hospital within a large, Northeastern U.S. city. Participants were 34 U.S.-born African American mothers of healthy term infants 0 to 3 months of age. Six focus groups were conducted using a 16-question, scripted interview guide. A number of complex factors that influenced breastfeeding initiation included certain cultural beliefs about sexuality, the influence of family and peer networks, information sources, intentions, and a variety of other barriers and facilitators. Our findings suggest that the decision to initiate breastfeeding is not solely determined by the woman within the African American community. Because this decision is contingent on multiple factors external to the woman, it is important to recognize the role that partners, grandmothers, communities, information sources, and health care providers/organizations play in women's decisions. Implementation of multilevel strategies is critical to increase breastfeeding initiation among African American mothers.


Height and weight of early 20th century Filipino men.
Recent anthropometric studies of Filipinos have concentrated on women and children. While present-day studies of Filipino men are few, scattered sources of historical height and weight samples exist and can be studied to estimate a rough baseline for comparison, as well as to study trends in the past. This paper estimates heights and weights of men in the Philippines about a century ago. Height-by-age profiles and comparisons to contemporary populations in south-east Asia as well as present day Filipinos provide context. One sample consisted of 843 prisoners from throughout the islands, who were measured by an American anthropologist in Manila. A previously overlooked published source included measurements of 1016 seamen, police and prison guards, and civil servants in Manila. A contemporary source also measured 100 relatively remote Igorrote in Luzon. Average heights fell in a relatively narrow range of 1.60-1.62 m, except for police who were subject to a minimum height requirement. Body mass index (BMI) fell in a broader range of 18.24-21.26. Some regional variation was also evident in the prisoner sample. Height-by-age profiles suggested some improvement in net nutritional conditions over the century. Heights of turn of the century Filipino men were not very different from men elsewhere in south-east Asia, nor from present-day Filipino men. To understand trends in heights over the longer term more samples of men in the present-day Philippines would be desirable.


Sequencing of hippocampal and cerebellar transcriptomes provides new insights into the complexity of gene regulation in the human brain.
The hippocampus and cerebellum represent anatomically and functionally distinct parts of the human brain. The RNA-Seq technique makes it possible to investigate the human transcriptome with unprecedented resolution, allowing identification of differential mRNA splicing and promoter usage on a genome-wide scale. We undertook whole-mRNA sequencing of samples from the human hippocampus and cerebellum. A bioinformatic analysis revealed distinct expression patterns of genes related to the molecular physiology of neurons and glial cells. Upregulated genes in hippocampal tissue included serpin peptidase inhibitor, clade A (SERPINA3), lymphocyte antigen 6 complex, locus H (LY6H) and transthyretin (TTR). In cerebellum, the cerebellin 3 precursor (CLBN3) and Zic family member 4 (ZIC4) genes were significantly upregulated. These changes were validated in independent donor samples by qRT-PCR. The hippocampus and the cerebellum showed striking differences in splicing patterns and promoter usage. A notable example of this was the gene for NGFI-A binding protein 2 (NAB2), which displayed tissue-specific isoforms which may affect its function as a transcriptional repressor.


Combination of berberine and ciprofloxacin reduces multi-resistant Salmonella strain biofilm formation by depressing mRNA expressions of luxS, rpoE, and ompR.
Bacterial biofilms have been demonstrated to be closely related to clinical infections and contribute to drug resistance. Berberine, which is the main component of Coptis chinensis, has been reported to have efficient antibacterial activity. This study aimed to investigate the potential effect of a combination of berberine with ciprofloxacin (CIP) to inhibit Salmonella biofilm formation and its effect on expressions of related genes (rpoE, luxS, and ompR). The fractional inhibitory concentration (FIC) index of the combination of berberine with CIP is 0.75 showing a synergistic antibacterial effect. The biofilm's adhesion rate and growth curve showed that the multi-resistant Salmonella strain had the potential to form a biofilm relative to that of strain CVCC528, and the antibiofilm effects were in a dose-dependent manner. Biofilm microstructures were rarely observed at 1/2 × MIC/FIC concentrations (MIC, minimal inhibition concentration), and the combination had a stronger antibiofilm effect than each of the antimicrobial agents used alone at 1/4 × FIC concentration. LuxS, rpoE, and ompR mRNA expressions were significantly repressed (p < 0.01) at 1/2 × MIC/FIC concentrations, and the berberine and CIP combination repressed mRNA expressions more strongly at the 1/4 × FIC concentration. The results indicate that the combination of berberine and CIP has a synergistic effect and is effective in inhibiting Salmonella biofilm formation via repression of luxS, rpoE, and ompR mRNA expressions.


Barriers and Facilitators to Provision of Influenza and Pneumococcal Vaccines in Home Health Care Agencies.
The recommendations for influenza and pneumococcal vaccines are widely known yet the rates of both immunizations for home health care patients are 70 percent or less. The purpose of this study was to identify the facilitators and barriers to immunizations ultimately to improve vaccination rates among home health care patients. Using a multi-case study approach with five agencies and one group of administrators, facilitators included providing patients with a vaccine "card" and using the agency electronic medical record (EMR) for decision support/reminders. We determined that there were patient barriers (misperceptions about vaccines in general, difficulty in recalling vaccine status) and provider barriers (misperceptions about vaccines among health care workers, home health care agencies not receiving accurate information from other providers or difficulty in determining vaccine status).


Beneficial effects of myocardial postconditioning are associated with reduced oxidative stress in a senescent mouse model.
There is at present a tragic lack of organs available for transplantation. This has led to the harvesting of hearts from older donors. Unfortunately, hearts from such donors are much more sensitive to ischemic insult. Models such as "Senescence Accelerated Mouse" Prone 8 (SAM-P8) can help understand this sensitivity. New cardioprotective techniques such as postconditioning (PostC) could be of interest in this context. We studied (1) senescence in vessels and hearts and (2) the ability of the senescent heart to adapt to an ischemia-reperfusion (I/R) sequence in the context of PostC. Isolated working mouse hearts (8 months) were subjected to total ischemia, followed by 36 min of reperfusion; PostC was performed in the first minutes of reperfusion as three 10-sec sequences of I/R. Superoxide anion (O2.-) production was evaluated on heart and aorta cryosections with the dihydroethidium staining method. The collagen content in aortas was quantified. The aortas of SAM-P8 mice showed a higher production of O2.- and a higher collagen content than did those of SAM-R1 mice (P<0.05). During reperfusion, SAM-P8 hearts showed the worst recovery of cardiac output. PostC significantly reduced reperfusion dysfunction (P<0.05) and was associated with a reduction in heart O2.- staining. These results indicate that SAM-P8 presents a high degree of cardiovascular oxidative stress and a higher susceptibility to I/R injury, which confirms the senescence of the cardiovascular system in these animals. However, they remain sensitive to cardioprotection afforded by in vitro PostC.


Reference Values for Cranial Morphology Based on Three-dimensional Scan Analysis in 1-month-old Healthy Infants in Japan.
Currently, molded helmet therapy is used to treat infants with deformational plagiocephaly. However, the indices of normal cranial shape remain unclear, and thus, the prevalence of deformational plagiocephaly is unknown, particularly in Japan. We investigated the reference values for cranial morphological characteristics in 1-month-old Japanese infants using a three-dimensional scanner, to determine the prevalence of deformational plagiocephaly. One hundred fifty-three healthy infants who visited three hospitals (from April 2020 to March 2021) were enrolled. Cranial shape was measured using a three-dimensional scanner and was analyzed using image analysis software. Outcome measures were cranial volume, length, width, length-width ratio, circumference, asymmetry, and vault asymmetry index; cephalic index; and anterior, posterior, and overall symmetry ratios. The cranial vault asymmetry index >3.5% or ≥10% were diagnosed as deformational or severe deformational plagiocephaly, respectively. The mean age at measurement was 35.7 days. The mean cranial volume was 559 mL; cranial length, 129 mm; cranial width, 110 mm; length-width ratio, 118%; cephalic index, 85.2%; cranial circumference, 377 mm, cranial asymmetry, 6.4 mm; cranial vault asymmetry index, 5.0%; and anterior, posterior, and overall asymmetry ratios, 93.1%, 91.3%, and 96.4%, respectively. The prevalence of deformational and severe deformational plagiocephaly was 64.7% and 6.6%, respectively. Sex-based differences were observed for cranial volume and width. The results obtained in this study can be considered standard values that can facilitate the differentiation of abnormal infant cranial morphological characteristics for Japanese medical practitioners.


Comparison of three adhesive systems in class II composite restorations in endodontically treated teeth: Influence of Er:YAG laser conditioning and gingival margin levels on microleakage.
Dental surface conditioning by Er:YAG laser is currently being investigated, as not all of the mechanisms and effects of this technique have been clearly studied. Thus, the aim of the present study was to assess the cervical microleakage of Class II resin composite restorations in endodontically treated teeth following either the respective conventional conditioning or additional Er:YAG laser conditioning, in association with varied adhesives. Standardized mesial-occlusal-distal cavities (two gingival walls positioned in dentin and enamel, respectively) were created in 60 extracted human premolar teeth. Following the completion of the endodontic therapy, the teeth were grouped into six categories based on conditioning modality and adhesive strategy as follows: group 1-37% phosphoric acid/Adper Single Bond 2 (ASB2); group 2-Er:YAG laser/37% phosphoric acid/ASB2; group 3-Clearfil SE Bond (CSE); group 4-Er:YAG laser/CSE; group 5-Adper Easy One (AEO); and group 6-Er:YAG laser/AEO. Specimens were submitted to thermocycling and dye penetration, followed by longitudinal sectioning. The dye penetration was evaluated using a stereomicroscope. One specimen from each group was assessed under a scanning electron microscope for adhesive interface analysis. No significant differences were found between the conditioning modalities, nor between the adhesive systems at both margins. Groups 1 and 2 showed a lower degree of microleakage in the enamel vs. dentin (p = 0.002). Group 2 showed a significantly lower incidence of microleakage in enamel vs. dentin (p = 0.005). CSE and AEO were comparable with that of ASB2 regarding sealing ability. Additional Er:YAG laser conditioning may be beneficial before ASB2 application in enamel. Key words:Endodontically treated teeth, etch-and-rinse adhesive, Er:YAG laser, gingival level, sealing ability, self-etch adhesive.


Induction of multiple independent T-cell lymphomas in rats inoculated with MOloney murine leukemia virus.
Tumor cell DNA derived from different lymphoid organs of 30 rats serially inoculated at birth with Moloney murine leukemia virus (MoMuLV) was examined by Southern blot analysis and hybridization to the following DNA probes: MoMuLV long terminal repeat (LTR), Moloney leukemia virus integration regions 1, 2, 3, and 4 (Mlvi-1, Mlvi-2, Mlvi-3, and Mlvi-4), T-cell receptor beta locus, and immunoglobulin heavy chain locus. This analysis revealed that the tumors segregating in different lymphoid organs in 10% of the animals were clonally unrelated. These findings are consistent with the hypothesis that the MoMuLV-induced rat thymic lymphomas are polyclonal in origin. At least two factors may be responsible for this phenomenon: (i) increase in the number of the available target cells in virus-infected animals, and (ii) genetic instability associated with provirus integration in the developing premalignant clones.


Optimizing the northern blot procedure.
We describe methods for preparing formaldehyde-agarose gels for use in Northern blotting which yield consistent high quality results. Using these methods, we tested seven different commercially available membranes in Northern blots. Each membrane was handled as specified by the manufacturer in a course of hybridization, stripping and rehybridization. Filter background was low in all cases, but the intensity of the signal generated by specific hybridization varied markedly between filters after both the first and second hybridization.


Mechanism of calcitriol regulating parathyroid cells in secondary hyperparathyroidism.
A common consequence of chronic renal disease is secondary hyperparathyroidism (SHPT) and is closely related to the mortality and morbidity of uremia patients. Secondary hyperparathyroidism (SHPT) is caused by excessive PTH production and release, as well as parathyroid enlargement. At present, the mechanism of cell proliferation in secondary hyperparathyroidism (SHPT) is not completely clear. Decreased expression of the vitamin D receptor (VDR) and calcium-sensing receptor (CaSR), and 1,25(OH)2D3 insufficiency all lead to a decrease in cell proliferation suppression, and activation of multiple pathways is also involved in cell proliferation in renal hyperparathyroidism. The interaction between the parathormone (PTH) and parathyroid hyperplasia and 1,25(OH)2D3 has received considerable attention. 1,25(OH)2D3 is commonly applied in the therapy of renal hyperparathyroidism. It regulates the production of parathormone (PTH) and parathyroid cell proliferation through transcription and post-transcription mechanisms. This article reviews the role of 1,25(OH)2D3 in parathyroid cells in secondary hyperparathyroidism and its current understanding and potential molecular mechanism.


Laparoscopic approach in the treatment of large leiomyoma of the lower third of the esophagus.
Leiomyoma of the lower third of the esophagus is a relatively rare disorder but the most common benign tumor of the esophagus. We present a case of an involuted esophageal leiomyoma, 11 cm in size, treated by the laparoscopic approach. The preoperative computed tomogram visualized a mass 3 × 1.5 cm in diameter in the lower esophagus without an eccentric lumen or compression of nearby organs. Resection of the tumor was indicated according to the patient's symptoms and to exclude malignancy. Laparoscopic enucleation of esophageal leiomyoma was performed. The overall operative time was 205 min. The diagnosis of leiomyoma was established on histopathology and immunohistochemistry staining. The patient resumed the intake of a normal diet on the 5th postoperative day and was discharged from hospital 8 days after the surgery. We have found this minimally invasive operation to be an effective and well-tolerated treatment option, determined by the experience of the surgeon.


High-Precision Tomato Disease Detection Using NanoSegmenter Based on Transformer and Lightweighting.
With the rapid development of artificial intelligence and deep learning technologies, their applications in the field of agriculture, particularly in plant disease detection, have become increasingly extensive. This study focuses on the high-precision detection of tomato diseases, which is of paramount importance for agricultural economic benefits and food safety. To achieve this aim, a tomato disease image dataset was first constructed, and a NanoSegmenter model based on the Transformer structure was proposed. Additionally, lightweight technologies, such as the inverted bottleneck technique, quantization, and sparse attention mechanism, were introduced to optimize the model's performance and computational efficiency. The experimental results demonstrated excellent performance of the model in tomato disease detection tasks, achieving a precision of 0.98, a recall of 0.97, and an mIoU of 0.95, while the computational efficiency reached an inference speed of 37 FPS. In summary, this study provides an effective solution for high-precision detection of tomato diseases and offers insights and references for future research.


Long genuine coronary artery lesions treated with stiff tubular or flexible coiled stents. A randomized angiographic follow-up study.
To investigate effects of stent flexibility on 6 months' clinical and angiographic outcome in long stented lesions. A total of 44 genuine coronary artery lesions (lesion length >20 mm and < or =30 mm) were randomized to implantation with a 30 mm long flexible coiled stainless steel stent (Freedom Force, Global Therapeutics) (n = 23) or a 30 mm long stiff tubular stainless steel stent (Crown, Johnson & Johnson) (n = 21). Target vessel revascularization was performed in 10 patients (45%) in the Freedom Force stent group, and in 7 patients (33%) in the Crown stent group (ns). No significant differences concerning minimum lumen diameter (MLD), early gain, late loss or binary restenosis rate were seen. In the Freedom Force stent group all restenoses were located within the stent. In the Crown stent group three (27%) of the restenoses were located at the edge of the stent (ns). In a limited number of patients no significant differences could be detected in clinical or angiographic parameters between patients treated with long tubular or long coiled stents.


DNA Barcoding through Quaternary LDPC Codes.
For many parallel applications of Next-Generation Sequencing (NGS) technologies short barcodes able to accurately multiplex a large number of samples are demanded. To address these competitive requirements, the use of error-correcting codes is advised. Current barcoding systems are mostly built from short random error-correcting codes, a feature that strongly limits their multiplexing accuracy and experimental scalability. To overcome these problems on sequencing systems impaired by mismatch errors, the alternative use of binary BCH and pseudo-quaternary Hamming codes has been proposed. However, these codes either fail to provide a fine-scale with regard to size of barcodes (BCH) or have intrinsic poor error correcting abilities (Hamming). Here, the design of barcodes from shortened binary BCH codes and quaternary Low Density Parity Check (LDPC) codes is introduced. Simulation results show that although accurate barcoding systems of high multiplexing capacity can be obtained with any of these codes, using quaternary LDPC codes may be particularly advantageous due to the lower rates of read losses and undetected sample misidentification errors. Even at mismatch error rates of 10(-2) per base, 24-nt LDPC barcodes can be used to multiplex roughly 2000 samples with a sample misidentification error rate in the order of 10(-9) at the expense of a rate of read losses just in the order of 10(-6).


Platelet reactivity in thromboelastometry. Revision of the FIBTEM test: a basic study.
This study aimed to investigate modifications to the FIBTEM test to better assess fibrinogen levels and the quality of fibrin polymerization in citrated blood using Multiplate impedance aggregometry to verify platelet inhibition. Blood samples from 26 healthy volunteers were subjected to thromboelastometry studies (EXTEM/FIBTEM tests) in accordance with the standard study protocol (cytochalasin D) and according to a modified protocol (synthetic IIbIIIa receptor antagonist vs. acetylsalicylic acid [ASA] + synthetic IIbIIIa receptor antagonist instead of cytochalasin D). Independent of thromboelastometry, Multiplate impedance aggregometry was used to assess the degree of restriction by the platelet blocked with the following treatments: (1) cytochalasin D, (2) synthetic IIbIIIa antagonist or (3) ASA + synthetic IIbIIIa antagonist to assess the aggregation response to activation with an agonist (ADP, collagen, thrombin receptor activating peptide-6 [TRAP-6], and arachidonic acid). Via aggregometry, cytochalasin D more weakly inhibited platelet aggregation than simultaneous administration of the -IIbIIIa receptor antagonist with ASA. However, total platelet aggregation inhibition was observed after simultaneous administration of cytochalasin D combined with a synthetic IIbIIIa receptor antagonist. In the thromboelastometry, a significant decrease of the A10, A20 and MCF parameters were observed in the EXTEM/FIBTEM tests after they were modified by the addition of a synthetic IIbIIIa receptor antagonist alone or in combination with ASA. In conclusion, in this Multiplate- and ROTEM-based laboratory approach, a two-way blockade (IIbIIIa-antagonist + cytochalasine D) was sufficient to completely inhibit procoagulant platelet function as observed by aggregometry and thromboelastometry.


The earliest case of extracranial aneurysm of the vertebral artery.
A lesion is described on the body of C4 from the skeleton of an adult male recovered from a 15th century site in Gloucester. The most plausible explanation for the lesion is that it represents the negative image of an extracranial aneurysm of the vertebral artery and thus is the earliest case described.


Altering the threshold of an excitable signal transduction network changes cell migratory modes.
The diverse migratory modes displayed by different cell types are generally believed to be idiosyncratic. Here we show that the migratory behaviour of Dictyostelium was switched from amoeboid to keratocyte-like and oscillatory modes by synthetically decreasing phosphatidylinositol-4,5-bisphosphate levels or increasing Ras/Rap-related activities. The perturbations at these key nodes of an excitable signal transduction network initiated a causal chain of events: the threshold for network activation was lowered, the speed and range of propagating waves of signal transduction activity increased, actin-driven cellular protrusions expanded and, consequently, the cell migratory mode transitions ensued. Conversely, innately keratocyte-like and oscillatory cells were promptly converted to amoeboid by inhibition of Ras effectors with restoration of directed migration. We use computational analysis to explain how thresholds control cell migration and discuss the architecture of the signal transduction network that gives rise to excitability.


[Differences in the quality of human albumin solutions for clinical use].
The differences in quality of 18 commercially available human albumine solutions (5%, 20%) are described. 12 of 20% albumine solutions and 5 of 5% albumine of different manufactures were testet. Results for albumine (mg/dl) vary between 82-89% under the declared value of 95% of total protein contents as far as 20% solution are concerned. All solutions have the declared minimal content of potassium as sodium is concerned they distinguish each other as semi or fully elektrolyt solutions. Values for monomer albumine which are measured by Sephadex-Chromatography range between 80,2% to 92% in 20% solutions, as for the 5% albumine solutions the fraction of monomers lies between 80-91% of the declared value of total protein. The fraction of macroaggregates lies between 1-11,7% in the 20% solutions. In 25% albumine solutions the highest ratio of 22,2% of macroaggregates was found. The difference in quality of solutions even within the same manifacturer demonstrates that there will be even differences in human albumine solutions in the future. Interchange of commercially available albumine solution is not selfevident.


Organisational barriers to the facilitation of overseas volunteering and training placements in the NHS.
Undertaking a period of voluntary work or a professional placement overseas has long been a feature of medical training in the UK. There are now a number of high profile National Health Service (NHS) initiatives aimed at increasing access to such opportunities for staff at all levels. We present findings from a qualitative study involving a range of NHS staff and other stakeholders which explored barriers to participation in these activities. A grounded theory methodology was drawn upon to conduct thematic based analysis. Our data included in-depth, semi-structured interviews with a range of returned volunteers, non-volunteers and other stakeholders (n = 51) who were, or had been, employed by the NHS. There are significant barriers to placement and volunteering activity stemming from structural and organisational shortcomings within the NHS. Difficulties in filling clinical roles has a significant impact on the ability of staff to plan and undertake independent placements. There is currently no clearly defined pathway within the NHS by which the majority of grades can apply for, or organise, a period of overseas voluntary or professional placement activity. There were divergent views on the relevance and usefulness of overseas professional placements. We argue that in the context of current UK policy initiatives aimed at facilitating overseas volunteer and professional placement activity, urgent attention needs to be given to the structural and organisational framework within which such initiatives will be required to work.


Granulomatous lobular mastitis: report of a case with previously undescribed histopathological abnormalities.
A 41-yr-old multiparous woman presented with a discrete breast lump which proved histologically to be an example of granulomatous lobular mastitis. The clinical and histological features were similar to those noted in previous reports. Additional histological features in the present case were an intense mononuclear cell infiltration of lobular and ductal epithelium, associated with nuclear fragments morphologically suggestive of apoptosis. These appearances, which have not previously been described, are illustrated, together with the more classical features of the condition well demonstrated by the present case. The novel histological features noted here suggest that the development of granulomatous lobular mastitis may be at least in part immunologically mediated, and that the cellular infiltrates seen may be a manifestation of cell-mediated destruction of mammary epithelium.


Effects of propofol on intraocular pressure in premedicated and nonpremedicated dogs with and without glaucoma.
OBJECTIVE To establish a study cutoff for evidence of glaucoma on the basis of IOP measurements from a large population of healthy dogs and to assess the effects of IV propofol administration on IOPs in premedicated and nonpremedicated dogs with and without glaucoma defined by this method. DESIGN Prospective, descriptive study. ANIMALS 234 client-owned dogs. PROCEDURES IOPs measured in 113 healthy dogs (226 eyes) were used to calculate an IOP value indicative of glaucoma. The IOPs were measured in an additional 121 dogs (237 eyes) undergoing ophthalmic surgery. Midazolam-butorphanol was administered IV as preanesthetic medication to 15 and 87 dogs with and without glaucoma, respectively. A placebo (lactated Ringer solution) was administered IV to 8 and 11 dogs with and without glaucoma, respectively. Anesthesia of surgical patients was induced with propofol IV to effect. The IOPs and physiologic variables of interest were recorded before (baseline) and after preanesthetic medication or placebo administration and after propofol administration. RESULTS An IOP > 25 mm Hg was deemed indicative of glaucoma. Compared with baseline measurements, mean IOP was increased after propofol administration in nonpremedicated dogs without glaucoma and unchanged in nonpremedicated dogs with glaucoma. Propofol-associated increases in IOP were blunted in premedicated dogs without glaucoma; IOP in affected eyes of premedicated dogs with glaucoma was decreased after preanesthetic medication and after propofol administration. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that preexisting IOP influences the response to anesthetic drugs, and administration of preanesthetic medication with muscle-relaxing properties may blunt or reduce propofol-induced increases in IOP. Further research with a larger number of dogs is needed to confirm our results in dogs with glaucoma.


Real-world experiences with direct-acting antiviral agents for chronic hepatitis C treatment.
As direct-acting antiviral (DAA) agents become more readily available for the treatment of chronic hepatitis C, it is important to understand real-world treatment experiences. In order to assess the effectiveness of DAA regimens and factors that influence sustained virologic response (SVR) rates in the Veterans Affairs healthcare system, we retrospectively identified veterans with chronic hepatitis C who were treated with DAAs from January 2014 to June 2015. We determined SVR rates and collected data on demographics, genotype (GT), previous interferon-based treatment, antiviral regimens, and co-morbidities (HIV, prior solid organ transplant, haemodialysis) for analysis. Of 15 720 veterans, the majority were infected with genotype 1a (GT1a, 60.5%). Excluding the special populations, the overall cohort SVR rate was 92%. Compared to treatment-experienced patients, treatment-naïve patients had significantly higher SVR rates (90% vs 92%, P = .006). Subgroups associated with lower likelihood of achieving SVR-included African Americans (OR 0.79, 95% CI 0.69-0.91), GT3 (OR 0.65, CI 0.50-0.86), and cirrhosis (OR 0.91, CI 0.84-0.99) or decompensated cirrhosis (ascites: OR 0.78, CI 0.67-0.91, variceal bleed: OR 0.75, CI 0.57-0.99). The only treatment regimen independently associated with lower SVR rates was SOF+RBV+IFN (OR 0.65, CI 0.50-0.84). Special populations achieved high SVR rates: HIV 92%, haemodialysis 93%, liver transplant 96% and renal transplant 94%. In conclusion, overall SVR rates were comparable to those reported in clinical trials and carried over to historically more difficult-to-treat patients. Several patient- and treatment-related factors were identified as independent predictors of treatment failure and suggest subgroups to target for efforts to improve therapeutic strategies.


Acquired aplastic anaemia in seven children with severe hepatitis with or without liver failure.
Aplastic anaemia following hepatitis may develop in as many as 1 of 3 patients with non-A, non-B and non-C hepatitis. Several causative factors have been discussed, such as viral infections and autoimmunity. Here we describe the natural history of this condition in 7 children and investigate possible hepatitis-causing agents. We reviewed the medical records, bone marrow and liver biopsies of 7 children with severe hepatitis, with or without liver failure, who subsequently had developed aplastic anaemia. The median time from onset of hepatic symptoms until diagnosed onset of aplasia was 54 days. No associated viral infections could be identified. On liver biopsy, a majority had lobular inflammation but lacked signs of autoimmune hepatitis, findings compatible with a viral aetiology. Three of 6 children had low reticulocyte counts already at onset of hepatitis. All, but one patient is alive at median follow-up of 8 years. The unknown pathogenetic mechanism appears to target liver and bone marrow simultaneously, because half of the children concomitantly had low reticulocyte counts and severe liver failure.


Bending of pinned dust-ion acoustic solitary waves in presence of charged space debris.
We consider a low temperature plasma environment in the low Earth orbital region in the presence of charged space debris particles. The dynamics of (2+1)-dimensional nonlinear dust-ion acoustic waves with weak transverse perturbation, generated in the system, is found to be governed by a forced Kadomtsev-Petviashvili equation, where the forcing term depends on charged space debris function. The bending phenomena of some exact dust-ion acoustic solitary wave solutions in the x-t and x-y planes are shown; they result from the consideration of different types of possible localized debris functions. A family of exact pinned accelerated solitary wave solutions has been obtained where the velocity changes over time but the amplitude remains constant. The shape of the debris function also changes during its propagation. Also, a special exact solitary wave solution has been derived for the dust-ion acoustic wave that gets curved in spatial dimensions with the curvature depending upon the nature of the forcing debris function. Such intricate solitary wave solutions may be useful in modeling real experimental data.


Recent paramethoxyamphetamine deaths.
Paramethoxyamphetamine (PMA) is a methoxylated phenethylamine derivative that has been used illicitly in Australia since late 1994. It is purportedly sold under the guise of "ecstasy", which is the colloquial name for methylenedioxymethamphetamine (MDMA). Methods for extraction, identification, and quantitation are presented. Toxicology findings in six fatalities involving the drug are discussed. Femoral blood PMA levels ranged from 0.24 to 4.9 mg/L (mean, 2.3 mg/L). Liver PMA levels ranged from 1.4 to 21 mg/kg (mean, 8.9 mg/kg). Other amphetamines were found in five of the six cases. Blood PMA levels in three nonfatal cases are also presented. PMA appeared to be more toxic than MDMA, and blood levels greater than 0.5 mg/L seemed likely to be associated with toxic effects.


Determining the Association between Language and Cognitive Tests in Poststroke Aphasia.
Individuals with aphasia are often excluded from studies exploring poststroke cognition because so many of the standard cognitive assessments rely on language ability. Our primary objective was to examine the association between performance on cognitive tests and performance on comprehension and naming tests in poststroke aphasia. Second, we aimed to determine the association between language performance and a real-life measure of cognition (Kettle Test). Third, we explored the feasibility of administering cognitive tests in aphasia. Thirty-six participants with poststroke aphasia and 32 controls were assessed on a battery of pen-and-paper cognitive tests recommended in stroke. Auditory comprehension was measured using the Comprehensive Aphasia Test and naming was measured using the Boston Naming Test. Twenty-two community dwelling participants with aphasia and controls were also asked to complete the Kettle Test. Multiple linear regressions were used to explore the relationship between language performance and performance on the cognitive tests. Feasibility was determined by quantifying missing data. The cognitive tests with the highest variance accounted for by auditory comprehension and naming were animal fluency (R2 = 0.67, R2 = 0.78) and the Hopkins Verbal Learning Test (recognition discrimination index) (R2 = 0.65, R2 = 0.78). All cognitive tests were significantly associated with auditory comprehension and naming, except for the Star Cancellation Test and the Kettle Test. Thirty-three percent of participants with aphasia were unable to complete all the cognitive tests. Language and non-linguistic cognitive processes are often interrelated. Most pen-and-paper cognitive tests were significantly associated with both auditory comprehension and naming, even in tests that do not require a verbal response. Language performance was not significantly associated with a real-life cognitive performance measure. Task instructions, stimuli, and responses for completion need to be tailored for individuals with aphasia to minimize the influence of language deficits when testing non-linguistic cognitive performance.


Indentation versus Rolling: Dependence of Adhesion on Contact Geometry for Biomimetic Structures.
Numerous biomimetic structures made from elastomeric materials have been developed to produce enhancement in properties such as adhesion, static friction, and sliding friction. As a property, one expects adhesion to be represented by an energy per unit area that is usually sensitive to the combination of shear and normal stresses at the crack front but is otherwise dependent only on the two elastic materials that meet at the interface. More specifically, one would expect that adhesion measured by indentation (a popular and convenient technique) could be used to predict adhesion hysteresis in the more practically important rolling geometry. Previously, a structure with a film-terminated fibrillar geometry exhibited dramatic enhancement of adhesion by a crack-trapping mechanism during indentation with a rigid sphere. Roughly isotropic structures such as the fibrillar geometry show a strong correlation between adhesion enhancement in indentation versus adhesion hysteresis in rolling. However, anisotropic structures, such as a film-terminated ridge-channel geometry, surprisingly show a dramatic divergence between adhesion measured by indentation versus rolling. We study this experimentally and theoretically, first comparing the adhesion of the anisotropic ridge-channel structure to the roughly isotropic fibrillar structure during indentation with a rigid sphere, where only the isotropic structure shows adhesion enhancement. Second, we examine in more detail the anomalous anisotropic film-terminated ridge-channel structure during indentation with a rigid sphere versus rolling to show why these structures show a dramatic adhesion enhancement for the rolling case and no adhesion enhancement for indentation.


Monte Carlo modelling of photodynamic therapy treatments comparing clustered three dimensional tumour structures with homogeneous tissue structures.
We explore the effects of three dimensional (3D) tumour structures on depth dependent fluence rates, photodynamic doses (PDD) and fluorescence images through Monte Carlo radiation transfer modelling of photodynamic therapy. The aim with this work was to compare the commonly used uniform tumour densities with non-uniform densities to determine the importance of including 3D models in theoretical investigations. It was found that fractal 3D models resulted in deeper penetration on average of therapeutic radiation and higher PDD. An increase in effective treatment depth of 1 mm was observed for one of the investigated fractal structures, when comparing to the equivalent smooth model. Wide field fluorescence images were simulated, revealing information about the relationship between tumour structure and the appearance of the fluorescence intensity. Our models indicate that the 3D tumour structure strongly affects the spatial distribution of therapeutic light, the PDD and the wide field appearance of surface fluorescence images.


Quantitative photoacoustic imaging for early detection of muscle ischemia injury.
Acute lower extremity ischemia is a limb-and life-threatening problem. The timing of clinical intervention is critical to achieving optimal outcomes. However, there has been a lack of effective techniques capable of evaluating muscle and limb damage. Microcirculatory injury is the initial pathological change during ischemic muscle injury. Here, we performed photoacoustic imaging (PAI) in real time to quantitatively detect the degree of microcirculatory injury of ischemic muscles in a rat model in which Evans blue (EB), which strongly binds to albumin in blood, was used as a nontoxic molecular PA probe. The right lower hind limbs of Sprague-Dawley (SD) rats were subjected to 2 or 3 hours of tourniquet-induced ischemia. Then, PA imaging of the tibialis anterior (TA) muscles in the anterior compartment was performed for 0-24 h after the release of compression. Twenty-four hours after reperfusion, rats were euthanized and examined for pathology, edema and muscle viability. Imaging at 680 nm on rats revealed that there was significant signal enhancement in the TA muscles of the two injury groups compared to the control group, and the 3-h injury group had significantly higher PA signal intensity than the 2-h injury group at each time point. Histopathology results obtained from both the normal and the damaged muscles correlated well with the PAI findings. In conclusion, PA imaging is a promising modality for quantitatively detecting limb and muscle ischemic injury and may pave the road for further clinical application.


The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression.
The kynurenine pathway metabolite kynurenic acid (KYNA), modulating glutamatergic and cholinergic neurotransmission, is increased in cerebrospinal fluid (CSF) of patients with schizophrenia or bipolar disorder type 1 with psychotic features. KYNA production is critically dependent on kynurenine 3-monooxygenase (KMO). KMO mRNA levels and activity in prefrontal cortex (PFC) are reduced in schizophrenia. We hypothesized that KMO expression in PFC would be reduced in bipolar disorder with psychotic features and that a functional genetic variant of KMO would associate with this disease, CSF KYNA level and KMO expression. KMO mRNA levels were reduced in PFC of bipolar disorder patients with lifetime psychotic features (P=0.005, n=19) or schizophrenia (P=0.02, n=36) compared with nonpsychotic patients and controls. KMO genetic association to psychotic features in bipolar disorder type 1 was studied in 493 patients and 1044 controls from Sweden. The KMO Arg(452) allele was associated with psychotic features during manic episodes (P=0.003). KMO Arg(452) was studied for association to CSF KYNA levels in an independent sample of 55 Swedish patients, and to KMO expression in 717 lymphoblastoid cell lines and 138 hippocampal biopsies. KMO Arg(452) associated with increased levels of CSF KYNA (P=0.03) and reduced lymphoblastoid and hippocampal KMO expression (P≤0.05). Thus, findings from five independent cohorts suggest that genetic variation in KMO influences the risk for psychotic features in mania of bipolar disorder patients. This provides a possible mechanism for the previous findings of elevated CSF KYNA levels in those bipolar patients with lifetime psychotic features and positive association between KYNA levels and number of manic episodes.


No need for nanny.
The term "nanny state" is regularly used to attack health groups or governments, especially by interest groups bereft of arguments and journalists in search of a cliché. It has become a special favourite of tobacco companies and their supporters. In the present work we argue that the term should be retired in favour of genuine debate on substantive issues.


Characterizing steady-state and transient properties of reaction-diffusion systems.
In the past, the study of reaction-diffusion systems has greatly contributed to our understanding of the behavior of many-body systems far from equilibrium. In this paper, we aim at characterizing the properties of diffusion-limited reactions both in their steady states and out of stationarity. Many reaction-diffusion systems have the peculiarity that microscopic reversibility is broken such that their transient behavior cannot be investigated through the study of most of the observables discussed in the literature. For this reason, we analyze the transient properties of reaction-diffusion systems through a specific work observable that remains well defined even in the absence of microscopic reversibility and that obeys an exact detailed fluctuation relation in cases where detailed balance is fulfilled. We thereby drive the systems out of their nonequilibrium steady states through time-dependent reaction rates. Using a numerical exact method and computer simulations, we analyze fluctuation ratios of the probability distributions obtained during the forward and reversed processes. We show that the underlying microscopic dynamics gives rise to peculiarities in the configuration-space trajectories, thereby, yielding prominent features in the fluctuation ratios.


[Phosphorus removal of agriculture wastewater through subsurface constructed wetland].
Phosphorus removal in subsurface constructed wetland treating agriculture non-pointed wastewater was studied in pilot-scale. The experimental results showed that the removal rates of TP increased with HRT increasing when the nominal hydraulic retention time was less than 5 days. The pH decreased distinctly when the retention time was too longer in the batch and sequence style, it may bring on a lower removel rate of TP. The amount of TP that can be removed by harvesting were about 15.8% and 9.5% compared to the total quantity of removing in Phragmitas communis and zizania caduciflora constructed system respectively. Temperature impacted on the removel of TP, the removel rate of TP decreased 30% in the winter compared to summuer.


Pulmonary function electronic monitoring devices: a randomized agreement study.
To compare in a clinical setting the within-session reproducibility of two pulmonary function electronic monitoring devices (PiKo-1; Ferraris Respiratory Europe; Hereford, UK; and Spirotel; MIR; Rome, Italy) with one mechanical device (Mini-Wright Peak-Flow Meter; Clement-Clarke International; Harlow, Essex, UK), and to evaluate the accuracy of these devices using as reference an office pneumotachograph. After detailed instructions, adults without airways diseases and patients with stable asthma attending an outpatient clinic performed four sets of expiratory maneuvers, one set for each device, in a strictly random order. Each set comprised three maneuvers with 2 to 3 min of rest between them. Reproducibility of FEV1 and peak expiratory flow (PEF) was assessed by a coefficient of variation (CV) and intraclass correlation coefficient (ICC), and accuracy was assessed by ICC and limits of agreement. Of the 38 participants evaluated, 71% were women and 61% had asthma. Ages ranged from 18 to 58 years, and FEV1 ranged from 1.2 to 4.8 L. In all monitoring devices, CV was < 6% and ICC was > 0.94 for the reproducibility of both FEV1 and PEF measurements. The accuracy of the PiKo-1 device was better for FEV1 (ICC = 0.98) than for PEF (ICC = 0.90). The Spirotel device had similar results for FEV1 and PEF (ICC = 0.95). The Mini-Wright device had the lowest accuracy (ICC = 0.87), particularly for PEF values < 500 L/min. These low-cost and easy-to-use electronic monitoring devices showed a very good reproducibility and were in agreement with the pneumotachograph. Therefore, the PiKo-1 and Spirotel devices seem adequate for both screening and monitoring. However, prospective studies are still needed to assess their long-term reproducibility and usability and, particularly, the effects on the improvement of respiratory care.


Learned Helplessness and Sexual Risk Taking in Adolescent and Young Adult African American Females.
Research involving adolescent and young African American (AA) females has demonstrated that they face uncontrollable obstacles which can interfere with the negotiation of safer sexual behaviors. If these obstacles are perceived as uncontrollable, then these females may be at risk for the development of Learned Helplessness (LH). As the LH model predicts, if these obstacles are believed not to be in their control, it may lead to deficits in motivational or cognitive decision-making, deficits that could certainly influence their sexual risk taking behaviors. Therefore, the primary objective for this pilot study was to trial the Learned Helplessness Scale (LHS) to examine the perceptions of LH in this population. A convenience sample of 50 adolescent and young AA females between the ages of 16 and 21 were recruited from two clinics in Southeast Michigan. Scores on the LHS ranged from 20 to 57, with a mean score of 39.1 (standard deviation = 10.49). The higher range of scores in the sample demonstrates a continuum of LH among the participants in the study.


Risk factors for psychiatric disturbance in children with intellectual disability.
Children with intellectual disability (ID) have a higher risk for psychiatric disturbance than their peers with normal intelligence, but research data on risk factors are insufficient and partially conflicting. The subjects comprised 75 children with ID aged 6-13 years. Data were obtained from case files and the following four questionnaires completed by their parents or other carers: Developmental Behaviour Checklist, American Association of Mental Deficiency (AAMD) Adaptive Behavior Scale, a questionnaire on additional disabilities, and a questionnaire on family characteristics and child development. The risk of psychopathology was most significantly increased by moderate ID, limitations in adaptive behaviour, impaired language development, poor socialization, living with one biological parent, and low socio-economic status of the family. The risk of psychopathology in children with ID is increased by factors related to family characteristics and child development. Identifying these factors will help diagnose and possibly prevent psychiatric disorders in these children.


Examining Healthcare Segregation Among Racial and Ethnic Minorities Receiving Spine Surgical Procedures in the State of Florida.
This was a retrospective review of the Florida Inpatient Dataset (2011-2014). To examine healthcare segregation among African American and Hispanic patients treated with one of four common spine surgical procedures. Racial and ethnic minorities are known to be at increased risk of adverse events after spine surgery. Healthcare segregation has been proposed as a source for these disparities, but has not been systematically examined for patients undergoing spine surgery. African American, Hispanic, and White patients who underwent one of the four lumbar spine surgical procedures under study were included. Volume cut-offs were previously established for surgical providers and hospitals. Surgeons and hospitals were dichotomized based on these metrics as low- or high-volume providers. Multivariable logistic regression analysis was used to determine the likelihood of patients receiving surgery from a low volume provider, adjusting for sociodemographic and clinical characteristics. African Americans were found to be at significantly increased odds of receiving surgery from a low-volume surgeon (P < 0.001) and were significantly more likely to receive surgery at a low-volume hospital (P < 0.007) for all procedures except decompression (P = 0.56). Like findings were encountered for Hispanic patients. Hispanic patients were 55% to three-times more likely to receive surgery from a low-volume surgeon depending on the procedure and 28% to 56% more likely to be treated at a low-volume hospital. African Americans were 34% to 82% more likely to receive surgery from a low-volume surgeon depending on the procedure and 10% to 17% more likely to be treated at a low-volume hospital. The results of this work identify the phenomenon of racial and ethnic healthcare segregation among low-volume providers for lumbar spine procedures in the State of Florida. This may be a contributing factor to the increased risk of adverse events after spine surgery known to exist among minorities. 3.


[Effects on the antibacterial activity of TiO(2) nanotubes with different diameters from ultraviolet ray-irradiation].
To study the effects of ultraviolet ray (UV)-irradiation on the surface characteristic and antibacterial activity of TiO(2) nanotubes with different diameters. TiO(2) nanotubes with different diameters were fabricated on polished pure titanium (PT) samples by anodization at 5, 10 and 20 V with PT as control. The samples were exposed to UV-irradiation for 24 h, then the characteristic and antibacterial activity were analyzed and evaluated. The surface topograph was observed by field emission scanning electron microscope (FE-SEM). Contract angle measurements were carried out with three liquids. Staphylococcus aureus (Sa) were used to evaluate the antibacterial activity of samples with the film contact method. The bacterial morphology was observed by FE-SEM. The bacterial adhesion and cell membrane injury were evaluated by fluorescent staining analysis under laser scanning confocal microscope (LSCM). After the TiO(2) nanotubes with different diameters were exposed to UV-irradiation, no change was observed in its surface topograph. With the increase of the diameters of nanotubes, each contract angle of nanotubes decreased, and bacterial FIt and dead/live ratio were also increased. We found 20 V FIt was the biggest (26.550 ± 2.940) and ranks the highest ratio of death/live (0.728 ± 0.091) among the others (P < 0.05). The UV-irradiation can decrease the contract angle of TiO(2) nanotubes and promote the Sa adhesion on nanotubes. Meanwhile, the antibacterial activity of TiO(2) nanotubes with different diameters was remarkably enhanced by UV-irradiation. Nanotubes anodized at 20 V showed the best antibacterial activity.


Overexpressed cell surface interleukin-4 receptor molecules can be successfully targeted for antitumor cytotoxin therapy.
A variety of human solid cancer cell lines and primary cell cultures has been reported to overexpress high-affinity receptors (R) for interleukin-4 (IL-4), a pleiotropic immunoregulatory cytokine. The significance of IL-4R expression is not known; however, IL-4 is able to upregulate adhesion molecules, inhibit cell proliferation, and mediate signal transduction in tumor cell lines. To target IL-4R, we produced a chimeric protein composed of a circular permuted IL-4 and a mutated form of Pseudomonas exotoxin [termed IL4(38-37)-PE38KDEL or cpIL4-PE]. The recombinant cpIL4-PE was highly cytotoxic to cancer cells, but not toxic to normal B cells, T cells, monocytes, and CD34+, even though these cells express detectable numbers of IL-4R. The cytotoxicity was specific because excess of recombinant IL-4 neutralized the cpIL4-PE effect. To further develop this molecule, in vivo antitumor activity was tested in animal models of human cancer. This agent showed remarkable antitumor activity in AIDS-Kaposi's sarcoma, glioblastoma multiforme, and breast cancer models in immunodeficient animals. cpIL4-PE caused partial or complete regression of established human tumors. Preclinical efficacy and toxicity studies provided a therapeutic window in which this cancer-targeted agent could be used. On the basis of these studies, we initiated a Phase I clinical trial for the treatment of recurrent glioblastoma multiforme. Our preliminary clinical results suggest that cpIL4-PE has antitumor activity against the deadliest form of brain tumors, without detectable toxicity to normal brain tissues. Thus, IL-4 receptors represent novel targets for cancer cytotoxin therapy.


Cross-species studies for target validation.
The completion of the genome sequences of several model organisms and the recent development of high throughput procedures to map genes, expression patterns and interactions is providing a steadily increasing number of candidate target genes. The function of most of these genes still remains unknown. Therefore, there is a growing demand in genetically tractable animal models in which the function of individual factors can be studied in large scale, particularly of those that are thought to segregate with human disorders. In this paper, current methods to validate target gene function and the advantages of different model organisms are compared.


Efficient single-cell oxygen consumption rate characterization based on frequency domain fluorescence lifetime imaging microscopy measurement and microfluidic platform.
Cell metabolism is critical in regulating normal cell functions to maintain energy homeostasis. In order to monitor cell metabolism, the oxygen consumption rate (OCR) of cells has been characterized as an important factor. In conventional cell analysis, the cells are characterized in bulk due to technical limitations. However, the heterogeneity between the cells cannot be identified. Therefore, single-cell analysis has been proposed to reveal cellular functions and their heterogeneity. In this research, an approach integrating a microfluidic device and widefield frequency domain fluorescence imaging lifetime microscopy (FD-FLIM) for single-cell OCR characterization in an efficient manner is developed. The microfluidic device provides an efficient platform to trap and isolate single cells in microwells with the buffer saline containing an oxygen-sensitive phosphorescent dye. The oxygen tension variation within the microwells can be efficiently estimated by measuring the fluorescence lifetime change using the FD-FLIM, and the OCR values of the single cells can then be calculated. In the experiments, breast cancer (MCF-7) cells are exploited for the OCR measurement. The results demonstrate the functionality of the developed approach and show the heterogeneity among the cells. The developed approach possesses great potential to advance cellular metabolism studies with single-cell resolution.


Aquaporin 4 is differentially increased and dislocated in association with tau and amyloid-beta.
Neurovascular-glymphatic dysfunction plays an important role in Alzheimer's disease and has been analysed mainly in relation to amyloid-beta (Aβ) pathology. Here, we aim to investigate the neurovascular alterations and mapping of aquaporin 4 (AQP4) distribution and dislocation associated with tau and Aβ. Perfusion, susceptibility weighted imaging and structural magnetic resonance imaging (MRI) were performed in the pR5 mouse model of 4-repeat tau and the arcAβ mouse model of amyloidosis. Immunofluorescence staining was performed using antibodies against AQP4, vessel, astroglia, microglia, phospho-tau and Aβ in brain tissue slices from pR5, arcAβ and non-transgenic mice. pR5 mice showed regional atrophy, preserved cerebral blood flow, and reduced cerebral vessel density compared to non-transgenic mice, while arcAβ mice showed cerebral microbleeds and reduced cerebral vessel density. AQP4 dislocation and peri-tau enrichment in the hippocampus and increased AQP4 levels in the cortex and hippocampus were detected in pR5 mice compared to non-transgenic mice. In comparison, cortical AQP4 dislocation and cortical/hippocampal peri-plaque increases were observed in arcAβ mice. Increased expression of reactive astrocytes were detected around the tau inclusions in pR5 mice and Aβ plaques in arcAβ mice. We demonstrated the neurovascular alterations, microgliosis, astrogliosis and increased AQP4 regional expression in pR5 tau and arcAβ mice. We observed a divergent region-specific AQP4 dislocation and association with phospho-tau and Aβ pathologies.


Pharmacogenomics and treatment for dementia induced by Alzheimer's disease.
Pharmacogenomics is the study of interindividual genetic variability, which plays a significant role in defining drug response and toxicity. As research has graduated from studying single candidate genes to whole-genome scans, pharmacogenomics is beginning to make its impact on the therapeutics of complex CNS disorders, such as schizophrenia, Parkinson's disease and Alzheimer's disease. Alzheimer's disease is a progressive complex disorder, where genetic predisposition interacts with environmental factors. With conventional therapeutics only providing symptomatic treatment, the current focus of the pharmaceutical industry is on novel strategies with an etiopathogenic orientation. In this review, we have summarized the current knowledge of pathogenetic mechanisms of Alzheimer's disease, with a focus on the known relevant molecules and the potential of pharmacogenomics in translating this knowledge of human genome variability into efficacious and safer therapeutics.


Teamwork in the operating department.
The Gynaecology theatre team of the Leicester Royal Infirmary NHS Trust were runners-up in the 1997 3M/NATN joint award. This article is a report of their work on the concept of teamwork and its benefits to the organisation and delivery of patient care in the operating department.


Estimating extracellular spike waveforms from CA1 pyramidal cells with multichannel electrodes.
Extracellular (EC) recordings of action potentials from the intact brain are embedded in background voltage fluctuations known as the "local field potential" (LFP). In order to use EC spike recordings for studying biophysical properties of neurons, the spike waveforms must be separated from the LFP. Linear low-pass and high-pass filters are usually insufficient to separate spike waveforms from LFP, because they have overlapping frequency bands. Broad-band recordings of LFP and spikes were obtained with a 16-channel laminar electrode array (silicone probe). We developed an algorithm whereby local LFP signals from spike-containing channel were modeled using locally weighted polynomial regression analysis of adjoining channels without spikes. The modeled LFP signal was subtracted from the recording to estimate the embedded spike waveforms. We tested the method both on defined spike waveforms added to LFP recordings, and on in vivo-recorded extracellular spikes from hippocampal CA1 pyramidal cells in anaesthetized mice. We show that the algorithm can correctly extract the spike waveforms embedded in the LFP. In contrast, traditional high-pass filters failed to recover correct spike shapes, albeit produceing smaller standard errors. We found that high-pass RC or 2-pole Butterworth filters with cut-off frequencies below 12.5 Hz, are required to retrieve waveforms comparable to our method. The method was also compared to spike-triggered averages of the broad-band signal, and yielded waveforms with smaller standard errors and less distortion before and after the spike.


Regression of atherosclerosis.
The reverse of progression of atherosclerotic disease is regression of atherosclerosis: established lesions get smaller. Animal experiments and post mortem findings have provided investigators with considerable evidence of the reversibility of atherosclerosis. It was, however, with arteriography in living man, as used in prospective intervention trials, that proof was given that atherosclerosis can be made to regress. The Leiden Intervention Trial and the Cholesterol Lowering Atherosclerosis Study (CLAS) both have shown that with aggressive lowering of serum cholesterol, be it with diet alone or with diet and cholesterol-lowering drugs, atherosclerosis growth can be retarded and reversed. The Leiden Intervention Trial and the CLAS study stress that cholesterol levels should be lowered in angina pectoris patients and in bypassed patients, whether their cholesterol levels are high or just slightly elevated.


[TREATMENT OF SCARS IN THE 21ST CENTURY].
Abnormal scars are a common complication of the wound healing process, associated with aesthetic, functional and psychological morbidities. The constant development of our understanding of the pathophysiology of scars has led to the development of different treatment modalities and protocols. Treatment during the early stages of wound healing is considered scar prevention and is associated with better cosmetic results than older mature scars. Several studies have demonstrated optimal results with therapeutic protocols combining different treatment modalities, the most important of them being laser technology. Every scar is unique and requires a customized approach and a combination of modalities to achieve the most aesthetic outcome.


Neuroanatomic Variations in Graves' Dysthyroid Ophthalmopathy as Studied With MRI.
To evaluate whether patients with Graves' dysthyroid ophthalmopathy (GDO) have changes in brain anatomy that can be assessed by neuroimaging as compared to age-matched controls. We examined 10 female, euthyroid patients with GDO and 14 age and gender matched controls using high-resolution structural MRI scanning. An automatic cortical segmentation algorithm was used to estimate the thickness of each subject's gray matter across the brain. The resulting cortical thickness measurements were transferred to a standard reference space via a template-based warping procedure. A statistical analysis of between-group cortical thickness differences using a general linear model with a combination of cluster-based and bootstrapped corrections for multiple comparisons was performed. Patients with GDO have statistically significant thinning of the gray matter sheet in a minimum of eight locations: six in the right hemisphere (insula, paracentral, precuneus, superior frontal cingulate, superioparietal and postcentral) and two in the left hemisphere (lateral occipital sulcus, fusiform gyrus). Left hemisphere thinning occurred in portions of the occipital lobe while right hemisphere thinning occurred in a set of frontal and parietal areas known to be involved in self-evaluation and emotional and cognitive regulation. Patients with GDO exhibit localized changes in gray matter thickness. These changes may be associated with cognitive changes reported by GDO patients. Further research before and after treatment with larger patient cohorts and experimental protocols including psychiatric evaluation and functional MRI are recommended.


DRB genotyping supports recessive inheritance of DR3-associated susceptibility to insulin-dependent diabetes mellitus.
The mode of inheritance of HLA-associated susceptibility to insulin-dependent diabetes mellitus was investigated by the antigen genotype frequency among patients method in a white Caucasian population and a North Indian Asian population. DR genotypes were determined by DRB/DQB RFLP analysis. In white Caucasians, simple recessive and simple additive inheritance of a single HLA-associated disease susceptibility allele were rejected (P less than .025 and P less than 10(-6), respectively). The data were compatible with a three-allele model of disease susceptibility. In North Indian Asians, simple additive inheritance was rejected (P less than 10(-6)). The observed genotype frequencies were compatible with a single DR3-associated disease susceptibility allele which is inherited recessively. These data show that study of DR genotypes in populations of different ethnic origins may further the understanding of inherited susceptibility to insulin-dependent diabetes mellitus.


Clinical evidence for a role of E2F1-induced replication stress in modulating tumor mutational burden and immune microenvironment.
DNA replication stress (RS) is frequently induced by oncogene activation and is believed to promote tumorigenesis. However, clinical evidence for the role of oncogene-induced RS in tumorigenesis remains scarce, and the mechanisms by which RS promotes cancer development remain incompletely understood. By performing a series of bioinformatic analyses on the oncogene E2F1, other RS-inducing factors, and replication fork processing factors in TCGA cancer database using previously established tools, we show that hyperactivity of E2F1 likely promotes the expression of several of these factors in virtually all types of cancer to induce RS and cytosolic self-DNA production. In addition, the expression of these factors positively correlates with that of ATR and Chk1 that govern the cellular response to RS, the tumor mutational load, and tumor infiltration of immune-suppressive CD4+Th2 cells and myeloid-derived suppressor cells (MDSCs). Consistently, high expression of these factors is associated with poor patient survival. Our study provides new insights into the role of E2F1-induced RS in tumorigenesis and suggests therapeutic approaches for E2F1-overexpressing cancers by targeting genomic instability, cytosolic self-DNA and the tumor immune microenvironment.


Enhanced hydrogel adhesion by polymer interdiffusion: use of linear poly(ethylene glycol) as an adhesion promoter.
The fracture energy required to separate layers of hydrogel films was investigated to evaluate the impact of bulk polymer diffusion on hydrogel/hydrogel adhesion and to obtain molecular information on the fracture energy in polymer mucoadhesion. Poly(ethylene glycol) (PEG) was incorporated in a hydrogel and was used as an adhesion promoter. The influence of PEG molecular weight and contact time on PEG diffusion across the hydrogel/hydrogel interface was investigated by using tensiometric studies and near-field FTIR microscopy. These experiments indicated that linear PEG diffusion enhanced the adhesion between the two hydrogel layers. The enhanced adhesion could not be explained by surface wetting phenomena alone. These results indicated that bulk diffusion of linear polymers such as PEG (adhesion promoter) incorporated into polymer networks (hydrogels) was an effective technique for enhancing gel/gel adhesion in various applications including polymer/mucus interactions in mucoadhesion and development of mucoadhesive controlled drug delivery systems.


Study of substrate inhibition by electrophoretically mediated microanalysis in partially filled capillary.
Substrate inhibition is a common phenomenon in enzyme kinetics. We report here for the first time its study by a combination of the electrophoretically mediated microanalysis (EMMA) methodology with a partial filling technique. In this setup, the part of capillary is filled with the buffer best for the enzymatic reaction whereas, the rest of the capillary is filled with the background electrolyte optimal for separation of substrates and products. In the case of haloalkane dehalogenase, a model enzyme selected for this study, the enzymatic reaction was performed in 20 mM glycine buffer (pH 8.6) whereas 20 mM beta-alanine-hydrochloric acid buffer (pH 3.5) was used as a background electrolyte in combination with direct detection at 200 nm. The whole study was performed on poorly soluble brominated substrate--1,2-dibromoethane. As a result it was first necessary to find the compromise between the concentrations of the enzyme and the substrate preserving both the adequate sensitivity of the assay and at the same time the attainable substrate solubility. By means of the developed EMMA methodology we were able to determine the Michaelis constant (K(M)) as well as the substrate inhibition constant (K(SI)). The value of K(M) and K(SI) obtained were 7.7+/-2.5 mM and 1.1+/-0.4 mM, respectively. Observation of the substrate inhibition of haloalkane dehalogenase by 1,2-dibromoethane is in accordance with previous literature data.


Apelin: A potential novel serum biomarker for early detection of diabetic nephropathy in patients with type 2 diabetes.
Diabetic nephropathy (DN) is the major cause of chronic renal failure, and proteinuria is an independent risk factor for the end stage renal disease. The random urine protein: creatinine ratio (P:C ratio) can accurately predict the amount of 24-hour urinary protein excretion. Apelin is thought to be associated with endothelial dysfunction, angiogenesis, and inflammation. This study investigated the apelin concentration and its association with the urine P:C ratio, and metabolic parameters in subjects with and without type 2 diabetes mellitus (T2D). This study involved 86 subjects: 56 with newly diagnosed and untreated T2D and 30 non-diabetic controls. All subjects underwent a complete clinical examination that included anthropometric and laboratory measurements. Twenty-four males and sixty-two females participated in this study, and their mean age was 52.27±11.34 years. There were no differences in age, thyrotropin-stimulating hormone (TSH), creatinine clearance, and apelin levels between groups. As expected, fasting plasma glucose, weight, body mass index, and HbA1C were higher in T2D subjects (p=0.001, p=0.02, p=0.03, and p=0.001, respectively). Although apelin levels were higher in the control group, the differences were not statistically significant (p=0.93). The P:C ratio levels were lower in the control group, and the differences were statistically significant (p=0.006). A Spearman correlation analysis revealed that serum apelin levels were not correlated with the urine P:C ratio. Our study demonstrates that T2D is associated with decreased serum apelin levels and increased urine P:C ratios compared to those in non-diabetic subjects. This association may depend on impaired glucose homeostasis. Our results show that the serum apelin levels were not correlated with the urine protein: creatinine ratio and provide further evidence regarding the relationship between apelin and DN.


Treadmill exercise prevents diabetes-induced increases in lipid peroxidation and decreases in Cu,Zn-superoxide dismutase levels in the hippocampus of Zucker diabetic fatty rats.
In the present study, we investigated the effects of treadmill exercise on lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) levels in the hippocampus of Zucker diabetic fatty (ZDF) rats and lean control rats (ZLC) during the onset of diabetes. At 7 weeks of age, ZLC and ZDF rats were either placed on a stationary treadmill or made to run for 1 h/day for 5 consecutive days at 16~22 m/min for 5 weeks. At 12 weeks of age, the ZDF rats had significantly higher blood glucose levels and body weight than the ZLC rats. In addition, malondialdehyde (MDA) levels in the hippocampus of the ZDF rats were significantly higher than those of the ZLC rats whereas SOD1 levels in the hippocampus of the ZDF rats were moderately decreased. Notably, treadmill exercise prevented the increase of blood glucose levels in ZDF rats. In addition, treadmill exercise significantly ameliorated changes in MDA and SOD1 levels in the hippocampus although SOD activity was not altered. These findings suggest that diabetes increases lipid peroxidation and decreases SOD1 levels, and treadmill exercise can mitigate diabetes-induced oxidative damage in the hippocampus.


Effects of Laughter Therapy on Immune Responses in Postpartum Women.
To examine the effects of laughter therapy on secretory IgA (sIgA) in postpartum women. The study used a nonequivalent control group with nonsynchronized design. The participants were 76 postpartum women who agreed to participate in this study and were selected by convenience sampling (experimental group, n = 38; control group, n = 38). The data were collected from December 15, 2009, to April 8, 2010. The experimental group participated in a postpartum laughter program from a laughter therapy expert for 60 minutes per session, twice a week for 2 weeks, for a total of four sessions. To evaluate the effects of the postpartum laughter program, sIgA levels in breast milk were measured. The data were analyzed using SPSS WIN 20.0 software. Immune response (sIgA) significantly differed between the experimental and control groups. A postpartum laughter program can be applied as a complementary and alternative intervention to postpartum women in a transitional mother-infant care center.


Theoretical description of efficiency enhancement in DSSCs sensitized by newly synthesized heteroleptic Ru complexes.
Recently, some new series of heteroleptic ruthenium-based dyes, the so-called RD dyes, were designed and synthesized showing better performances compared to the well-known homoleptic N719. In this work, using the density-functional theory and its time-dependent extension, we have investigated the electronic structure and absorption spectra of these newly synthesized dyes, and compared the results to those of N3 dye to describe the variations of the properties due to the molecular engineering of the ancillary ligand. We have shown that the calculation results of the absorption spectra for these dyes using the PBE0 for the exchange-correlation functional are in better agreement with the experiment than using B3LYP or range-separated CAM-B3LYP. We have also derived a formula based on the DFT and used it to visually describe the level shifts in a solvent. The higher Jsc observed in these new dyes is explained by the fact that here, in contrast to N3, the excitation charge was effectively transferred to the anchoring ligand. Furthermore, we have shown that the difference dipole moment vectors of the ground and excited states can be used to determine the charge-transfer direction in an excitation process. Finally, different electron lifetimes observed in these dyes are explained by investigating the adsorption geometries and the relative orientations of iodine molecules in different "dyeI2" complexes.


Emerging Receptor Tyrosine Kinase Drug Targets: Implications for Antibody-Based Therapies for Oncology and Immunologic Disorders.
Protein kinases play a critical regulatory role in essentially every aspect of cell biology. Of the 518 known kinases, the most successful class for drug targeting is the receptor tyrosine kinase (RTK) family consisting of 58 distinct and diverse members. RTKs regulate a broad range of cellular functions, including proliferation, differentiation, survival, and apoptosis and have been intensively studied in development and cancer. Targeting of RTKs has resulted in many marketed small molecule and antibody-based drugs in a number of different solid tumors and hematological malignancies, and more recently in inflammatory diseases such as idiopathic pulmonary fibrosis. In this review, we discuss some of the RTKs in cancer in which drugs targeting the ErbB family (EGFR, HER2, and ErbB3) and KIT have had meaningful clinical benefit to cancer patients, RTKs' emerging role in regulating innate immunity, and the potential to explore targeting RTKs outside of oncology.