Associations Between the Neighborhood Environment and Moderate-to-Vigorous Walking in New Zealand Children: Findings from the URBAN Study.
Urban design may affect children's habitual physical activity by influencing active commuting and neighborhood play. Our objective was to examine associations between neighborhood built-environment features near children's homes and objectively measured physical activity. We used geographical information system (GIS) protocols to select 2016 households from 48 low- and high-walkability neighborhoods within four New Zealand cities. Children (n = 227; mean age ± standard deviation [SD] 9.3 ± 2.1 years) from the selected households wore accelerometers that recorded physical activity in the period 2008-2010. We used multilevel linear models to examine the associations of GIS and street-audit measures, using the systematic pedestrian and cycling environmental scan (SPACES), of the residential environment (ranked into tertiles) on children's hourly step counts and proportions of time spent at moderate-to-vigorous intensity on school and non-school days. During school-travel times (8:00-8:59 a.m. and 15:00-15:59 p.m.), children in the mid-tertile distance from school (~1 to 2 km) were more active than children with shorter or longer commute distances (1290 vs. 1130 and 1140 steps·h(-1); true between-child SD 440). After school (16:00-17:59 p.m.), children residing closest to school were more active (890 vs. 800 and 790 steps·h(-1); SD 310). Neighborhoods with more green space, attractive streets, or low-walkability streets showed a moderate positive association on non-school day moderate-to-vigorous steps, whereas neighborhoods with additional pedestrian infrastructure or more food outlets showed moderate negative associations. Other associations of residential neighborhoods were unclear but, at most, small. Designing the urban environment to promote safe child-pedestrian roaming may increase children's moderate-to-vigorous physical activity.


Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: final results of a double-blind, placebo-controlled phase III trial.
Cancer patients receiving chemotherapy experience thromboembolic complications associated with the use of long-term indwelling central venous catheters (CVCs). This prospective, double-blind, placebo-controlled, multicenter study evaluated whether prophylactic treatment with a low molecular weight heparin could prevent clinically relevant catheter-related thrombosis. Patients with cancer undergoing chemotherapy for at least 12 weeks (n=439) were randomly assigned, in a 2:1 ratio, to receive either dalteparin (5000 IU) or placebo, by subcutaneous injection, once daily for 16 weeks. Patients underwent upper extremity evaluation with either venography or ultrasound at the time of a suspected catheter-related complication (CRC) or upon completion of study medication. The primary end point, as determined by a blinded adjudication committee, was the occurrence of a CRC, defined as the first occurrence of any one of the following: clinically relevant catheter-related thrombosis that was symptomatic or that required anticoagulant or fibrinolytic therapy; catheter-related clinically relevant pulmonary embolism; or catheter obstruction requiring catheter removal. There was no significant difference in the frequency of CRCs between the dalteparin arm (3.7%) and the placebo arm (3.4%; P=0.88), corresponding to a relative risk of 1.0883 (95% confidence interval 0.37-3.19). No difference in the time to CRC was observed between the two arms (P=0.83). There was no significant difference between the dalteparin and placebo groups in terms of major bleeding (1 versus 0) or overall safety. Dalteparin prophylaxis did not reduce the frequency of thromboembolic complications after CVC implantation in cancer patients. Dalteparin was demonstrated to be safe over 16 weeks of treatment in these patients.


Yttrium-Catalyzed ortho-Selective C-H Borylation of Pyridines with Pinacolborane.
This work reports a site-selective C-H borylation of pyridines at the ortho-position with pinacolborane enabled by an yttrocene catalyst. The reaction provides a new family of 2-pyridyl boronates with a broad substrate scope and high atom efficiency. The resultant boronates were able to undergo a variety of transformations, e.g., oxidation, Suzuki-Miyaura coupling, Chan-Lam amination and etherification. Catalytic intermediates, including ortho-C-H metalated and borylated complexes, were isolated from stoichiometric experiments and confirmed by single-crystal X-ray diffraction.


Blueprint for action: steps toward a high-quality, high-value maternity care system.
Childbirth Connection hosted a 90th Anniversary national policy symposium, Transforming Maternity Care: A High Value Proposition, on April 3, 2009, in Washington, DC. Over 100 leaders from across the range of stakeholder perspectives were actively engaged in the symposium work to improve the quality and value of U.S. maternity care through broad system improvement. A multi-disciplinary symposium steering committee guided the strategy from its inception and contributed to every phase of the project. The "Blueprint for Action: Steps Toward a High Quality, High Value Maternity Care System", issued by the Transforming Maternity Care Symposium Steering Committee, answers the fundamental question, "Who needs to do what, to, for, and with whom to improve the quality of maternity care over the next five years?" Five stakeholder workgroups collaborated to propose actionable strategies in 11 critical focus areas for moving expeditiously toward the realization of the long term "2020 Vision for a High Quality, High Value Maternity Care System", also published in this issue. Following the symposium these workgroup reports and recommendations were synthesized into the current blueprint. For each critical focus area, the "Blueprint for Action" presents a brief problem statement, a set of system goals for improvement in that area, and major recommendations with proposed action steps to achieve them. This process created a clear sightline to action that if enacted could improve the structure, process, experiences of care, and outcomes of the maternity care system in ways that when anchored in the culture can indeed transform maternity care.


Wasting and death in cattle associated with chronic grazing of Brachiaria decumbens.
Progressive wasting was observed in 4/1000 steers grazing Brachiaria decumbens pastures. Yellow liver and whitish hard nodules in the mesenteric and hepatic lymph nodes were observed at necropsy. At histologic examination multifocal accumulation of foamy macrophages were in the livers, spleens, lmph nodes, and intestinal submucosa. It is suggested that the wasting syndrome was due to the intestinal granulomatous lesions of B decumbens.


[Characteristics and pathological basis of tumor doubling time in lung cancer].
It is difficult to make a definite diagnosis of lung cancer only based on the morphological features. As the tumor doubling time is a good index of tumor growth, the diagnosis of lung cancer can be substantiated by measuring the tumor doubling time. Recently, the researches using high resolution CT (HRCT) or multi-detector row CT (MDCT) to calculate the tumor doubling time of lung cancer and the clinical applications have made some progress. In this paper, we reviewed the pathological basis and characteristics of tumor doubling time in lung cancer.


Dimerization A Key Mechanism of Receptor Tyrosine Kinase Activation.
Receptor tyrosine kinase superfamily includes a group of growth factor receptors with intrinsic tyrosine kinase activity which share similar molecular structure. Their ligand-induced activation is mediated primarily by the receptor dimerization. It was proposed that ligand-induced homo- or hetero- dimerization is essential for the activation of receptor kinase however, the mechanisms of receptor dimerization are different. This review introduces the ligand-induced dimerization of different receptor tyrosine kinase subclasses and concentrates on heterodimerization between members of EGF receptor family, resulting the various cellular signaling pathways.


SMYD3 promotes aerobic glycolysis in diffuse large B-cell lymphoma via H3K4me3-mediated PKM2 transcription.
Genetic abnormalities in histone methyltransferases (HMTs) frequently occur in diffuse large B-cell lymphoma (DLBCL) and are related to its progression. SET and MYND domain containing 3 (SMYD3) is an HMT that is upregulated in various tumors and promotes their malignancy. However, to the best of our knowledge, the function of SMYD3 in DLBCL has not been investigated thus far. In the present study, 22 HMT genes related to cancer development were first selected according to current literature, and it was found that high SMYD3 expression was significantly associated with poor progression-free survival in patients with DLBCL. SMYD3 protein levels were upregulated and positively associated with poor prognosis and poor responsiveness to chemotherapy in patients with DLBCL. Functional examinations demonstrated that SMYD3 increased cell proliferation and the flux of aerobic glycolysis in DLBCL cells in vitro and in vivo and decreased cell sensitivity to doxorubicin in vitro. Moreover, SMYD3 could directly bind to specific sequences of Pyruvate Kinase M2 (PKM2) and promote DLBCL cell proliferation and aerobic glycolysis via H3K4me3-mediated PKM2 transcription. Clinically, SMYD3 expression positively correlated with that of PKM2, and high SMYD3 was significantly associated with high maximum standardized uptake value (SUVmax) detected by [(18)F]-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (PET/CT) in DLBCL samples. Concomitant expression of SMYD3 and PKM2 positively correlated with poor progression-free and overall survival in patients with DLBCL and may serve as novel biomarkers in DLBCL.


Sampling methods, dispersion patterns, and fixed precision sequential sampling plans for western flower thrips (Thysanoptera: Thripidae) and cotton fleahoppers (Hemiptera: Miridae) in cotton.
A 2-yr field study was conducted to examine the effectiveness of two sampling methods (visual and plant washing techniques) for western flower thrips, Frankliniella occidentalis (Pergande), and five sampling methods (visual, beat bucket, drop cloth, sweep net, and vacuum) for cotton fleahopper, Pseudatomoscelis seriatus (Reuter), in Texas cotton, Gossypium hirsutum (L.), and to develop sequential sampling plans for each pest. The plant washing technique gave similar results to the visual method in detecting adult thrips, but the washing technique detected significantly higher number of thrips larvae compared with the visual sampling. Visual sampling detected the highest number of fleahoppers followed by beat bucket, drop cloth, vacuum, and sweep net sampling, with no significant difference in catch efficiency between vacuum and sweep net methods. However, based on fixed precision cost reliability, the sweep net sampling was the most cost-effective method followed by vacuum, beat bucket, drop cloth, and visual sampling. Taylor's Power Law analysis revealed that the field dispersion patterns of both thrips and fleahoppers were aggregated throughout the crop growing season. For thrips management decision based on visual sampling (0.25 precision), 15 plants were estimated to be the minimum sample size when the estimated population density was one thrips per plant, whereas the minimum sample size was nine plants when thrips density approached 10 thrips per plant. The minimum visual sample size for cotton fleahoppers was 16 plants when the density was one fleahopper per plant, but the sample size decreased rapidly with an increase in fleahopper density, requiring only four plants to be sampled when the density was 10 fleahoppers per plant. Sequential sampling plans were developed and validated with independent data for both thrips and cotton fleahoppers.


Serum-derived bovine immunoglobulin for children with diarrhea-predominant irritable bowel syndrome.
Oral serum-derived bovine immunoglobulin (SBI)/protein isolate is a medical food intended to manage chronic diarrhea. It has been shown to improve pain and diarrhea in adults with diarrhea-predominant irritable bowel syndrome (d-IBS). To determine if SBI can improve symptoms in children with d-IBS. We performed a randomized, double-blind, placebo-controlled, pilot study (NCT02609529) to evaluate the effectiveness of SBI in children 8-18 years with d-IBS. We recorded stool number, abdominal pain, and stool form in all patients for 1 week and then assigned the patients at a ratio of 2:1 to treatment with SBI 5 g BID or placebo for 3 weeks. The patients and their parents completed the Pediatric Quality of Life Inventory™ for Gastrointestinal Symptoms (PedsQOL) and the Pediatric Functional Disability Index (FDI). In addition, complete blood counts and serum chemistries were recorded at the start and end of treatment to evaluate safety. Fifteen patients (nine SBI, six placebo) completed the study. Both SBI and placebo groups reported nonstatistical reductions in stool frequency per week. The SBI group showed a significant reduction in stool frequency at weeks 1 and 2 but not at the end of treatment. The SBI group also demonstrated statistical improvements in abdominal pain and stool form by 3 weeks. The placebo group did not achieve similar improvements. The overall FDI and PedsQOL scores, as well as PedsQOL subscale scores for pain, discomfort when eating, diarrhea, worry about stomach aches, and communication, improved significantly in the SBI group, but not in the placebo group. No serious adverse events occurred. Serum chemistries and hemograms were normal at baseline and at the end of study in all patients. In this single-center, exploratory pilot study, we demonstrated that 10 g SBI per day was safe in children with d-IBS and improved symptoms. Larger studies, with longer treatment duration, seem warranted based on these initial positive results.


Distinctive damage patterns on THA metal bearing surfaces: case studies.
Retrieval analysis of total joint arthroplasty components has primarily focused on assessing wear or other damage to polyethylene components. As damage to the opposing bearing surface can accelerate polyethylene wear and damage, and especially with the use of hard-on-hard articulations, retrieval analysis benefits from incorporating evaluation of hard bearing surfaces as well. The purpose of this study is to report six case studies of metal bearing surfaces with distinctive damage patterns, to interpret them in the context of adverse events plausibly responsible for their creation, and to suggest their likely clinical or scientific significance. The specific damage patterns reported here are 1) extensive scraping, 2) circumferential discoloration, 3) a long chain of periodic micro-indentations, 4) pitting with deposits, 5) scratches with small-radius directional changes, and 6) indentation with scraping.


Implication of the miR-184 and miR-204 competitive RNA network in control of mouse secondary cataract.
The high recurrence rate of secondary cataract (SC) is caused by the intrinsic differentiation activity of residual lens epithelial cells after extra-capsular lens removal. The objective of this study was to identify changes in the microRNA (miRNA) expression profile during mouse SC formation and to selectively manipulate miRNA expression for potential therapeutic intervention. To model SC, mouse cataract surgery was performed and temporal changes in the miRNA expression pattern were determined by microarray analysis. To study the potential SC counterregulative effect of miRNAs, a lens capsular bag in vitro model was used. Within the first 3 wks after cataract surgery, microarray analysis demonstrated SC-associated expression pattern changes of 55 miRNAs. Of the identified miRNAs, miR-184 and miR-204 were chosen for further investigations. Manipulation of miRNA expression by the miR-184 inhibitor (anti-miR-184) and the precursor miRNA for miR-204 (pre-miR-204) attenuated SC-associated expansion and migration of lens epithelial cells and signs of epithelial to mesenchymal transition such as α-smooth muscle actin expression. In addition, pre-miR-204 attenuated SC-associated expression of the transcription factor Meis homeobox 2 (MEIS2). Examination of miRNA target binding sites for miR-184 and miR-204 revealed an extensive range of predicted target mRNA sequences that were also a target to a complex network of other SC-associated miRNAs with possible opposing functions. The identification of the SC-specific miRNA expression pattern together with the observed in vitro attenuation of SC by anti-miR-184 and pre-miR-204 suggest that miR-184 and miR-204 play a significant role in the control of SC formation in mice that is most likely regulated by a complex competitive RNA network.


[Screening and identification of a single chain antibody fragment].
To screen and identify anti- Aflatoxin B1 single chain antibodies (scFv) from Tomlinson (I) library. The phages absorbed on the ELISA plate were eluted by four methods including glycine buffer elution, trypsin elution, AFB1 competitive elution and competitive elution following trypsin treatment. The phage positive clones were transformed into Escherichia coli HB2151 and soluble scFv protein was expressed with the induction of Isopropyl beta-D-1-Thiogalavtopy ranoside (IPTG). The scFv was identified by ELISA and DNA sequence. Comparing the four methods, we found that the most efficient way to get positive clones was competitive elution following trypsin treatment. Obtainning two positive clones that could bind specifically with free AFB1, which their relative affinity were 0.4 microg/mL and 0.7 microg/mL, respectively. DNA sequencing results showed that the scFv belonged to human immunoglobulin variable region. The specific human scFv could be obtained with phage antibody library, and our method provided an alternative for screening recombinant antibody against anti-hapten.


Cloning and expression of a Kv1.2 class delayed rectifier K+ channel from canine colonic smooth muscle.
A cDNA (CSMK1) encoding a delayed rectifier K+ channel of the Kv1.2 class was cloned from canine colonic circular smooth muscle and expressed in Xenopus oocytes. These channels appear to be uniquely expressed in gastrointestinal muscles and may participate in the electrical slow wave activity. Functional expression of CSMK1 in Xenopus oocytes demonstrated a K+ current that activated in a voltage-dependent manner upon depolarization. This current was highly sensitive to 4-aminopyridine (IC50, 74 microM). A low-conductance K+ channel was identified in inside-out patches from oocytes injected with CSMK1. This channel displayed a linear current-voltage relation with a slope conductance of 14 pS. The channels were blocked in a concentration-dependent manner by 4-aminopyridine. Northern blot analysis demonstrated that CSMK1 is expressed in a wide variety of gastrointestinal smooth muscles. Portal vein, renal artery, and uterus do not express CSMK1, suggesting that, among smooth muscles, expression of this K+ channel may be restricted to gastrointestinal smooth muscles. CSMK1 is 91% homologous to RAK, a delayed rectifier K+ channel cloned from rat heart, but displays unique pharmacological properties and tissue distribution.


Living donor liver transplantation for hepatocellular carcinoma at the University of Tokyo Hospital.
Living donor liver transplantation (LDLT) is an established treatment not only for those with end-stage liver disease but for those with hepatocellular carcinoma (HCC) developing in cirrhotic liver. The aim of this study was to present a single-center experience of LDLT for HCC at the University of Tokyo Hospital, Japan. Among 573 liver transplant recipients from January 1996 until the end of 2015, 139 patients have been indicated LDLT for the treatment of HCC, and were the subjects of the present study. We use the expanded criteria for HCC as follows; the number of tumor should be five or less, and the maximum diameter of the tumor should be 5 cm or less, without the distant metastasis nor the vascular invasion (Tokyo criteria, 5-5 rule). We also focused on the identification of the incidental intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular carcinoma/cholangiocarcinoma (cHCC-CC) in liver explants. The overall 1-, 5-, and 10-year recurrence-free and patient survival rates were 95%, 91%, and 91%, 91%, and 80%, 78%, respectively. The 1-, 3-, and 5-year cumulative recurrence rate was 5%, 6%, and 6% for within Milan, 0%, 8%, and 8% for beyond Milan/within Tokyo, and 33%, 50%, and 50% for beyond Tokyo, respectively, demonstrating the significantly impaired outcome of those beyond Tokyo criteria (P<0.001). The high alpha-fetoprotein (AFP) value (≥400 ng/mL), the high des-gamma-carboxy prothrombin (DCP) value (≥200 mAU/mL) and beyond the Tokyo criteria were proved to be significant predictors for the HCC recurrence, but the size or the type of the partial graft was not associated. Incidental ICC and cHCC-CC were found in one and two patients, respectively, with the size of less than 2 cm in all cases. ICC was not detected in preoperative evaluation but cHCC-CCs were misdiagnosed as HCC preoperatively. All three patients were alive without recurrence with a follow-up period of 2 to 14 years. The present results of our institution seem acceptable in terms of the recurrence-free and patient survival. The issues of the expansion of indication, living donor vs. deceased donor for HCC, and liver transplantation (LT) for cholangiocarcinoma are still left to be investigated in future studies.


Protein kinase D enzymes: novel kinase targets in pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDA) is characterized by advanced stage desmoplastic tumors with a high prevalence of genetic abnormalities. Occurrence of PDA is linked to activating Kras mutations and aberrant epidermal growth factor receptor signaling, leading to additional activation of wild-type Kras. As Kras is difficult to target, there is a constant need to identify novel targets acting downstream of this molecule in driving the formation or progression of PDA. Recently, it was shown that protein kinase D enzymes not only are increasingly expressed in PDA but also causatively linked to the development and progression of this cancer. They act downstream of both mutant Kras and growth factors and therefore may represent ideal novel targets.


Vitamin A Deficiency, Anemia, and Nutritional Status of under 5-Year Children from Northeast India.
Vitamin A deficiency (VAD) and Anemia are important public health nutritional problems in India. To assess nutritional status and prevalence and correlates of undernutrition, anemia, and VAD among children. A community-based cross-sectional study was carried out adopting systematic random sampling. Information on socio-demographic particulars was collected and 20 μL blood was collected for hemoglobin and free-flowing drop on Whatman filter paper for Vitamin A estimation. Hemoglobin was estimated using indirect cyanmethemoglobin and Vitamin A by high-pressure liquid chromatography. Nutritional status was assessed using the WHO Child Growth Standard. The overall prevalence of anemia and VAD was 68% and 59%, respectively, while underweight, stunting, and wasting was 30%, 55%, and 11%, respectively, among under 5 year children. Stepwise logistic regression analysis revealed no significant association of anemia and VAD with any sociodemographic variables, while the odd of stunting was four times higher among children of mothers engaged in labor and two times among children from low-income group, while underweight was two times higher among children from households not having sanitary latrine. Exclusive breastfeeding was observed to be associated with undernutrition among infants. Anemia, VAD, and stunting were high among children. Low intakes of green leafy vegetables and milk and milk product may be the reasons for the higher prevalence of anemia and VAD. There is a need to strengthen supplementation of iron and folic acid tablets and Vitamin A and also public distribution system.


Effects on nasal airflow and resistance using two different RME appliances: a randomized controlled trial.
To evaluate and compare the effects of tooth-borne (TB) and tooth-bone-borne (TBB) rapid maxillary expansion (RME) on nasal airflow and resistance. Fifty-four consecutive patients who met the eligibility criteria were recruited from September 2010 to December 2015. Of these 54 subjects, 40 agreed to participate in the part of the study involving evaluation of nasal flow and resistance. The 40 subjects were allocated to either the TB group, mean age 9.7 years (SD 1.5), or the TBB group, mean age 10.2 years (SD 1.4). All subjects performed rhinomanometric registration at baseline (T0), but only 30 attended the post-expansion registration (T1), of whom 16 had been randomized to the TB group and 14 to the TBB group. The study outcomes, nasal airflow and nasal airway resistance, were evaluated with linear regression adjusted for baseline variable of the outcome to compare the study groups with complete cases strategy as well as after multiple imputation (MI). Participants were randomly allocated in blocks of different sizes, using the concealed allocation principle in a 1:1 ratio. The randomization list was computer generated to ensure homogeneity between groups. Blinding was done only for outcome assessor due to clinical limitations. The care providers at the ENT unit who conducted all the rhinomanometry examinations were blinded to which group the patients were allocated to. Complete case analysis showed significantly higher post-expansion nasal airflow values for the TBB group compared with the TB group, mean difference 51.0 cm3/s (P = 0.018). The evaluation after MI showed a similar significant mean difference, 52.7 cm3/s (P = 0.020) in favour of the TBB group when taking into account the missing values from the T1 examination. Even reduction in nasal airway resistance showed similar pattern in favour of the TBB group. Our results represent the short-term effects. A longer follow-up period would have been preferable. The TBB RME induced significantly higher nasal airway flow and lower nasal resistance values than TB RME. It might be wiser to use TBB RME in cases with constricted maxilla and upper airway obstruction. This trial was not registered in any external sites. The protocol was not published before trial commencement.


Integrating blood cell mechanics, platelet adhesive dynamics and coagulation cascade for modelling thrombus formation in normal and diabetic blood.
Normal haemostasis is an important physiological mechanism that prevents excessive bleeding during trauma, whereas the pathological thrombosis especially in diabetics leads to increased incidence of heart attacks and strokes as well as peripheral vascular events. In this work, we propose a new multiscale framework that integrates seamlessly four key components of blood clotting, namely transport of coagulation factors, coagulation kinetics, blood cell mechanics and platelet adhesive dynamics, to model the development of thrombi under physiological and pathological conditions. We implement this framework to simulate platelet adhesion due to the exposure of tissue factor in a three-dimensional microchannel. Our results show that our model can simulate thrombin-mediated platelet activation in the flowing blood, resulting in platelet adhesion to the injury site of the channel wall. Furthermore, we simulate platelet adhesion in diabetic blood, and our results show that both the pathological alterations in the biomechanics of blood cells and changes in the amount of coagulation factors contribute to the excessive platelet adhesion and aggregation in diabetic blood. Taken together, this new framework can be used to probe synergistic mechanisms of thrombus formation under physiological and pathological conditions, and open new directions in modelling complex biological problems that involve several multiscale processes.


EDTA clearance in monitoring cisplatin dose escalation in patients with bulky metastatic germ cell tumors of the testis.
A fast cisplatin clearance may reduce exposure time of tumor cells to the drug, and thus impair the expected effects of dose escalation. This hypothesis was tested in 23 patients with bulky metastatic germ cell tumors of the testis, treated with etoposide, bleomycin and high-dose cisplatin (60 mg/m2/24 h x 4). The daily dose was retrospectively calculated in mg/l EDTA clearance/24 h. A daily dose of 60 mg/m2 of cisplatin in a person with a body surface of 1.7 m2 and EDTA clearance of 100 ml/min was equivalent to 0.69 mg cisplatin/l EDTA clearance/24 h. In the whole group, 10 patients had complete remission (CR), 10 partial response (PR) and 3 progressive disease (PD). The mean daily cisplatin dose (mean) in the whole group was 0.86 mg/l EDTA clearance/24 h (range 0.35-2.00). For patients with CR, mean +/- SD was 1.00 +/- 0.46, for those with PR 0.80 +/- 0.44, and for those with PD only 0.61 +/- 0.07. A cisplatin dose over 0.86 mg/l EDTA clearance/24 h x 4 was obtained in 6/10 patients with CR versus 2/13 patients with PR + PD. Patients with PD received a significantly lower cisplatin dose than the whole group (0.61 versus 0.86 mg cisplatin/l EDTA clearance/24 h x 4.) The difference between the average toxicity grade after cisplatin dose over and below 0.69 mg/l EDTA clearance/24 h x 4 was significant only for leukocytes (WHO grade 2.17 versus 1.36). Thus, the effective escalated dose of cisplatin should preferably be calculated not per m2 body surface but per 1 liter EDTA clearance. The 'ideal' escalated dose might be about 0.86-1.0 mg cisplatin/l EDTA clearance 24 h x 4.


Myocardial infarction models in NOD/Scid mice for cell therapy research: permanent ischemia vs ischemia-reperfusion.
Myocardial infarction animal studies are used to study disease mechanisms and new treatment options. Typically, myocardial infarction (MI) is induced by permanent occlusion of the left anterior descending artery. Since in MI patients coronary blood flow is often restored new experimental models better reflecting clinical practice are needed. Here, permanent ischemia MI (PI group) was compared with transient ischemia (45 min) (IR group) in immunodeficient NOD/Scid mice. Cardiac function, infarct size, wall thickness and total collagen deposition were significantly reduced only in PI mice. Cardiac inflammatory cells and serum cytokine levels were less dynamic in IR animals compared to PI. So although IR better reflects clinical practice, it is secondary to PI for investigating cell therapy, since it induces too little damage to provide a measurable therapeutic window. MI did result in significant changes in the inflammatory state, indicating this immunodeficient mouse strain is valuable to study human cell therapy.


Structure-activity relationships of monoterpenes and acetyl derivatives against Aedes aegypti (Diptera: Culicidae) larvae.
Dengue fever virus transmitted by Aedes aegypti causes lethal mortalities of human beings, and, because of the lack of any vaccine, management of this vector, especially with phytochemicals, is essential. In the present investigation, the structure-activity relationship of monoterpenes and their acetyl derivatives was studied to identify structural features that are responsible for mosquitocidal activity. Derivatization of monoterpenes (eugenol, geraniol, linalool, L-menthol and terpeniole) followed by structure-activity relationship studies identified all five acetyl derivatives as having enhanced mosquitocidal activity against fourth-instar larvae of Aedes aegypti. Acetylation of the hydroxyl group in general increased activity in comparison with hydroxyl compounds. Based on LC50 values (ppm), the activities could be placed in the following order: eugenyl acetate (50.2) > linalyl acetate (119.7) > terpinyl acetate (287.1) > menthyl acetate (308.4) > geranyl acetate (325.5), as compared with monoterpenoids: eugenol (82.8) > linalool (242.6) > terpineol (331.7) > L-menthol (365.8) > geraniol (415.0). In eugenyl acetate, the presence of an aromatic ring and a side chain with an allylic double bond makes it most effective. Bioactive functional groups identified in the study may contribute to the understanding of larvicidal activity of acetyl derivatives and may help in the development of ecofriendly mosquito larvicidal compounds.


Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers.
Neurostimulation applied from deep brain stimulation (DBS) electrodes is an effective therapeutic intervention in patients suffering from intractable drug-resistant epilepsy when resective surgery is contraindicated or failed. Inhibitory DBS to suppress seizures and associated epileptogenic biomarkers could be performed with high-frequency stimulation (HFS), typically between 100 and 165 Hz, to various deep-seated targets, such as the Mesio-temporal lobe (MTL), which leads to changes in brain rhythms, specifically in the hippocampus. The most prominent alterations concern high-frequency oscillations (HFOs), namely an increase in ripples, a reduction in pathological Fast Ripples (FRs), and a decrease in pathological interictal epileptiform discharges (IEDs). In the current study, we use Temporal Interference (TI) stimulation to provide a non-invasive DBS (130 Hz) of the MTL, specifically the hippocampus, in both mouse models of epilepsy, and scale the method using human cadavers to demonstrate the potential efficacy in human patients. Simulations for both mice and human heads were performed to calculate the best coordinates to reach the hippocampus. This non-invasive DBS increases physiological ripples, and decreases the number of FRs and IEDs in a mouse model of epilepsy. Similarly, we show the inability of 130 Hz transcranial current stimulation (TCS) to achieve similar results. We therefore further demonstrate the translatability to human subjects via measurements of the TI stimulation vs. TCS in human cadavers. Results show a better penetration of TI fields into the human hippocampus as compared with TCS. These results constitute the first proof of the feasibility and efficiency of TI to stimulate at depth an area without impacting the surrounding tissue. The data tend to show the sufficiently focal character of the induced effects and suggest promising therapeutic applications in epilepsy.


Biological Properties of Vitamins of the B-Complex, Part 1: Vitamins B1, B2, B3, and B5.
This review summarizes the current knowledge on essential vitamins B1, B2, B3, and B5. These B-complex vitamins must be taken from diet, with the exception of vitamin B3, that can also be synthetized from amino acid tryptophan. All of these vitamins are water soluble, which determines their main properties, namely: they are partly lost when food is washed or boiled since they migrate to the water; the requirement of membrane transporters for their permeation into the cells; and their safety since any excess is rapidly eliminated via the kidney. The therapeutic use of B-complex vitamins is mostly limited to hypovitaminoses or similar conditions, but, as they are generally very safe, they have also been examined in other pathological conditions. Nicotinic acid, a form of vitamin B3, is the only exception because it is a known hypolipidemic agent in gram doses. The article also sums up: (i) the current methods for detection of the vitamins of the B-complex in biological fluids; (ii) the food and other sources of these vitamins including the effect of common processing and storage methods on their content; and (iii) their physiological function.


The role of hyperbaric oxygen therapy in the prevention and management of radiation-induced complications of the head and neck - a systematic review of literature.
Radiation therapy for the treatment of head and neck cancer can injure normal tissues and have devastating side effects. Hyperbaric oxygen (HBO) is known to reduce the severity of radiation-induced injury by promoting wound healing. While most of the research in literature has focused on its efficacy in osteonecrosis, HBO has other proven benefits as well. The aim of this review was to identify the various benefits of hyperbaric oxygen therapy in patients who have undergone radiation for head and neck cancer. An electronic database search was carried out to identify relevant articles and selected articles were reviewed in detail. The quality of evidence for each benefit, including preserving salivary gland function, preventing osteonecrosis, dental implant success, and overall quality of life, was evaluated. Evidence showed that HBO was effective in improving subjective symptoms of xerostomia, swallowing, speech and overall quality of life. There was no conclusive evidence to show that HBO improved implant survival, prevented osteonecrosis, or improved salivary gland function. The high costs and accessibility of HBO therapy must be weighed against the potential benefits to each patient.


Bmi1 regulates mitochondrial function and the DNA damage response pathway.
Mice deficient in the Polycomb repressor Bmi1 develop numerous abnormalities including a severe defect in stem cell self-renewal, alterations in thymocyte maturation and a shortened lifespan. Previous work has implicated de-repression of the Ink4a/Arf (also known as Cdkn2a) locus as mediating many of the aspects of the Bmi1(-/-) phenotype. Here we demonstrate that cells derived from Bmi1(-/-) mice also have impaired mitochondrial function, a marked increase in the intracellular levels of reactive oxygen species and subsequent engagement of the DNA damage response pathway. Furthermore, many of the deficiencies normally observed in Bmi1(-/-) mice improve after either pharmacological treatment with the antioxidant N-acetylcysteine or genetic disruption of the DNA damage response pathway by Chk2 (also known as Chek2) deletion. These results demonstrate that Bmi1 has an unexpected role in maintaining mitochondrial function and redox homeostasis and indicate that the Polycomb family of proteins can coordinately regulate cellular metabolism with stem and progenitor cell function.


Biodegradable tocopherol acetate as a drug carrier to prevent ureteral stent-associated infection.
Biomaterial-centred bacterial infections present common and challenging complications with medical implants like ureteral stent which provide substratum for the biofilm formation. Hence the purpose of this study is to make antibacterial stent surface with biodegradable polymer (tocopherol acetate) and anti-infective agents (norfloxacin and metronidazole) using a modified dip-coating procedure. This is done by impregnating the stent pieces in the anti-infective solution (a mixture of norfloxacin-metronidazole and polymer) for uniform surface coating (drug-carrier-coated stents). After coating, agar diffusion test was performed as qualitative test to find out the sensitivity of coated stents against the clinical isolates, Staphylococcus epidermidis and Escherichia coli. Quantitative test was measured by calculating the numbers of adhered bacteria on coated and uncoated stents by incubating the stent pieces in artificial urine. Difference in the number of viable bacteria adhered on the surface of coated and uncoated stents were statistically calculated using chi square test with p < 0.05 considered significant. The stent colonising ability of Staphylococcus epidermidis and Escherichia coli in a controlled environment chamber was determined using two-challenge dose of the isolates by in vitro challenge test. In qualitative test, the zone of inhibition around the coated stents showed sensitivity against the clinical isolates. In quantitative test, the number of adhered bacteria on the surface of coated stents was reduced to a significant level (p < 0.05). The polymer, tocopherol acetate is highly biodegradable in nature. Due to its degrading ability in body tissues, it releases the anti-infective drugs at a constant and sustained rate.


Beta 2-glycoprotein-1 (apolipoprotein H) excretion in chronic renal tubular disorders: comparison with other protein markers of tubular malfunction.
Urinary beta 2-glycoprotein-1 was measured in 60 patients with conditions recognised as causing renal tubular impairment and compared with established markers of early tubular malfunction. Increased beta 2-glycoprotein-1 excretion was found in 49 (82%) of the subjects; raised excretion of alpha 1-microglobulin, retinol-binding protein, and beta 2-microglobulin was found in 46 (77%), 45 (75%), and 31 (52%), respectively, and increased urinary N-acetyl-beta-D-glucosaminidase activity in 32 of 54 of the subjects (59%). The increase was particularly pronounced in those with proximal tubule malfunction, although considerable variation occurred. beta 2-glycoprotein-1 was shown to be stable in urine over the physiological pH range, and it is concluded that its measurement provides a means of detecting chronic malfunction of the renal tubules that is marginally more sensitive than assays of alpha 1-microglobulin or retinol-binding protein, and more reliable than assays of beta 2-microglobulin or N-acetyl-beta-D-glucosaminidase.


[A woman with right-sided abdominal pain].
A 59-year-old woman presented with right-sided abdominal pain. Ultrasound was suggestive of acute appendicitis. Laparoscopy showed inflammation of a solitary caecal diverticulum, a rare congenital malformation. Uncomplicated caecal diverticulitis can mimic appendicitis clinically and sonographically, but does not require surgical intervention. An additional CT-scan can clarify the diagnosis.


Explaining ionic liquid water solubility in terms of cation and anion hydrophobicity.
The water solubility of salts is ordinarily dictated by lattice energy and ion solvation. However, in the case of low melting salts also known as ionic liquids, lattice energy is immaterial and differences in hydrophobicity largely account for differences in their water solubility. In this contribution, the activity coefficients of ionic liquids in water are split into cation and anion contributions by regression against cation hydrophobicity parameters that are experimentally determined by reversed phase liquid chromatography. In this way, anion hydrophobicity parameters are derived, as well as an equation to estimate water solubilities for cation-anion combinations for which the water solubility has not been measured. Thus, a new pathway to the quantification of aqueous ion solvation is shown, making use of the relative weakness of interactions between ionic liquid ions as compared to their hydrophobicities.


RTS, a rice anther-specific gene is required for male fertility and its promoter sequence directs tissue-specific gene expression in different plant species.
A tapetum-specific gene, RTS, has been isolated by differential screening of a cDNA library from rice panicles. RTS is a unique gene in the rice genome. RNA blot analysis and in situ hybridization indicates that this gene is predominantly expressed in the anther's tapetum during meiosis and disappears before anthesis. RTS has no introns and encodes a putative polypeptide of 94 amino acids with a hydrophobic N-terminal region. The nucleotide and deduced amino acid sequence of the gene do not show significant homology to any known sequences. However, a sequence in the promoter region, GAATTTGTTA, differs only by one or two nucleotides from one of the conserved motifs in the promoter region of two pollen-specific genes of tomato. Several other sequence motifs found in other anther-specific promoters were also identified in the promoter of the RTS gene. Transgenic and antisense RNA approaches revealed that RTS gene is required for male fertility in rice. The promoter region of RTS, when fused to the Bacillus amyloliquefaciens ribonuclease gene, barnase, or the antisense of the RTS gene, is able to drive tissue-specific expression of both genes in rice, creeping bentgrass (Agrostis stolonifera L.) and Arabidopsis, conferring male sterility to the transgenic plants. Light and near-infrared confocal microscopy of cross-sections through developing flowers of male-sterile transgenics shows that tissue-specific expression of barnase or the antisense RTS genes interrupts tapetal development, resulting in deformed non-viable pollen. These results demonstrate a critical role of the RTS gene in pollen development in rice and the versatile application of the RTS gene promoter in directing anther-specific gene expression in both monocotyledonous and dicotyledonous plants, pointing to a potential for exploiting this gene and its promoter for engineering male sterility for hybrid production of various plant species.


Perspectives on patient-doctor communication.
Until recently, the content, structure, and function of communication between doctors and patients has received little attention and has been excluded from the realm of scientific inquiry; as a result, most clinicians have had little formal training in communication skills. In this paper leaders in doctor-patient communication present four approaches that are currently used as the basis for clinical training and research, summarize the progress made in forming a consensus, and outline the implications of these perceptions for practicing physicians.


Variation in pediatric hospitalists' use of proven and unproven therapies: a study from the Pediatric Research in Inpatient Settings (PRIS) network.
Undesirable practice variation remains a major concern with the quality of the healthcare system. While care in pediatric hospitalist systems has been demonstrated to be efficient, neither the quality of care nor determinants of variation in pediatric hospitalist systems are well understood. To measure variation in pediatric hospitalists' reported use of common inpatient therapies, and to test the hypothesis that variation in reported use of proven therapies is lower than variation in reported use of unproven therapies. We conducted a survey of pediatric hospitalists in the US and Canada. Respondents reported their frequency of using 14 therapies in the management of common conditions. Each therapy was determined to be of proven or unproven effectiveness using published critical appraisals. Variation in reported use of proven and unproven therapies was compared. 67% (213/320) of surveyed individuals participated. Little variability existed in reported use of albuterol and corticosteroids in asthma (4-6% of respondents reported not often using them) and systemic dexamethasone in bronchiolitis (12% of respondents reported using it more than rarely). Moderate to high variation existed in reported use of all other therapies studied. Variation in reported use of proven therapies was significantly less than variation in reported use of unproven therapies (15.5 +/- 12.5% vs. 44.6 +/- 20.5%). Substantial variation exists in hospitalists' reported management of common pediatric conditions. Variation is significantly lower for strongly evidence-based therapies. To decrease undesirable variation in care, a stronger evidence base for inpatient pediatric care must be built.


Connecting dental education to other health professions.
The health care delivery system is poised for substantial change in the coming years. The foremost vector driving this change is economics. However, use of evidence-based principles of practice and a high desire, if not a national mandate, for increased quality in health care delivery are also very important factors. Nestled within this large national health care debate are a set of issues that directly impact dental education and practice. Among them is the potential impact of expanded intraprofessional and interprofessional collaborations among dentists, dental therapists, dental hygienists, and nurse practitioners, among others, in search of better oral and general health care for all Americans. This article explores many of the issues involved in this possible transition with special reference to the impact of the changes on dental education.


[Repair of widely infected scalp defect and osteomyelitis with free radial forearm flap: a case report].
A 60-year-old female was admitted with large frontal scalp defect associated with osteomyelitis due to chronic infection. Debridement of the infected scalp and frontal bone and the transplantation of the free radial forearm flap with vascular anastomosis was carried out. The wound cured uneventfully. Cranioplasty was performed ten months after the first operation. Transplantation of free radial forearm flap was first reported in 1982 by Song in China and has proved to be a very effective operative method, especially for the repair of large infected wounds. This is because good blood supply results from the anastomosis of larger vessels, and its cleansing effects can eradicate infections and prompt rapid wound healing.


In Silico Prediction of Compounds Binding to Human Plasma Proteins by QSAR Models.
Plasma protein binding (PPB) is a significant pharmacokinetic property of compounds in drug discovery and design. Due to the high cost and time-consuming nature of experimental assays, in silico approaches have been developed to assess the binding profiles of chemicals. However, because of unambiguity and the lack of uniform experimental data, most available predictive models are far from satisfactory. In this study, an elaborately curated training set containing 967 diverse pharmaceuticals with plasma-protein-bound fractions (fb ) was used to construct quantitative structure-activity relationship (QSAR) models by six machine learning algorithms with 26 molecular descriptors. Furthermore, we combined all of the individual learners to yield consensus prediction, marginally improving the accuracy of the consensus model. The model performance was estimated by tenfold cross validation and three external validation sets comprising 242 pharmaceutical, 397 industrial, and 231 newly designed chemicals, respectively. The models showed excellent performance for the entire test set, with mean absolute error (MAE) ranging from 0.126 to 0.178, demonstrating that our models could be used by a chemist when drawing a molecular structure from scratch. Meanwhile, structural descriptors contributing significantly to the predictive power of the models were related to the binding mechanisms, and the trend in terms of their effects on PPB can serve as guidance for the structural modification of chemicals. The applicability domain was also defined to distinguish favorable predictions from unfavorable predictions.


Is Artificial Intelligence (AI) a Pipe Dream? Why Legal Issues Present Significant Hurdles to AI Autonomy.
Proponents of artificial intelligence (AI) technology have suggested that in the near future, AI software may replace human radiologists. Although assimilation of AI into the specialty has occurred more slowly than predicted, developments in machine learning, deep learning, and neural networks suggest that technologic hurdles and costs will eventually be overcome. However, beyond these technologic hurdles, formidable legal hurdles threaten the impact of AI on the specialty. Legal liability for errors committed by AI will influence the ultimate role of AI within radiology and also influence whether AI remains a simple decision support tool or develops into an autonomous member of the health care team. Additional areas of uncertainty include the potential application of products liability law to AI and the approach taken by the U.S. FDA in potentially classifying autonomous AI as a medical device. The current ambiguity of the legal treatment of AI will profoundly influence development of autonomous AI given that vendors, radiologists, and hospitals will be unable to reliably assess their liability associated with implementing such tools. Advocates of AI in radiology and health care in general need to lobby for legislative action to better clarify the liability risks of AI in a way that does not deter technologic development.


Initial management of advanced Burkitt lymphoma in children: is there still a place for surgery?
This retrospective study compared the overall survival, the event-free survival, and the timing of chemotherapy in patients with advanced Burkitt lymphoma with and without laparotomy. Thirty-five patients with advanced abdominal Burkitt lymphoma treated at least partially at the Centre Léon Bérard between 1981 and 1992 were included in this study. The diagnosis was obtained by laparotomy (LAP group) in 21 patients (17 stage III, 4 stage IV) and by other methods (non-LAP group) in 14 patients (5 stage III, 9 stage IV). The overall survival (71 and 93%) and the event-free survival (66 and 79%) were similar in the LAP and non-LAP groups, and the relapse rate was five (three local) in the LAP group compared with three (none local) in the non-LAP group. The local complication rate (9 of 21 versus 2 of 14) and the toxic death rate (2 of 21 versus 1 of 14) were slightly higher in the LAP group. Laparotomy also caused delays in therapy and increased the overall hospital stay. The mean interval from diagnosis to the start of the fourth course of chemotherapy was 57 days compared with 48 days and the average hospital stay was 44.4 days compared with 39 days for the LAP and non-LAP groups, respectively. Because advanced Burkitt lymphoma can be diagnosed by fine-needle aspiration, and chemotherapy cures more than 80% of the patients, there is no need for initial surgery, apart from acute emergencies. Furthermore, laparotomy delay chemotherapy and might reduce the survival rate.


RNA helicase activity of the plant virus movement proteins encoded by the first gene of the triple gene block.
Cell-to-cell and long-distance transport of some plant viruses requires coordinated action of three movement proteins encoded by triple gene block (TGB). The largest of TGB proteins, TGBp1, is a member of the superfamily I of DNA/RNA helicases and possesses a set of conserved helicase sequence motifs necessary for virus movement. A recombinant His-tagged form of TGBp1 of two hordeiviruses and potato virus X, a potexvirus, produced in Escherichia coli had unwinding activity on a partially duplexed RNA, but not DNA substrate. The helicase activity of these proteins was dependent on Mg2+ and ATP. The isolated C-terminal half of the PSLV TGBp1 retaining all helicase motifs was also able to unwind RNA duplex.


Why I am not a "mental health consumer".
"Mental health consumer" is now a widely-accepted term used to identify individuals living with mental illness. Though this language may be an improvement over the word "patient," it can still be limiting and disempowering. The author explains her concern regarding the word "consumer" and explores the advantages of using the term "psychiatric disability" to describe the experience of those who live with mental illness.


Lipid Transfer Proteins (LTPs)-Structure, Diversity and Roles beyond Antimicrobial Activity.
Lipid transfer proteins (LTPs) are among the most promising plant-exclusive antimicrobial peptides (AMPs). They figure among the most challenging AMPs from the point of view of their structural diversity, functions and biotechnological applications. This review presents a current picture of the LTP research, addressing not only their structural, evolutionary and further predicted functional aspects. Traditionally, LTPs have been identified by their direct isolation by biochemical techniques, whereas omics data and bioinformatics deserve special attention for their potential to bring new insights. In this context, new possible functions have been identified revealing that LTPs are actually multipurpose, with many additional predicted roles. Despite some challenges due to the toxicity and allergenicity of LTPs, a systematic review and search in patent databases, indicate promising perspectives for the biotechnological use of LTPs in human health and also plant defense.


Paravalvular leak prediction after transcatheter aortic valve replacement with self-expandable prosthesis based on quantitative aortic calcification analysis.
Paravalvular leak (PVL) is one of the most common complications of transcatheter aortic valve replacement (TAVR) and affects short- and long-term outcomes. The aim of this study was to identify the computed tomography (CT) imaging biomarkers that allow PVL after TAVR to be predicted. Patients were included who had severe aortic valve stenosis, had undergone TAVR with a self-expanding valve, and had undergone a pre-procedural CT scan. Data on baseline characteristics, procedural and long-term outcomes were collected retrospectively. We used MATLAB software with a self-developed algorithm for CT scan analysis and found parameters that quantified aortic valve calcifications (AVC) in detail. Fifty patients were included. The identified CT-derived parameters included AVC size, volume, thickness and density, as well as calcium radial distribution. The volume of the largest calcium block, calcium perimeter and calcium size (assessed by Feret's diameter) showed a strong association with PVL occurrence after TAVR (P=0.012, P=0.001 and P=0.045, respectively). The prognostic model showed that a 10 mm2 increase in the local AVC amount in each valve section was associated with a 9.8% (95% CI: 2-18%; P=0.019) increase in the risk of PVL occurrence in the corresponding area after TAVR. ROC analysis revealed that the cut-off point of the AVC area was 96.5 mm2 in the polar coordinate system presentation. Kaplan-Meier curves showed worse PVL-free survival in patients with more than 96.5 mm2 of calcium area (P=0.013; log-rank). Quantitative AVC assessment for PVL prediction may play an important role in screening before TAVR. In future, the use of quantitative AVC assessment as an imaging biomarker in TAVR candidates and the creation and extension of an online database containing quantitative AVC parameters may help to identify high PVL risk patients.


[Preclinical management of accident trauma patients in the large city].
Congested urban areas make specific demands on emergency medical systems (EMS); Berlin as an example, structural and logistic necessities of EMS are demonstrated. Short response times, a narrow hospital net and short transport times suggest the possibility to minimize prehospital care for the traumatised patient. Pathophysiology of severe trauma and accepted basic principles of primary care, the pattern of multiple injuries and a low rate of necessary emergency operations, as well as frequently unavoidable secondary transports to appropriate hospitals contradict such consequences. With modern preclinical emergency care enough time is gained to primarily reach an even more distant but competent trauma centre. A high number of secondary transports from low level hospitals of more distant rural regions shows the importance of concentrated high level medicine in urban areas and proves the necessity of qualified inter-hospital transport systems.


Regulation of apoptosis through cysteine oxidation: implications for fibrotic lung disease.
Tissue fibrosis is believed to be a manifestation of dysregulated repair following injury, in association with impaired reepithelialization, and aberrant myofibroblast activation and proliferation. Numerous pathways have been linked to the pathogenesis of fibrotic lung disease, including the death receptor Fas, which contributes to apoptosis of lung epithelial cells. A redox imbalance also has been implicated in disease pathogenesis, although mechanistic details whereby oxidative changes intersect with profibrotic signaling pathways remain elusive. Oxidation of cysteines in proteins, such as S-glutathionylation (PSSG), is known to act as a regulatory event that affects protein function. This manuscript will discuss evidence that S-glutathionylation regulates death receptor induced apoptosis, and the potential implications for cysteine oxidations in the pathogenesis of in fibrotic lung disease.


Palmitoylation of bovine opsin and its cysteine mutants in COS cells.
Previously, bovine rhodopsin has been shown to be palmitoylated at cysteine residues 322 and 323. Here we report on palmitoylation of bovine opsin in COS-1 cells following expression of the synthetic wild-type opsin gene and several of its cysteine mutants in the presence of [3H]palmitic acid. Two moles of palmitic acid are introduced per wild-type opsin molecule in thioester linkages. Palmitoylation is abolished when both Cys-322 and Cys-323 are replaced by serine residues. Replacement of Cys-322 by serine prevents palmitoylation at Cys-323, whereas replacement of the latter with serine allows palmitoylation at Cys-322. Opsin mutants that evidently do not contain a Cys-110/Cys-187 disulfide bond and presumably remain in the endoplasmic reticulum are not palmitoylated. Replacement of Cys-140 or Cys-185 reduces the extent of palmitoylation of the opsin. Lack of palmitoylation at Cys-322 and/or Cys-323 does not affect 11-cis-retinal binding, absorption maximum or extinction coefficient of the chromophore, the bleaching behavior of the chromophore, or the light-dependent binding and activation of transducin. Mutants containing serine substitutions at Cys-140 or Cys-323 showed reduced light-dependent phosphorylation by rhodopsin kinase.


A healthy start is the first step in a healthy life.
Babies are most vulnerable during delivery and in the first critical hours after birth. This vulnerability is reflected in the high numbers who die at birth or shortly after. Worldwide, some 4.3 million newborn babies die every year--8 every minute. For each baby who dies, many more are severely damaged, facing lifelong handicaps such as cerebral palsy, seizures, and severe learning difficulties. When a baby dies at childbirth or shortly afterwards, there is a cause. And for most of these newborn deaths the cause is avoidable. Often the cause of death is related to the lack of or inadequate care of the mother during pregnancy and delivery. The same interventions are needed to ensure the health and survival of both mothers and baby. In addition, the baby needs special care during the first critical hours and days of life. Safe motherhood means care for the newborn as well as for the mother. This issue of Safe Motherhood features care of the newborn child and on how maternal care and newborn care are related. Much of the information seems obvious, and yet it cannot be so obvious if our societies tolerate millions of newborn deaths each year. Babies would survive to live useful and productive lives if they and their mothers were given more care, help and forethought as they make their first appearance in this world.


Spinal cord cultured neurons: an in vitro model to study GABA synaptic pharmacology.
In summary, spinal cord cultured neurons provide an in vitro model for studying GABA synaptic pharmacology. GABAA agonists stimulate 36Cl-influx in these cells in a concentration-dependent manner. The enhancing effect of GABA is potentiated by BZ agonists, inhibited by GABA antagonists, and attenuated by the inverse agonist beta-carboline, DMCM. These cells also exhibit the specific binding of [3H]flunitrazepam with a pharmacological specificity of the central BZ receptors. Finally, BZ receptors are coupled to GABA, barbiturate, and picrotoxin sites in these cells, as indicated by allosteric interactions both by binding and 36Cl-influx assay.


[X-ray computed tomographic diagnosis of primary cardiac malignant lymphoma in AIDS].
Primary lymphomas rarely affect the heart. The myocardial disease is usually latent and the diagnosis is based on post mortem observations. The cardiac symptoms do not reveal the disease and symptomatology is not specific. Our observation shows the complementarity of non invasive techniques, for a better screening of cardiac tumoral forms. Although echocardiography is the main examination, CT scan provides a detection of infiltrative forms and of extracardiac extension. Concurrently, MRI remains the method of choice to display beginning infiltrative forms, revealed by pericardial effusion in AIDS disease.


Irritable Bowel Syndrome Therapeutic Has Broad-Spectrum Antimicrobial Activity.
Otilonium bromide is a poorly absorbed oral medication used to control irritable bowel syndrome. It is thought to act as a muscle relaxant in the intestine. Here, we show that otilonium bromide has broad-spectrum antibacterial and antifungal activity, including against multidrug-resistant strains. Our results suggest otilonium bromide acts on enteric pathogens and may offer a new scaffold for poorly absorbed intestinal antimicrobial therapy.


Helicity-Dependent Cross Sections for the Photoproduction of π^{0} Pairs from Nucleons.
The double-polarization observable E and helicity-dependent cross sections σ_{1/2}, σ_{3/2} have been measured for the photoproduction of π^{0} pairs off quasifree protons and neutrons at the Mainz MAMI accelerator with the Crystal Ball/TAPS setup. A circularly polarized photon beam was produced by bremsstrahlung from longitudinally polarized electrons and impinged on a longitudinally polarized deuterated butanol target. The reaction products were detected with an almost 4π covering calorimeter. The results reveal for the first time the helicity- and isospin-dependent structure of the γN→Nπ^{0}π^{0} reaction. They are compared to predictions from reaction models in view of nucleon resonance contributions and also to a refit of one model that predicted results for the proton and for the neutron target. The comparison of the prediction and the refit demonstrates the large impact of the new data.


Phosphine-Triggered Selectivity Switch in Silver-Catalyzed o-Alkynylbenzohydroxamic Acid Cycloisomerizations.
A silver-catalyzed cycloisomerization reaction of a series of o-alkynylbenzohydroxamic acids is reported. Several 5-exo-dig and 6-endo-dig modes of cyclization were observed with the nitrogen or oxygen atoms of the amide group acting as nucleophiles. The selectivity was strongly dependent on the silver salt used and on the presence of triphenylphosphine as an additive. Indeed, while the use of Ag2O at room temperature allowed the isolation of isobenzofuran-1-one oximes (7 compounds, 48-92% yield), [Ag(Im)]n with the concomitant addition of 2 equiv of PPh3 led to a switch in selectivity and to a family of isoindolin-1-ones (10 compounds, 59-87%).


Effects of 2-ethylhexanoic acid on reproduction and postnatal development in Wistar rats.
Reproductive toxicity of 2-ethylhexanoic acid (2-EHA) was studied in Wistar rats. The animals (24 animals per sex per group) were given 2-EHA as a sodium salt in drinking water at daily doses of 100, 300, or 600 mg/kg. Control animals received plain water. Male rats were exposed to 2-EHA for 10 weeks and females for 2 weeks prior to mating, both sexes during the mating period and females during the entire gestation and lactation period. 2-EHA caused a slight but dose-dependent decrease in fertility; time to mating increased at 300 and 600 mg/kg and even total infertility ensued. 2-EHA slightly decreased sperm quality in males. The spermatozoa were significantly less motile at 100 and 600 mg/kg and abnormal sperm occurred more frequently at the two highest dose levels. The average litter size was reduced by 16% in the dose group receiving 600 mg/kg. The birth weights of the pups were unaffected but the body weight gain was transiently slower during lactation at 600 mg/kg. Several pups appeared abnormal (kinky tail, lethargic, slightly paralyzed legs) and the physical development assessed by several landmarks (opening of eyes, eruption of teeth, hair growth) and reflexes (grip reflex, cliff avoidance) was delayed at 300 and 600 mg/kg. In another experiment, a single dose of 600 mg/kg 2-EHA was given to pregnant females by gavage on Gestational Day 4, 5, 6, or 7 and the number of implantations were counted on Gestational Day 10. Administration on Day 6 decreased the number of implantations and caused resorptions.(ABSTRACT TRUNCATED AT 250 WORDS)


What has changed in brachial plexus surgery?
Brachial plexus injuries, in all their severity and complexity, have been extensively studied. Although brachial plexus injuries are associated with serious and often definitive sequelae, many concepts have changed since the 1950s, when this pathological condition began to be treated more aggressively. Looking back over the last 20 years, it can be seen that the entire approach, from diagnosis to treatment, has changed significantly. Some concepts have become better established, while others have been introduced; thus, it can be said that currently, something can always be offered in terms of functional recovery, regardless of the degree of injury. Advances in microsurgical techniques have enabled improved results after neurolysis and have made it possible to perform neurotization, which has undoubtedly become the greatest differential in treating brachial plexus injuries. Improvements in imaging devices and electrical studies have allowed quick decisions that are reflected in better surgical outcomes. In this review, we intend to show the many developments in brachial plexus surgery that have significantly changed the results and have provided hope to the victims of this serious injury.


Relationship between cerebral hypoxic tissue volume and prognosis after stroke.
Between 50 and 70% of stroke survivors suffer from severe disabilities such as paralysis and aphasia. Poor stroke outcome is a reflection of our incomplete understanding of the underlying mechanisms, and hence the capacity to implement appropriate treatment(s). We evaluated hypoxic tissue after stroke and patient condition severity and prognosis. Hypoxic tissue volume was quantified within 14 days after stroke. Patients were classified as hypoxic positive or negative. Patients were evaluated at imaging and 21 days later. Prognosis was assessed at 30 and 90 days. Significant improvement was shown in hypoxia-positive (vs. hypoxia-negative) patients (p < 0.05). There were significant positive relationships between the volume of hypoxic tissue and the improvement in specialized test scores at 90 days (p < 0.05 for both). Presence of hypoxic tissue within 14 days after cerebral stroke was related to recovery at 3 weeks and prognosis at 90 days. The assessment of hypoxic tissue volume after stroke may be useful in predicting patient recovery.


Ciliary defects and genetics of primary ciliary dyskinesia.
Cilia are evolutionarily conserved structures that play key roles in diverse cell types. Motile cilia are involved in the most prominent ciliopathy called primary ciliary dyskinesia (PCD) that combines respiratory symptoms, male infertility, and, in nearly 50% cases, situs inversus. The diagnosis of PCD relies on the identification of ciliary abnormalities that mainly concern outer and/or inner dynein arms (ODA, IDA). PCD is a genetic condition, usually inherited as an autosomal recessive trait. To date, six genes have been clearly implicated in PCD. Two "major" genes, DNAI1 and DNAH5, underlie PCD in nearly half of the patients with ODA defects, whereas RPGR, DNAH11 and TXNDC3 are implicated in rare families with specific phenotypes (retinitis pigmentosa, abnormal beating of structurally normal cilia, and situs ambiguous, respectively). The relative contribution of DNAI2 is currently being assessed. In all the other patients with ODA or other ultrastructural defects, the causative genes remain to be identified.


Laboratory Hybridization Between the Green Lacewings Chrysoperla comanche (Neuroptera: Chrysopidae) and Chrysoperla rufilabris, Predators of the Asian Citrus Psyllid.
Chrysoperla comanche (Banks) and its sibling species Chrysoperla rufilabris (Burmeister) are voracious predators of the Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), an invasive pest that vectors a bacterium responsible for the lethal and incurable citrus greening disease. The Comanche lacewing naturally occurs in Southern California, whereas C. rufilabris is currently one of only two commercially available green lacewing in the United States. These sister species can be separated by larval morphological traits, by differences in courtship songs, and possibly by three nuclear genes wingless, PepCK, ATPase, yet they are not distinguishable based on the mitochondrial barcode gene (COI). Releasing in a new area a biological control agent capable of hybridizing with a resident species may pose risks that range from local displacement to irreversible loss of genetic identity. Therefore, we performed no-choice laboratory crosses to assess pre- and postzygotic isolation. We show that fertile and viable hybrid progeny could be readily obtained in interspecific crosses and backcrosses and, although there is a trend toward lower hybrid fitness, postzygotic isolation is overall weak and might not prevent loss of genetic identity under natural conditions. It remains to be determined if differences in courtship songs will prevent hybridization in the wild, as shown for other green lacewings. We also report a low prevalence of Rickettsia infection in both species.


Potential for expanded power in linkage studies using the ALLEGRO and MERLIN software programs.
Multipoint linkage analysis in complex diseases requires the use of fast algorithms that can handle many markers and a large number of moderately sized pedigrees with unknown mode of inheritance. This need has led to the development of several competitive software programs. We recently completed a genomic screen of neural tube defects using GENEHUNTER-PLUS and the more recent ALLEGRO. The ALLEGRO software was found to offer expanded power for linkage studies, particularly for childhood onset diseases like neural tube defects, though the results must be treated with caution.


Protein kinases and protein phosphatases encoded in the Ciona robusta genome.
Protein kinases (PKs) and protein phosphatases (PPs) regulate the phosphorylation of proteins that are involved in a variety of biological processes. To study such biological processes systematically, it is important to know the whole repertoire of PKs and PPs encoded in a genome. In the present study, we surveyed the genome of an ascidian (Ciona robusta or Ciona intestinalis type A) to comprehensively identify the genes that encoded PKs and PPs. Because ascidians belong to the sister group of vertebrates, a comparison of the whole repertoire of PKs and PPs of ascidians with those of vertebrates may help to delineate the complements of these proteins that were present in the last common ancestor of these two groups of animals. Our results show that the repertory of PPs was much more expanded in vertebrates than the repertory of PKs. We also showed that approximately 75% of PKs and PPs were expressed during development from eggs to larvae. Thus, the present study provides catalogs for PKs and PPs encoded in the ascidian genome. These catalogs will be useful for systematic studies of biological processes that involve phosphorylation and for evolutionary studies of the origin of vertebrates.


Lysis of erythrocytes and leukocytes in traumatic lumbar punctures.
We created "bloody taps" by adding homologous blood to acellular samples of CSF and counted the RBCs and WBCs at specific time intervals. After two hours at room temperature (22 degrees C), 40% of the WBCs in the traumatic tap had lysed. At 4 degrees C, 15% of the cells lysed in the same period of time. After five hours at 22 degrees C, 53% of the WBCs had lysed, while refrigeration reduced this figure to 31%. The clinical implications of these data are clear. If a sample of CSF is not promptly refrigerated and analyzed, WBC lysis will result in a false impression of the number of WBCs that are present. This lysis of WBCs reduces the reliability of the corrective formula that uses CSF and blood RBC and WBC counts to estimate the number of WBCs in CSF that are attributable to contamination with blood.


Comparison of bias adjustment methods in meta-analysis suggests that quality effects modeling may have less limitations than other approaches.
The quality of primary research is commonly assessed before inclusion in meta-analyses. Findings are discussed in the context of the quality appraisal by categorizing studies according to risk of bias. The impact of appraised risk of bias on study outcomes is typically judged by the reader; however, several methods have been developed to quantify this risk of bias assessment and incorporate it into the pooled results of meta-analysis, a process known as bias adjustment. The advantages, potential limitations, and applicability of these methods are not well defined. Comparative evaluation of the applicability of the various methods and their limitations are discussed using two examples from the literature. These methods include weighting, stratification, regression, use of empirically based prior distributions, and elicitation by experts. Use of the two examples from the literature suggest that all methods provide similar adjustment. Methods differed mainly in applicability and limitations. Bias adjustment is a feasible process in meta-analysis with several strategies currently available. Quality effects modelling was found to be easily implementable with fewer limitations in comparison to other methods.


Comparability of social anhedonia across epidemiological dimensions: A multinational study of measurement invariance of the Revised Social Anhedonia Scale.
Social anhedonia, or the loss of motivation in and pleasure from social engagement, is an important feature in understanding the etiology and outcome of various psychopathologies. While the Revised Social Anhedonia Scale (RSAS) represents one of the most commonly used self-report measures of social anhedonia, little is known regarding the construct comparability across populations. We examined measurement invariance of the full and brief RSAS in a diverse, international sample of 14,064 participants across nine epidemiological dimensions, including gender, age, ethnicity, education, community income, continent, migrant status, ethnic density, and urbanicity. Both the full and brief RSAS, as represented by a three-factor structure, achieved metric invariance for all dimensions. The full version showed considerable scalar noninvariance for ethnicity and continent, which was significantly reduced in the brief version. These findings suggest that while the scales measure the same construct across diverse groups, mean comparisons are only appropriate for the brief, and not the full, version. Future research may consider using the brief RSAS to ensure cross-national comparability. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Glutamate Attenuates the Survival Property of IGFR through NR2B Containing N-Methyl-D-aspartate Receptors in Cortical Neurons.
Glutamate-induced neurotoxicity is involved in various neuronal diseases, such as Alzheimer's disease. We have previously reported that glutamate attenuated the survival signaling of insulin-like growth factor-1 (IGF-1) by N-methyl-D-aspartate receptors (NMDARs) in cultured cortical neurons, which is viewed as a novel mechanism of glutamate-induced neurotoxicity. However, the phosphorylation sites of IGF-1 receptor (IGF-1R) affected by glutamate remain to be elucidated, and importantly, which subtype of NMDARs plays a major role in attenuating the prosurvival effect of IGF-1 is still unknown. In the present study, glutamate was found to attenuate the tyrosine phosphorylation of the IGF-1R and the prosurvival effect of IGF-1 in primary cultured cortical neurons. NMDAR inhibitors, MK801 and AP-5, blocked the inhibitory effect of glutamate on the phosphorylation of IGF-1R and increased cell survival, while DNQX, LY341495, and CPCCOEt had no effect. Interestingly, we found that glutamate decreased the phosphorylation of tyrosine residues 1131, 1135/1136, 1250/1251, and 1316, while it had no effect on tyrosine 950 in cortical neurons. Moreover, using specific antagonists and siRNA to downregulate individual NMDAR subunits, we found that the activation of NR2B-containing NMDARs was essential for glutamate to inhibit IGF-1 signaling. These findings indicate that the glutamate-induced attenuation of IGF-1 signaling is mediated by NR2B-containing NMDARs. Our study also proposes a novel mechanism of altering neurotrophic factor signaling by the activation of NMDARs.


[Squamous cell carcinoma of the anal canal showing pathological complete response after S-1 plus radiotherapy -a case report].
The patient was a 53-year-old woman who underwent colonoscopy for anal pain and melena. We diagnosed her with Stage I (T2N0M0) anal canal squamous cell carcinoma by biopsy specimen and CT scan. We recommended chemo-radiotherapy because she hoped to keep her anus. For this patient, we planned an S-1 administration at a dose of 120 mg/ body/day for consecutive 14 days followed by 7 days of rest period with whole pelvis and bilateral inguinal radiation (total 45 Gy/25 Fr). Then we added a booster radiation (14 Gy/7 Fr) to a local area for 5 days followed by 2 days of rest period. After 2 weeks of chemo-radiotherapy, we could not detect any tumors by colonoscopy. We diagnosed it as a pathological complete response for biopsy specimen.


Foreign body associated infection.
One of the major complications associated with the use of medical devices and implants is foreign body associated infection. Its significance in modern medicine and its pathogenesis are discussed. Adherence to and colonization of a foreign body material and the interference of microbial products with the host defence are critical steps leading to foreign body infections. Therapy is difficult and hence the immediate administration of antibiotics and the removal of an infected device or implant is still preferred. New strategies for the prevention of foreign body infections are briefly introduced.


Optimizing number of postoperative visits after cataract surgery: Safety perspective.
To evaluate safety perspectives when the standard routine after cataract surgery is no planned postoperative visit. Eye Clinic, Sunderby Hospital, Luleå, Norrbotten County, Sweden. Prospective case series. All cataract surgery cases during a 1-year period were included. The study group had the standard routine at the clinic, that is, no planned postoperative visit for patients without comorbidity and uneventful surgery. For the control group, patients who had surgery during 1 month of the 1-year period were chosen. All these patients had a planned postoperative visit. All surgeons involved were experienced. The outcome measures were any planned postoperative visit, any complication and/or adverse event, postoperative corrected distance visual acuity (CDVA), and any postoperative control/contact initiated by the patient. The study comprised 1249 patients (1115 in the study group and 134 in the control group). No significant differences in demographics, postoperative CDVA, frequency of planned visits because of ocular comorbidity, or postoperative patient-initiated contacts were found between the 2 groups. Of the 1249 patients, 9% (117 patients) initiated a postoperative contact, of whom 26% (30 patients) also had a scheduled visit. The reasons for the patient-initiated contacts were visual disturbance, redness and/or chafing, pain, and anxiety. An evaluation of all medical records 2 years postoperatively found no reports of missed adverse events. It was possible to refrain from planned postoperative visits for patients having uncomplicated cataract surgery. However, preoperatively, patients with comorbidities should be provided with individual planning of their postoperative follow-up. Preoperative counseling is important, and the clinic must have resources to answer questions from patients and be prepared for additional unplanned postoperative visits.


Ectopic ACTH syndrome due to Grawitz tumor.
An extremely unusual case of adrenocorticotropin (ACTH)-producing Grawitz tumor is reported in a 56-year-old female. The clinical feature of the patient was compatible with Cushing's syndrome. The plasma levels of ACTH and cortisol were markedly elevated. At autopsy, a left renal tumor was demonstrated and its histopathological diagnosis was renal cell carcinoma (Grawitz tumor). The adrenal gland was bilaterally enlarged with diffuse hyperplasia of the fasciculate zone. The adenohypophyseal cells were atrophic and showed Crooke's degeneration. The tumor contained extremely high levels of ACTH, beta-lipotropin and beta-endorphin. The presence of large molecular weight forms of ACTH has also been demonstrated by a Sephadex G-50 gel filtration of the tumor extract. We authors believe that this is the first documented case of ACTH-producing Grawitz tumor in the literature.


Reproducibility of resting peripheral blood flow using strain gauge plethysmography.
The purpose of this study was to examine the intra-tester and inter-tester reliability of strain gauge plethysmography (SGP) using the Hokanson EC-5R plethysmograph among three investigators. An arterial inflow test was performed by each of the investigators on fifteen college-aged volunteers at the forearm and calf sites. Intra-tester reliability was assessed by analyzing three serial measurements obtained at both sites. Intertester reliability was assessed in two ways: first, by having the three investigators obtain and analyze their own recordings, and, second, by having all three investigators (Testers 1, 2, and 3) analyze SGP recordings obtained by the most experienced investigator (Tester 1). The mean coefficient of variation (CV) for the intra-tester analysis was similar at the forearm (4.9%) and calf (4.0%) sites. The inter-tester analysis revealed that there were no significant differences among the three testers at either site when investigators obtained and analyzed their own waveforms. The CV calculated from the means of the three investigators was greater at the forearm site (10.7%) than at the calf site (2.5%). Similarly, when Testers 2 and 3 analyzed Tester 1's waveforms there were no significant differences found among testers at either site and the CV was less than when each investigator obtained his/her own waveforms. Strain gauge plethysmography blood flow measures obtained by experienced testers, under controlled laboratory conditions, are reproducible. The small variability in blood flow that exists is more attributable to variability in the acquisition of the waveforms than in the analysis of the waveforms.


Beneficial Metabolic Effects of Duodenal Jejunal Bypass Liner for the Treatment of Adipose Patients with Type 2 Diabetes Mellitus: Analysis of Responders and Non-Responders.
Implantation of a duodenal-jejunal endoluminal bypass liner (DJBL) has shown to induce weight loss and to improve metabolic parameters. DJBL is a reversible endoduodenal sleeve mimicking duodenal bypass while lacking risks and limitations of bariatric surgery.Effects on metabolic control, body mass parameters, appetite regulation, glucose tolerance, organ health, and lipid profile were determined in 16 morbidly overweight patients with type 2 diabetes mellitus. In addition, relevant hormones (leptin, ghrelin, gastric inhibitory peptide, glucagon-like peptide, and insulin) were measured by enzyme-linked immunosorbent assay (ELISA) and chemiluminescent microparticle immunoassay (CMIA) at 0, 1, 32, and 52 weeks post-implant following a mixed meal tolerance test. Lipoprotein subclasses were analysed by proton nuclear magnetic resonance (1H NMR) spectrometry. DJBL provoked weight loss, a decrease in fat mass, and an improvement in insulin resistance and hepatic function in most but not all of the patients, but in the long term did not increase gut hormone fasting levels pointing to a combined effect of more than gut parameters alone. Lipidome analysis was done in 10 patients, allowing classification to responders and non-responders by reduction of sLDL-p subfraction; and to further analyse the atherogenic profile. Responders showed an overall more pronounced effect regarding improvement of HbA1c, BMI, and HOMA index.Implantation of a DJBL in obese type 2 diabetes patients does not per se lead to an improvement of the metabolic situation. Further analyses including larger cohorts have to be performed to identify responding patients, to better treat non-responders and to analyse the key effectors.


Surface Functionalization of Poly(l-lactide-co-glycolide) Membranes with RGD-Grafted Poly(2-oxazoline) for Periodontal Tissue Engineering.
Bone tissue defects resulting from periodontal disease are often treated using guided tissue regeneration (GTR). The barrier membranes utilized here should prevent soft tissue infiltration into the bony defect and simultaneously support bone regeneration. In this study, we designed a degradable poly(l-lactide-co-glycolide) (PLGA) membrane that was surface-modified with cell adhesive arginine-glycine-aspartic acid (RGD) motifs. For a novel method of membrane manufacture, the RGD motifs were coupled with the non-ionic amphiphilic polymer poly(2-oxazoline) (POx). The RGD-containing membranes were then prepared by solvent casting of PLGA, POx coupled with RGD (POx_RGD), and poly(ethylene glycol) (PEG) solution in methylene chloride (DCM), followed by DCM evaporation and PEG leaching. Successful coupling of RGD to POx was confirmed spectroscopically by Raman, Fourier transform infrared in attenuated reflection mode (FTIR-ATR), and X-ray photoelectron (XPS) spectroscopy, while successful immobilization of POx_RGD on the membrane surface was confirmed by XPS and FTIR-ATR. The resulting membranes had an asymmetric microstructure, as shown by scanning electron microscopy (SEM), where the glass-cured surface was more porous and had a higher surface area then the air-cured surface. The higher porosity should support bone tissue regeneration, while the air-cured side is more suited to preventing soft tissue infiltration. The behavior of osteoblast-like cells on PLGA membranes modified with POx_RGD was compared to cell behavior on PLGA foil, non-modified PLGA membranes, or PLGA membranes modified only with POx. For this, MG-63 cells were cultured for 4, 24, and 96 h on the membranes and analyzed by metabolic activity tests, live/dead staining, and fluorescent staining of actin fibers. The results showed bone cell adhesion, proliferation, and viability to be the highest on membranes modified with POx_RGD, making them possible candidates for GTR applications in periodontology and in bone tissue engineering.


Genomic Organization of the B3-Domain Transcription Factor Family in Grapevine (Vitis vinifera L.) and Expression during Seed Development in Seedless and Seeded Cultivars.
Members of the plant-specific B3-domain transcription factor family have important and varied functions, especially with respect to vegetative and reproductive growth. Although B3 genes have been studied in many other plants, there is limited information on the genomic organization and expression of B3 genes in grapevine (Vitis vinifera L.). In this study, we identified 50 B3 genes in the grapevine genome and analyzed these genes in terms of chromosomal location and syntenic relationships, intron-exon organization, and promoter cis-element content. We also analyzed the presumed proteins in terms of domain structure and phylogenetic relationships. Based on the results, we classified these genes into five subfamilies. The syntenic relationships suggest that approximately half of the genes resulted from genome duplication, contributing to the expansion of the B3 family in grapevine. The analysis of cis-element composition suggested that most of these genes may function in response to hormones, light, and stress. We also analyzed expression of members of the B3 family in various structures of grapevine plants, including the seed during seed development. Many B3 genes were expressed preferentially in one or more structures of the developed plant, suggesting specific roles in growth and development. Furthermore, several of the genes were expressed differentially in early developing seeds from representative seeded and seedless cultivars, suggesting a role in seed development or abortion. The results of this study provide a foundation for functional analysis of B3 genes and new resources for future molecular breeding of grapevine.


An Application of the Reasoned Action Approach to Bystander Intervention for Sexual Assault.
The high prevalence of sexual assault in US college campuses has led to a widespread implementation of bystander intervention programs aimed at preventing sexual assault. The current study examines predictors of college students' intentions to engage in bystander intervention through the theoretical lens of the reasoned action approach. An online survey with college students (N = 186) was conducted at a large Midwestern university. Our results indicated experiential attitudes, instrumental attitudes, descriptive norms, autonomy, and capacity, each positively associated with participants' intentions to intervene to stop a sexual assault. Against expectations, injunctive norms were unrelated to bystander intervention intentions. Finally, in addition to these main effects, an experiential attitude by autonomy interaction was also observed. The results are discussed with a focus on the theoretical and practical implications of our findings.


Syncope in elderly patients. Why their risk is higher.
The elderly are at increased risk for syncope not only because of physiologic changes due to aging but also because they have a higher incidence of chronic illness and use a greater number of medications that may cause orthostatic hypotension. Although evaluation should emphasize cardiovascular and neurologic components, the cause may remain elusive in as many as 50% of patients.


Compact models for carrier-injection silicon microring modulators.
We propose compact DC and small-signal models for carrier-injection microring modulators that accurately describe the DC characteristics (resonance wavelength, quality factor, and extinction ratio) and the high frequency performance. The proposed theoretical models provide physical insights of the carrier-injection microring modulators with a variety of designs. The DC and small-signal models are implemented in Verilog-A for SPICE-compatible simulations.


Simple prognostic factors and change of inflammatory markers in patients with severe coronavirus disease 2019: a single-center observational study.
The aim of this study was to investigate the prognostic factors and evaluate the change in inflammatory markers of patients with coronavirus disease 2019 (COVID-19) requiring mechanical ventilation. This retrospective observational study conducted from April 1, 2020, to February 18, 2021, included 97 adult patients who required mechanical ventilation for severe COVID-19 pneumonia and excluded nonintubated patients with a positive COVID-19 polymerase chain reaction test and those who had any obvious bacterial infection on admission. All patients were followed up to discharge or death. We obtained clinical information and laboratory data including levels of presepsin, interleukin-6, procalcitonin, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody every day. Poor outcome was defined as death or receiving a tracheostomy during hospitalization, and favorable outcome was defined as discharge after extubation. Differences (median [interquartile range]) were detected in age (76 [70-82] versus 66 [55-74] years), day from the onset of first symptoms to admission for mechanical ventilation (5 [3-7] versus 10 [8-12] days), and P/F ratio (i.e., ratio of arterial oxygen concentration to the fraction of inspired oxygen) after intubation (186 [149-251] versus 236 [180-296]) in patients with poor outcome versus those with favorable outcome on admission. Serum SARS-CoV-2 antibody levels had already increased on admission in patients with favorable outcome. We determined the day from the onset of first symptoms to admission for mechanical ventilation to be one of the independent prognostic factors of patients with COVID-19 (adjusted odds ratio 0.69, confidence interval 0.56-0.85). These results may contribute to understanding the mechanism of progression in severe COVID-19 and may be helpful in devising an effective therapeutic strategy.


Characterization of proteinases from Antarctic krill (Euphausia superba).
Fractions of three trypsin-like proteinases, TL I, TL II, and TL III, a chymotrypsin-like proteinase, CL, two carboxypeptidase A enzymes, CPA I and CPA II and two carboxypeptidase B enzymes, CPB I and CPB II, from Antarctic krill (Euphausia superba) have been characterized with respect to purity by the means of capillary electrophoresis, CE, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The masses of the trypsin-like and chymotrypsin-like proteinases were determined to be 25,020, 25,070, 25,060, and 26,260Da for TL I, TL II, TL III, and CL, respectively. The masses of the CPA enzymes are likely 23,170 and 23,260Da, whereas the CPB enzyme masses likely are 33,730 and 33,900Da. The degradation efficiency and cleavage pattern of the trypsin-like proteinases were studied with native myoglobin as a model substrate using CE, MALDI-TOF-MS, and nanoelectrospray mass spectrometry (nESI-MS). The degradation efficiency of the trypsin-like proteinases was found to be approximately 12 and 60 times higher compared to bovine trypsin at 37 degrees C and 1-3 degrees C, respectively. All three fractions of trypsin-like proteinases showed a carboxypeptidase activity in combination with their trypsin activity.