Rural and urban primary care physician professional beliefs and quality improvement behaviors.
We evaluated whether primary care physicians (PCPs) from urban and rural practices differ on attitudes and behaviors related to quality improvement (QI) activities, patient relationships, and professionalism/self-regulation. Data from a national survey that assessed physician attitudes and behaviors based on the Physician Charter on Medical Professionalism were used. Of the 1,891 survey respondents, N = 840 were PCPs (n = 274 family medicine (response rate = 67.5%); n = 257 general internal medicine (60.8%); and n = 309 pediatricians (72.7%)). Using Rural-Urban Commuting Area (RUCA) codes, PCPs were classified as urban and rural according to their practice ZIP code. A total of n = 691 physicians were urban and n = 127 rural. Attitudes regarding participating in QI did not differ by practice location; however, rural PCPs were more likely to have reviewed an other physician's records for QI than urban PCPs (65.6% vs 48.0%, P < .001). Rural physicians were more likely to agree that physicians should talk with their patients about the cost of care than urban PCPs (40.5% vs 29.2%, P = .02). While all PCPs endorsed attitudes regarding the importance of professional behaviors (eg, reporting impaired/incompetent colleagues, disclosing medical errors) at generally similar levels, their behaviors differed. More rural physicians had a personal knowledge of an impaired/incompetent physician than urban physicians (20.7% vs 12.7%, P = .02). PCPs from rural and urban areas share similar attitudes regarding the importance of participating in QI and fulfilling professional responsibilities. However, certain behaviors (eg, knowledge of impaired colleagues) do differ. These results should be confirmed in larger studies of rural PCPs.


Xylan binding subsite mapping in the xylanase from Penicillium simplicissimum using xylooligosaccharides as cryo-protectant.
Following a recent low-temperature crystal structure analysis of the native xylanase from Penicillium simplicissimum [Schmidt et al. (1998) Protein Sci. 7, 2081-2088], where an array of glycerol molecules, diffused into the crystal during soaking in a cryoprotectant, was observed within the active-site cleft, we utilized monomeric xylose as well as a variety of linear (Xn, n = 2 to 5) and branched xylooligomers at high concentrations (typically 20% w/v) as cryoprotectant for low-temperature crystallographic experiments. Binding of the glycosidic moiety (or its hydrolysis products) to the enzyme's active-site cleft was observed after as little as 30 s soaking of a native enzyme crystal. The use of a substrate or substrate analogue as cryoprotectant therefore suggests itself as a simple and widely applicable alternative to the use of crystallographic flow-cells for substrate-saturation experiments. Short-chain xylooligomers, i.e., xylobiose (X2) and xylotriose (X3), were found to bind to the active-site cleft with its reducing end hydrogen-bonded to the catalytic acid-base catalyst Glu132. Xylotetraose (X4) and -pentaose (X5) had apparently been cleaved during the soaking time into a xylotriose plus a monomeric (X4) or dimeric (X5) sugar. While the trimeric hydrolysis product was always found to bind in the same way as xylotriose, the monomer or dimer yielded only weak and diffuse electron density within the xylan-binding cleft, at the opposite side of the active center. This suggests that the two catalytic residues divide the binding cleft into a "substrate recognition area" (from the active site toward the nonreducing end of a bound xylan chain), with strong and specific xylan binding and a "product release area" with considerably weaker and less specific binding. The size of the substrate recognition area (3-4 subsites for sugar rings) explains enzyme kinetic data, according to which short oligomers (X2 and X3) bind to the enzyme without being hydrolyzed.


A derivatization approach using pyrylium salts for the sensitive and simple determination of sulfide in spring water by high performance liquid chromatography.
A high-performance liquid chromatography method based on pre-column derivatization with the pyrylium salts (4-[p-(N,N-dimethylamino)phenyl]-2,6-diphenylpyrylium perchlorate (LN1) and 2,4,6-triphenylpyrylium tetrafluoroborate (L1)) has been developed for the determination of sulfide. After the reaction of sulfide ions with LN1 or L1 aiming at the formation of the corresponding thiopyrylium derivatives LN3 or L3, they were separated on a C18 column using phosphate buffer and acetonitrile as eluent, and afterwards detected with a UV/vis detector. By using the described method, sulfide ions can be determined in the range of 5.12-486.4 μg·L(-1) or 1.024-20.48 μg·L(-1) by means of L1 or LN1, respectively. In our experiments, the relative standard deviation was not higher than 2% and the recovery coefficient was in the range of 88-102%. The proposed method was applied to the determination of sulfide in spring water samples from Busko Zdrój and Uniejów health resorts located in Poland.


A descriptive study of the interactive guided imagery experience.
The purpose of this Study was to describe the experience of participating in Interactive Guided Imagery (IGI) from the perspective of clients. A qualitative descriptive design guided the research. Ten clients who had engaged in IGI, each with an R.N., IGI-certified practitioner, composed the sample. To explore participants' perceptions of their IGI experience, data were gathered through semistructured, in-depth interviews. Data analysis was carried out through data coding, categorizing, and subcategorizing; thematic synthesis; and structuring of relationships. Six primary themes emerged to compose the description of the experience of participating in IGI: the client's lived experience, use of a nonordinary state of consciousness, the guide, the guide-client relationship, influencing factors, and the results of IGI use. Based on the primary themes and their interrelationships, a model of the IGI experience was developed. The description and the model of the IGI experience provide the basis for further nursing knowledge development of the IGI modality.


Reproductive Maternal and Newborn Health Providers' Assessment of Facility Preparedness and Its Determinants during the COVID-19 Pandemic in Lagos, Nigeria.
The global COVID-19 pandemic is predicted to compromise the achievement of global reproductive, maternal, and newborn health (RMNH) targets. The objective of this study was to determine the health facility (HF) preparedness for RMNH service delivery during the outbreak from the perspective of RMNH providers and to determine what factors significantly predict this. An anonymous cross-sectional online survey of RMNH providers was conducted from to July 1-21, 2020 in Lagos State, Nigeria. We conducted a descriptive and ordinal regression analysis, with RMNH worker perception of HF preparedness for RMNH service delivery during the outbreak as the dependent variable. In all, 256 RMNH workers participated, 35.2% reported that RMNH services were unavailable at some time since March 2020, 87.1% felt work-related burnout, 97.7% were concerned about the availability of personal protective equipment (PPE) and related guidelines, and only 11.7% were satisfied with the preparedness of their HFs. Our final model was a statistically significant predictor of RMNH worker perception of HF preparedness explaining 54.7% of the variation observed. The most significant contribution to the model was communication by HF management (likelihood ratio chi-square [LRCS]: 87.94, P < 0.001) and the availability of PPE and COVID-19 guidelines (LRCS: 15.43, P < 0.001). A one-unit increase in the level of concern about the availability of PPE and COVID-19 guidelines would increase the odds of observing a higher category of satisfaction with HF COVID-19 preparedness. Adequate support of RMNH providers, particularly provision of PPE and guidelines, and appropriate communications about COVID-19 should be prioritized as part of HF preparedness.


Noun/verb distinction in English stress homographs: an ERP study.
Sensitivity to speech rhythm, especially the pattern of stressed and unstressed syllables, is an important aspect of language acquisition and comprehension from infancy through adulthood. In English, a strong correlation exists between speech rhythm and grammatical class. This property is well illustrated by a particular group of noun/verb homographs that are spelled the same but are pronounced with a lexical stress on the first syllable when used as a noun or on the second syllable when used as a verb. The purpose of this study was to further examine the neural markers of speech rhythm and its role in word recognition. To this end, event-related brain potentials were recorded while participants listened to spoken sentences containing a stress homograph either in a noun or a verb position. The rhythmic structure of the stress homographs was manipulated so that they were pronounced with a stress pattern that either matched or mismatched their grammatical class. Results of cluster-based permutation tests on the event-related brain potentials revealed larger negativities over the centrofrontal scalp regions when the stress homographs were mispronounced, in line with previous studies on lexical ambiguity resolution. In addition, differences between rhythmically unexpected nouns and verbs could be seen as early as 200 ms, suggesting that listeners are sensitive to statistical properties of their language rhythm. Together, these results support the hypothesis that information about speech rhythm is rapidly integrated during speech perception and contributes to lexical retrieval.


Topical erythromycin vs blank vehicle in a multiclinic acne study.
A stable solution of erythromycin was developed using a vehicle of ethanol, propylene glycol, and citric acid buffer. In a controlled, randomized, double-blind comparison, a 2% solution of erythromycin applied to moderately severe facial acne was found to be superior to the blank vehicle in reducing the number of inflamed papules. During a period of 12 weeks, such papules were reduced by 56% in the erythromycin group, compared with 33% in the blank vehicle group. In the erythromycin group, 62% of the subjects had a good or excellent response, compared with 27% of those in the blank vehicle group. Adverse effects were similar in type in both groups and included redness, scaling, dryness, oiliness, burning, itching, and irritation of the eyes. No allergic reactions or skin infections were encountered.


Pharmacokinetics and safety of extemporaneously compounded valacyclovir oral suspension in pediatric patients from 1 month through 11 years of age.
Valacyclovir provides enhanced acyclovir bioavailability in adults, but limited data are available in children. Children 1 month through 5 years of age with or at risk for herpesvirus infection received a single 25 mg/kg dose of extemporaneously compounded valacyclovir oral suspension (n = 57), whereas children 1 through 11 years of age received 10 mg/kg valacyclovir oral suspension twice daily for 3-5 days (herpes simplex virus infection) (n = 28) or 20 mg/kg 3 times daily for 5 days (varicella-zoster virus infection) (n = 27). Blood samples for pharmacokinetic analysis were collected during the 6 h after the first dose. Safety was monitored throughout the studies. Dose proportionality in the maximum observed concentration (C(max)) of acyclovir and the area under the concentration-time curve from time zero extrapolated to infinity (AUC(0-infinity)) existed across the 10 to 20 mg/kg valacyclovir dose range. For children 2 through 5 years of age, an increase in dose from 20 to 25 mg/kg resulted in near doubling of the C(max) and AUC(0-infinity). Among infants 1 through 2 months of age receiving 25 mg/kg, the mean AUC(0-infinity) and C(max) were higher ( approximately 60% and 30%, respectively) than those among older infants and children receiving the same dose. Valacyclovir oral suspension was well tolerated. No clinically significant trends were noted in clinical chemical, hematologic, or urinalysis values from screening to follow-up. Among children 3 months through 11 years of age, the 20 mg/kg dose of this formulation of valacyclovir oral suspension produces favorable acyclovir blood concentrations and is well tolerated. A dosing recommendation cannot be made for infants <3 months of age because of decreased clearance in this age group. Trial registration. ClinicalTrials.gov identifier: NCT00297206 .


Unlocking the Mystery of the Therapeutic Effects of Chinese Medicine on Cancer.
Over the past decade, the rise of cancer immunotherapy has coincided with a remarkable breakthrough in cancer therapy, which attracted increased interests in public. The scientific community clearly showed that the emergence of immunotherapy is an inevitable outcome of a holistic approach for cancer treatment. It is well established that traditional Chinese medicine (TCM) utilizes the principle of homeostasis and balance to adjust the healthy status of body. TCM treatment toward cancer has a long history, and the diagnosis and treatment of tumors were discussed in the ancient and classical literatures of Chinese medicine, such as the Yellow Emperor's Inner Canon. Precious heritage has laid the foundation for the innovation and development of cancer treatment with TCM. The modern study indicated that TCM facilitates the treatment of cancer and enhances the survival rate and life expectancy of patients. However, the pharmacological mechanisms underlying these effects are not yet completely understood. In addition, physicians cannot always explain why the TCM treatment is effective and the mechanism of action cannot be explained in scientific terms. Here, we attempted to provide insights into the development of TCM in the treatment and interpret how TCM practitioners treat cancer through six general principles of TCM by using modern scientific language and terms based on newly discovered evidence.


Prenylated xanthones and benzophenones from the fruits of Garcinia bracteata and their potential antiproliferative and anti-inflammatory activities.
Ten previously undescribed compounds, including five prenylated xanthones (1-5), two caged xanthones (16-17) and three rearranged benzophenones (27-29), together with nineteen known compounds were isolated from the fruits of Garcinia bracteata. Their structures were established on the basis of spectroscopic analysis, electronic circular dichroism calculations, and X-ray crystallographic data. Compound 17 was a caged xanthone bearing a rare 8, 8a-epoxy moiety. Compound 28 belonged to the rearranged benzophenones with rare 2, 7-dioxabicyclo-[2.2.1] heptane moiety fused at C-2 and C-3 respectively. The antiproliferative and anti-inflammatory activities of all isolated compounds were evaluated. Compounds 23 and 24 exhibited remarkable inhibitory activities against three human cancer cell lines (HepG2, T98, MCF-7) with IC50 values ranging from 3.21 ± 1.00 to 6.27 ± 1.03 μM. Moreover, compounds 20 and 24 also displayed significant inhibitory effects against NO production with IC50 values of 1.22 ± 0.01 and 1.77 ± 0.23 μM respectively. These results enrich the structural diversities of xanthones and benzophenones from Garcinia plants. Neobractatin (24) due to its anti-tumor and anti-inflammatory effects is worth further investigation in anticancer research.


Socio-demographic correlates of childlessness: an analysis of the 1971 Canadian census.
"The purpose of this paper is to examine childless women and the different socio-demographic characteristics associated with this demographic pattern. The study focuses on the proportion of ever-married and currently married women 15 years of age and over who were childless in 1971. The data source is the 1971 Canadian census 1 percent sample tape based on individual files, which yields a total sample of 46,376 women from all across Canada. The major correlations with childlessness among these women are age and marriage duration. The longer (and earlier) a woman is married, the lower the levels of childlessness when obvious demographic factors are controlled." It is found that "ascribed characteristics of ever-married women provide no meaningful associations to childlessness, and this description is applicable to the variables of religion, ethnicity, mother tongue, home language, and place of birth. Achieved characteristics, especially among the younger cohorts of women, are more revealing, and women who have higher family incomes, higher levels of education, who are living in large urban places and are involved in the labor force (among themselves highly correlated variables) generally have higher rates of childlessness. Implications of these findings are discussed."


2-(2-Meth-oxy-phen-oxy)pyrazine.
A significant twist is observed in the title molecule, C(11)H(10)N(2)O(2), as seen in the dihedral angle between the pyrazine and benzene rings of 72.79 (8)°. The meth-oxy group is almost coplanar with the benzene ring to which it is attached [C-O-C-C torsion angle = 175.83 (15)°]. Centrosymmetric dimers are formed in the crystal structure which are held together by weak π-π inter-actions between pyrazine rings [centroid-centroid distance = 3.8534 (10) Å].


Effects of cannabis oil extract on immune response gene expression in human small airway epithelial cells (HSAEpC): implications for chronic obstructive pulmonary disease (COPD).
Chronic obstructive pulmonary disease (COPD) is commonly associated with both a pro-inflammatory and a T-helper 1 (Th1) immune response. It was hypothesized that cannabis oil extract can alleviate COPD symptoms by eliciting an anti-inflammatory Th2 immune response. Accordingly, the effects of cannabis oil extract on the expression of 84 Th2 and related immune response genes in human small airways epithelial cells (HSAEpC) were investigated. HSAEpC from a single donor were treated with three dilutions of a standardized cannabis oil extract (1:400, 1:800 and 1:1600) along with a solvent control (0.25% [2.5 ul/ml] ethanol) for 24 h. There were four replicates per treatment dilution, and six for the control. RNA isolated from cells were employed in pathway-focused quantitative polymerase chain reaction (qPCR) microarray assays. The extract induced significant (P < 0.05) changes in expression of 37 tested genes. Six genes (CSF2, IL1RL1, IL4, IL13RA2, IL17A and PPARG) were up-regulated at all three dilutions. Another two (CCL22 and TSLP) were up-regulated while six (CLCA1, CMA1, EPX, LTB4R, MAF and PMCH) were down-regulated at the 1:400 and 1:800 dilutions. The relationship of differentially-expressed genes of interest to biologic pathways was explored using the Database for Annotation, Visualization and Integrated Discovery (DAVID). This exploratory investigation indicates that cannabis oil extract may affect expression of specific airway epithelial cell genes that could modulate pro-inflammatory or Th1 processes in COPD. These results provide a basis for further investigations and have prompted in vivo studies of the effects of cannabis oil extract on pulmonary function. NONE (all in vitro experiments).


Fluoroscopically guided transesophageal echocardiogram in a patient with esophageal stents.
A 73-year-old man with history of coronary artery disease and bypass surgery, atrial fibrillation, and left lower lobe non-small cell lung cancer was admitted with recurrent pneumonia and was referred for transesophageal echocardiogram for suspected aortic valve endocarditis by transthoracic echocardiography. The patient had a history of radiation treatment for lung cancer 6 years ago. He had subsequently developed esophageal strictures requiring repeated dilatations, and eventually repeated esophageal stenting. Recurrent aspiration pneumonia led to the discovery of stent erosion into his trachea leading to tracheoesophageal fistula. A covered Y tracheal stent was placed to close the fistulous tract, but persistent aspiration was noted. The cross-sectional diameter of the esophageal stents was determined to be larger than the transesophageal echocardiography (TEE) probe. TEE was performed under fluoroscopy for added safety. The esophageal stent position was confirmed with fluoroscopy before and after the procedure and the TEE probe remained inside the distal stent in the midesophageal position during the entire procedure. Small mobile vegetation was seen on the right coronary cusp and the noncoronary cusp showed a smaller vegetation. The patient tolerated the procedure well and there were no complications. Infectious disease consultation was obtained and antibiotic regimen was modified accordingly. Although there are studies addressing the safety of TEE in patients with esophageal varices, to our knowledge, there is no report of TEE being performed in patients with esophageal or tracheoesophageal stents. This case illustrates that TEE may be performed in patients with esophageal stents under careful fluoroscopic guidance. (Echocardiography 2012;29:E5-E7).


Radiofrequency Ablation of Parathyroid Glands to Treat a Patient With Hypercalcemia Caused by a Novel Inactivating Mutation in CaSR.
We identified a novel inactivating mutation in the calcium-sensing receptor (CaSR) gene in a patient with refractory hypocalciuric hypercalcemia and analyzed its function. The effectiveness of radiofrequency ablation of the parathyroid glands to treat hypercalcemia caused by this mutation was explored. Clinical data of patients before and after radiofrequency ablation were retrospectively analyzed. The CaSR mutation (D99N) found in the patient was studied in cell lines. HEK-293 cells were transfected with plasmids containing wild-type (WT) or mutant CaSR genes (D99N and W718X). Expression levels of the respective CaSR proteins were measured, and their functions were assessed by examining the effect of NPS R-568 (a CaSR agonist) on intracellular Ca2+ oscillations and that of exogenous parathyroid hormone (PTH) on intracellular cyclic adenosine monophosphate (cAMP) levels. The effectiveness of pharmacological treatment was poor, whereas radiofrequency ablation of the parathyroid glands resulted in controlled blood calcium and PTH levels in the patient. In cell lines, upon NPS R-568 administration, the amplitude of intracellular Ca2+ oscillations in the D99N group was lower than that in the WT group and higher than that in the W718X group. Upon administration of PTH, intracellular cAMP levels in the D99N group were higher than those in the WT group and lower than those in the W718X group. The homozygous mutation D99N reduced CaSR activity and caused more severe hypocalciuric hypercalcemia. For patients with this type of hypercalcemia and poor response to pharmacological treatments, radiofrequency ablation of the parathyroid glands may be a suitable treatment option.


Red-mediated transposition and final release of the mini-F vector of a cloned infectious herpesvirus genome.
Bacterial artificial chromosomes (BACs) are well-established cloning vehicles for functional genomics and for constructing targeting vectors and infectious viral DNA clones. Red-recombination-based mutagenesis techniques have enabled the manipulation of BACs in Escherichia coli without any remaining operational sequences. Here, we describe that the F-factor-derived vector sequences can be inserted into a novel position and seamlessly removed from the present location of the BAC-cloned DNA via synchronous Red-recombination in E. coli in an en passant mutagenesis-based procedure. Using this technique, the mini-F elements of a cloned infectious varicella zoster virus (VZV) genome were specifically transposed into novel positions distributed over the viral DNA to generate six different BAC variants. In comparison to the other constructs, a BAC variant with mini-F sequences directly inserted into the junction of the genomic termini resulted in highly efficient viral DNA replication-mediated spontaneous vector excision upon virus reconstitution in transfected VZV-permissive eukaryotic cells. Moreover, the derived vector-free recombinant progeny exhibited virtually indistinguishable genome properties and replication kinetics to the wild-type virus. Thus, a sequence-independent, efficient, and easy-to-apply mini-F vector transposition procedure eliminates the last hurdle to perform virtually any kind of imaginable targeted BAC modifications in E. coli. The herpesviral terminal genomic junction was identified as an optimal mini-F vector integration site for the construction of an infectious BAC, which allows the rapid generation of mutant virus without any unwanted secondary genome alterations. The novel mini-F transposition technique can be a valuable tool to optimize, repair or restructure other established BACs as well and may facilitate the development of gene therapy or vaccine vectors.


Predictive validity of Rappaport's Disability Rating Scale in subjects with acute brain dysfunction.
We implemented a correlational study to evaluate the effectiveness of Rappaport's Disability Rating Scale in predicting length of hospital stay and discharge status. We evaluated 128 patients who had had cerebrovascular accidents or head injuries using Rappaport's Disability Rating Scale and documented their lengths of stay and discharge dispositions. Significant correlations were obtained between initial Disability Rating scores and lengths of hospital stay (r = .50, p less than .01), discharge Disability Rating scores (r = .66, p less than .01), and discharge status (r = .40, p less than .01). Higher initial ratings of disability were associated with higher discharge ratings and longer terms of hospitalization. Higher ratings of disability were also associated with discharge to another treatment facility rather than home. Despite this evidence supporting the predictive validity of Rappaport's Disability Rating Scale, accurate prediction of length of hospitalization remains difficult because of extreme sample variability. Areas of further investigation are considered.


Magnetic Poly(N-isopropylacrylamide) Nanocomposites: Effect of Preparation Method on Antibacterial Properties.
The most challenging task in the preparation of magnetic poly(N-isopropylacrylamide) (Fe3O4-PNIPAAm) nanocomposites for bio-applications is to maximise their reactivity and stability. Emulsion polymerisation, in situ precipitation and physical addition were used to produce Fe3O4-PNIPAAm-1, Fe3O4-PNIPAAm-2 and Fe3O4-PNIPAAm-3, respectively. Their properties were characterised using scanning electron microscopy (morphology), zeta-potential (surface charge), thermogravimetric analysis (stability), vibrating sample magnetometry (magnetisation) and dynamic light scattering. Moreover, we investigated the antibacterial effect of each nanocomposite against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Both Fe3O4-PNIPAAm-1 and Fe3O4-PNIPAAm-2 nanocomposites displayed high thermal stability, zeta potential and magnetisation values, suggesting stable colloidal systems. Overall, the presence of Fe3O4-PNIPAAm nanocomposites, even at lower concentrations, caused significant damage to both E. coli and S. aureus DNA and led to a decrease in cell viability. Fe3O4-PNIPAAm-1 displayed a stronger antimicrobial effect against both bacterial strains than Fe3O4-PNIPAAm-2 and Fe3O4-PNIPAAm-3. Staphylococcus aureus was more sensitive than E. coli to all three magnetic PNIPAAm nanocomposites.


[Regulation of BMP signaling].
Bone morphogenetic proteins (BMPs), members of transforming growth factor-beta (TGF-beta) superfamily, bind to two different serine/threonine kinase receptors, and mediate their signals through Smad-dependent and -independent pathways. Intracellular signaling of BMPs is regulated by various modifiers and post-transcriptional modifications including phosphorylation and ubiquitination.


Envy and help giving.
In this research, we explored and demonstrated a relatively implicit and covert means of undermining envied targets-namely, helping them in a way that retains their future dependence, rather than in a way that increases their autonomy. In four studies, we varied our envy manipulations, measured the extent to which these manipulations trigger malicious motivations, and examined the consequences in terms of intended (Studies 1-2) and actual (Studies 3-4) helping behaviors. In Study 4, we also measured and tested the role of individual differences in terms of proneness to malicious versus benign envy. Taken together, our findings suggest that the extent to which envy toward superior versus neutral peers activates malicious motivations negatively impacts peoples' willingness to provide these superior peers with help, particularly with autonomous help. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Staging of breast cancer in the neoadjuvant setting.
The use of neoadjuvant chemotherapy has become more prevalent in the treatment of breast cancer patients. The finding of a pathologic complete response to neoadjuvant chemotherapy (no evidence of residual invasive cancer in the breast and lymph nodes at the time of surgical resection) has been shown to correlate with improved survival. The current version of the American Joint Committee on Cancer (AJCC) staging for breast cancer has a pretreatment clinical stage designation that is determined by clinical and radiographic examination of the patient and a postoperative pathologic stage classification based on the findings in the breast and regional lymph nodes removed at surgery. Pathologic staging has not been validated for patients receiving neoadjuvant chemotherapy; thus, prognosis is determined for these patients based on the pretreatment clinical stage. We hypothesized that clinical and pathologic staging variables could be combined with biological tumor markers to provide a novel means of determining prognosis for patients treated with neoadjuvant chemotherapy. Two scoring systems, based on summing binary indicators for clinical and pathologic substages, negative estrogen receptor status, and grade 3 tumor pathology, were devised to predict 5-year patient outcomes. These scoring systems facilitated separation of the study population into more refined subgroups by outcome than the current AJCC staging system for breast cancer, and provide a novel means for evaluating prognosis after neoadjuvant therapy.


[A randomized comparative study assessing once versus twice a day treatment of benign prostatic hyperplasia with terazosin].
We compared the efficacy of once a day administration of terazosin hydrochloride with that of twice a day administration for benign prostatic hyperplasia (BPH) patients. Forty-two patients with BPH were randomly assigned to receive a maximum dose of 2 mg terazosin either once (n = 21) or twice (n = 21) a day. International prostate symptom score (IPSS), uroflowmetry and side effect profile were determined before and 4 weeks after randomization. Both groups were similar with respect to patient age, baseline IPSS and prostate volume. After 4 weeks of treatment with terazosin, significant improvement in IPSS, maximum flow rate and mean flow rate were observed in both groups. However, these improvements did not differ significantly between them. In addition, there were no differences in side effects between the groups. In conclusion, once a day administration of terazosin hydrochloride is as effective and safe as twice a day administration in patients with BPH.


Patterns of Peripheral Nerve and Tendon Injury in Hand Trauma Patients in a Tertiary Care Hospital of Pakistan.
Introduction Traumatic injury to peripheral nerves is a major medical problem worldwide. Moreover, injury to the hand and wrist can lead to extreme morbidity and disable the injured for life. In this study, we highlight the most commonly damaged nerves and tendons that get ruptured in different types of hand trauma patients. No recent study has been done to document the etiologies and quantify the patterns of nerve and tendon involvement in hand injuries to the best of our knowledge. Methodology This was a cross-sectional study conducted at the largest trauma center in the city and the Plastic and Reconstructive Surgery ward of Civil Hospital, Karachi. A convenient sampling of 200 patients was done with the help of a preformed, well-structured questionnaire. Patients whose hand was injured solely were included in the study and those with the involvement of the whole limb or other parts of the body were excluded. Results We found that most males between the ages of 11 and 20 years presented predominantly with right-hand injury while working with machines. Nerve injury proved to be a rare occurrence. However, combined nerve injury of the ulnar, median, and radial nerve was seen in poly digit trauma. The median nerve was the most commonly damaged nerve in poly digit trauma. Among the tendon injuries, the incidence of combined tendon injury was the greatest. The flexor digitorum superficialis was the most common tendon injured overall. Conclusion This study significantly states that tendons are frequently injured in hand accidents. Plastic surgeons must also be aware of optimal nerve repair and reconstruction techniques to limit the physical disabilities and economic burden arising from nerve injury of the dominant hand.


Thymidylate synthase protein expression and activity are related to the cell proliferation rate in human cancer cell lines.
To ascertain whether the expression and enzyme activity of thymidylate synthase (TS) are related to the rapidity of cell proliferation in human cancer cell lines. Ten asynchronously growing human cancer cell lines of different origin were used, characterised by various doubling times. TS expression was evaluated by western blot analysis using the TS 106 monoclonal antibody. TS activity was determined by the enzyme catalytic assay. The quantitative variation of TS in different phases of the cell cycle was investigated using two parameter flow cytometry for the TS protein and DNA analysis. The number of proliferating cells was evaluated by Ki67 immunostaining. TS expression and activity were significantly related to each other (r = 0.765; p = 0.01) and to the cell doubling time (r = -0.899; p < 0.001 and r = -0.919; p < 0.001, respectively). Ki67 immunolabelling showed no association between the number of cycling cells and TS protein expression and activity. Two parameter flow cytometry indicated that differences of TS expression in the cell lines were not related to the cell cycle phases or to the proportion of S phase cells. These results show that the expression and activity of the TS protein in asynchronously growing cancer cells are significantly related to the cell doubling time; the faster the cell proliferation, the greater the expression and activity of TS. These findings could explain why TS values are of prognostic value per se and why tumours with high TS expression benefit more from chemotherapy.


Thrombosis in continuous-flow left ventricular assist devices: pathophysiology, prevention, and pharmacologic management.
Continuous-flow left ventricular assist devices reduce short-term mortality and improve quality of life in patients with end-stage heart failure. Unfortunately, device-related complications remain common, with many patients experiencing adverse events within the first year. New literature suggests that rates of device-related thrombosis may be increasing since 2011, which is particularly troublesome given that this pathology can result in a disabling stroke, organ damage, and death. In 2013, a group of practitioners in the field of mechanical circulatory support published a treatment algorithm based on their expert opinion. However, a comprehensive review of the pharmacotherapy of this condition is lacking. A search of the literature revealed 20 separate publications of case reports or case series describing outcomes associated with the use of drug therapy for suspected pump thrombosis. Each of these experiences was limited by small sample size, nonrandomized treatment allocation, and nonstandardized medication dosing. Data describing the outcomes of surgical versus medical management of device thrombosis are also sparse, with only three published reports identified. Based on the review of this limited literature, surgical management appears to be the preferred treatment modality, especially in those with organ hypoperfusion or hemodynamic instability. In patients ineligible for surgery, pharmacotherapy options remain limited. Use of all drug classes described in the literature for the HeartMate II device-fibrinolytics, glycoprotein IIb/IIIa inhibitors, and direct thrombin inhibitors-was hindered by either marginal efficacy or bleeding. Based on historical experience with unfractionated heparin in patients under HeartMate II support, we recommend this agent as a possible option for those with suspected pump thrombosis in lieu of surgical device exchange. For the HeartWare HVAD, limited data suggest that direct intraventricular administration of alteplase may be an acceptable treatment alternative. Additional research is clearly needed to further delineate the role of pharmacotherapy and to identify the optimal agent for managing this potentially life-threatening condition.


Laparoscopic hepatectomy for extrahepatic growing tumor. Surgical strategy based on extrahepatic growing index.
This article describes the operative procedures, varying difficulties, and required instrumentation for performing laparoscopic hepatectomy (LH) on the basis of a lesion's extrahepatic growing (EG) index, as calculated by computed tomography (CT). Laparoscopic partial hepatectomy cases were divided into the following two groups: an EG tumor group (n = 11) and an intrahepatic tumor group (n = 8). The surgical procedures, operative results, and laparoscopic instrumentation for these two groups were compared based on the EG index (/cm2; maximum diameter of tumor pedicle/maximum vertical diameter of tumor/area of the tumor). The mean operative time was significantly shorter and the mean blood loss was significantly less in the EG tumor group than in the intrahepatic tumor group. In addition, in the EG tumor group, there were significant differences in mean operative time and mean blood loss related to the values associated with the EG index (p <0.05, P <0.01). The selection of laparoscopic instruments was based on the EG index, as follows: (a) lesions with an EG index >5/cm2 underwent resection in combination with a microwave tissue coagulator and an ultrasonic surgical aspirator (13 cases, including intrahepatic tumor cases); (b) lesions with an EG index of 5-15/cm2 underwent resection in combination with a microwave tissue coagulator and laparosonic coagulating shears (four cases); (c) lesions with an EG index <%15/cm2 underwent resection with a laparoscopic linear stapler (two cases). Our preliminary experience leads us to believe that it is useful to calculate the EG index by CT scan before formulating the technical strategy for a subsequent LH procedure.


Contrasting mechanisms for photodissociation of methyl halides adsorbed on thin films of C6H6 and C6F6.
The mechanisms for photodissociation of methyl halides (CH3X, X = Cl, Br, I) have been studied for these molecules when adsorbed on thin films of C6H6 or C6F6 on copper single crystals, using time-of-flight spectroscopy with 248 nm and 193 nm light. For CH3Cl and CH3Br monolayers adsorbed on C6H6, two photodissociation pathways can be identified - neutral photodissociation similar to the gas-phase, and a dissociative electron attachment (DEA) pathway due to photoelectrons from the metal. The same methyl halides adsorbed on a C6F6 thin film display only neutral photodissociation, with the DEA pathway entirely absent due to intermolecular quenching via a LUMO-derived electronic band in the C6F6 thin film. For CH3I adsorbed on a C6F6 thin film, illumination with 248 nm light results in CH3 photofragments departing due to neutral photodissociation via the A-band absorption. When CH3I monolayers on C6H6 thin films are illuminated at the same wavelength, additional new photodissociation pathways are observed that are due to absorption in the molecular film with energy transfer leading to dissociation of the CH3I molecules adsorbed on top. The proposed mechanism for this photodissociation is via a charge-transfer complex for the C6H6 layer and adsorbed CH3I.


Immunolabeling of cells grown attached to a substratum or in suspension with actin antibodies.
Actin is a major component of all eukaryotic cells and is highly conserved across species. The different isoforms of actin show a very high degree of homology, and almost all actins bind cytochalasins, phallotoxins, and DNase I. Actin is important for maintaining cell shape and for myosin-based movements in cells. In addition, the actin cytoskeleton is involved in localization of other molecules in the cytoplasm and in cellular compartmentalization. Polyclonal and monoclonal antibodies with different specificities are commercially available for labeling actin-containing structures in cells. This article describes a protocol for immunolabeling actin that works well for cells grown in tissue culture as monolayers and for cells grown in suspension cultures that can be attached to polylysine-coated coverslips.


Analysis of the proliferative potential of residual tumor after radiosurgery for intraparenchymal brain metastases.
A retrospective immunohistochemical study of radiosurgically treated brain metastases was performed to determine whether residual tumor has reduced proliferative potential. The monoclonal antibodies MIB-10 and PC-10 were used as markers for proliferation. The experimental group consisted of pathological specimens obtained from five patients in whom brain metastasis previously had been treated with radiosurgery. Pathological specimens obtained from 10 patients with brain metastases, matched in histology to diseases in the experimental group but untreated by radiosurgery, served as controls. A significant decrease in proliferative indices was observed in metastatic brain cancers after radiosurgery (p < 0.001). These results indicate that the persistent tumor that is present at the site of a metastasis previously treated with radiosurgery is less viable and may not in itself be a significant finding.


Acute hemorrhagic encephalomyelitis in childhood: Case report and literature review.
Acute disseminated encephalomyelitis (ADEM) is an inflammatory immune-mediated disorder which is more common in pediatric patients. The clinical setting is characterized by a rapid onset of encephalopathy and multifocal neurological features. Acute hemorrhagic encephalomyelitis (AHEM) is considered a rare form of ADEM. This report shows a 2-year-old patient who presented with the classical features of ADEM and after 8 weeks developed severe neurological worsening. The second magnetic resonance image (MRI) showed hemorrhagic lesions. Differences in prognosis between ADEM and AHEM justify the investigation of AHEM whenever a patient has neurological recrudescence in a known patient of ADEM.


Transient ischemic attack as a medical emergency.
Since transient ischemic attack (TIA) is regarded as a medical emergency with high risk for early stroke recurrence, the underlying mechanisms should be immediately clarified to conclude a definitive diagnosis and provide early treatment. Early risk stratification using ABCD(2) scores can predict the risk of ischemic stroke occurring after TIA. Carotid ultrasonography (US) can evaluate the degree of stenosis, plaque properties and flow velocity of ICA lesions. High-risk mobile plaques can be classified by carotid US, and aortogenic sources of emboli can be detected by transesophageal echocardiography. Cardiac monitoring and blood findings are thought to play a key role in a diagnosis of cardioembolic TIA. Diffusion-weighted imaging (DWI)-MRI and MR angiography are also indispensable to understand the mechanism of TIA and cerebral circulation. To prevent subsequent stroke arising from TIA, antiplatelet and anticoagulant therapies should be started immediately along with comprehensive management of life-style, hypertension, diabetes mellitus, dyslipidemia and other atherosclerotic diseases. Carotid endarterectomy and endovascular intervention are critical for treating symptomatic patients with significant stenosis of ICA. A novel concept of acute cerebrovascular syndrome (ACVS) has recently been advocated to increase awareness of TIA among citizens, patients and medical professionals. TIA should be recognized as the last opportunity to avoid irreversible ischemic stroke and its sequelae. The clinical relevance of the new concept of ACVS is advocated by early recurrence after TIA, analysis of high-risk TIA, treatment strategies and the optimal management of TIA. Raising TIA awareness should also proceed across many population sectors.


Temporal course of late rectal toxicity & impact of intervention in patients undergoing radiation for cervical cancer.
: There is limited information available on the temporal course of late stage radiotherapy adverse effects. The present study reports on the temporal course of late toxicities after chemoradiation and brachytherapy. : Women with cervical cancer who presented with late toxicity after (chemo) radiation were included in the study. Grade of toxicity (Clinical Toxicity Criteria for Adverse Events version 4.03) and type of intervention were recorded at three-monthly interval for the first year and then six monthly until 24 months. Direct cost for the management of toxicity was calculated. Univariate analysis was performed to understand the impact of various factors on persistence of toxicity. : Ninety two patients were included in this study. Grades I, II, III and IV toxicities were observed in 50 (54%), 33 (36%), 7 (8%) and 2 (2%) patients, respectively, at first reporting. Patients spent a median of 12 (3-27) months with toxicity. At 12 months, 48/92 (52.2%) patients had a complete resolution of toxicity, whereas 27/92 (29.3%) patients had low grade (I-II) persistent toxicity. Only 6/92 (6.5%) patients who had grade III-IV toxicity had resolution to a lower grade. Four (4.3%) patients died due to toxicity. At 24 months, 9 (10%) patients continued to have grade ≥ III toxicity. On an average, 7 (2-24) interventions were required for the clinical management of late toxicity and median direct cost incurred was ₹ 50,625 (1,125-303,750). : In this study late radiation toxicity resolved within 12 months in more than half of patients. However, others are likely to have had persistent lower grade toxicity or progression to higher grade. Structured strategies are hence needed for the effective management of late toxicities.


Combination of Suspension Array and Mycelial Growth Assay for Detecting Multiple-Fungicide Resistance in Botrytis cinerea in Hebei Province in China.
To provide a high-throughput, efficient, and accurate method to monitor multiple-fungicide resistance of Botrytis cinerea in the field, we used the suspension array, sequencing, and mycelial growth assay in our research. Discriminating-dose bioassays for detecting carbendazim, diethofencarb, boscalid, and iprodione resistance (CarR, DieR, BosR, and IprR, respectively) were used to analyze 257 isolates collected from Hebei Province in China during 2016 and 2017. High resistance frequencies to carbendazim (100%), diethofencarb (92.08%), and iprodione (86.59%) were detected. BosR isolates accounted for 11.67% of the total. In addition, 103 isolates were randomly selected for phenotype and genotype detection. The high-throughput suspension array was utilized to detect eight genotypes simultaneously, including BenA-E198, BenA-198A, SdhB-H272, SdhB-272Y, BcOS1-I365, BcOS1-365S, erg27-F412, and erg27-412S, which were associated with resistance toward carbendazim or diethofencarb, boscalid, iprodione, and fenhexamid (FenR), respectively. Most of the benzimidazole-resistant isolates (81.55%) possessed the E198V mutation in the BenA gene. Ninety-three isolates with dual resistance to carbendazim and diethofencarb showed the E198V/K mutation. All BosR isolates carried the H272R mutation in the SdhB gene. The I365S and Q369P+N373S (66.99%) mutations in the BcOS1 gene were more frequently observed. No mutation was detected in the erg27 gene in Hebei isolates. There were 13 resistance profile phenotypes. Phenotypes with triple resistance were the most common (83.50%), and CarRDieRBosSIprRFenS was the major type. CarR isolates that carried E198V/K/A were all highly resistant (HR) and only one F200Y mutant was moderately resistant (MR) to carbendazim. Isolates that possessed E198V/K were MR or HR to diethofencarb. BosR isolates that possessed H272R mutation were lowly resistant (LR). IprR isolates were all LR or MR. The distribution of half maximal effective concentrations of CarR isolates with E198V/K mutations and IprR isolates with Q369P+N373S mutations significantly increased from 2016 to 2017. Combined with our observations, a combination method of the high-throughput suspension array and the mycelial growth assay was suggested to accurately monitor multiple resistance of B. cinerea in the field.


Noninvasive electrical stimulation as an adjunct to fusion procedures: a systematic review and meta-analysis.
Noninvasive electrical stimulation represents a distinct group of devices used to augment fusion rates. However, data regarding outcomes of noninvasive electrical stimulation have come from a small number of studies. The goal of this systematic review and meta-analysis was to determine outcomes of noninvasive electrical stimulation used as an adjunct to fusion procedures to improve rates of successful fusion. PubMed, Embase, and the Cochrane Clinical Trials database were searched according to search strategy and PRISMA guidelines. Random-effects meta-analyses of fusion rates with the three main modalities of noninvasive electrical stimulation, capacitively coupled stimulation (CCS), pulsed electromagnetic fields (PEMFs), and combined magnetic fields (CMFs), were conducted using R version 4.1.0 (The R Foundation for Statistical Computing). Both retrospective studies and clinical trials were included. Animal studies were excluded. Risk-of-bias analysis was performed with the Risk of Bias 2 (RoB 2) and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tools. Searches of PubMed, Embase, and the Cochrane Clinical Trials database identified 8 articles with 1216 participants meeting criteria from 213 initial results. There was a high overall risk of bias identified for the majority of randomized studies. No meta-analysis could be performed for CCS as only 1 study was identified. Meta-analysis of 6 studies of fusion rates in PEMF did not find any difference between treatment and control groups (OR 1.89, 95% CI 0.36-9.80, p = 0.449). Meta-analysis of 2 studies of CMF found no difference in fusion rates between control and treatment groups (OR 0.90, 95% CI 0.07-11.93, p = 0.939). Subgroup analysis of PEMF was limited given the small number of studies and patients, although significantly increased fusion rates were seen in some subgroups. This meta-analysis of clinical outcomes and fusion rates in noninvasive electrical stimulation compared to no stimulation did not identify any increases in fusion rates for any modality. A high degree of heterogeneity between studies was noted. Although subgroup analysis identified significant differences in fusion rates in certain groups, these findings were based on a small number of studies and further research is needed. This analysis does not support routine use of these devices to augment fusion rates, although the data are limited by a high risk of bias and a small number of available studies.


Modulation of the absorption, fluorescence, and liquid-crystal properties of functionalised diarylethene derivatives.
Systematic variation of the molecular symmetry in a photochromic system based on a 1,2-bis(2-methylbenzo[b]thiophen-3-yl)hexafluorocyclopentene group, connected by decyl spacers to two cyanobiphenyl groups as mesogens, allows for a systematic investigation of the correlations between molecular shape and symmetry, electronic effects, photochromic conversion and liquid-crystalline properties.


A comparative study on the raft chemical properties of various alginate antacid raft-forming products.
Research to measure the chemical characterization of alginate rafts for good raft performance and ascertain how formulation can affect chemical parameters. A selection of alginate formulations was investigated all claiming to be proficient raft formers with significance between products established and ranked. Procedures were selected which demonstrated the chemical characterization allowing rafts to effectively impede the reflux into the esophagus or in severe cases to be refluxed preferentially into the esophagus and exert a demulcent effect, with focus of current research on methods which complement previous studies centered on physical properties. The alginate content was analyzed by a newly developed HPLC method. Methods were used to determine the neutralization profile and the acid neutralization within the raft determined along with how raft structure affects neutralization. Alginate content of Gaviscon Double Action (GDA) within the raft was significantly superior (p < .0001) to all competitor products. The two products with the highest raft acid neutralization capacity were GDA and Rennie Duo, the latter product not being a raft former. Raft structure was key and GDA had the right level of porosity to allow for longer duration of neutralization. Alginate formulations require three chemical reactions to take place simultaneously: transformation to alginic acid, sodium carbonate reacting to form carbon dioxide, calcium releasing free calcium ions to bind with alginic acid providing strength to raft formation. GDA was significantly superior (p <.0001) to all other comparators.


A putative peroxidase cDNA from turnip and analysis of the encoded protein sequence.
A putative peroxidase cDNA was isolated from turnip roots (Brassica napus L. var. purple top white globe) by reverse transcriptase-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). Total RNA extracted from mature turnip roots was used as a template for RT-PCR, using a degenerated primer designed to amplify the highly conserved distal motif of plant peroxidases. The resulting partial sequence was used to design the rest of the specific primers for 5' and 3' RACE. Two cDNA fragments were purified, sequenced, and aligned with the partial sequence from RT-PCR, and a complete overlapping sequence was obtained and labeled as BbPA (Genbank Accession No. AY423440, named as podC). The full length cDNA is 1167bp long and contains a 1077bp open reading frame (ORF) encoding a 358 deduced amino acid peroxidase polypeptide. The putative peroxidase (BnPA) showed a calculated Mr of 34kDa, and isoelectric point (pI) of 4.5, with no significant identity with other reported turnip peroxidases. Sequence alignment showed that only three peroxidases have a significant identity with BnPA namely AtP29a (84%), and AtPA2 (81%) from Arabidopsis thaliana, and HRPA2 (82%) from horseradish (Armoracia rusticana). Work is in progress to clone this gene into an adequate host to study the specific role and possible biotechnological applications of this alternative peroxidase source.


Anastomoses between bronchial and coronary circulation in a porcine model: computed tomographic and angiographic demonstration.
Although the importance of the bronchial arteries is evident in modern day thoracic surgery, the significance of their communications with coronary arteries has yet to be appreciated, especially in cases of heart-lung transplantation and aortic aneurysm repair. We conducted a study to demonstrate the coronary-bronchial anastomotic routes in a porcine model using angiography and computed tomography. Six young female white pigs were used. The heart and lungs were removed en bloc, including the lower trachea and oesophagus. Digital subtraction angiography of the bronchial circulation and spiral computed tomography scan were performed in a three-phase study before and after administration of contrast medium. This was achieved by infusion either into the cannulated bronchial artery or into the aortic root. Macroscopic evaluation was carried out using latex infusion into the bronchial or coronary circulation. We demonstrated communications between the bronchial and coronary systems in 5 of 6 subjects. This communication was located at the left atrial wall and the posterior and anterior wall of the left ventricle. In one case there were further anastomoses around the right atrial wall. There were communications between the left coronary arteries and the bronchial arteries in the majority of cases. Digital subtraction angiography and spiral computer tomography scan can demonstrate these communications directly and indirectly by measurements of contrast enhancement within the heart wall. Our study emphasises the importance of the bronchial arteries in cases of heart-lung transplantation and repair of thoracic aortic aneurysms.


Quality of life for critical care patients: a concept analysis.
Confusion, misunderstanding, and ethical concerns may interfere with patients' choices for appropriate treatment and subsequent quality of life. Such concerns did not originate from recent technological advances but from the ancient Greeks and Romans who honored health more than life, and the early Christians who honored life more than health. These opposing concepts reflect differing notions of quality of life. Determining the quality of life involves personal issues--the cognitive ability to evaluate one's own life; the perception of a satisfactory state of social, emotional, physical, and mental health; and an acceptable feeling of well-being despite physical limitations. In contrast, and often conflict, are objective evaluations of treatment outcomes, morbidity/mortality statistics, cost/benefit analyses, and age studies performed in an attempt to determine quality of life by persons other than the patient.


Triplet repeat polymorphism in the transmembrane region of the MICA gene in celiac disease.
Celiac disease (CD) is characterized by a striking expansion of gamma delta T cells in the intestine. These cells interact with MICA, a cell surface protein encoded by a major histocompatibility complex gene. We investigated whether MICA gene polymorphism could contribute to susceptibility to CD. DNA typing for HLA-DR, DQA1, DQB1, TNF-308, TNFa, TNFb and a triplet repeat polymorphism in the transmembrane region of the MICA gene were carried out. We performed case-control stratified association studies and transmission disequilibrium tests. Our results indicate that although there is no primary association between MICA polymorphism and CD, there is, in addition to HLA-DQ, a second susceptibility locus on the 8.1 ancestral haplotype in strong linkage disequilibrium with MICA A5.1 allele.


Mortality, Morbidity and Related Outcomes Following Perioperative Blood Transfusion in Patients with Major Orthopaedic Surgery: A Systematic Review.
Benefits and risks of liberal and restrictive transfusion regimens are under on-going controversial discussion. This systematic review aimed at assessing both regimens in terms of pre-defined outcomes with special focus on patients undergoing major orthopaedic surgery. We performed a literature search for mortality, morbidity and related outcomes following peri-operative blood transfusion in patients with major orthopaedic surgery in electronic databases. Combined outcome measure estimates were calculated within the scope of meta-analyses including randomised clinical trials comparing restrictive versus liberal blood transfusion regimens (e.g. MH risk ratio, Peto odds ratio). A total of 880 publications were identified 15 of which were finally included (8 randomised clinical trials (RCTs) with 3,693 patients and 6 observational studies with 4,244,112 patients). Regarding RCTs, no significant differences were detected between the transfusion regimes for all primary outcomes (30-day mortality, thromboembolic events, stroke/transitory ischaemic attack, myocardial infarction, wound infection and pneumonia) and a secondary outcome (length of hospital stay), whereas there was a significantly reduced risk of receiving at least one red blood concentrate under a restrictive regimen. The results of this systematic review do not suggest an increased risk associated with either a restrictive or a liberal transfusion regimen in patients undergoing major orthopaedic surgery.


Biologically active transcripts of a large satellite RNA from arabis mosaic nepovirus and the importance of 5' end sequences for its replication.
Synthetic transcripts of a satellite RNA associated with a lilac isolate of arabis mosaic nepovirus (ArMV) were made from cDNA clones. Transcripts having either six (M1R) or 29 (M3R) extra nucleotides at their 5' ends replicated in the presence of ArMV genomic RNA in manually inoculated Chenopodium quinoa plants, even though M1R also differs from the native sequence at nucleotide position 2. Transcript 12R, which has 11 guanosyl residues and 27 other nucleotides not present in the natural satellite RNA at its 5' end, and also lacks the two 5'-terminal nucleotides (UA), replicated inefficiently, both in transformed tobacco plants and in plants that had been manually inoculated. Transcripts from another construct (M2R) lacking eight 5'-terminal bases of the native sequence did not multiply in plants. Each of these transcripts directed the in vitro synthesis of a protein (Mr 39K) encoded by satellite RNA, although 12R was the least efficient message. Analysis of the 5'-terminal sequences in progeny RNA from M1R showed that the non-native bases were removed and the second nucleotide corrected, suggesting that VPg plus a few initial 5'-terminal bases might serve as a primer for plus-strand synthesis of this satellite RNA. When M1R was inoculated with genomic RNAs from ArMV of ash or ivy, the transcripts replicated and were encapsidated. However, when the same amounts of M1R were inoculated with genomic RNAs of ArMV from hop or sugar-beet, progeny of the transcripts were not detected either in virions or in plants. Less surprisingly, this RNA transcript did not multiply in the presence of dogwood mosaic, strawberry latent ringspot, grapevine fanleaf or cherry leaf roll nepoviruses.


Rapid Removal of Acid Red 88 by Zeolite/Chitosan Hydrogel in Aqueous Solution.
In the present study, we developed a new adsorbent product with zeolite crosslinked chitosan (ZL-CH hydrogel) to remove acid red 88 (AR88) in an aqueous solution. The effects of several factors, such as the comparison of ZL-CH hydrogel and the absence of chitosan, pH, adsorbent dosage, initial AR88 concentration, contact time, and ion strength, were determined. Obtained results showed that ZL-CH hydrogel improved AR88 removal compared to the absence of chitosan, with an adsorption capacity of 332.48 mg/g in equilibrium time of 1 min, and adding ionic strength had no significant effect. However, with optimal conditions at pH 2.0, dry ZL-CH became hydrogel due to protonation of amino and hydroxyl groups through hydrogen bonds in the AR88 solution. Volume fraction and interaction force decreased with increasing porosity, leading to an increase in adsorption capacity and swelling ratio. Experimental data of the adsorption process showed the Freundlich isotherm model. The equilibrium for adsorption and swelling kinetics studies showed and fitted a pseudo-second-order model. NaOH was successful as a desorbing agent with 93.8%, and it followed the pseudo-second-order kinetics model. The recycling process indicates great potential for AR88 removal.


Results of biceps tenotomy for treatment of pathology of the long head of the biceps brachii.
Historically, the surgical treatment of bicipital pathology has been a variety of tenodesis techniques. The purpose of this study is to report the results of simple biceps tenotomy for the treatment of bicipital pathology. Thirty shoulders in 30 consecutive patients who had a simple arthroscopic biceps tendon release were reviewed. Data was collected according to the method of the American Shoulder and Elbow Surgeons (ASES) shoulder evaluation form. Outcome was assessed with the rating system of the ASES. The mean ASES shoulder score was 81.8. There was a significant reduction in pain and improvement in function after the procedure. The complication rate was 13.3%. Bicipital pathology is a significant cause of morbidity around the shoulder. The results of this study demonstrate that functional outcome as measured by the ASES scoring system can be very good with an arthroscopic biceps tendon release for the treatment of biceps tendon pathology.


Acceptor (CF3)PCPH pincer reactivity with (PPh3)3Ir(CO)H.
The syntheses of Ir(I) and Ir(III) complexes incorporating the electron-withdrawing pincer ligand (1,3-C(6)H(4)(CH(2)P(CF(3))(2))(2)) ((CF(3))PCPH) with (PPh(3))(3)Ir(CO)H and subsequent chemistry are reported. Under ambient conditions, reaction of 1 equiv. (CF(3))PCPH with (PPh(3))(3)Ir(CO)H gave the mono-bridged complex [Ir(CO)(PPh(3))(2)(H)](2)(μ-(CF(3))PCPH) (1). Reaction of (PPh(3))(3)Ir(CO)H with excess (CF(3))PCPH and MeI gave the doubly-bridged complex [Ir(CO)(PPh(3))(H)](2)(μ-(CF(3))PCPH)(2) (2), whereas the tetrameric oligomer [Ir(CO)(PPh(3))(H)](4)(μ-(CF(3))PCPH)(4) (2-sq) was obtained from a 1:1 ligand:metal mixture in benzene in the presence of excess MeI. At higher temperatures (165 °C) the reaction of (CF(3))PCPH with (PPh(3))(3)Ir(CO)H afforded the 5-coordinate Ir(I) complex ((CF(3))PCP)Ir(CO)(PPh(3)) (3). Complex 3 shows mild catalytic activity for the decarbonylation of 2-naphthaldehyde in refluxing diglyme (162 °C).


The relationship between running speed and measures of vertical jump in professional basketball players: a field-test approach.
The purpose of this study was to examine the relationship between vertical jump measures and sprint speed over 10, 20, and 40 m in professional basketball players. Thirty-three professional basketball players aged (±SD) (27.4 ± 3.3 years), body mass (89.8 ± 11.1 kg), and stature (192 ± 8.2 cm) volunteered to participate in this study. All participants were tested on squat jump, countermovement jump, and 40-m running speed. The results show that all jump measures in absolute terms were correlated significantly to running performance over 10-, 20-, and 40-m sprint times. None of the jumping performance peak powers and reactive strength were found to have a correlation to running speed times in absolute term. Furthermore, all jump height measures relative to body mass except reactive strength had a marked and significant relationship with all sprint performance times. The results of this study indicate that while there is a strong and marked relationship between 10-, 20-, and 40-m sprint, there is also a considerable variation within the factors that contribute to performance over these distances. This may indicate that, separate training strategies could be implemented to improve running speed over these distances.


Early understanding and production of graphic symbols.
Young children's ability to understand and produce graphic symbols within an environment of social communication was investigated in two experiments. Children aged 2, 3, and 4 years produced graphic symbols of simple objects on their own, used them in a social communicative game, and responded to experimenter's symbols. In Experiment 1 (N = 48), 2-year-olds did not effectively produce symbols or use the experimenter's symbols in the choice task, whereas 3- and 4-year-olds improved their drawings following the game and performed above chance with the experimenter's symbols. Ability to produce an effective graphic symbol was correlated with success on a task that measured understanding of the experimenter's symbols, supporting the claim that children's ability to produce a graphic symbol rests on the understanding of the symbolic function of pictures. In Experiment 2, 32 children aged 3 and 4 years improved their third set of drawings when they received feedback that their drawings were not effective communications. The results suggest that production and understanding of graphic symbols can be facilitated by the same social factors that improve verbal symbolic abilities, thereby raising the question of domain specificity in symbolic development.


Age estimation of immature human skeletal remains from the metaphyseal and epiphyseal widths of the long bones in the post-natal period.
This study provides regression and classical calibration models for the estimation of age from the dimensions of the metaphyses and epiphyses of the six long bones. A sample of 148 known sex and age individuals (56 females and 92 males), aged between birth and 12 years of age, selected from Portuguese and English skeletal collections. Age estimation models were obtained separately for each sex and for the sexes combined, for the entire sample and for the sample divided into two subsamples at the age of 2 years. The best performing epiphysis is the proximal epiphysis of the tibia. For the metaphyses, the distal metaphysis of the tibia and the proximal metaphysis of the femur are best for individuals below and above 2 years of age, respectively. Growth of the metaphyses is similar to that of the diaphysis. Results suggest that age can be as accurately estimated from the width of the metaphyses and epiphyses as from the length of the diaphyses, or as from the length of the deciduous and permanent teeth. These models may be useful for fragmentary material in both archaeological and forensic contexts. However, due to the background of the samples, the models would be most applicable to individuals exposed to adverse environmental conditions during growth and development. Metaphyseal and epiphyseal widths may be less affected by ecological conditions than diaphyseal length.


Determinants of the Spatial Distributions of Elemental Carbon and Particulate Matter in Eight Southern Californian Communities.
Emerging evidence indicates that near-roadway pollution (NRP) in ambient air has adverse health effects. However, specific components of the NRP mixture responsible for these effects have not been established. A major limitation for health studies is the lack of exposure models that estimate NRP components observed in epidemiological studies over fine spatial scale of tens to hundreds of meters. In this study, exposure models were developed for fine-scale variation in biologically relevant elemental carbon (EC). Measurements of particulate matter (PM) and EC less than 2.5 μm in aerodynamic diameter (EC2.5) and of PM and EC of nanoscale size less than 0.2 μm were made at up to 29 locations in each of eight Southern California Children's Health Study communities. Regression-based prediction models were developed using a guided forward selection process to identify traffic variables and other pollutant sources, community physical characteristics and land use as predictors of PM and EC variation in each community. A combined eight-community model including only CALINE4 near-roadway dispersion-estimated vehicular emissions accounting for distance, distance-weighted traffic volume, and meteorology, explained 51% of the EC0.2 variability. Community-specific models identified additional predictors in some communities; however, in most communities the correlation between predicted concentrations from the eight-community model and observed concentrations stratified by community were similar to those for the community-specific models. EC2.5 could be predicted as well as EC0.2. EC2.5 estimated from CALINE4 and population density explained 53% of the within-community variation. Exposure prediction was further improved after accounting for between-community heterogeneity of CALINE4 effects associated with average distance to Pacific Ocean shoreline (to 61% for EC0.2) and for regional NOx pollution (to 57% for EC2.5). PM fine spatial scale variation was poorly predicted in both size fractions. In conclusion, models of exposure that include traffic measures such as CALINE4 can provide useful estimates for EC0.2 and EC2.5 on a spatial scale appropriate for health studies of NRP in selected Southern California communities.


Incidence, causes, and severity of high school football injuries on FieldTurf versus natural grass: a 5-year prospective study.
Numerous injuries have been attributed to playing on artificial turf. Recently, FieldTurf was developed to duplicate the playing characteristics of natural grass. No long-term study has been conducted comparing game-related, high school football injuries between the 2 playing surfaces. High school athletes would not experience any difference in the incidence, causes, and severity of game-related injuries between FieldTurf and natural grass. Prospective cohort study. A total of 8 high schools were evaluated over 5 competitive seasons for injury incidence, injury category, time of injury, injury time loss, player position, injury mechanism, primary type of injury, grade and anatomical location of injury, type of tissue injured, head and knee trauma, and environmental factors. Findings per 10 team games indicated total injury incidence rates of 15.2 (95% confidence interval, 13.7-16.4) versus 13.9 (95% confidence interval, 11.9-15.6). Minor injury incidence rates of 12.1 (95% confidence interval, 10.5-13.6) versus 10.7 (95% confidence interval, 8.7-12.7), substantial injury incidence rates of 1.9 (95% confidence interval, 1.4-2.6) versus 1.3 (95% confidence interval, 0.8-2.1), and severe injury incidence rates of 1.1 (95% confidence interval, 0.7-1.7) versus 1.9 (95% confidence interval 1.2-2.8) were documented on FieldTurf versus natural grass, respectively. Multivariate analyses indicated significant playing surface effects by injury time loss, injury mechanism, anatomical location of injury, and type of tissue injured. Higher incidences of 0-day time loss injuries, noncontact injuries, surface/epidermal injuries, muscle-related trauma, and injuries during higher temperatures were reported on FieldTurf. Higher incidences of 1- to 2-day time loss injuries, 22+ days time loss injuries, head and neural trauma, and ligament injuries were reported on natural grass. Although similarities existed between FieldTurf and natural grass over a 5-year period of competitive play, both surfaces also exhibited unique injury patterns that warrant further investigation.


Prothrombin Complex Concentrates for Coagulopathy in Liver Disease: Single-Center, Clinical Experience in 105 Patients.
Patients with liver disease frequently develop coagulopathy, and fresh frozen plasma is traditionally used for correction of coagulopathy to manage and prevent bleeding. Prothrombin complex concentrates (PCCs) offer an attractive alternative because they are more readily available and avoid large-volume transfusion. This retrospective, single-center study reviewed clinical use of PCC in patients with acute/chronic liver disease. A total of 105 patients with 194 episodes of PCC administration were reviewed. Data pertaining to indication, dosing, effectiveness, and safety were collected. The effect of PCC on coagulation was analyzed in patients for whom coagulation results were available 7 hours before and after PCC. Data on thromboembolic events and mortality within 4 weeks of PCC administration were captured. Most patients (77%) had chronic liver disease; the remainder had acute liver failure. Indications for PCC were preprocedure prophylaxis and treatment for active/recent bleeding in 48% and 52% of 194 treatment episodes, respectively. The median dose of PCC administered was 22 IU/kg (interquartile range, 16-29 IU/kg). Before PCC administration, 45% of patients had an international normalized ratio (INR) greater than 2.0, and 36% had fibrinogen levels of at least 1.5 g/L. PCC produced statistically significant reductions in prothrombin time and INR (coadministration with fibrinogen or cryoprecipitate: 3.1 versus 1.9; P < 0.001; no coadministration: 2.3 versus 1.8; P < 0.001). Three patients with multiple risk factors developed thrombotic events (hepatic artery thrombosis, incidental bilateral pulmonary embolism, nonocclusive portal vein thrombosis); there were no cardiovascular or cerebrovascular adverse events. Overall, 46 patients died of causes unrelated to PCC treatment. Conclusion: In patients with liver disease, PCC therapy was effective in improving coagulation test results without an excess of thrombotic events. Further assessment of PCC as hemostatic therapy in this setting is required.


Surgical management after active surveillance for low-risk prostate cancer: pathological outcomes compared with men undergoing immediate treatment.
Study Type--Therapy (case control) Level of Evidence 3b. What's known on the subject? and What does the study add? The risks of delayed radical prostatectomy for men who progress on active surveillance are largely unknown. Two series have reported that prostatectomy after active surveillance has similar results to immediate therapy. Our data add to this growing body of evidence that appropriately selected men with prostate cancer can undergo active surveillance with delayed prostatectomy without added risk of missing an opportunity for cure as the majority of tumours remain organ confined. • To compare the pathological outcomes of men undergoing radical prostatectomy (RP) after a period of active surveillance (AS) with those of a similar risk group undergoing immediate surgery. • We identified men through our institutional database who underwent RP within 6 months of diagnosis or after a period of AS. The primary outcome of the present study was Gleason upgrade to ≥7 after prostatectomy. • Pathological stage and positive surgical margin rate were assessed as secondary outcomes. Binomial logistic regression models were used to determine associations of treatment subgroups with pathological upgrade, upstage and positive margins. • Thirty-three men with initially low-risk cancer features underwent RP after a median (range) of 18 (7-76) months of AS. A total of 278 men with low-risk disease features underwent immediate RP within 6 months of diagnosis. Rates of Gleason upgrading to ≥7, pathological category pT3 and positive surgical margins did not differ significantly from the immediate RP group. • On multivariate analysis of low-risk patients, adjusting for baseline pathological features, treatment group (AS followed by prostatectomy vs immediate prostatectomy) was not associated with Gleason upgrading (odds ratio, OR, 0.35; 95% CI, 0.12-1.04), non-organ-confined disease (OR, 1.67; 95% CI, 0.32-8.65) or positive surgical margins at prostatectomy (OR, 0.95; 95% CI, 0.16-5.76). • The present analysis did not show an association between RP after a period of AS and adverse pathological features for men with low-risk disease.


A New Method for Functional Evaluation of Motor Commands in Patients with Cerebellar Ataxia.
Quantitative evaluation of motor functions of patients with cerebellar ataxia is vital for evidence-based treatments and has been a focus in previous investigations of movement kinematics. Due to redundancy of the musculoskeletal system, muscle activities contain more information than the movement kinematics. Therefore, it is preferable to analyze causal anomalies of muscle activities to evaluate motor functions in patients. Here we propose a new method to evaluate the motor functions at the level of muscle activities and movement kinematics. Nineteen patients and 10 control subjects performed two movement tasks of the wrist joint, a step-tracking task and a pursuit task, with a manipulandum. The movements of the wrist joint and activities of the four wrist prime movers were recorded. We developed a linear model for the wrist joint to approximate the causal relationship between muscle activities and movement kinematics in terms of the wrist joint torque. We used a canonical correlation analysis to verify the causality between the muscle activities and the movement kinematics in the model. We found that the activities of the four muscles were related almost entirely to the position and velocity, with negligible correlation with the acceleration of the wrist joint. Moreover, the ratio of the weights for position- and velocity-related torque components characterized the contents of the muscle activities in terms of the movement kinematics. Next, we compared the ratios for the two movement tasks between the controls and patients. In control subjects, the ratios indicated clear task-specific changes that conformed to the functional requirements of the tasks. In contrast, in patients, the task-specific changes diminished highly significantly. The present results indicate that this ability to accommodate motor commands to the task requirements provides a novel quantitative parameter to characterize motor functions in patients with cerebellar ataxia.


Evolutionary lineages of nickel hyperaccumulation and systematics in European Alysseae (Brassicaceae): evidence from nrDNA sequence data.
Nickel (Ni) hyperaccumulation is a rare form of physiological specialization shared by a small number of angiosperms growing on ultramafic soils. The evolutionary patterns of this feature among European members of tribe Alysseae (Brassicaceae) are investigated using a phylogenetic approach to assess relationships among Ni hyperaccumulators at the genus, species and below-species level. Internal transcribed spacer (ITS) sequences were generated for multiple accessions of Alysseae. Phylogenetic trees were obtained for the genera of the tribe and Alyssum sect. Odontarrhena. All accessions and additional herbarium material were tested for Ni hyperaccumulation with the dimethylglyoxime colorimetric method. Molecular data strongly support the poorly known hyperaccumulator endemic Leptoplax (Peltaria) emarginata as sister to hyperaccumulator species of Bornmuellera within Alysseae. This is contrary to current assumptions of affinity between L. emarginata and the non-hyperaccumulator Peltaria in Thlaspideae. The lineage Bornmuellera-Leptoplax is, in turn, sister to the two non-hyperaccumulator Mediterranean endemics Ptilotrichum rupestre and P. cyclocarpum. Low ITS sequence variation was found within the monophyletic Alyssum sect. Odontarrhena and especially in A. murale sensu lato. Nickel hyperaccumulation was not monophyletic in any of three main clades retrieved, each consisting of hyperaccumulators and non-hyperaccumulators of different geographical origin. Nickel hyperaccumulation in Alysseae has a double origin, but it did not evolve in Thlaspideae. In Bornmuellera-Leptoplax it represents an early synapomorphy inherited from an ancestor shared with the calcicolous, sister clade of Mediterranean Ptilotrichum. In Alyssum sect. Odontarrhena it has multiple origins even within the three European clades recognized. Lack of geographical cohesion suggests that accumulation ability has been lost or gained over the different serpentine areas of south Europe through independent events of microevolutionary adaptation and selection. Genetic continuity and strong phenotypic plasticity in the A. murale complex call for a reduction of the number of Ni hyperaccumulator taxa formally recognized.


Glycoprotein V: the predominant target antigen in gold-induced autoimmune thrombocytopenia.
Autoimmune thrombocytopenia is generally caused by autoantibodies against glycoprotein (GP) IIb-IIIa or GPIb-IX and occasionally against GPIa-IIa or GPV. By investigating 38 rheumatoid arthritis (RA) patients on gold therapy, 10 with profound thrombocytopenia and 28 nonthrombocytopenic controls, we showed that in all 10 patients with thrombocytopenia, the platelet autoantibodies preferentially targeted GPV but the presence of gold was not required for their reactivity. Elevated levels of platelet-associated IgG (PAIgG) were observed in 8 of the 10 patients in whom the tests were performed. In 5 patients with sufficient autologous platelets, the GPV specificity of PAIgG was confirmed. Tests with GPV transfectants revealed that the antibodies reacted with GPV independent of GPIb alpha, GPIb beta, or GPIX. Autoantibodies recognizing GPV were not seen in the 28 nonthrombocytopenic control RA patients. Thus, GPV seems to be targeted in gold-induced autoimmune thrombocytopenia.


Therapeutic itinerary of severe malaria in adults admitted to a teaching hospital in Dakar, Senegal.
Despite prevention efforts, malaria remains a public health problem. This was a prospective study conducted between October and December 2010 that aimed to describe the therapeutic route of adults presenting with severe malaria prior to being admitted to Fann Teaching Hospital in Dakar, Senegal. A total of 90 patients were included. The majority of them had consulted a public or private health care facility (92%) prior to admission. First consultation occurred on average two days after the onset of the disease. Self-medication (67.4%) and traditional medicine (26.1%) were the main causes of delaying care. Early care and adequate management are needed to reduce malaria mortality.


Outcomes following medical termination versus prolonged pregnancy in women with severe preeclampsia before 26 weeks.
To compare maternal complications and describe neonatal outcomes in women with severe preeclampsia at ≤ 26+0 weeks in two countries with different management policies: expectant management (Brazil) versus termination of pregnancy (France). We conducted a retrospective comparative study by reviewing the medical records of women with severe preeclampsia at ≤ 26+0 weeks, from January 2010 to June 2018, in two centers: Hospital das Clínicas da Faculdade de Medicina, in Sao Paulo, Brazil (where medical abortion is forbidden in this indication) and Hôpital Antoine-Béclère, Clamart, France (where medical termination is accepted). We collected information on maternal characteristics, laboratory tests, maternal complications and fetal and newborn characteristics. We used Student's t-test and the Mann-Whitney U nonparametric test to compare quantitative variables, and Chi-square test or Fisher's exact test to evaluate the associations between the qualitative variables. There was no between-group difference in maternal complications during hospitalization (p = 0.846). In Brazil, the rate of cesarean section was 66.7%, and 20% of patients had vertical incision. The rate of spontaneous fetal death was 35.6% and among the live-born infants 26.6% were discharged from hospital. In France, one patient had a cesarean section with vertical incision. When comparing termination of pregnancy to expectant management in severe preeclampsia before 26 weeks, maternal complications were equivalent but maternal reproductive future might have been compromised in 20% of cases due to a higher risk of uterine rupture in subsequent pregnancies for patients having classic cesarean (vertical incision). 26.6% of children survived the neonatal period when pregnancy was pursued, however we lack information on their long-term follow-up.


The origin and role of MHC class I-associated self-peptides.
Under steady-state conditions, cell surface major histocompatibility complex (MHC) I molecules are associated with self-peptides collectively referred to as the self-MHC I immunopeptidome (SMII). The SMII regulates all key events that occur during the lifetime of CD8 T cells in the thymus and in the periphery. The SMII derives mainly from rapidly degraded proteins and contains a tissue-specific signature. Peptide-source proteins derive from all cell compartments but are enriched in RNA- and DNA-binding proteins, cyclins and cyclin-dependent kinases, ribosomal constituents, and chaperones. Cell stress, infection, and transformation can modify the repertoire of peptides in the SMII. Constitutive MHC I presentation of self-peptides is fraught with the risk of autoimmunity, and there is the need for complex self-tolerance mechanisms. However, self-peptide/MHC I complexes are essential for the development of "classic adaptive" TCRalphabeta CD8 T cells and directly contribute to CD8 T-cell responses against pathogens and transformed cells.


A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1).
A new method for the cytofluorimetric analysis of mitochondrial membrane potential in intact cells has been developed by using the lipophilic cationic probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1), whose monomer emits at 527 nm after excitation at 490 nm. Depending on the membrane potential, JC-1 is able of forming J-aggregates that are associated with a large shift in emission (590 nm). The color of the dye changes reversibly from green to greenish orange as the mitochondrial membrane becomes more polarized. In two human cell lines (K562 and U937), we have studied by flow cytometry the changes in membrane potential provoked by the K+ ionophor valinomycin, a drug known to affect mitochondrial membrane potential, while the K+/H+ ionophor nigericin, known to affect intracellular pH but not mitochondrial membrane potential, was used as control. The incubation with valinomycin for 10 min. at 37 degrees C in a low K+ medium provoked a marked and dose-dependent reduction in JC-1 greenish orange fluorescence, while nigericin had no effect.


Single-case design standards: An update and proposed upgrades.
In this paper, we provide a critique focused on the What Works Clearinghouse (WWC) Standards for Single-Case Research Design (Standards 4.1). Specifically, we (a) recommend the use of visual-analysis to verify a single-case intervention study's design standards and to examine the study's operational issues, (b) identify limitations of the design-comparable effect-size measure and discuss related statistical matters, (c) review the applicability and practicality of Standards 4.1 to single-case designs (SCDs), and (d) recommend inclusion of content pertaining to diversity, equity, and inclusion in future standards. Within the historical context of the WWC Pilot Standards for Single-Case Design (1.0), we suggest that Standards 4.1 may best serve as standards for meta-analyses of SCDs but will need to make clear distinctions among the various types of SCD studies that are included in any research synthesis. In this regard, we argue for transparency in SCD studies that meet design standards and those that do not meet design standards in any meta-analysis emanating from the WWC. The intent of these recommendations is to advance the science of SCD research both in research synthesis and in promoting evidence-based practices.


Mitochondrial peroxiredoxin 3 regulates sensory cell survival in the cochlea.
This study delineates the role of peroxiredoxin 3 (Prx3) in hair cell death induced by several etiologies of acquired hearing loss (noise trauma, aminoglycoside treatment, age). In vivo, Prx3 transiently increased in mouse cochlear hair cells after traumatic noise exposure, kanamycin treatment, or with progressing age before any cell loss occurred; when Prx3 declined, hair cell loss began. Maintenance of high Prx3 levels via treatment with the radical scavenger 2,3-dihydroxybenzoate prevented kanamycin-induced hair cell death. Conversely, reducing Prx3 levels with Prx3 siRNA increased the severity of noise-induced trauma. In mouse organ of Corti explants, reactive oxygen species and levels of Prx3 mRNA and protein increased concomitantly at early times of drug challenge. When Prx3 levels declined after prolonged treatment, hair cells began to die. The radical scavenger p-phenylenediamine maintained Prx3 levels and attenuated gentamicin-induced hair cell death. Our results suggest that Prx3 is up-regulated in response to oxidative stress and that maintenance of Prx3 levels in hair cells is a critical factor in their susceptibility to acquired hearing loss.


RNAi reveals anti-apoptotic and transcriptionally repressive activities of DAXX.
The function of DAXX, a highly conserved mammalian gene, has remained controversial; this is due, in part, to its identification in a variety of yeast two-hybrid screens. Targeted deletion in the mouse revealed that DAXX is essential for embryonic development. Furthermore, the increased levels of apoptosis observed in Daxx-knockout embryos and embryonic stem cell lines suggested that DAXX functions in an anti-apoptotic capacity. In contrast, overexpression studies showed that DAXX may promote apoptosis. Additional studies showed that, when overexpressed, DAXX could function as a transcriptional repressor. To clarify these matters, we have used RNAi to deplete endogenous DAXX and thereby assess DAXX function in cell lines previously tested in overexpression studies. Increased apoptosis was observed in DAXX-depleted cells, showing DAXX to be anti-apoptotic. The apoptosis induced by the absence of DAXX was rescued by Bcl-2 overexpression. In addition, transcriptional derepression was observed in RNAi-treated cells, indicating the ability of endogenous DAXX to repress gene expression and allowing for the identification of novel targets of DAXX repression, including nuclear factor kappaB (NF-kappaB)- and E2F1- regulated targets. Thus, depletion of DAXX by RNAi has verified the crucial role of endogenous DAXX as an anti-apoptotic regulator, and has allowed the identification of probable physiological targets of DAXX transcriptional repression.


Genotyping and phenotyping cytochrome P450: perspectives for cancer treatment.
As most anticancer agents display a narrow therapeutic window, patients may be susceptible to (extreme) toxicities or a lowered therapeutic outcome if not dosed adequately. Therefore, it is important to study factors which affect the pharmacokinetics and pharmacodynamics of these drugs. Among these, the contribution of genetic variation in drug metabolizing enzymes on the metabolism of anticancer agents has gathered interest, as it may potentially explain a substantial amount of interpatient variability in pharmacokinetics and drug response. Cytochrome P450, an oxidative enzyme-system involved in the breakdown of many drugs, is currently studied for correlations between genetic polymorphisms and anticancer drug metabolism. Also, alternative ways to predict the expression of cytochrome P450 have been developed (phenotyping measures) which may have additional value in creating a lowered interpatient variability, to minimize side-effects and maximize therapeutic efficacy.


Metal toxicity in the central nervous system.
The nervous system is the principal target for a number of metals. Inorganic compounds of aluminum, arsenic, lead, lithium, manganese, mercury, and thallium are well known for their neurological and behavioral effects in humans. The alkyl derivatives of certain metals--lead, mercury and tin--are specially neurotoxic. Concern over human exposure and in some cases, outbreaks of poisoning, have stimulated research into the toxic action of these metals. A number of interesting hypotheses have been proposed for the mechanism of lead toxicity on the nervous system. Lead is known to be a potent inhibitor of heme synthesis. A reduction in heme-containing enzymes could compromise energy metabolism. Lead may affect brain function by interference with neurotransmitters such as gamma-amino-isobutyric acid. There is mounting evidence that lead interferes with membrane transport and binding of calcium ions. Methylmercury produces focal damage to specific areas in the adult brain. One hypothesis proposes that certain cells are susceptible because they cannot repair the initial damage to the protein sythesis machinery. The developing nervous system is especially susceptible to damage by methylmercury. It has been discovered that microtubules are destroyed by this form of mercury and this effect may explain the inhibition of cell division and cell migration, processes that occur only in the developmental stages. These and other hypotheses will stimulate considerable experimental challenges in the future.


Preservation of native conformation during aluminium-induced aggregation of tau protein.
Aluminium exposure has been shown to result in aggregation of microtubule-associated protein tau in vitro. In the light of recent observations that the native random structure of tau protein is maintained in its monomeric and dimeric states as well as in the paired helical filaments characteristic of Alzheimer's disease, it is likely that factors playing a causative role in neurofibrillary pathology would not drastically alter the native conformation of tau protein. We have studied the interaction of tau protein with aluminium using circular dichroism (CD) and 27Al NMR spectroscopy. The CD studies revealed a five-fold increase in the observed elipticity of the tau-aluminium assembly. The increase in elipticity was not associated with a change in the general conformation of the protein and was most likely due to an aggregation of the tau protein induced by aluminium. 27Al NMR spectroscopy confirmed the binding of aluminium to tau protein. Hyperphosphorylation of tau in Alzheimer's disease is known to be associated with defective microtubule assembly in this condition. Abnormally phosphorylated tau exists in a polymerized form in the paired helical filaments (PHF) which constitute the neurofibrillary tangles found in Alzheimer's disease. While it is hypothesized that its altered biophysical characteristics render abnormally phosphorylated tau resistant to proteolysis, causing the formation of stable deposits, the sequence of events resulting in the polymerization of tau are little understood, as are the additional factors or modifications required for this process. Based on the results of our spectroscopic studies, a model for the sequence of events occurring in neurofibrillary pathology is proposed.


[Circulatory behavior in critically ill patients during hemodialysis].
Haemodynamic data were obtained during haemodialysis on 21 occasions in 7 patients with septicaemia and pancreatitis, and in 5 patients with primary renal failure without septicaemia or pancreatitis. In the former group of patients there was a lowering of the blood pressure 30, 60, 90 and 120 minutes after haemodialysis had been initiated, which was significantly greater than in the later group. The drop in the blood pressure was caused by a decreased cardiac output. The pulmonary wedge pressure dropped in all patients. Peripheral resistance and heart rate did not change during the whole procedure.