Hearing loss in workers exposed to carbon disulfide and noise.
Simultaneous exposure to carbon disulfide and noise may have a combined effect on hearing impairment. In this study we investigated hearing loss in 131 men with exposure to noise [80-91 A-weighted decibels; dB(A)] and CS(2) (1.6-20.1 ppm) in a viscose rayon plant. These men were compared with 105 men in the adhesive tape and electronic industries who were exposed to noise only and with 110 men employed in the administrative office of the rayon plant who were exposed to low noise and no CS(2). We conducted interviews to obtain sociodemographic information and exposure assessments, and we performed physical examinations, including hearing tests. Results showed that the prevalence of hearing loss of > 25 dB hearing loss (dBHL) in rayon workers (67.9%) was much higher than that in administrative workers (23.6%) and in the adhesive tape and electronic industrial workers (32.4%). Hearing loss occurred mainly for speech frequencies of 0.5, 1, and 2 kHz. When the CS(2) exposure was measured by the product of CS(2 )exposure level and employment years, the adjusted odds ratios of hearing loss of > 25 dBHL in rayon workers, compared with administrative workers, were 3.8 [95% confidence interval (CI), 1.5-9.4] for those with the exposure of 37-214 year-ppm, 14.2 (95% CI, 4.4-45.9) with 215-453 year-ppm exposure, and 70.3 (95% CI, 8.7-569.7) with exposure of > 453 year-ppm. The study suggests that CS(2) exposure enhances human hearing loss in a noisy environment and mainly affects hearing in lower frequencies.


Effects of the antibiotics Gentamicin on the postembryonic development of Chrysomya putoria (Diptera: Calliphoridae).
We evaluate the effects the antibiotic Gentamicin on the development of Chrysomya putoria (Wiedemann, 1818). Third-generation, first-instar larvae were reared in a climatic chamber on 60 g of homogenate + agar 65% and were treated with three concentrations of Gentamicin: 4.44 mg/ml, 13.33 mg/ml, and 66.66 mg/ml. The control consisted of distilled water. The relationships between mean body mass of mature larvae (measured after diet abandonment, in batches of five individuals), duration of larval and pupal stages, and overall duration of development were analyzed. The actual sex ratio was compared against the expected using the chi square. None of the parameters measured differed significantly among the four treatments, with one exception: when Gentamicin concentration was 13.33 mg/ml, larval viability differed significantly from the control. All larvae from all treatments were considered normal. We conclude that the antibiotic did not significantly alter the development of C. putoria (Wiedemann) (Diptera: Calliphoridae).


Effects of an intratracheally delivered anti-inflammatory protein (rhCC10) on physiological and lung structural indices in a juvenile model of acute lung injury.
Mechanical ventilation results in acute lung trauma that can stimulate processes that alter lung development. Activation of matrix metalloproteinases (MMPs) and their tissue-produced inhibitors (TIMPs) is initiated by the inflammatory response to mechanical ventilation and are involved in breakdown of the basement membrane and parenchymal modeling. The aim of this study was to test the hypothesis that rhCC10, a lung anti-inflammatory mediator, would foster improved lung function, structural preservation, and a reduction in net MMP activity in a juvenile model of acute lung injury. Twenty-four juvenile rabbits were saline-lavage-injured and treated with 100 or 25 mg/kg surfactant (Survanta, Ross Labs) with or without rhCC10 (Claragen, Inc.; n=6 per group). Animals were ventilated for 4 h, then euthanized for in vitro surfactant function analysis, lung histomorphometry, and analysis of MMP-2, MMP-7, and MMP-9 and TIMPs 1 and 2 in the lung. Apical lung expansion, reduced with the lower dose of surfactant, was partially restored with the addition of rhCC10. Alveolar septal wall thickness was reduced (p<0.05) with low-dose surfactant plus rhCC10 compared to high-dose surfactant alone. Increased within-group variance in MMP-2 and MMP-9 proteolytic activity was found with the low-dose surfactant and was abolished with rhCC10. MMP-7 was reduced (p<0.05) with rhCC10 administration, independent of surfactant dose. Intratracheal administration of the anti-inflammatory rhCC10 resulted in preserved lung structure and MMP/TIMP profile after 4 h of mechanical ventilation, in a surfactant dose-dependent manner.


Strategy for chromosomal assignment of expressed sequences derived from heteronuclear RNA.
The chromosomal localization of transcribed sequences/genes is one of the objectives of the human genome project. Here, we describe a novel strategy for fast and dependable chromosomal assignment of expressed sequences that contain Alu sequences. Alu-PCR was performed on cDNA that was derived from heteronuclear (hn) RNA. hn-cDNA libraries are utilized for the identification of genes from extended human chromosomal regions or entire chromosomes. For chromosomal assignment, Alu-PCR products larger than 500 bp were hybridized against genomic DNA of somatic cell hybrids that was also amplified by Alu-PCR. Hybridization signals obtained within 2-3 h of exposure allow localization of cDNA-derived Alu-PCR products to single chromosomes. This technique is particularly useful for the analysis of cDNA libraries derived from hn-RNA. Using hn-cDNA clones from different chromosomes, we demonstrate the accuracy and reliability of the mapping strategy.


Predictors of Poor Outcomes in Pediatric Venoarterial Extracorporeal Membrane Oxygenation.
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides respiratory and hemodynamic support to pediatric patients in severe cardiac failure. We aim to identify risk factors associated with poorer outcomes in this population. A retrospective chart review was conducted of pediatric patients requiring VA-ECMO support for cardiac indications at our institution from 2004 to 2015. Data were collected on demographics, indication, markers of cardiac output, ventricular assist device (VAD) insertion, heart transplantation, or left atrial (LA) decompression. Univariate Cox proportional hazards models were used to calculate hazard ratios (HRs) for variables associated with the composite primary outcome of transplant-free survival (TFS). Of the 68 reviewed patients, 65% were male, 84% were white, 38% had a prior surgery, 13% had a prior transplant, 10% had a prior ECMO support, and 87.5% required vasoactive support within six hours of cannulation. The ECMO indications included congenital heart disease repaired >30 days prior (12%), cardiomyopathy (41%), posttransplant rejection (7%), and cardiorespiratory failure (40%). The TFS was 54.5% at discharge and 47.7% at one year. Predictors of transplant and/or death include epinephrine use (hazard ratio [HR] = 2.269, P = .041), elevated lactate (HR = 1.081, P = 0005), and elevated creatinine (HR = 1.081, P = .005) within six hours prior to cannulation. Sixteen (23.6%) patients underwent LA decompression. Placement of VAD occurred in 16 (23.5%) patients, for which nonwhite race (HR = 2.94, P = .034) and prior ECMO (HR = 3.42, P = .053) were the only identified risk factors. Need for VA-ECMO for cardiac support carries high inpatient morbidity and mortality. Epinephrine use and elevated lactate and creatinine were associated with especially poor outcomes. Patients who survived to discharge had good short-term follow-up results.


Imaging modalities (MRI, CT, PET/CT), indications, differential diagnosis and imaging characteristics of cystic mediastinal masses: a review.
Cystic mediastinal masses have traditionally represented a diagnostic dilemma with differentiation of malignant masses a particular area of concern. Each imaging modality has strengths and weaknesses in mediastinal imaging-computed tomography (CT) offers increased spatial resolution at the cost of poorer soft tissue differentiation and requiring ionizing radiation, while magnetic resonance imaging (MRI) offers superior soft tissue contrast/characterization at significantly greater cost. Ultrasound offers real-time visualization but is operator and tissue dependent. [18F]fluoro-D-glucose (F-18 FDG) positron emission tomography (F-18 FDG PET) CT provides functional information, but poorer spatial resolution. Recent advances have focused upon the use of magnetic resonance imaging to aid in characterization of cystic mediastinal lesions, particularly in the context of indeterminate CT findings. The mediastinum may be divided into three anatomic compartments: prevascular, visceral, and paravertebral. All three compartments extend superiorly from the thoracic inlet and inferiorly to the diaphragm. These compartments provide a useful framework for categorizing normal and pathologic mediastinal processes. In this article, we will review the imaging characteristics of mediastinal cystic lesions via a case-based review divided by anatomical mediastinal compartments. Characteristic imaging features and troubleshooting are particular areas of focus. Normal variants that may mimic cystic pathology are discussed. The roles of CT and MRI will be emphasized. Cases from our institution are presented as illustrative examples.


The exosome and trans-acting small interfering RNAs regulate cuticular wax biosynthesis during Arabidopsis inflorescence stem development.
The primary aerial surfaces of land plants are covered with a cuticle, a protective layer composed of the cutin polyester matrix and cuticular waxes. Previously, we discovered a unique mechanism of regulating cuticular wax biosynthesis during Arabidopsis (Arabidopsis thaliana) stem elongation that involves ECERIFERUM7 (CER7), a core subunit of the exosome. Because loss-of-function mutations in CER7 result in reduced expression of the wax biosynthetic gene CER3, we proposed that CER7 is involved in degrading a messenger RNA encoding a CER3 repressor. To identify this putative repressor, we performed a cer7 suppressor screen that resulted in the isolation of the posttranscriptional gene-silencing components RNA-DEPENDENT RNA POLYMERASE1 and SUPPRESSOR OF GENE SILENCING3, indicating that small RNAs regulate CER3 expression. To establish the identity of the effector RNA species and determine whether these RNAs control CER3 transcript levels directly, we cloned additional genes identified in our suppressor screen and performed next-generation sequencing of small RNA populations that differentially accumulate in the cer7 mutant in comparison with the wild type. Our results demonstrate that the trans-acting small interfering RNA class of small RNAs are the effector molecules involved in direct silencing of CER3 and that the expression of five additional genes (EARLY RESPONSE TO DEHYDRATION14, AUXIN RESISTANT1, a translation initiation factor SUI1 family protein, and two genes of unknown function) is controlled by both CER7 and trans-acting small interfering RNAs.


Isopropanol vapor inhalation oncogenicity study in Fischer 344 rats and CD-1 mice.
The potential oncogenic effects of isopropanol, a widely used solvent, were investigated. Four groups of animals, each consisting of 75 CD-1 mice/sex and 75 Fischer 344 rats/sex, were exposed to isopropanol vapor (CAS No. 67-63-0) at target concentrations of 0 (filtered air control), 500, 2500, or 5000 ppm. Animals assigned to the core group (55 mice/sex/group and 65 rats/sex/group) were exposed for 6 hr/day, 5 consecutive days/week for at least 78 weeks for the mice or 104 weeks for the rats. Ten mice/sex/group and 10 rats/sex/group were assigned to an interim euthanasia group and were terminated during Weeks 54 and 73, respectively. In addition, 10 mice/sex/group were assigned to a recovery group and did not receive any further exposure following Week 53 but were retained until the core group of animals was euthanized. Transient signs of narcosis were observed for both mice and rats during exposure to 2500 and 5000 ppm and following exposure for mice from the 5000-ppm group. Increased mortality (100% versus 82% for controls) and a decreased mean survival time (577 days versus 631 days for controls) were noted for male rats from the 5000-ppm group. Increases in body weight and/or body weight gain were typically observed for both sexes of mice and rats from the 2500- and 5000-ppm groups throughout the study. Urinalysis and urine chemistry changes indicative of impaired kidney function (i.e., decreased osmolality and increased total protein, volume, and glucose) were noted for male rats from the 2500-ppm group as well as for male and female rats from the 5000-ppm group. At the interim euthanasia, a concentration-related increase in testes weight (absolute and relative as a percentage of body and brain weight) was observed for male rats. Concentration-related increases in absolute and relative liver weight (as a percentage of body weight) were observed for male and female mice. In addition, increased absolute and/or relative (as a percentage of body and brain weight) liver and kidney weights were observed for male and/or female rats from the 2500- and 5000-ppm groups. At necropsy, an increased incidence of seminal vesicle enlargement was observed grossly for male mice from the 2500- and 5000-ppm groups. Microscopically, some of the nonneoplastic lesions noted for mice included an increased incidence of ectasia of the seminal vesicles for male mice from the 2500- and 5000-ppm groups, minimal renal tubular proteinosis for male and female mice from all isopropanol groups, and renal tubular dilation for female mice from the 5000-ppm group. A number of nonneoplastic lesions were observed for male and female rats from the 2500- and 5000-ppm groups, with the most significant lesions being observed in the kidney and associated with chronic renal disease. The lesions noted with increased severity and/or frequency included mineralization, tubular dilation, glomerulosclerosis, interstitial nephritis, interstitial fibrosis, hydronephrosis, and transitional cell hyperplasia. The only tumor type increased in incidence during the study was interstitial cell adenomas of the testes in male rats. However, the increase in these adenomas was not believed to be exposure-related due to an unusually low incidence observed for the control group. There were no increased frequencies of neoplastic lesions noted for male or female mice or for female rats from any isopropanol exposure group. Chronic renal disease was attributed to be the main cause of death for male and female rats from the 5000-ppm group and was also considered to account for much of the mortality observed for male rats from the 2500-ppm group. In conclusion, the no-observed-effect level (NOEL) for toxic effects for both rats and mice was 500 ppm. The NOEL for oncogenicity effects for both mice and rats was determined to be greater than 5000 ppm.


Good girls and boys: findings from a cross-sectional survey on adolescent rights, relationships, and sexuality in an urban informal settlement in India.
Around 20% of India's population are adolescents aged 10-19 years. Our objective was to strengthen program interventions on gender equity, health, and participation by gauging adolescents' levels of understanding and opinions. In a cross-sectional survey, we interviewed 2005 adolescents on their opinions on rights, friendship and sex, sexual refusal and coercion, and communication with family, using a two-stage probability proportional to size sample. Opinions on gender allocations were generally equitable, although females supported clothing proscriptions. Premarital sex, multiple partners, masturbation and non-heterosexual partnerships were frowned upon. Few respondents said that they felt pressure to be sexually active, 79% said that sexual coercion was a form of violence, but 14% of older adolescents said that it would be unreasonable to refuse sex. Our interviews described young people negotiating the terrain between perceived normative expectations and contemporary aspirations, showing limited manoeuvring within assumed gender roles in which family control was prominent.


Fulvestrant in heavily pretreated metastatic breast cancer: is it still effective as a very advanced line of treatment?
Over 75% of postmenopausal patients with metastatic breast cancer have hormone receptor-positive tumors. Endocrine therapy, with its more favorable toxicity profile than chemotherapy, is the preferred treatment modality for these patients. To assess our experience with fulvestrant, an antiestrogen, in an advanced phase of treatment, after progression on the classical anti-estrogen (tamoxifen) and aromatase inhibitors The study group comprised 46 patients with metastatic breast cancer treated with fulvestrant during the years 2002-2006. Fulvestrant was given monthly until disease progression or unacceptable toxicity. The median number of fulvestrant cycles was 4.14 (range 1-32). Four patients are still on the treatment. The reasons for treatment discontinuation include disease progression (n=40), refusal (n=1), and allergic reaction (n=1). Ten patients (22%) achieved partial response and 22 (47%) had stable disease. Fourteen (30%) had disease progression with a response rate of 22% and a clinical benefit of 67%, and 14 (30%) had stable disease for > 6 months. Twenty-five patients (54%) are still alive, 4 (9%) without and 21 (45%) with disease progression. With a median follow-up of 15 months (range 1-30.1), the median time to progression was estimated to be 4 months (95% confidence interval 3.1-4.9), and the estimated overall survival 20.1 (95% CI 13.6 to upper limit; not reached yet). The 1 year estimated survival is 67%. In terms of late-phase administration, fulvestrant still appears to have a good clinical effect, with a time to progression of 4 months and a clinical benefit > 60%, notably accompanied by only very mild toxicity. Irrespective of the line of treatment the patients received, the 4 month time to progression was constant and the medication was still working effectively in a very late line of treatment in metastatic breast cancer. Fulvestrant offers clinical benefit with very mild toxicity in a very heavily pretreated population and the medication is recommended, even in patients who received many lines of chemotherapy.


Effects of onboard insecticide use on airline flight attendants.
Flight attendants (FAs) exposed to insecticide spray in an aircraft were compared with unexposed subjects for neurobehavioral function, pulmonary function, mood states, and symptoms. The 33 symptomatic FAs were self-selected, and 5 had retired for disability. Testing procedures included balance, reaction time, color discrimination, visual fields, grip strength, verbal recall, problem solving, attention and discrimination functions, and long-term memory functions. Measurements were expressed as a percentage of their predicted values (derived from unexposed controls), and the author compared the means of the percentage predicted values by analysis of variance. Symptom frequencies and Profile of Mood States (POMS) scores were assessed. FAs were significantly more impaired than controls with respect to balance with eyes closed, grip strength, and color discrimination. Nearly half had 3 or more abnormal neurobehavioral functions, after adjustment was made for age, sex, and education level. Neither elevated POMS scores nor frequencies of average symptoms correlated with their numbers of abnormal measurements. Occupational exposure to synthetic pyrethrin insecticides on airliners was associated with neurobehavioral impairment and disability retirement.


Identification and characterization of a novel autolysin (Aae) with adhesive properties from Staphylococcus epidermidis.
Staphylococcus epidermidis biofilm formation on polymer surfaces is considered a major pathogenicity factor in foreign-body-associated infections. Previously, the 148 kDa autolysin AtlE from S. epidermidis, which is involved in the initial attachment of the cells to polymer surfaces and also binds to the extracellular matrix protein vitronectin, was characterized. Here, the characterization of a novel autolysin/adhesin (Aae) in S. epidermidis is described. Aae was identified as a 35 kDa surface-associated protein that has bacteriolytic activity and binds vitronectin. Its N-terminal amino acid sequence was determined and the respective gene, aae, was cloned. DNA-sequence analysis revealed that aae encodes a deduced protein of 324 amino acids with a predicted molecular mass of 35 kDa. Aae contains three repetitive sequences in its N-terminal portion. These repeats comprise features of a putative peptidoglycan binding domain (LysM domain) found in a number of enzymes involved in cell-wall metabolism and also in some adhesins. Expression of aae by Escherichia coli and subsequent analysis revealed that Aae possesses bacteriolytic activity and adhesive properties. The interaction of Aae with fibrinogen, fibronectin and vitronectin was found to be dose-dependent and saturable and to occur with high affinity, by using the real-time Biomolecular Interaction Analysis (BIA). Aae binds to the Aalpha- and Bbeta-chains of fibrinogen and to the 29 kDa N-terminal fragment of fibronectin. In conclusion, Aae is a surface-associated protein with bacteriolytic and adhesive properties representing a new member of the staphylococcal autolysin/adhesins potentially involved in colonization.


A matter of trust: a qualitative comparison of the determinants of COVID-19 vaccine hesitancy in Taiwan, the United States, the Netherlands, and Haiti.
COVID-19 vaccination is an effective intervention preventing individuals from contracting SARS-CoV-2 or transmitting the virus to others. However, in many countries, vaccine hesitancy has impeded the progress of mass vaccination to reach herd immunity. This study aimed to understand the similarities and differences in the determinants of COVID-19 vaccine hesitancy in Taiwan, the United States, the Netherlands, and Haiti. A qualitative study was conducted by face-to-face interviews with participants in Taiwan and remote online interviews with participants in the United States, the Netherlands, and Haiti. In total, 47 interviews were conducted. A reflective thematic analysis was employed to analyze the collected data. Distrust of COVID-19 vaccines was reported by the participants in all countries. A perception of a lack of necessity or urgency to be vaccinated was reported by the Taiwanese and Haitian participants. Lack of knowledge regarding COVID-19 vaccines was reported by the Taiwanese, U.S. and Haitian participants, contributing to hesitation or refusal to vaccination. Regarding misinformation and rumors, misinformation was found among a few Taiwanese and Dutch participants. Additionally, rumors concerning COVID-19 vaccines were mentioned by the Dutch and Haitian participants. Furthermore, a lack of verified information was reported by the participants in all four countries. Overall, the current study suggests that vaccine hesitancy exists among participants in Taiwan, the United States, the Netherlands, and Haiti. Building trust in the COVID-19 vaccine, cultivating vaccine literacy, clarifying misinformation and rumors concerning COVID-19 vaccines, and providing verified information are critical for increasing public acceptance of the COVID-19 vaccine.


Late weaning: the most significant risk factor in the development of iron deficiency anaemia at 1-2 years of age.
The global prevalence of iron deficiency anaemia in young children is quite high and children between the ages of 1-2 years are at maximum risk. The complications of anaemia are well known, and side effects may go unnoticed and may have an adverse effect on child's life. Therefore, prevention of anaemia becomes enormously important, and the need to look for parameters and predisposing factors that may lead to iron deficiency anaemia in small children is imperative. This study was designed to determine the association of iron deficiency anaemia with late weaning in 1-2 years of children. A case control study was conducted from July 1993-July 1995, at the Community Health Centre (CHC), of the Aga Khan University Hospital, at Karachi, Pakistan. The study included 50 cases and 100 controls. A questionnaire was filled by mothers after taking consent. Data was analyzed by chi-square; t-tests, bivariate analysis and multiple logistic regression. Through bivariate analyses, late weaning, family income, mother's education, the numbers of pregnancies, live births and living children, were found to be statistically significant. These variables were run through a multiple logistic regression model and late weaning was found to be the most significant. 60% of cases and 9% of controls were weaned late (p < 0.001). The mean age of weaning was 7.04 months among cases and 4.46 months among controls (p < 0.001). Among all the variables studied, late weaning was the most important predictor of iron deficiency anaemia in 1-2 years of age.


Donor site sequelae after autologous breast reconstruction with an extended latissimus dorsi flap.
The indications for autologous reconstruction are increasing. The standard procedure is the transverse rectus abdominis muscle flap; however, this flap has contraindications and drawbacks. The latissimus dorsi muscle flap is simple and reliable. Hokin et al. demonstrated in 1983 that this flap can be extended and used for breast reconstruction without an implant. Since then, it has been widely studied in this setting and is known to provide good aesthetic results. Dorsal sequelae, conversely, were not appraised. The aim of this study was to assess objective and subjective dorsal sequelae after the harvest of an extended flap. Forty-three consecutive patients who had had breast reconstruction with an autologous latissimus dorsi flap were assessed by a surgeon and a physiotherapist for muscular strength and shoulder mobility. Patient opinion was studied through a questionnaire. Mean delay between the operation and the evaluation was 19 months. Early complications, mainly dorsal seromas, were frequent after the harvest of an extended flap (72 percent). There was no late morbidity and, especially, no flap loss or partial necrosis. As for functional results, 37 percent of the patients had complete adjustment and 70 to 87 percent demonstrated no change in shoulder strength. Sixty percent of the patients experienced no limitation in everyday life, and 90 percent said they would undergo this procedure again. The authors show that dorsal sequelae after an extended latissimus dorsi flap are minimal and that this technique compares favorably with the transverse rectus abdominis muscle flap.


Circ_ZFR affects FABP7 expression to regulate breast cancer progression by acting as a sponge for miR-223-3p.
Breast cancer (BC) is a common malignancy in women. Circular RNAs (circRNAs) have been reported to play a key role in the development of BC; however, the effect of circular RNA zinc finger RNA binding protein (circ_ZFR) in BC is unknown. Abundances of circ_ZFR, fatty acid binding protein 7 (FABP7), and microRNA-223-3p (miR-223-3p) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The circular structure of circ_ZFR was validated by RNase R treatment. Cell proliferation, migration, invasion, and apoptosis were assessed by colony formation, cell counting kit-8, Transwell, flow cytometry assays, respectively. All protein levels were determined by Western blot. Dual-luciferase reporter assay was used to confirm the relationship between miR-223-3p and circ_ZFR or FABP7. A xenograft model was established to understand the effect of circ_ZFR on BC cell growth in vivo. The expression levels of circ_ZFR and FABP7 were higher in BC tissues and cell lines, whereas miR-223-3p expression was lower. Knockdown of circ_ZFR or FABP7 in BC cells reduced proliferation, migration, invasion, and epithelial mesenchymal transition (EMT), and induced apoptosis in vitro, whereas the opposite effects were observed in circ_ZFR-overexpressed cells. Furthermore, circ_ZFR might act as a sponge for miR-223-3p to regulate FABP7 expression, thereby promoting the progression of BC cells in vitro and in vivo. Circ_ZFR might act as a miRNA sponge for miR-223-3p to regulate FABP7, thereby promoting proliferation, migration, invasion, and EMT of BC cells, and inhibiting cell apoptosis.


Aqueous Dispersions of Silica Stabilized with Oleic Acid Obtained by Green Chemistry.
The present study describes for the first time the synthesis of silica nanoparticles starting from sodium silicate and oleic acid (OLA). The interactions between OLA and sodium silicate require an optimal OLA/OLANa molar ratio able to generate vesicles that can stabilize silica particles obtained by the sol-gel process of sodium silicate. The optimal molar ratio of OLA/OLANa can be ensured by a proper selection of OLA and respectively of sodium silicate concentration. The titration of sodium silicate with OLA revealed a stabilization phenomenon of silica/OLA vesicles and the dependence between their average size and reagent's molar ratio. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) measurements emphasized the successful synthesis of silica nanoparticles starting from renewable materials, in mild condition of green chemistry. By grafting octadecyltrimethoxysilane on the initial silica particles, an increased interaction between silica particles and the OLA/OLANa complex was achieved. This interaction between the oleyl and octadecyl chains resulted in the formation of stable gel-like aqueous systems. Subsequently, olive oil and an oleophylic red dye were solubilized in these stable aqueous systems. This great dispersing capacity of oleosoluble compounds opens new perspectives for future green chemistry applications. After the removal of water and of the organic chains by thermal treatment, mesoporous silica was obtained.


A PHYLOGENETIC ANALYSIS OF CHARACTER DISPLACEMENT IN CARIBBEAN ANOLIS LIZARDS.
Twenty-seven islands in the Lesser Antilles contain either one or two species of Anolis lizards. On nine of the ten two-species islands, the species differ substantially in size; 16 of the 17 one-species islands harbor an intermediate-sized species. Two processes could produce such a pattern: size adjustment (or character displacement), in which similar-sized species evolve in different directions in sympatry; and size assortment, in which only different-sized species can successfully colonize the same island together. Previous analyses implicitly have assumed that size is evolutionarily plastic and determined solely by recent ecological conditions, and consequently have tested the hypothesis that character displacement has occurred on each of the ten two-species islands. Other studies have focused only on size assortment. By analyzing such patterns in a phylogenetic context, I explicitly consider historical effects and can distinguish between size adjustment and size assortment. Using a minimum evolution algorithm, I assess evidence for size adjustment by partitioning changes in size along branches of the phylogenetic tree. Size evolution appears rare (a minimum of 4-7 instances of substantial size evolution). In the northern (but not the southern) Lesser Antilles, size change was significantly greater when a descendant taxon occurred on a two-species island and its hypothetical ancestor occurred on a one-species island, thus supporting the size adjustment hypothesis, though size adjustment might have occurred only once. The relative rarity of size evolution suggests that size assortment might be responsible for nonrandom patterns. In both the northern and southern Lesser Antilles, a null model of no size assortment is convincingly rejected. Closely related taxa, however, are usually similar in size, and hybridization between species has been reported. Consequently, similar-sized species might not coexist because they interbreed and coalesce into one gene pool. A null model that only allows species from different "clades" to co-occur is rejected for the northern Lesser Antilles, but is ambiguous with regard to the southern Lesser Antilles. Thus, competitive exclusion is probably responsible for the pattern of size assortment in the northern Lesser Antilles; both competitive exclusion and interbreeding of closely related species of similar size might be responsible for the patterns evident in the southern Lesser Antilles.


Toward intracellular targeted delivery of cancer therapeutics: progress and clinical outlook for brain tumor therapy.
A number of anti-cancer drugs have their targets localized to particular intracellular compartments. These drugs reach the targets mainly through diffusion, dependent on biophysical and biochemical forces that allow cell penetration. This means that both cancer cells and normal cells will be subjected to such diffusion; hence many of these drugs, like chemotherapeutics, are potentially toxic and the concentration achieved at the site of their action is often suboptimal. The same relates to radiation that indiscriminately affects normal and diseased cells. However, nature-designed systems enable compounds present in the extracellular environment to end up inside the cell and even travel to more specific intracellular compartments. For example, viruses and bacterial toxins can more or less specifically recognize eukaryotic cells, enter these cells, and direct some protein portions to designated intracellular areas. These phenomena have led to creative thinking, such as employing viruses or bacterial toxins for cargo delivery to cells and, more specifically, to cancer cells. Proteins can be genetically engineered in order to not only mimic what viruses and bacterial toxins can do, but also to add new functions, extending or changing the intracellular routes. It is possible to make conjugates or, more preferably, single-chain proteins that recognize cancer cells and deliver cargo inside the cells, even to the desired subcellular compartment. These findings offer new opportunities to deliver drugs/labels only to cancer cells and only to their site of action within the cells. The development of such dual-specificity vectors for targeting cancer cells is an attractive and potentially safer and more efficacious way of delivering drugs. We provide examples of this approach for delivering brain cancer therapeutics, using a specific biomarker on glioblastoma tumor cells.


Endocrine pancreatic tumors in von Hippel-Lindau disease: clinical, histological, and genetic features.
Endocrine pancreatic tumors (EPTs) in von Hippel-Lindau (VHL) disease pose difficult management problems. We aimed to assess (1) the accuracy of somatostatin receptor scintigraphy, (2) histological features with focus on malignancy and genotype-phenotype correlations, and (3) prognosis of VHL-EPT. Thirty-five patients with EPT-VHL (20 women; median age, 37 years) from 29 families were studied. Histological diagnosis was available in 29 patients. Endocrine pancreatic tumor patients were treated surgically (n = 22), medically (n = 8), or followed (n = 5). Somatostatin receptor scintigraphy was performed in 27 patients. Germinal alterations of the VHL gene were determined. Tumors were malignant in 58% of patients. Somatostatin receptor scintigraphy was positive in 60% of cases, and weak expression of the somatostatin receptor type 2A was found in 47% of tumors. In operated patients, there was no mortality or tumor relapse (median follow-up, 5 [1-10] years). Mortality rate due to EPT was 6%. Germinal mutations were mainly located in exons 3 and 1, and a specific mutation (P86S) was identified. Most EPTs in VHL patients are somatostatin receptor scintigraphy-positive and malignant, without correlation with the VHL genotype. Surgical resection is often required, but prognosis of these EPTs seems to be fairly good.


Immune complex deposition in Bowman's capsule is associated with parietal podocytes.
We have recently documented the presence of podocytes lining part of Bowman's capsule at the vascular pole, in adult human kidney. In this study, we describe the deposition of immune complexes in Bowman's capsule in association with these parietal podocytes. We examined 1 year's consecutive human renal biopsies (n = 170). Transmission electron microscopy (TEM) revealed 18 cases in which parietal podocytes were present. Of these 18, there were 11 cases of glomerulonephritis, in which immune complexes were demonstrated in the capillary tuft by both TEM and direct immunofluorescence microscopy. In seven of these 11 cases, TEM showed immune complex-type deposits in Bowman's capsule, always associated with parietal podocytes. These deposits were similar in size, appearance, and distribution to the deposits in the capillary tuft. By contrast, non-specific electron densities within Bowman's capsule were found beneath both squamous parietal cells and parietal podocytes. In four cases, Bowman's capsule also showed focal positive immunostaining for complement components and/or fibrinogen. Both parietal and visceral podocytes showed similar fusion of pedicles. We suggest that filtration through parietal podocytes may be responsible for immune complex deposition and subsequent damage to the vascular pole of the glomerulus in human renal disease.


Optimization of co-evolution analysis through phylogenetic profiling reveals pathway-specific signals.
The exponential growth in available genomic data is expected to reach full sequencing of a million genomes in the coming decade. Improving and developing methods to analyze these genomes and to reveal their utility is of major interest in a wide variety of fields, such as comparative and functional genomics, evolution and bioinformatics. Phylogenetic profiling is an established method for predicting functional interactions between proteins based on similarities in their evolutionary patterns across species. Proteins that function together (i.e. generate complexes, interact in the same pathways or improve adaptation to environmental niches) tend to show coordinated evolution across the tree of life. The normalized phylogenetic profiling (NPP) method takes into account minute changes in proteins across species to identify protein co-evolution. Despite the success of this method, it is still not clear what set of parameters is required for optimal use of co-evolution in predicting functional interactions. Moreover, it is not clear if pathway evolution or function should direct parameter choice. Here, we create a reliable and usable NPP construction pipeline. We explore the effect of parameter selection on functional interaction prediction using NPP from 1028 genomes, both separately and in various value combinations. We identify several parameter sets that optimize performance for pathways with certain biological annotation. This work reveals the importance of choosing the right parameters for optimized function prediction based on a biological context. Source code and documentation are available on GitHub: https://github.com/iditam/CompareNPPs. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Malathion-induced granulosa cell apoptosis in caprine antral follicles: an ultrastructural and flow cytometric analysis.
Organophosphate pesticides (OPs) like malathion interfere with normal ovarian function resulting in an increased incidence of atresia and granulosa cell apoptosis that plays a consequential role in the loss of ovarian follicles or follicular atresia. The aim of present study was to assess malathion-induced (100 nM) reproductive stress, ultrastructural damage and changes in apoptosis frequency in ovarian granulosa cells of antral follicles. Transmission electron microscopy (TEM) was employed for ultrastructural characterization, oxidative stress was evaluated using thiobarbituric acid reactive substances (TBARS) assay to measure lipid peroxidation, and apoptosis was quantified via flow cytometry. By TEM, apoptosis was identified by the presence of an indented nuclear membrane with blebbing, pyknotic crescent-shaped fragmented nuclei, increased vacuolization, degenerating mitochondria, and lipid droplets. The results indicate a significant increase in malondialdehyde (MDA) level (nmols/g wet tissue) at a 100 nM dose of malathion i.e. 7.57±0.033*, 8.53±0.12*, and 12.87±0.78** at 4, 6, or 8 h, respectively, as compared with controls (6.07±0.033, p<0.01*, p<0.05**) showing a positive correlation between malathion-induced lipid peroxidation and percentage of granulosa cell apoptosis (r=1; p<0.01). The parallel use of these three methods enabled us to determine the role of malathion in inducing apoptosis as a consequence of cytogenetic damage and oxidative stress generated in granulosa cells of antral follicles.


Engineering of TEV protease variants with redesigned substrate specificity.
Due to their ability to catalytically cleave proteins and peptides, proteases present unique opportunities for the use in industrial, biotechnological, and therapeutic applications. Engineered proteases with redesigned substrate specificities have the potential to expand the scope of practical applications of this enzyme class. We here apply a combinatorial protease engineering-based screening method that links proteolytic activity to the solubility and correct folding of a fluorescent reporter protein to redesign the substrate specificity of tobacco etch virus (TEV) protease. The target substrate EKLVFQA differs at three out of seven positions from the TEV consensus substrate sequence. Flow cytometric sorting of a semi-rational TEV protease library, consisting of focused mutations of the substrate binding pockets as well as random mutations throughout the enzyme, led to the enrichment of a set of protease variants that recognize and cleave the novel target substrate.


New dimensions in vascular engineering: opportunities for cancer biology.
Angiogenesis is a fundamental prerequisite for tissue growth and thus an attractive target for cancer therapeutics. However, current efforts to halt tumor growth using antiangiogenic agents have been met with limited success. A reason for this may be that studies aimed at understanding tissue and organ formation have to this point utilized two-dimensional cell culture techniques, which fail to faithfully mimic the pathological architecture of disease in an in vivo context. In this issue of Tissue Engineering, the work of Fischbach-Teschl's group manipulate such variables as oxygen concentration, culture three-dimensionality, and cell-extracellular matrix interactions to more closely approximate the biophysical and biochemical microenvironment of tumor angiogenesis. In this article, we discuss how novel tissue engineering platforms provide a framework for the study of tumorigenesis under pathophysiologically relevant in vitro culture conditions.


Digestible lysine requirement of gilts with high genetic potential for lean gain, in relation to the level of energy intake.
One hundred gilts were used to determine the optimal ratio between ileal digestible lysine and digestible energy in the diet, and the effect of energy intake level on this optimal ratio for gilts with high genetic potential for lean gain, between 20 and 45 kg BW. In a 2 x 15 factorial arrangement the pigs were fed either 2.5 or 3.0 times the energy requirements for maintenance. Average daily lysine intake in the treatment period ranged from 6.4 to 18.2 g/d in 15 graduated steps. The first 12 increments were .74 g/d, and the last two increments were 1.48 g/d. Average daily gain (ADG), gain/feed, and protein deposition increased curvilinearly (P < .01) with increasing lysine intake. The ADG was maximized at 606 and 768 g/d, gain/feed was maximized at .564 and .604 kg/kg, and protein deposition was maximized at 108 and 128 g/d at the low- and high-energy levels, respectively. The ratio between lipid and protein deposition decreased curvilinearly with increasing lysine intake (P < .01) and reached a minimum of .53 and .75 at the low- and high-energy levels, respectively. The lysine requirements (ileal digestible lysine/DE, grams/megaJoule), determined with a linear-plateau model, were .57 for ADG and gain/feed, and .62 for protein deposition. These estimated requirements were similar for the two energy levels. Consequently, approximately .60 g of ileal digestible lysine/MJ of DE was required to optimize performance in gilts with high genetic potential for lean gain, irrespective of the feed intake level. In addition, a factorial model to estimate the lysine/energy requirements is proposed.


Regulation of the insulin antagonistic protein tyrosine phosphatase 1B by dietary Se studied in growing rats.
Protein tyrosine phosphatase 1B (PTP1B) is a key enzyme in the counterregulation of insulin signaling, and its physiological modulation depends on H2O2 and glutathione (GSH). Se via GSH peroxidases (GPxs) and its specific metabolism is involved in the removal of H2O2 and in the regulation of GSH metabolism. Recent results from animal trials and epidemiological studies with humans have shown that a high GPx1 activity or a permanent surplus of Se may promote the development of obesity and diabetes. Our nutrition physiological study with 7 x 7 growing rats was carried out to examine if PTP1B is modulated by Se supplements and, thus, may represent one trigger mediating these undesirable metabolic effects of Se. One group of rats was fed an Se-deficient diet for 8 weeks. The diets of the other six groups contained Se as selenite or selenate according to the recommendations (0.20 mg/kg diet) and at two supranutritional levels (1.00 and 2.00 mg/kg diet). All Se-supplemented animals featured a significantly higher body weight (6-14%) compared to their Se-deficient companions. Expression and activity of GPx1 in the liver of Se supplemented animals was 10- and 70-fold higher compared to Se deficiency. The detailed study of PTP1B regulation using an enzymatic assay and Western Blot analysis with an antibody against protein glutathionylation revealed that PTP1B was significantly up-regulated by both a maximization of GPx1 activity and by increasing dietary Se supply, reducing its inhibition via glutathionylation. Selenate effected a stronger PTP activation compared to selenite. In conclusion, our results suggest that the modulation of PTP1B activity may represent one plausible mechanism by which a long-term intake of Se supplements exceeding the requirements can promote the development of obesity and diabetes and needs further intensive investigation.


Two- and three-dimensional ultrasound imaging to facilitate detection and targeting of taut bands in myofascial pain syndrome.
Ultrasound imaging has gained acceptance in pain management interventions. Features of myofascial pain syndrome have been explored using ultrasound imaging and elastography. There is a paucity of reports showing the benefit clinically. This report provides three-dimensional features of taut bands and highlights the advantages of using two-dimensional ultrasound imaging to improve targeting of taut bands in deeper locations. Fifty-eight-year-old man with pain and decreased range of motion of the right shoulder was referred for further management of pain above the scapula after having failed conservative management for myofascial pain syndrome. Three-dimensional ultrasound images provided evidence of aberrancy in the architecture of the muscle fascicles around the taut bands compared to the adjacent normal muscle tissue during serial sectioning of the accrued image. On two-dimensional ultrasound imaging over the palpated taut band, areas of hyperechogenicity were visualized in the trapezius and supraspinatus muscles. Subsequently, the patient received ultrasound-guided real-time lidocaine injections to the trigger points with successful resolution of symptoms. This is a successful demonstration of utility of ultrasound imaging of taut bands in the management of myofascial pain syndrome. Utility of this imaging modality in myofascial pain syndrome requires further clinical validation.


Repair kinetics of DNA-DSB induced by X-rays or carbon ions under oxic and hypoxic conditions.
We studied the relation between initial DNA double-strand breaks (DNA-DSB) and the rejoining kinetics of the strand breaks, as well as the OER (oxygen enhancement ratio) after low- and high-LET (linear energy transfer) radiations. CHO cells were exposed to 200 kVp X-rays or 80 keV/microm carbon ions under oxic and hypoxic conditions. DNA-DSB in the cells were analyzed by a static-field gel electrophoresis (SFGE). The kinetics of the rejoining could be described by a sum of fast and slow components. The initial released DNA after X-ray irradiation was higher for cells irradiated under an oxic condition than that under a hypoxic condition. The OER of DNA-DSB after X-ray irradiation was 5.7. This value decreased rapidly to be 3.4 with the fast component by 15 minutes. On the other hand, the OER of DNA-DSB after carbon ion irradiation was 2.2, and this value was not changed by rejoining incubation. The OER values for cell killing were 2.8 and 1.8 after X-ray and carbon ion irradiations, respectively. These values matched to the OER for DNA-DSB with complete rejoining. We conclude that the rejoining of DNA-DSB is an important factor in the mechanism of the oxygen effect.


Development of an (X, eX) spectrometer for measuring the energies of the scattered photon and recoil electron.
The design and performance of a new spectrometer for coincidence measurements between the Compton scattered photon and the recoil electron are described. Coincidence measurements give direct information on the three-dimensional electron momentum density (EMD) of condensed matter. The present spectrometer measures energy spectra of both the photon and the electron. The energy spectrum of electrons is measured by a time-of-flight method using single-bunch operation at the Photon Factory Accumulator Ring (PF-AR). The energy resolution obtained for the recoil electron is 190 eV, which is better than that of the photon detector, so that a momentum resolution of the three-dimensional EMD of 0.3 atomic units can be achieved.


Impact of Isolation During the COVID-19 Pandemic on the Patient Burden of Parkinson's Disease: A PMD Alliance Survey.
As the COVID-19 pandemic resulted in social restrictions around the globe, this cross-sectional survey aimed to assess the impact of social isolation on self- or proxy-reported symptoms of Parkinson's disease (PD) during the pandemic. The survey was distributed among 7109 subscribers of the Parkinson and Movement Disorders Alliance (PMD Alliance) News and Information list and was open only to people with PD (PwP) and care partners (CP, defined as main caregivers of PwP and serving as proxy respondents). No attempt was made to identify PwP and CP pairs. The survey was distributed online using Survey Monkey between 01/06/2021 and 02/27/2021. Respondents were grouped by level of social support from outside of their household during the pandemic (decreased or maintained [ie, the same as pre-pandemic or increased]). Of 7109 invited participants, 718 responded to the survey (response rate 10.1%). PwP (self-reports) accounted for 70.6% of respondents and CP (proxy reports) for 29.4%. Decreased social support from outside of the household during the COVID-19 pandemic (58.5% of all responses) was significantly associated with increases in sadness/depression and anxiety, compared with maintained levels of social support (p < 0.0001 for both comparisons). It was also associated with increased burden of several non-motor (decline in memory, problem solving, or communication, p = 0.0009; new or worsening confusion, p < 0.0001; new or worsening delusions, p = 0.018) and motor PD symptoms. Decline in social support from outside of the household during the COVID-19 pandemic showed a statistically significant and negative association with the burden of mood and non-motor symptoms of PD. These results call for increased vigilance towards non-motor symptoms in PwP experiencing social isolation and highlight the need for stronger provider focus on encouraging PwP and their CPs to build and maintain social connections and engagements.


An overview of the pharmacology of rocuronium bromide in experimental animals.
In various animal species anaesthetized with a-chloralose (cats and pigs) or pentobarbitone (Beagle dogs and Rhesus monkeys), rocuronium has been shown to be a readily reversible, non-depolarizing neuromuscular blocking agent with a similar duration of action as vecuronium but a 6-10 fold lower potency. The outstanding features of its action is rapidity of onset. It is not expected to have any marked cardiovascular or autonomic side-effects when used in the neuromuscular blocking dose range. There is no evidence of any selective pre-junctional effect and there is no clinically relevant inhibition of acetycholinesterase. Screening in rats has not demonstrated any oestrogenic, androgenic, anabolic, glucocorticoid-like or gonad-inhibiting properties, although there was a slight increase in pituitary weight in male rats.


The long-term spatial-temporal trends and burden of esophageal cancer in one high-risk area: A population-registered study in Feicheng, China.
Feicheng County is a high-risk area for esophageal cancer in Shandong province, China. It is important to determine the long-term spatio-temporal trends in epidemiological characteristics and the burden of esophageal cancer, especially since the implementation of the national esophageal cancer screening program for early detection and treatment in 2005. The data collected in Feicheng County from 2001 to 2012 was extracted from the whole-population cancer registry system. The incidence, mortality, disability-adjusted life years (DALY) and changing trends in esophageal cancer according to age and sex were calculated and described. The incidence rate of esophageal cancer in Feicheng was consistently high, and increased significantly for male, but not for female from 2001 to 2012, according to the joinpoint regression analysis. The highest and lowest yearly crude incidence rates were 160.78 and 95.97 per 100000 for males, and 81.36 and 52.17 per 100000 for females. The highest and lowest crude yearly mortality rates were 122.26 and 94.40 per 100000 for males, and 60.75 and 49.35 per 100000for females. Esophageal squamous cell carcinoma was the main pathology type and the tumor location changed significantly from 2001 to 2012. Overall, the DALY remained roughly stable and was estimated as 11.50 for males and 4.90 for females per 1000 people. The burden was mainly caused by premature death. There is an obvious spatial pattern in the distribution of incidence density and burden. Esophageal cancer remains a public health issue in Feicheng County with a high incidence, mortality and disease burden. The incidence and burden have obvious spatial heterogeneity, and further studies should be conducted to identify geographical risk factors for precise local prevention and control measures.


Fitness of Cry1A-resistant and -susceptible Helicoverpa armigera (Lepidoptera: Noctuidae) on transgenic cotton with reduced levels of Cry1Ac.
The performance of Helicoverpa armigera (Hübner) on 15-wk-old cotton plants was compared for a susceptible strain, a near-isogenic laboratory-selected strain, and F1 progeny of the two strains. Glasshouse experiments were conducted to test the three insect types on conventional plants and transgenic plants that produced the Bacillus thuringiensis (Bt) toxin Cry1Ac. At the time of testing (15 wk), the Cry1Ac concentration in cotton leaves was 75% lower than at 4 wk. On these plants, < 10% of susceptible larvae reached the fifth instar, and none survived to pupation. In contrast, survival to adulthood on Cry1Ac cotton was 62% for resistant larvae and 39% for F1 larvae. These results show that inheritance of resistance to 15-wk-old Cry1Ac cotton is partially dominant, in contrast to results previously obtained on 4-wk-old Cry1Ac cotton. Growth and survival of resistant insects were similar on Cry1Ac cotton and on non-Bt cotton, but F1 insects developed more slowly on Cry1Ac cotton than on non-Bt cotton. Survival was lower and development was slower for resistant larvae than for susceptible and F1 larvae on non-Bt cotton. These results show recessive fitness costs are associated with resistance to Cry1Ac.


Oral ibandronate: a less frequently administered therapeutic option for postmenopausal osteoporosis.
Osteoporosis is a severe condition, associated with significant disability as a result of fragility fractures and increased mortality. Oral bisphosphonates effectively reduce the risk of osteoporotic fracture and are generally well tolerated. Unfortunately, patient outcomes are often compromised by suboptimal therapeutic adherence. In other disease areas, reduced dosing frequency has been shown to improve therapeutic adherence. A positive impact for adherence has been observed with a reduction in the bisphosphonate dosing frequency from daily to weekly. However, overall adherence remains suboptimal. Ibandronate is a potent nitrogen-containing bisphosphonate specifically designed for less frequent than weekly administration, without compromise for efficacy or tolerability. This article reviews the pharmacology, efficacy and tolerability of oral ibandronate when administered with extended dosing intervals in postmenopausal osteoporosis.


Use of standardised patients in optometry training.
Clinical relevance: The ability to articulate clinical findings to patients through effective communication is a key skill in all health-care professions.Background: Unannounced standardised patients (SPs) are successful in measuring quality of clinical care provided by qualified optometrists but have not been used in optometry training. Final-year undergraduate optometry students examine members of the public during primary care clinics observed by visiting clinical tutors (VCTs) who provide individualised feedback, highlighting areas for improvement. This pilot study investigates whether unannounced SPs can be used as an additional resource providing enhanced feedback on communication skills in undergraduate optometry education.Methods: Two SPs received intensive training on reporting on students eye examinations and communication skills through completion of pre-designed checklists for each patient encounter. Each SP presented 16 times as an unannounced patient for routine eye examinations. SPs' comments on communication skills of 32 students during 32 examinations was compared to feedback from 10 VCTs. SPs' performance was monitored to ensure consistency. Evaluation of differences in quality and quantity of feedback provided by SPs and VCTs was performed using thematic analysis and chi-squared tests. Student feedback on the use of SPs was obtained on completion of the study.Results: Qualitative thematic analysis revealed six overarching themes emerging from 64 sets of feedback. SPs gave significantly more feedback, both positive comments and comments with recommendations, than VCTs for the (a) total number of comments for each theme (p = 0.0000) and (b) detail and depth of these comments. Students reported that SPs commented on aspects of communication (e.g., establishing rapport and body language) not noted by VCTs.Conclusions: Unannounced SPs can provide enhanced feedback on communication skills to final-year undergraduate optometry students. Students greatly valued VCTs feedback; however, they felt SPs commented on elements of communication not noted by VCTs.


Berlin in Motion: Interprofessional teaching and learning for students in the fields of medicine, occupational therapy, physiotherapy and nursing (INTER-M-E-P-P).
The Berlin project "Interprofessional teaching and learning in medicine, occupational therapy, physiotherapy and nursing" (INTER-M-E-P-P) pursues the goal of developing and testing interprofessional courses in an exemplary manner, and then implement these into their regular study programs. Under the direction of a steering committee of the participating institutions, professions and status groups, interprofessional courses were designed, carried out and evaluated. Specific to this project are the participation of students in the steering committee, and the accompanying of external supervision. The evaluation integrates the perspectives of all project participants, and combines quantitative and qualitative methods. INTER-M-E-P-P established cooperative structures between the participating universities and programs. Three courses were designed, taught and evaluated in an interprofessional manner. The various curricula, organizational patterns and locations of the study paths led to a great need for resources in regard to planning and implementation. This process can be made difficult by any stereotypes or preconceptions inherent to those doing the planning; however, under external supervision, the individual professional viewpoints can still be broadened and enriched. A sustainable implementation of interprofessional education into the curricula of health science study programs is currently complicated by barriers such as different geographical locations and differing university regulations concerning study and testing. Implementation will require long-term support at the university as well as at political levels.


Zebrafish - An emerging model to explore thyroid hormone transporters and psychomotor retardation.
Thyroid hormones (THs) regulate a variety of fundamental physiological processes, including the development and maintenance of the brain. For decades, it was thought that THs enter the cells by passive diffusion. However, it is now clear that TH transport across the cell membrane requires specific transporter proteins that facilitate the uptake and efflux of THs. Several thyroid hormone transmembrane transporters (THTTs) have been identified, including monocarboxylate transporter 8 (MCT8), MCT10, and organic anion transporting polypeptide 1C1 (OATP1C1). The critical role of THTTs in regulating metabolism and brain function is demonstrated in the Allan-Herndon-Dudley syndrome (AHDS), an X-linked psychomotor retardation associated with mutations in the MCT8/SLC16A2 gene. In addition to traditional research on humans, cell-lines, and rodents, the zebrafish has recently emerged as an attractive model to study THTTs and neuroendocrinological-related disorders. In this review, we describe the unique contribution of zebrafish studies to the understanding of the functional role of THTTs in live animals, and how this transparent vertebrate model can be used for translational studies on TH-related disorders.


[Results of toothlessness treatment by calottic method in the Cracow modification. Clinical studies].
The purpose of the paper was to control the new method of teeth positioning in complete dentures based on the modification of callottic method in clinical practice. Clinical studies depended on occlusion and articulation estimation, examination of denture statics, control of occlusion height and registration of the patients' subjective experiences. They concerned 81 toothless patients divided into 2 groups according to the specific classification and wearing complete dentures in which the teeth had been positioned according to the modified method and Gysi-Fischer' method. In the groups of patients under examination that had teeth positioned according to the modified method significantly better results of the values estimated than in comparative groups have been achieved. It has been found that using the modified method smooth OA surface of artifical teeth is obtained without necessity of its correction satisfactory denture statics is obtained and rehabilitation of mastication function and adaptation to the dentures take place in a short period of time.


The relevance of enzyme specificity for coenzymes and the presence of 6-phosphogluconate dehydrogenase for polyhydroxyalkanoates production in the metabolism of Pseudomonas sp. LFM046.
Reconstruction of genome-based metabolic model is a useful approach for the assessment of metabolic pathways, genes and proteins involved in the environmental fitness capabilities or pathogenic potential as well as for biotechnological processes development. Pseudomonas sp. LFM046 was selected as a good polyhydroxyalkanoates (PHA) producer from carbohydrates and plant oils. Its complete genome sequence and metabolic model were obtained. Analysis revealed that the gnd gene, encoding 6-phosphogluconate dehydrogenase, is absent in Pseudomonas sp. LFM046 genome. In order to improve the knowledge about LFM046 metabolism, the coenzyme specificities of different enzymes was evaluated. Furthermore, the heterologous expression of gnd genes from Pseudomonas putida KT2440 (NAD+ dependent) and Escherichia coli MG1655 (NADP+ dependent) in LFM046 was carried out and provoke a delay on cell growth and a reduction in PHA yield, respectively. The results indicate that the adjustment in cyclic Entner-Doudoroff pathway may be an interesting strategy for it and other bacteria to simultaneously meet divergent cell needs during cultivation phases of growth and PHA production.


Perioperative Teaching and Feedback: How are we doing in Canadian OTL-HNS programs?
Discrepancies between resident and faculty perceptions regarding optimal teaching and feedback during surgery are well known but these differences have not yet been described in Otolaryngology - Head and Neck Surgery (OTL-HNS). The objectives were thus to compare faculty and resident perceptions of perioperative teaching and feedback in OTL-HNS residency programs across Canada with the aim of highlighting potential areas for improvement. An anonymous electronic questionnaire was distributed to residents and teaching faculty in OTL-HNS across Canada with additional paper copies distributed at four institutions. Surveys consisted of ratings on a 5-point Likert scale and open-ended questions. Responses among groups were analysed with the Wilcoxon-Mann Whitney test, while thematic analysis was used for the open-ended questions. A total of 143 teaching faculty and residents responded with statistically significant differences on 11 out of 25 variables. Namely, faculty reported higher rates of pre and intra-operative teaching compared to resident reports. Faculty also felt they gave adequate feedback on residents' strengths and technical skills contrary to what the residents thought. Both groups did agree however that pre-operative discussion is not consistently done, nor is feedback consistently given or sought. Faculty and residents in OTL-HNS residency programs disagree on the frequency and optimal timing of peri-operative teaching and feedback. This difference in perception emphasizes the need for a more structured approach to feedback delivery including explicitly stating when feedback is being given, and the overall need for better communication between residents and staff.


AIDS in India: a report of three cases with review of literatures.
Sera from 3500 individuals including patients of non-Hodgkin's lymphoma, patients with sexually transmitted diseases, leprosy, jail inmates, healthy laboratory workers and patients on hemodialysis were screened for antibodies against human immunodeficiency virus (HIV) as a sero surveillance exercise of one of the centers set up by the India Council of Medical Research at the Postgraduate Institute of Medical Education & Research, Candigarh. Three individuals were found to be strongly positive by ELISA using the Wellcozyme kit, with no background noise in the population studies. These three patients were also evaluated by the Western blot technique and showed strong antibody reaction to all the major gene products. It was also possible to ascertain the approximate incubation period of infection in a case who rapidly developed full blown AIDS and died of wasting syndrome. Comprehensive data of 14 cases was also collected from all the centers in India and in every case one could trace the contact outside India. None of the 3 cases studied at our center had Kaposi's sarcoma. These observations could be important landmarks in the epidemiology of AIDS in India.


Annotating RNA motifs in sequences and alignments.
RNA performs a diverse array of important functions across all cellular life. These functions include important roles in translation, building translational machinery and maturing messenger RNA. More recent discoveries include the miRNAs and bacterial sRNAs that regulate gene expression, the thermosensors, riboswitches and other cis-regulatory elements that help prokaryotes sense their environment and eukaryotic piRNAs that suppress transposition. However, there can be a long period between the initial discovery of a RNA and determining its function. We present a bioinformatic approach to characterize RNA motifs, which are critical components of many RNA structure-function relationships. These motifs can, in some instances, provide researchers with functional hypotheses for uncharacterized RNAs. Moreover, we introduce a new profile-based database of RNA motifs--RMfam--and illustrate some applications for investigating the evolution and functional characterization of RNA. All the data and scripts associated with this work are available from: https://github.com/ppgardne/RMfam.


Classic anthropometric and body composition indicators can predict risk of metabolic syndrome in elderly.
Although a variety of classical body measurements have been used to assess adiposity, it is still uncertain which is the best indicator to predict effects arising from the accumulation of body fat (BF) in the elderly. The objective of this study was to analyze different classical anthropometric and body composition measurements and their potential for predicting metabolic syndrome (MS) in elderly women. There were 113 women (60-83 years old) participating in the study, all of whom had their anthropometric, biochemical, hemodynamic and health conditions evaluated. Statistical analysis consisted of correlation coefficient and receiver operating characteristic (ROC) curves, and calculation of the area under the curve. The waist-hip ratio (WHR) and waist circumference correlated with three (hyperglycemia, hypertriglyceridemia and low concentrations of high density lipoprotein-cholesterol) of the seven cardiometabolic risk factors studied. Body mass index, BF, percentage of BF, and the sum of skinfolds were less related to metabolic risk factors. Among the indicators used to characterize central adiposity, WHR was the index that showed the greatest area under the ROC curve. It is suggested that the WHR, an indicator of abdominal adiposity, should be incorporated into the identification of risk of MS in elderly women.


Surgical and conservative treatment of cervical spondylotic radiculopathy and myelopathy.
One hundred and fourteen patients were admitted to our department for evaluation of their cervical spondylogenetic symptoms, including local cervical pain, radiculopathy and myelopathy. This retrospective study gives the results, expressed as improved, unchanged or worse, of anterior surgery, posterior surgery and conservative treatment. Local cervical pain improved in about half of the patients, without any difference between the groups. The effect of surgery on radiculopathy was superior to that of conservative treatment, 71 percent and 74 percent respectively, being improved after anterior and posterior surgery, compared to 19 percent in the conservatively treated group. The majority of patients with myelopathy were treated with posterior surgery and 69 percent had improved. The results were not influenced by the patients age or the duration of symptoms. It is argued that the positive effects of surgery on the radiculopathy are due to a segmental stabilisation rather then to decompression. The immediate post-operative improvement of the myelopathy is undoubtedly caused by the decompression while the long-termed improvement cannot with certainty be attributed to the operation.


Combining multi-criteria decision analysis with GIS approaches for decentralized organic wastes composting plants site selection in Tiassalé, Southern Côte d'Ivoire.
In recent years, decentralized composting appeared as one of the most appropriate treatment options for organic waste valorization in low- and middle-income countries. In Cote d'Ivoire, a pilot project has proved the feasibility of organic municipal solid waste composting for the city of Tiassalé. However, numerous issues still need to be addressed for the establishment of a sustainable decentralized composting system in this city. One of the key issues is site selection. Until now, there is no clear model for such plant site selection. In this study, multi-criteria decision analysis (MCDA) and geographical information system (GIS) approaches were combined to develop an appropriate model for selecting decentralized composting sites in the city of Tiassalé. The methodology used involved two different and complementary phases. First, MCDA and GIS techniques were used to identify the most suitable site areas. Seven criteria clustered in three main factors (environmental, social and economic), and five constraints were considered in the analysis process. Second, five sites were selected within the most suitable areas after a basic field visit and ranked using the Analytic Hierarchy Process. The results showed that the most suitable spaces for decentralized composting plant siting represent only 2.6% of the study area. The investigation yielded on the selection of the two best options for decentralized composting plant siting for the city of Tiassalé. This study proved that the combination of MCDA and GIS is a practical and efficient method to identify suitable sites for decentralized composting plants.


[The philosophy of hospices. The St Luke's Hospice establishment in Hellerup, evaluation of the first year].
The purpose of the article is to present collected data from the first year following the establishment of Sankt Lukas Hospice in Hellerup in Denmark and to expound on the philosophy of hospices. Eighty-five patients were admitted to the hospice over the period from 1st October, 1992 to 30th September, 1993, of whom 80 patients died during the first admission phase. The median age upon admission was 72 years (range 29 to 97). In 57.7% of the cases the primary approach came from the patient or from the patient's relatives. All patients had been diagnosed with either a disseminated malignant disease or AIDS. The median length of admission was 13 days (range 1 to 191). Taking into consideration that the hospice as an independent institution is new in Denmark, one can conclude that the number of inquiries which resulted in admission is sufficient to form the basis for a debate on the more widespread establishment of hospices in Denmark. An important aspect at the preliminary examination is the patient's acknowledgement and accept of the fact that curative medical treatment ceases, and that future medical treatment from now on will be purely palliative.


Age-Related Reduced Somatosensory Gating Is Associated with Altered Alpha Frequency Desynchronization.
Sensory gating (SG), referring to an attenuated neural response to the second identical stimulus, is considered as preattentive processing in the central nervous system to filter redundant sensory inputs. Insufficient somatosensory SG has been found in the aged adults, particularly in the secondary somatosensory cortex (SII). However, it remains unclear which variables leading to the age-related somatosensory SG decline. There has been evidence showing a relationship between brain oscillations and cortical evoked excitability. Thus, this study used whole-head magnetoencephalography to record responses to paired-pulse electrical stimulation to the left median nerve in healthy young and elderly participants to test whether insufficient stimulus 1- (S1-) induced event-related desynchronization (ERD) contributes to a less-suppressed stimulus 2- (S2-) evoked response. Our analysis revealed that the minimum norm estimates showed age-related reduction of SG in the bilateral SII regions. Spectral power analysis showed that the elderly demonstrated significantly reduced alpha ERD in the contralateral SII (SIIc). Moreover, it was striking to note that lower S1-induced alpha ERD was associated with higher S2-evoked amplitudes in the SIIc among the aged adults. Conclusively, our findings suggest that age-related decline of somatosensory SG is partially attributed to the altered S1-induced oscillatory activity.


Potential Effect of Low-Rise, Downcast Artificial Lights on Nocturnally Migrating Land Birds.
Artificial light at night (ALAN) on tall or upward-pointed lighting installations affects the flight behavior of night-migrating birds. We hypothesized that common low-rise lights pointing downward also affect the movement of nocturnal migrants. We predicted that birds in flight will react close to low-rise lights, and be attracted and grounded near light sources, with a stronger effect on juveniles during their autumn migration. We conducted a controlled longitudinal experiment with light-emitting diode floodlights and considered nearby structures that turn on lights at night. We analyzed 1501 high-resolution 3D nocturnal flight paths of free-flying migrants and diurnally captured 758-2009 birds around experimental lights during spring and autumn 2016, and spring 2017. We identified change points along flight paths where birds turned horizontally or vertically, and we considered these indicative of reactions. Flight paths with and without reactions were generally closer to our experimental site in spring than in autumn when the lights were on. Reactions were up to 40% more likely to occur in autumn than in spring depending on the threshold magnitude of turning angle. Reactions in spring were up to ∼60% more likely to occur at ∼35 m from the lights than at >1.5 km. In autumn, some vertical reactions were ∼40% more likely to occur at ∼50 m from the lights than at >2.2 km. Interactions between distance to lights and visibility or cloud cover were consistent with known effects of ALAN on nocturnal migrants. Under poor visibility, reactions were up to 50% more likely to occur farthest from structures in spring, but up to 60% more likely to occur closest to lights in autumn. Thus, the effects of ALAN on night-migrating land birds are not limited to bright lights pointing upward or lights on tall structures in urban areas. Diurnal capture rates of birds were not different when lights were on or off for either season. To our knowledge, this is the first study to show that low-rise lights pointing downward affect night-migrating birds. Although the interpreted reactions constitute subtle modifications in the linearity of flight paths, we discuss future work that could verify whether the protection of nocturnal migrants with lights-out programs would have greater impact if implemented beyond urban areas and include management of low-rise lights.


Preparation and Characterization of a Novel Tragacanth Gum/Chitosan/Sr-Nano-Hydroxyapatite Composite Membrane.
It is a great challenge to obtain an ideal guided bone regeneration (GBR) membrane. In this study, tragacanth gum (GT) was introduced into a chitosan/nano-hydroxyapatite (CS/n-HA) system. The effects of different component ratios and strontium-doped nano-hydroxyapatite (Sr-HA) on the physical-chemical properties and degradation behavior of the CS/Sr-n-HA/GT ternary composite membrane were investigated using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), contact angle, electromechanical universal tester and in vitro soaking in simulated body fluid (SBF). The results showed that CS could be ionically crosslinked with GT through electrostatic interaction, and Sr-n-HA was loaded via hydrogen bond, which endowed the GT/CS/n-HA composite membrane with good tensile strength and hydrophilicity. In addition, the results of immersion in SBF in vitro showed that CS/n-HA/GT composite membranes had different degradation rates and good apatite deposition by investigating the changes in pH value, weight loss, water absorption ratio, SEM morphology observation and tensile strength reduction. All results revealed that the CS/Sr-n-HA/GT (6:2:2) ternary composite membrane possessed the strongest ionic crosslinking of GT and CS, which was expected to obtain more satisfactory GBR membranes, and this study will provide new applications of GT in the field of biomedical membranes.


Fatigability as a Predictor of Subclinical and Clinical Anemia in Well-Functioning Older Adults.
Anemia is a common condition in older adults for which fatigue, the primary symptom, often goes unrecognized as individuals typically equilibrate their activity to avoid fatigue. Whether assessing fatigability (i.e., susceptibility to fatigue) facilitates identification of anemia is unknown. This study examines the association between fatigability and prevalent, incident, and persistent subclinical and clinical anemia in well-functioning older adults. Longitudinal analysis of 905 well-functioning men and women aged 60 to 89 years and followed for 1 to 5 years from the Baltimore Longitudinal Study of Aging conducted at the National Institute on Aging, Clinical Research Unit, Baltimore, MD. Perceived fatigability was assessed as a rating of perceived exertion (RPE) from 6 to 20 following a 5-minute treadmill walk at 1.5 mph (.67 m/s); fatigue was assessed as reported unusual tiredness in the past month. Clinical anemia was defined using World Health Organization hemoglobin cutpoints of below 13 g/dL and below 12 g/dL for men and women, respectively, and subclinical anemia was defined as 13.0 to 13.9 g/dL and 12.0 to 12.9 g/dL, respectively. Overall, 14% of participants had clinical and 30% had subclinical anemia at baseline. Each increment (1 RPE) of fatigability was associated after covariate adjustment with 14% (95% confidence interval [CI] = 5-25%, P = .005) and 8% (CI = 1-17%; P = .031), respectively, greater likelihood of prevalent clinical and subclinical anemia. An average of 2.2 years later, each 1 RPE increment in baseline fatigability predicted an 11% (CI = 2-20%; P = .016) higher likelihood of incident and/or persistent subclinical and clinical anemia. Reports of unusual tiredness were associated with prevalent subclinical anemia only. This study provides evidence that perceived fatigability may help identify well-functioning older adults with borderline to clinical anemia who are on a trajectory of persistently suboptimal or worsening hemoglobin status. Assessing fatigability may facilitate earlier diagnosis of health conditions that underlie persistent suboptimal hemoglobin status. J Am Geriatr Soc 68:2297-2302, 2020.


Comparison between unilateral curved and bilateral straight percutaneous vertebral augmentation in the treatment of osteoporotic vertebral compression fractures: A meta-analysis.
The aim of this meta-analysis was to compare the efficacy and safety of unilateral curved and bilateral straight percutaneous vertebral augmentation (PVA) in the treatment of osteoporotic vertebral compression fractures (OVCFs). We performed a comprehensive literature search from electronic databases including Springer, Web of Science, PubMed, Cochrane Library databases and ScienceDirect up to July 2022. Three randomized-controlled trials (RCTs) and one retrospective study which met the inclusion criteria were analyzed. There were significant differences in the operative time, injected bone cement volume, bone cement leakage rate and X-ray frequency between the bilateral straight PVA and unilateral curved PVA. No significant differences were found regarding postoperative Cobb angle, Visual Analog Scale or Oswestry Disability Index between the two groups. Compared to bilateral straight PVA, unilateral curved PVA may decrease operative time, injected bone cement volume, bone cement leakage rate, and X-ray frequency in the treatment of OVCFs. However, the Cobb angle, pain, and clinical scores are comparable. Due to the limited quality and data of the evidence currently available, more high-quality RCTs are required.


Rejection-(dis)identification and ethnic political engagement among first-generation Latino immigrants to the United States.
Immigrants to the United States face rejection from other Americans on the basis of their ethnic group membership. Among members of ethnic minority groups who were born in the United States, rejection is tied to higher ethnic identification and less positive attitudes toward the national majority. Relatively little research has examined this relationship among first-generation immigrants (i.e., people who were born in another country but who migrated to the United States) or has considered political engagement on behalf of one's ethnic group as an outcome. In this study we examined the relationship among ethnic-based rejection, ethnic and national identification, and ethnic political engagement among first-generation Latino immigrants in the northeastern United States. We found that first-generation Latino immigrants who perceived ethnic-based rejection were less likely to identify with Americans and less likely to report willingness to engage politically on behalf of their ethnic group in the United States. Perceived rejection was not significantly associated with ethnic identification, which was not related to ethnic political engagement. The study demonstrates that ethnic-based rejection has unique implications for identification and ethnic political engagement among first-generation Latino immigrants.


Xeniaphyllane-derived terpenoids from the formosan soft coral Sinularia gibberosa.
New xeniaphyllane-derived metabolites (1-7) were isolated from the EtOAc extract of the Formosan soft coral Sinularia gibberosa. The structures and relative configurations of these compounds were elucidated on the basis of extensive spectroscopic analysis (including 2D NMR) and by comparison of their spectral data with those of related compounds. In vitro cytotoxic evaluation of the above metabolites towards a limited panel of cancer cell lines is also described.


Comparison of conventional and integrated pest management programs in public schools.
This study compared an integrated pest management (IPM) program with conventional, calendar-based pest control in nine North Carolina elementary schools. Both programs primarily targeted the German cockroach, Blattella germanica (L.). The IPM program relied heavily on monitoring and baiting, whereas the conventional approach used baseboard and crack-and-crevice sprays of insecticides. Within the constraints of an existing pest management contract, we quantified service duration, materials used, cost, levels of cockroach infestation, and the pesticide residues generated by the two service types. IPM services were significantly more time-consuming than conventional services, resulting in a significantly higher cost associated with labor. Nevertheless, the two types of treatments incurred similar total costs, and the efficacy of both treatments was also similar. Most importantly, pest monitoring, a central element of the IPM program, revealed few cockroaches and indicated that most of the conventional treatments were unnecessary. Environmental residues of the organophosphate pesticides acephate, chlorpyrifos, and propetamphos were significantly higher in swab samples taken in the conventionally treated schools. This study demonstrates that an IPM program is an appropriate and preferable alternative to conventional methods of pest control in the school environment.


Filamentation with nonlinear Bessel vortices.
We present a new type of ring-shaped filaments featured by stationary nonlinear high-order Bessel solutions to the laser beam propagation equation. Two different regimes are identified by direct numerical simulations of the nonlinear propagation of axicon focused Gaussian beams carrying helicity in a Kerr medium with multiphoton absorption: the stable nonlinear propagation regime corresponds to a slow beam reshaping into one of the stationary nonlinear high-order Bessel solutions, called nonlinear Bessel vortices. The region of existence of nonlinear Bessel vortices is found semi-analytically. The influence of the Kerr nonlinearity and nonlinear losses on the beam shape is presented. Direct numerical simulations highlight the role of attractors played by nonlinear Bessel vortices in the stable propagation regime. Large input powers or small cone angles lead to the unstable propagation regime where nonlinear Bessel vortices break up into an helical multiple filament pattern or a more irregular structure. Nonlinear Bessel vortices are shown to be sufficiently intense to generate a ring-shaped filamentary ionized channel in the medium which is foreseen as opening the way to novel applications in laser material processing of transparent dielectrics.


Investigating Undergraduate Biology Students' Science Identity Production.
Identity production is a complex process in which a person determines who he or she is via internal dialogue and sociocultural participation. Understanding identity production is important in biology education, because students' identities impact classroom experiences and their willingness to persist in the discipline. Thus, we suggest that educators foster spaces where students can engage in producing science identities that incorporate positive perceptions of who they are and what they have experienced. We used Holland's theory of identity and Urrieta's definitions of conceptual identity production (CIP) and procedural identity production (PIP) to explore the process of students' science identity production. We interviewed 26 students from five sections of a general biology course for majors at one higher education institution. The interview protocol included items about students' identities, influential experiences, perceptions of science, and perceptions of their classroom communities. From the interviews, we developed hierarchical coding schemes that focused on characterizing students' CIP and PIP. Here, we describe how students' socially constructed identities (race, gender, etc.) and their experiences may have impacted the production of their science identities. We found that authoring (i.e., making meaning of) experiences and recognition by others as a community member influenced students' science identity production.


Development and application of a hybrid method involving interpolation and ab initio calculations for the determination of transition states.
Transition state search algorithms, such as the nudged elastic band can fail, if a good initial guess of the transition state structure cannot be provided. The growing string method (GSM) [J. Chem. Phys. 120, 7877 (2004)] eliminates the need for an initial guess of the transition state. While this method only requires knowledge of the reactant and product geometries, it is computationally intensive. To alleviate the bottlenecks in the GSM, several modifications were implemented: Cartesian coordinates were replaced by internal coordinates, the steepest descent method for minimization of orthogonal forces to locate the reaction path was replaced by the conjugate gradient method, and an interpolation scheme was used to estimate the energy and gradient, thereby reducing the calls to the quantum mechanical (QM) code. These modifications were tested to measure the reduction in computational time for four cases of increasing complexity: the Muller-Brown potential energy surface, alanine dipeptide isomerization, H abstraction in methanol oxidation, and C-H bond activation in oxidative carbonylation of toluene to p-toluic acid. These examples show that the modified GSM can achieve two- to threefold speedups (measured in terms of the reduction in actual QM gradients computed) over the original version of the method without compromising accuracy of the geometry and energy of the final transition state. Additional savings in computational effort can be achieved by carrying out the initial search for the minimum energy pathway (MEP) using a lower level of theory (e.g., HF/STO-3G) and then refining the MEP using density functional theory at the B3LYP level with larger basis sets (e.g., 6-31G( *), LANL2DZ). Thus, a general strategy for determining transition state structures is to initiate the modified GSM using a low level of theory with minimal basis sets and then refining the calculation at a higher level of theory with larger basis sets.


Multidrug resistance in heart transplant patients: a preliminary communication on a possible mechanism of therapy-resistant rejection.
Multidrug resistance refers to a complex cellular phenotype, the hallmark of which is cross-resistance to multiple drugs, for example, chemotherapeutic agents, that are unrelated to the selecting agent in structure, cellular target, and mode of action. The expression of this multidrug resistance is connected with the overexpression of P-glycoprotein. By applying the method of immunocytochemical assay, we have demonstrated the appearance of the multidrug-resistant phenotype (P-glycoprotein+ cells, multidrug-resistant cells) in mononuclear cells of the peripheral blood from 32/49 patients receiving triple-drug (azathioprine, steroids, cyclosporine) immunosuppressive therapy after heart transplantation. In the group of patients showing not only the presence of cells with multidrug-resistant phenotype in the peripheral blood, but also a significant increase in the number of these cells during the interval of observation (0 to 767 days)-16/32/49 cases--a significantly increased incidence of acute rejection episodes could be demonstrated. This supports the hypothesis of a possible existence of a therapy-resistant form of acute rejection, with an involvement of mechanisms of multidrug-resistance playing a role in its causal development.


Intraosseous cavernous haemangioma of the inferior turbinate.
Intraosseous cavernous haemangiomas usually occur in the vertebral and calvarial bones, and account for <1% of primary bone tumours. Nasal cavity intraosseous cavernous haemangiomas are extremely rare. We present a case of a 47-year-old woman with an incidental left inferior turbinate mass noted on CT scan for an unrelated pathology. She had no rhinological symptoms other than a 2-year history of left-sided nasal obstruction. Preoperative imaging failed to determine the aetiology of the mass. The lesion, contiguous with the left inferior turbinate, was successfully resected via an endoscopic approach. Histopathological examination of the resected specimen demonstrated a left inferior turbinate intraosseous cavernous haemangioma.


Chorea: non-genetic causes.
The aim of this article is to review the literature on the non-genetic causes of chorea. The differential diagnosis of the large number of causes of sporadic chorea is often a challenging task. Interest has also been growing in the possibility that the mechanism responsible for Sydenham's chorea plays a role in the pathogeneis of other neuropsychiatric disorders. Stroke is the main cause of sporadic chorea. Sydenham's chorea shares clinical features with tic disorders, such as obsessive-compulsive disorder and attention deficit hyperactivity disorder. However, there are unequivocal differences between Sydenham's chorea and Tourette's syndrome. There is initial evidence suggesting the beneficial effect of immunosuppression in Sydenham's chorea. Other autoimmune causes of chorea include systemic lupus erythematosus as well as paraneoplastic syndromes. The growing list of drugs associated with chorea include lamotrigine, methadone and lithium. Among infectious agents, HIV is the leading reported cause of chorea. Patients with sporadic chorea require a thorough work up because numerous causes can lead to this condition. It remains unconfirmed whether the pathogenic mechanisms of Sydenham's chorea are responsible for other conditions such as isolated obsessive-compulsive disorder or Tourette's syndrome. Drugs and infectious agents, especially HIV, are often implicated in the causes of chorea.


[Failure to Remove Long-Term Indwelling Central Venous Catheters in Two Patients].
The use ofa central venous(CV)port system has become common for the treatment of patients with tumors. We report on the failure to remove CV catheters in 2 patients. The first patient was a 50 years woman with acute myeloid leukemia. She underwent CV port implantation via the left brachial approach 11 years previously. The second patient was an 80 years man with a lower gingival carcinoma. He underwent CV port implantation via the left brachial approach 6 years previously. CV catheter removal was attempted in both patients, but was unsuccessful because of strong adhesion to the vessel wall. Based on our experience, if catheter removal is impossible, its retention is more suitable.


The role of beta-lactamase-producing bacteria in respiratory tract infections.
Staphylococcus aureus, Haemophilus influenzae, Bacteroides sp. (Bacteroides melaninogenicus, Bacteroides oralis, and Bacteroides fragilis), peptostreptococci and fusobacterium sp. are important pathogens in respiratory tract infections (RTI). These organisms are often recovered mixed with other aerobic, facultative and anaerobic bacteria. A recent increase in numbers of bet-lactamase producing strains of anaerobic gram-negative bacteria in RTI has been associated with increased failure rates of penicillins in eradication of these infections. These infections include chronic otitis media, chronic sinusitis and mastoiditis, chronic recurrent tonsillitis and lung abscesses. The indirect pathogenicity of these organisms is apparent through their ability not only to survive penicillin therapy but also to protect penicillin susceptible pathogens from that drug. These direct and indirect virulence characteristics of anaerobic bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections.