Surgical treatment of 224 cases of big acoustic neurinoma with special consideration on 76 cases treated microsurgically.
Two hundred and twenty four cases of acoustic neurinoma, bigger than 4 cm in diameter were operated by suboccipital approach in the past 30 years. Among them, 148 cases were operated before the year of 1978 with conventional microsurgical technic, and 76 cases were operated since 1979 with microsurgical technic. In the former group of cases, the percentage of total removal of tumor was 83.8% and the mortality rate was 5.4%. In the latter group, all tumors were totally removed, there was no mortality, the facial nerve was preserved anatomically in 86.8% of cases and functionally in 71.1%, and the cochlear function was preserved in 21.1% of cases. In 5 cases, the severed ends of the facial nerve were anastomosed intracranially. All of them had their facial nerve function recovered. The historicals of surgery of acoustic neurinoma in China are reviewed. The operative technic used by the author is presented briefly. The factors influencing the preservation of the facial nerve are discussed.


Lrrcc1 and Ccdc61 are conserved effectors of multiciliated cell function.
Ciliated epithelia perform essential functions in animals across evolution, ranging from locomotion of marine organisms to mucociliary clearance of airways in mammals. These epithelia are composed of multiciliated cells (MCCs) harboring myriads of motile cilia, which rest on modified centrioles called basal bodies (BBs), and beat coordinately to generate directed fluid flows. Thus, BB biogenesis and organization is central to MCC function. In basal eukaryotes, the coiled-coil domain proteins Lrrcc1 and Ccdc61 have previously been shown to be required for proper BB construction and function. Here, we used the Xenopus embryonic ciliated epidermis to characterize Lrrcc1 and Ccdc61 in vertebrate MCCs. We found that they both encode BB components, localized proximally at the junction with striated rootlets. Knocking down either gene caused defects in BB docking, spacing and polarization. Moreover, their depletion impaired the apical cytoskeleton and altered ciliary beating. Consequently, cilia-powered fluid flow was greatly reduced in morphant tadpoles, which displayed enhanced mortality when exposed to pathogenic bacteria. This work illustrates how integration across organizational scales make elementary BB components essential for the emergence of the physiological function of ciliated epithelia.


Fluctuating heat stress during development exposes reproductive costs and putative benefits.
Temperature and thermal variability are increasing worldwide, with well-known survival consequences. However, effects on other potentially more thermally sensitive reproductive traits are less understood, especially when considering thermal variation. Studying the consequences of male reproduction in the context of climate warming and ability to adapt is becoming increasingly relevant. Our goals were to test how exposure to different average temperatures that either fluctuated or remained constant impacts different male reproductive performance traits and to assess adaptive potential to future heat stress. We took advantage of a set of Drosophila melanogaster isogenic lines of different genotypes, exposing them to four different thermal conditions. These conditions represented a benign and a stressful mean temperature, applied either constantly or fluctuating around the mean and experienced during development when heat stress avoidance is hindered because of restricted mobility. We measured subsequent male reproductive performance for mating success, fertility, number of offspring produced and offspring sex ratio, and calculated the influence of thermal stress on estimated heritability and evolvability of these reproductive traits. Both costs and benefits to different thermal conditions on reproductive performance were found, with some responses varying between genotypes. Mating success improved under fluctuating benign temperature conditions and declined as temperature stress increased regardless of genotype. Fertility and productivity were severely reduced at fluctuating mean high temperature for all genotypes, but some genotypes were unaffected at constant high mean temperature. These more thermally robust genotypes showed a slight increase in productivity under the fluctuating benign condition compared to constant high temperature, despite both thermal conditions sharing the same temperature for 6 hr daily. Increasing thermal stress resulted in higher heritability and evolvability. Overall, the effects of temperature on reproductive performance depended on the trait and genotype; performance of some traits slightly increased when high temperatures were experienced for short periods but decreased substantially even when experiencing a benign temperature for a portion of each day. While thermal stress increased genetic variation that could provide adaptive potential against climate warming, this is unlikely to compensate for the overall severe negative effect on reproductive performance as mean temperature and variance increase.


Complications and Outcomes After Gynecomastia Surgery: Analysis of 204 Pediatric and 1583 Adult Cases from a National Multi-center Database.
Gynecomastia is a common disease that is prevalent across all age groups of boys and men. Although benign in nature, it can lead to psychological and social distress, prompting affected patients to seek medical attention. Management strategies include observation and drug therapy, yet surgical procedures remain the hallmark of treatment. The goal of this study was to analyze patient demographics, outcomes, and complication rates of gynecomastia surgery in a large multi-institutional cohort. We performed a retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program adult and pediatric databases to produce two cohorts that underwent gynecomastia surgical repair. The two populations were compared for comorbidities, perioperative details, and complication rates. Multivariate analyses helped detect risk factors associated with adverse events. A total of 204 pediatric and 1583 adult male patients were identified in our analysis. Mean ages were 15.8 and 39.6 years, respectively. A BMI of 28.2 in the latter cohort revealed an overweight adult population. Preoperative comorbidities (0.0-4.9% in children, 0.0-6.4% in adults) and American Society of Anesthesiologists scores (ASA 1 + 2: 98.5 and 82.7%) symbolized a healthy population. Procedures were subsequently performed mostly as outpatient (84.3 and 93.9%) and with short hospitalization durations (0.27 and 0.06 days). Our results demonstrated low surgical (3.9 and 1.9%) and medical (0.0 and 0.3%) complications within the standardized 30-day postoperative period. Children and adolescents, however, required double mean operative times compared to adults (111.3 vs 56.7 min). Operative gynecomastia treatment remains a safe treatment modality across all age groups. Patients with known preoperative medical or surgical comorbidities necessitate more extensive perioperative assessment and monitoring. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


The effectiveness of treating irrigation water using ultraviolet radiation or sulphuric acid fertilizer for reducing generic Escherichia coli on fresh produce-a controlled intervention trial.
The aims of this study were to: (i) estimate the effectiveness of ultraviolet radiation (UV) and sulphuric acid-based fertilizer (SA), at reducing levels of generic Escherichia coli in surface irrigation water and on produce and surface soil in open produce fields; and (ii) describe the population dynamics of generic E. coli in produce fields. Spinach and cantaloupe plots were randomly assigned to control, UV or SA treatment groups. Irrigation water was inoculated with Rifampicin-resistant E. coli prior to treatment. More than 75% of UV- and SA-treated tank water samples had counts below the detection limit, compared to a mean count of 3·3 Log10 CFU per ml before treatment. Levels of Rifampicin-resistant E. coli in soil and produce both increased and decreased over 10-15 days after irrigation, depending on the plot and time-period. UV and SA treatments effectively reduce the levels of E. coli in surface irrigation water. Their effectiveness at reducing contamination on produce was dependent on environmental conditions. Applying wait-times after irrigation and prior to harvest is not a reliable means of mitigating against contaminated produce. The results are of timely importance for the agricultural industry as new FSMA guidelines require producers to demonstrate a low microbial load in irrigation water or allow producers to apply a wait-time to mitigate the risk of contaminated produce.


Projections of substance P, vasoactive intestinal peptide and tyrosine hydroxylase immunoreactive nerve fibres in the canine intestine, with special reference to the innervation of the circular muscle.
Antisera raised against neuron specific enolase (NSE), substance P, vasoactive intestinal peptide (VIP) and tyrosine hydroxylase (TH) were used to reveal nerve fibres in the wall of the canine small and large intestine. The circular muscle of the colon was innervated by nerve fibre bundles that ran parallel to the muscle throughout its thickness. A plexus of fibre bundles was found against the inner (submucosal) surface of the circular muscle. Fibres with substance P, VIP and TH immunoreactivity all contributed to this innervation. The circular muscle of the small intestine was distinctly separated into outer and inner layers by a dense plexus of nerve fibres, the deep muscular plexus. The outer and inner circular muscle were innervated by substance P, VIP and TH fibres. Extrinsic denervation through the severing of nerve fibres in the mesentery caused TH fibres in the intestine to degenerate, but had no detectable effect on the fibres with substance P or VIP immunoreactivity. Myectomy (the removal of the myenteric plexus from the full circumference of the intestine over a distance of 2-3 cm), performed 7-13 days before tissue was taken, resulted in an almost complete loss of substance P fibres from the circular muscle of the colon and the outer circular muscle of the small intestine. However, many fibres persisted in the deep muscular plexus of the small intestine, and most fibres remained in its inner circular muscle. The changes in distribution of VIP fibres were almost identical, except that a small proportion of reactive fibres remained in the circular muscle of the colon and the outer circular muscle of the small intestine. It is concluded that the circular muscle layers of the small intestine and colon have dual sources of intrinsic nerve supply: the myenteric ganglia supply fibres primarily to the outer part of the muscle and the submucous ganglia supply fibres to the inner muscle. The present study further demonstrated that VIP fibres ran anally in the myenteric plexus of both the small and large intestine, whereas substance P fibres ran orally in the large intestine and both orally and anally in the small intestine. The innervation of the muscularis mucosae and mucosa by substance P and VIP fibres was not affected by myectomy or extrinsic denervation, and these structures are therefore likely to be innervated by nerve cells in the submucous ganglia.


Neural Correlates of Orthographic Access in Mandarin Chinese Writing: An fMRI Study of the Word-Frequency Effect.
Writing is an essential tool for human communication and involves multiple linguistic, cognitive, and motor processes. Chinese, a logographic writing system, differs remarkably from the writing systems of alphabetic languages. The neural substrates of Chinese writing are largely unknown. Using functional magnetic resonance imaging (fMRI) in a copying task, this study probed the neural underpinnings of orthographic access during Mandarin Chinese writing by employing the word-frequency effect. The results showed that writing low-frequency characters evoked greater activation in the bilateral superior/middle/inferior frontal gyrus, superior/inferior parietal lobule, and fusiform gyrus than writing high-frequency characters. Moreover, psychophysiological interaction (PPI) analysis demonstrated that the word-frequency effect modulated functional connectivity within the frontal-occipital networks and the parietal-occipital networks. Together, these findings illustrate the neural correlates of orthographic access for Mandarin Chinese writing, shedding new light on the cognitive architecture of writing across various writing systems.


Patient Interest in the Development of a Center for Ehlers-Danlos Syndrome/Hypermobility Spectrum Disorder in the Chicagoland Region.
The Ehlers-Danlos Syndromes (EDS) are a set of connective tissue disorders that are hereditary in nature and characterized by joint hypermobility and tissue fragility. The complex nature of this unique patient population requires multidisciplinary care, but appropriate centers for such care do not exist in large portions of the country. Need for more integrated services has been identified in the Chicagoland region. In order to explore and begin to address barriers to seeking out appropriate care facing EDS patients in this region, we developed an online survey which we circulated through EDS social media groups for Chicagoland patients. Three hundred and nine unique respondents participated. We found that there exists a strong medical need for and interest in the development of a center in the region, and participants reported that, if made available to them, that they would make extensive and regular use of such a facility. We conclude that the establishment of a collaborative medical center specializing in the diagnosis and treatment of EDS, HSD, and related disorders in the Chicagoland area would greatly benefit patients by providing comprehensive care, alleviate the burden on overworked healthcare providers, and generate revenue for medical facilities.


Trees in trees a report from remote Australia.
Anemochory or Ornithochory does not adequately explain the amount, size or distribution of woody epiphytes here in outback NSW Australia. In a semi-arid ecosystem, epiphytes should be short-lived and randomly dispersed not clustered around old Aboriginal campsites or along their ancient paths aka songlines. These enduring trees in trees we call TinTs, have been here much longer than European Australians. We are hoping to attract archaeobotanical or ethnobotanical research to help us recover the knowledge of the ancestors or at least assist us in protecting these arboreal oddities from future resource extraction activities.


A further examination of the "epidemiologic paradox": birth outcomes among Latinas.
Low rates of low birthweight (LBW) among foreign-born Latinas of low socioeconomic status have been called the "epidemiologic paradox." This study examined the extent to which the paradox can be explained by differential distribution of risk factors. The data source was the 1996-1997 New York City Birth File with 78,364 singleton births to Latinas. Ancestries included Colombians, Dominicans, Ecuadorians, Mexicans, Puerto Ricans and other Hispanics. First, a logistic regression was used to predict a LBW birth with ancestry and birthplace as the only independent variables. Demographic, medical and behavioral risks were added in subsequent regression models. The LBW rate for the sample was 6.8%, with significant differences between birthplace subgroups and among ancestries. Puerto Ricans had the highest LBW rates, 9.1% for the mainland-born and 9.2% for the island-born. In separate regressions for six ancestry groups, birthplace was a significant predictor of LBW only among Mexicans and other Hispanics. In this population-based study of Latina women in New York City, the positive birth outcomes of foreign-born women are largely due to their more favorable distribution of behavioral risk factors. The "epidemiologic paradox" does not account for the LBW rates among Puerto Ricans in New York City, a high percentage of whom are mainland-born (73.4%). Compared to other Latinas, Puerto Rican women are likely to have experienced far more years of acculturation, which can result in negative health behaviors.


UK media responses to HIV through the lens of COVID-19: a study of multidirectional memory.
This article proposes correlations and parallels in UK newsprint media coverage of the COVID-19 and HIV/AIDS pandemics through engagement with Michael Rothberg's model of multidirectional memory. It achieves this via qualitative and quantitative analysis of newsprint media during selected timelines of the respective outbreaks. Although the COVID-19 outbreak, which originated in Wuhan, China in 2019 and spread globally, has prompted reference to a number of previous traumatic events, including 9/11 and the Holocaust, one might contend that it correlates most closely with HIV/AIDS given the latter's ongoing nature and worldwide reach. COVID-19, having infected 629 million people since December 2019 with 6.5 million deaths by November 2022, still presents a global threat through which we might read the trauma of HIV, a disease that has thus far seen 32.7 million deaths and has infected 75.7 million people worldwide. This relationship exists despite the fact that the two viruses and their effects differ markedly: HIV is a retrovirus, has a long incubation time, is transmitted via bodily fluids, has a low risk of infectivity via everyday contact and, to date, no fully effective vaccine has been developed. Contrastingly, COVID-19 is a coronavirus, has a short incubation time, is transmitted via contact and airborne respiratory aerosols, has a high risk of infectivity via everyday contact, and investment in vaccine development has been significant, with several vaccines now successfully developed. Nonetheless, while the two viruses and their prognoses are quite different and government strategies have followed highly divergent trajectories, certain parallels are apparent to the extent that one might read HIV/AIDS through the lens of COVID-19. It is therefore argued here that the connections between these two traumatic events constitute what Rothberg terms 'multidirectional memory' whereby we understand one traumatic event through another.


Secondhand Smoke Exposure in Lao People's Democratic Republic: Results From the 2015 National Adult Tobacco Survey.
Objectives: Second-hand smoke (SHS) exposure causes >600,000 deaths annually worldwide, however, information regarding SHS exposure in Lao People's Democratic Republic (Lao PRD) is limited; we report SHS exposure prevalence at home, inside workplaces, and indoor public spaces in Lao PDR. Methods: Data were from the 2015 Lao National Adult Tobacco Survey, a nationally representative sample of 7,562 participants aged ≥15 years recruited through a stratified 2-stage cluster sampling approach. Results: 88.3% (83.9% of non-smokers) reported SHS exposure at home and 63.0% (54.0% of non-smokers) at workplaces. Among non-smokers, women had greater exposure at home than men (86.6 vs. 77.0%). Lower education levels were associated with exposure at home or the workplace. 99.2% reported SHS exposure at any public place; specifically for restaurants/food stores 57.7%, government offices 56.2%, public transport 31.6%, and health care facilities 11.7%. Conclusion: SHS exposure at home and workplace in Lao PDR is among the highest in South-East Asia. Comprehensive smoke-free policies at government-owned workplaces and facilities, stricter enforcement of these smoke-free policies, and strategies to encourage smoke-free environments at homes and in public places are urgently needed.


Macula Society Collaborative Retrospective Study of Ocriplasmin for Symptomatic Vitreomacular Adhesion.
To assess anatomic and visual outcomes of ocriplasmin use for symptomatic vitreomacular adhesion (VMA). Retrospective chart review. Macula Society members were surveyed online to collect data on ocriplasmin for symptomatic VMA. Clinical and optical coherence tomography data were collected using standardized data entry forms. There were 208 patients (208 eyes) with symptomatic VMA followed at least 3 weeks after receiving ocriplasmin. At baseline, VMA was focal (<1500 μm) in 179 eyes (86%), broad in 9 eyes (4%), and not reported in 20 eyes (10%). A full-thickness macular hole (MH) was present in 75 eyes (36%); size was <400 μm in 62 eyes (82%). Baseline mean visual acuity was approximately 20/63. Of the 204 eyes with ≥12 weeks follow-up, pars plana vitrectomy (PPVx) was performed in 12 (6%) by 4 weeks, 31 (15%) by 12 weeks, and 64 (31%) by the last visit. VMA had resolved by 12 weeks with ocriplasmin alone in 83 of 191 eyes (43%) by week 12 and in 148 of 200 eyes (74%) by the last visit, including eyes undergoing PPVx. Among eyes with a baseline MH, closure was achieved with ocriplasmin alone in 10 of 65 (15%) by 1 week, 26 of 74 (35%) by 4 weeks, and 30 of 75 (40%) at the last visit. Mean change in visual acuity at the last visit compared with baseline was -0.06±0.40 logarithm of the minimum angle of resolution (logMAR) (modest vision improvement) (P = 0.03). At the last visit, visual acuity improved by ≥2 lines in 69 eyes (35%) and by ≥3 lines in 54 eyes (27%). Visual acuity decreased ≥2 lines in 35 eyes (18%) and by 3 lines in 27 eyes (14%) at the final visit. Complications included photopsias (15%), dimness of vision (14%), decreased color vision (10%), MH development (5%), macular retinal pigment epithelium atrophy (2.7%), retinal detachment (1.9%), and retinal tear (1.4%). No endophthalmitis cases were reported. Physician-reported outcomes on ocriplasmin use confirmed VMA release in 45% and closure of MH in 40% of eyes without PPVx. Visual acuity decreased in approximately 20% of eyes. Adverse events were not infrequent and suggest caution when considering ocriplasmin use.


Percutaneous radiologic gastrostomy using the one-anchor technique in patients after partial gastrectomy.
The purpose of our study was to assess the feasibility of performing percutaneous radiologic gastrostomy (PRG) in patients who had undergone partial gastrectomy and to evaluate factors associated with technical success. Nineteen patients after partial gastrectomy, who were referred for PRG between April 2006 and April 2012, were retrospectively analyzed. The remnant stomach was punctured using a 21-gauge Chiba-needle. A single anchor was used for the gastropexy and a 12-Fr or 14-Fr gastrostomy tube was inserted. Data were collected regarding the technical success, procedure time, and presence of any complications. Univariable analyses were performed to determine the factors related to the technical success. Percutaneous radiologic gastrostomy was technically successful in 10 patients (53%), while a failed attempt and failure without an attempt were observed in 5 (26%) and 4 (21%) patients, respectively. Percutaneous radiologic jejunostomy was successfully performed in 9 patients who experienced technical failure. In the 10 successful PRG cases, the mean procedure time was 6.35 minutes. Major complications occurred in 2 patients, tube passage through the liver and pneumoperitonum in one and severe hemorrhage in the other. The technical success rate was higher in patients with Billroth I gastrectomy (100%, 6/6) than in patients with Billroth II gastrectomy (31%, 4/13) (p = 0.011). Percutaneous radiologic gastrostomy can be successfully performed using the one-anchor technique in approximately half of the patients after partial gastrectomy.


Appearance before performance? Nutritional constraints on life-history traits, but not warning signal expression in aposematic moths.
Trade-offs have been shown to play an important role in the divergence of mating strategies and sexual ornamentation, but their importance in explaining warning signal diversity has received less attention. In aposematic organisms, allocation costs of producing the conspicuous warning signal pigmentation under nutritional stress could potentially trade-off with life-history traits and maintain variation in warning coloration. We studied this with an aposematic herbivore Arctia plantaginis (Arctiidae), whose larvae and adults show extensive variation in aposematic coloration. In larvae, less melanic coloration (i.e. larger orange patterns) produces a more efficient warning signal against predators, whereas high amounts of melanism (smaller orange pattern) enhance thermoregulation, correlate with better immunity and make individuals harder to detect for naïve predators. We conducted a factorial rearing experiment with larvae originating from lines selected for either small or large orange signal size, which were reared on an artificial diet that had either low or high protein content. Protein content of the diet is critical for melanin production. We measured the effects of diet on individual coloration, life-history traits, immune defence and reproductive output. We also compared the responses to dietary conditions between the small and large larval signal genotypes. Protein content of the diet did not affect warning coloration in the larval stage, but larval signal sizes differed significantly among selection lines, confirming that its variation is mainly genetically determined. In adults, signal line or diet did not affect coloration in hindwings, but males' forewings had more melanin on the high than on low protein diet. Contrary to coloration, diet quality had a stronger impact on life-history traits: individuals developed for longer had smaller hindwing sizes in females and lower immune defence on the low protein content diet compared with the high. These costs were higher for more melanic larval signal genotypes in terms of development time and female hindwing size. We conclude that low plasticity in warning signal characteristics makes signal expression robust under varying dietary conditions. Therefore, variation in diet quality is not likely to constrain signal expression, but can have a bigger impact on performance.


Left atrial remodeling in acute anterior myocardial infarction.
Our goal in this study was to examine the changes in the left atrial functions over a period of 3 months by using left atrial volume measurements in patients with anterior myocardial infarction (MI). Seventy-three patients with anterior MI who consulted our hospital in the first 12 hours starting from the onset of the chest pain and who exhibited ST elevation were enrolled in the study. The left atrial functions of the patients were evaluated by transthoracic echocardiography for a total number of four times; first at the time of the visit to the hospital, then in the first week, and then in the first and third months. Eight (10.95%) of the 73 patients included in the study died during the follow-up. The remaining 65 patients completed the 3-month study period. Of these 65 patients, primary percutaneous transluminal coronary angioplasty (PTCA) was performed for 24 (36.9%) patients and thrombolytic therapy was given to 13 (20%), whereas 28 (43.1%) patients were given only medical treatment. Left atrium (LA) maximum transverse diameter, LA maximum, minimum, and presystolic volume, LA active emptying volume and fraction were found to increase significantly in comparison to baseline detected for this parameter in the first and third months (P < 0.001). However, LA passive emptying volume and fraction was found to decrease significantly in comparison to baseline detected for this parameter in the first and third months (P < 0.001). An increase in the diameter, volume, and dimensions of LA during atrial remodeling was detected. LA passive emptying fraction was found to decrease, whereas atrial active emptying function was found to increase to compensate for this change.


Dextranated poly(urethane amine)s designed for systemic gene delivery in ovarian cancer therapy.
Herein, comb-shaped polycations with neutral dextran as the main chain and folate-coupled bioreducible poly(urethane amine) (PUA) as the graft were designed and prepared as non-viral vectors for intravenous gene delivery targeting in tumor-bearing nude mice. Herein, primary amine-terminal PUAs with varied degrees of polymerization (DP) were prepared and then conjugated to dextrans with different molecular weights (5 kDa or 10 kDa), producing comb-shaped dextran-PUA polycations (denoted as Dex-PUA). The terminal group of the PUA graft could be further modified with folate, yielding folate-coupled Dex-PUA (denoted as Dex-PUA-FA). These comb-shaped polycations can condense genes into colloidal stable polyplexes under physiological conditions. However, these nano-polyplexes liberated genes in response to a reductive intracellular environment. In vitro transfection experiments showed that Dex10k-PUA40-FA, with 10 kDa dextran and a PUA oligomer with DP 40, induced the best transfection efficiency against SKOV-3 ovarian cancer cells in 10% serum. In vivo, the Dex10k-PUA40-FA polyplexes were applicable for intravenous gene delivery targeting SKOV-3 tumors in nude mice, affording a higher level of gene accumulation in the tumor as compared to Dex10k-PUA40 polyplexes lacking folate. Additionally, in vivo gene therapy showed that using a small hairpin RNA-silencing vascular endothelial growth factor, the Dex10k-PUA40-FA polyplexes exerted significant growth inhibition of SKOV-3 tumors with negligible systemic toxicity. The results of this study highlight dextranated PUA as a safe and robust gene vector for non-viral cancer gene therapy.


[Evaluation of Factor Structure and Construct Validity of the 12-Item Short Version of the OPD Structure Questionnaire (OPD-SQS) in Psychosomatic Patients].
Screening for personality dysfunction is regarded as increasingly important for treatment planning in clinical settings as this allows to determine specific clinical pathways in an early stage. Recently, the 12-item OPD Structure Questionnaire (OPD-SQS) was developed for this purpose and initial results of the factor structure and validity have been published. This study aimed to investigate and validate the OPD-SQS in further patient samples beyond the team of developers and to provide reference values. Data was assessed in psychosomatic outpatients (N=565) and inpatients (N=670) at Charité - Universitätsmedizin Berlin between 2012 and 2016. To examine the factor structure of the OPD-SQS confirmatory factor analyses (CFA) were applied in both samples. To evaluate construct validity, a SKID-II-Interview was performed in N=105 patients and narcissism inventory (NI-90) was completed by N=160 patients. In addition, a range of instruments reflecting emotional, social and physical health were assessed. Bivariate correlations were performed to analyze relations between these instruments and the OPD-SQS. CFAs indicated a good to satisfying fit for the proposed model including 3 factors. A Bifactormodel resulted in very good modelfit. Analyses of construct validity resulted in high positive correlations of OPD-SQS with dimensional SCID-II scores, SKID-II interviews, and NI-90 confirming convergent validity. Results for discriminant validity were heterogeneous. Medium to high correlations were found with a range of instruments including D-CAT (depression), A-CAT (anxiety), S-CAT (stress), and PHQ-15 (somatic symptoms). Subsequent analyses revealed, that the factor self-perception is potentially being influenced by current depression and anxiety. Analyses showed only minor differences of correlations between OPD-SQS subscales and other instruments. The OPD-SQS seems to be appropriate for screening of personality dysfunction. However, other aspects of psychopathology are gathered in addition. Therefore, further investigation of the patients' personality structure such as an OPD interview may be added in clinical settings.


Effect of Internet use for searching information on vaccination on the uptake of human papillomavirus vaccine in France: A path-analysis approach.
Internet is a popular source of information regarding vaccination. This study aimed to determine whether there is a negative association between Internet use among French vaccine-hesitant mothers and HPV vaccine uptake by their daughters, and to gain insight into the pathways that would link Internet use to the lack of HPV vaccine uptake. We conducted a pooled cross-sectional analysis across the 2015, 2016, 2017 and 2018 Vaccinoscopie® Survey. Multivariate logistic regression and path models were used in the analysis. The study sample included a total of 2038 respondent mothers. Of those, 89 (4.4%) declared having never been in the situation of searching for information regarding a vaccination they had hesitated about, leaving 1949 mothers for the present analysis. Approximately 24% (466/1949) of the mothers declared using the Internet as a source of vaccine information. In multivariate logistic regression adjusted for physician recommendation of HPV vaccination, attitudes towards vaccines in general, perception of HPV vaccine usefulness, maternal level of education, region of residence, and the survey year, the use of Internet by the mothers was significantly associated with a lower HPV vaccination among their daughters (adjusted odds ratio (aOR), 0.66; 95% confidence interval (CI), 0.47-0.91). Path analysis further confirmed the negative effect of Internet use (β = -0.10, standard error (SE) = 0.02, P < 0.0001), highlighting how the Internet plays a detrimental role in HPV vaccine uptake through a lower perceived level of HPV vaccine usefulness, a lower perceived level of information on childhood vaccination, and unfavorable attitudes towards vaccination in general.


Regeneration of a distinctive set of axosomatic contacts in the leech central nervous system.
The nociceptive sensory neurons (N cells) in the leech Hirudo medicinalis contact other neurons through conventional synapses in the neuropile and through baskets of processes that wrap the somata of particular cells. These axosomatic contacts are made with the pressure (P) and N sensory neurons in the adjacent segmental ganglia, but not with cells within the same ganglion as the wrapping cell. Physiological evidence indicates that these contacts may be synaptic, although conventional synapses have not been observed with electron microscopy. After they have been injured, lateral N cell processes can grow into the anterior adjacent ganglion and regenerate somatic contacts. In general, regenerated N cell processes wrap the same somata as do intact N cells, but they often wrap fewer somata. However, six of 14 regenerated N cells also wrapped the soma of a small posterior cell that was contacted in only one of 120 normal ganglia examined. It thus appears that the growing processes of an injured N cell select certain cell somata to wrap, but that the selection is somewhat broader than that in the embryonic leech.


Arp2/3-dependent pseudocleavage [correction of psuedocleavage] furrow assembly in syncytial Drosophila embryos.
In syncytial blastoderm Drosophila embryos, actin caps assemble during telophase. As the cell cycle progresses through interphase, these small caps expand and fuse to form pseudocleavage furrows that are structurally related to the cleavage furrows that assemble during somatic cell division. The molecular mechanism driving cell cycle coordinated actin reorganization from the caps to the furrows is not understood. We show that Drosophila embryos contain a typical Arp2/3 complex and that components of this complex localize to the margins of the expanding caps, to mature pseudocleavage furrows, and to somatic cell cleavage furrows during the postcellularization embryonic divisions. A mutation that disrupts the arpc1 subunit of Arp2/3 leads to spindle fusions that are characteristic of pseudocleavage furrow disruption. By contrast, this mutation does not significantly affect nuclear positioning during interphase, which is dependent on actin cap function. In vivo analysis of actin reorganization demonstrates that the arpc1 mutation does not prevent assembly of small actin caps but blocks cap expansion and furrow assembly as the cell cycle progresses through interphase. The scrambled gene is also required for cap expansion and furrow assembly, and Scrambled is required for Arp2/3 localization to the cap margins. The Drosophila Arp2/3 complex and Scrambled protein are required for actin cap expansion and pseudocleavage furrow formation during the syncytial blastoderm divisions. We propose that Scrambled-dependent localization of Arp2/3 to the margins of the expanding caps triggers local actin polymerization that drives cap expansion and pseudocleavage furrow assembly.


Reversible cerebral vasoconstriction syndrome.
Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache associated with multifocal vasoconstriction of cerebral arteries in patients without aneurysmal subarachnoid hemorrhage (SAH). The vasoconstriction reverts within three months. We report a 44-year-old man who had a thunderclap headache during sexual intercourse. A similar episode occurred at rest 36 hours later. The patient had already experienced a thunderclap headache 10 years earlier, during coitus. There were no abnormalities on examination. His brain computed tomography scan was normal and cerebrospinal fluid analysis showed no xanthochromia, 15 WBC/mm³ and 10 RBC/mm³. Lumbar puncture was repeated two days later (WBC = 3/mm³ and RBC = 43/mm³). An initial digital cerebral angiography showed a diffuse segmental intracerebral vasospasm. A new angiography after 15 days was normal. He remains headache-free after twenty six months. In conclusion, patients who have thunderclap headache with normal brain CT and cerebrospinal fluid without xantochromia should be investigated for this syndrome.


Clinical experience with adalimumab in a multicenter Swiss cohort of patients with Crohn's disease.
Controlled clinical trials have demonstrated the efficacy and safety of adalimumab in patients with moderate-to-severe Crohn's disease (CD), but there is, however, only limited long-term experience with adalimumab in daily practice. To assess the long-term effectiveness and safety of adalimumab in a multicenter cohort of practice-based patients with moderate-to-severe CD. We retrospectively reviewed the charts of CD patients who received adalimumab over a 3-year period. Disease severity was scored using the Harvey-Bradshaw index (HBI). Remission was defined as an HBI of <or=4 and response as a reduction in the HBI of >3 points at evaluation compared to the baseline. Univariate logistic regression analysis was used to identify the predictive variables associated with response. The charts of 55 patients were reviewed; remission and response rates observed at weeks 4-6 were 52.7 and 83.6%, respectively. Remission was maintained at weeks 12, 24 and 52 in 89.6, 72.4 and 44.7% of patients, respectively. Remission and response rates were not influenced by smoking status, disease location or duration, the first month total dose, or previous infliximab therapy. The remission rate at weeks 4-6 was significantly higher in patients intolerant of infliximab as compared to those who lost response to this drug. Adalimumab was well tolerated overall. Adalimumab can be considered a suitable option in patients with moderate-to-severe CD, demonstrating sustained long-term effectiveness.


Multiple retinoic acid response elements cooperate to enhance the inducibility of CYP26A1 gene expression in liver.
CYP26A1, which catalyzes the oxidation of all-trans (at)-retinoic acid (RA), is induced moderately by RA in numerous tissues, but is highly responsive in liver. To understand this difference, we have examined the CYP26A1 gene sequence, identified multiple RA response elements (RAREs) and tested them functionally in HepG2 cells as model hepatocytes, and in the liver of vitamin A (VA)-adequate and -deficient rats. Analysis of a 2.2 kbp 5'-flanking region upstream of the CYP26A1 transcription start site (TSS) identified 3 conserved hexameric direct repeat-5 elements, RARE1, -2 and -3, and a half site, RARE4. The full-length promoter containing all 4 elements was sufficient and necessary to increase promoter activity similar to levels of endogenous CYP26A1 mRNA produced in HepG2 cells treated with at-RA. In DNA binding and chromatin immunoprecipitation assays, the binding of RARs to the proximal RARE1 and distal RARE2, -3, and -4 regions of the CYP26A1 promoter was increased in RA-treated HepG2 cells, and greater in VA-sufficient than VA-deficient liver. Moreover, RA increased the binding of RNA polymerase-II in the distal as well as the proximal region, indicating that the distal region may be looped to become positioned close to the TSS, a process favored by retinoic acid receptors. The results support a cooperative model in which the functioning of multiple RAREs may account for the strong inducibility of CYP26A1 in liver, which, in turn, may be important physiologically for restoring retinoid homeostasis when the concentration of RA rises.


Renal clearance, tissue distribution, and CA-125 responses in a phase I trial of suramin.
Suramin was administered to 49 patients in a Phase I cancer trial with real-time pharmacokinetic monitoring and dose individualization to achieve targeted mean plasma concentrations of 210 and 155 mg/liter during the 7-day period between days 15 and 22. Pharmacokinetic sampling after doses on days 1, 3, 5, and 8 was used to modify weekly suramin doses, beginning on day 15, in an attempt to achieve specific averaged plasma concentrations of 210 and 155 mg/liter. A 200-mg test dose was not effective in prospectively determining individual pharmacokinetic parameters and dosage requirements. Patients with peak plasma suramin concentrations in excess of 350 mg/liter may be more likely to experience neurotoxicity (P = 0.06), but there was no statistically significant effect of peak suramin concentration or of cumulative dose. Biopsy and autopsy tissue samples demonstrated low penetration of suramin into brain tissue and muscle but good penetration into prostate and other visceral organs. Prospective use of surrogate substrates for CYP1A2, CYP3A3/4, and CYP2D6 showed no consistent effect of suramin on these enzymes. Although a correlation between creatinine clearance and suramin renal clearance was found (r2 = 0.38; P < 0.00005), there was no correlation between creatinine clearance and total suramin clearance (P = 0.21). No suramin dose modification for renal or hepatic dysfunction can be supported at this time. Three of four ovarian cancer patients demonstrated a drop in CA-125 serum concentrations during suramin treatment.


A Journey to Reach the Ovary Using Next-Generation Technologies.
Although effective in terms of the chances of future live birth, the current methods for fertility preservation, such as oocyte, embryo, or ovarian tissue cryopreservation, cannot be offered to all cancer patients in all clinical contexts. Expanding options for fertility preservation is crucial to addressing the need to encompass all situations. One emerging strategy is pharmacoprotection, a non-invasive approach that has the potential to fill existing gaps in fertility preservation. In addition to the identification of the most effective therapeutic agents, the potential for off-target effects remains one of the main limitations of this strategy for clinical application, particularly when healthy ovarian tissue is targeted. This review focuses on the advances in pharmacoprotective approaches and the challenge of targeting the ovaries to deliver these agents. The unique properties of gold nanoparticles (AuNPs) make them an attractive candidate for this purpose. We discuss how AuNPs meet many of the requirements for an ideal drug delivery system, as well as the existing limitations that have hindered the progression of AuNP research into more clinical trials. Additionally, the review highlights microRNA (miRNA) therapy as a next-generation approach to address the issues of fertility preservation and discusses the obstacles that currently impede its clinical availability.


Indicators of dental anxiety in children just prior to treatment.
We evaluated the relationship between child dental anxiety and selected child and parental characteristics. Children and their parents were interviewed at the New York University, College of Dentistry, Pediatric Dentistry Clinic. The Children's Fear Survey Schedule - Dental Subscale (CFSS-DS) evaluated child self-reported anxiety; the Modified Dental Anxiety Scale (MDAS) measured self-reported parental anxiety when the parent received dental treatment. Ninety-three children and their parents completed the questionnaires. Mean CFSS-DS scores were higher for girls than boys (32.5 vs. 26.3, p=0.003) and for children whose accompanying parents had MDAS scores of 11+ vs. ≥ 11 (32.8 vs. 26.6, p=0.001). There was little difference in mean CFSS-DS scores among those aged 6-10 yrs. vs. 11-14 yrs. (30.1 vs. 29.3). Significant correlations were found between CFSS-DS and both gender (Spearman's rho, rs=0.31) and MDAS scores (rs=0.33), but not between CFSS-DS and child age (rs=-0.05). Controlling simultaneously for gender, MDAS score and child age, a high CFSS-DS score (38+ vs. ≥ 38) was positively associated with girls (ORadj=3.76, 95% CI: 1.13-12.54) and an MDAS score of ≤ 15 vs. ≥ 11 (ORadj=2.50, 0.73-8.54), but weakly and inversely associated with age (ORadj=0.80, 0.25-2.52). Child gender and parental anxiety are indicators of child dental anxiety.


A review of the current evidence for the use of angiotensin-receptor blockers in chronic heart failure.
Angiotensin-converting enzyme (ACE) inhibitors have a central role in the management of heart failure, reflecting the contribution of the renin-angiotensin-aldosterone system to the pathophysiology of the condition. Angiotensin-receptor blockers (ARBs) bind specifically to the angiotensin type 1 receptor and may offer further benefits compared with ACE inhibitors. Candesartan, losartan and valsartan have all been evaluated in large clinical outcome trials in heart failure. They display marked differences in pharmacokinetics and receptor-binding properties that may contribute to observed differences in outcome. ELITE II found no significant difference in outcome with losartan as compared with captopril. In the Val-Heft trial, valsartan reduced heart failure hospitalisations when added to conventional therapy including an ACE inhibitor in most patients, but had no effect on mortality. The CHARM programme showed that candesartan reduced morbidity and mortality in heart failure with reduced systolic function, both when added to ACE inhibitor therapy or when used as an alternative in patients who are intolerant to ACE inhibitors. Moreover, the CHARM-preserved study suggested that candesartan is beneficial in patients with heart failure and preserved left-ventricular systolic function. A growing body of evidence show that ARBs are an important contribution to the pharmaceutical management of patients with heart failure.


Diagnostic Value of Convex Probe Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Mediastinal Tuberculous Lymphadenitis: A Systematic Review and Meta-Analysis.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been widely used in the diagnosis of mediastinal lymphadenopathies. Here, we performed a systematic review and meta-analysis to explore the diagnostic value of EBUS-TBNA in mediastinal tuberculous lymphadenopathy (TBLA). PubMed, EMBASE, and Sinoced were systematically searched for articles published in English or Chinese that reported the diagnostic yield of EBUS-TBNA in mediastinal TBLA. The quality of studies was assessed using the QualSyst tool. Using 95% confidence intervals (CI), the diagnostic yields of EBUS-TBNA were calculated for the individual studies, and the results were then pooled using a random-effects model. Heterogeneity and publication bias were also assessed. A total of 14 studies, consisting of 684 patients with mediastinal TBLA, were finally included. The pooled diagnostic yield of EBUS-TBNA for mediastinal TBLA was 80% (95% CI: 74-86%). Significant heterogeneity (I2=77.9%) and significant publication bias were detected (Begg's test p=0.05 and Egger's test p=0.02). From subgroup analyses, significant differences in the diagnostic yield of EBUS-TBNA were associated with Asian vs. European (UK) studies, retrospective vs. prospective studies, those employing rapid on-site cytological evaluation vs. not, those employing different anesthetic types, and those employing smear vs. culture. However, microbiological examination and the number of lymph node passes did not have a significant effect on the diagnostic yield of EBUS-TBNA. Fifteen minor complications for EBUS-TBNA were reported. EBUS-TBNA appears to be an efficacious and safe procedure and should be used as an initial diagnostic tool for mediastinal TBLA.


Asbestos content in lungs of occupationally and nonoccupationally exposed individuals.
Previous reports have indicated that a majority of the population has asbestos bodies within their lungs. These studies generally have been carried out using cohorts from urban environments. The present study compares the asbestos body levels from three unique cohorts: (1) a nonoccupationally exposed group from a large urban environment having a relatively low asbestos content, (2) patients with lung cancer from a nonurban setting, and (3) amosite asbestos workers, who worked and lived in a rural setting. The number of asbestos bodies in both the urban nonoccupationally exposed group and the patients with lung cancer was generally found to be low or below limits of detectability, with the exceptions being those persons in whom an occupational exposure was eventually found. The ferruginous body content of the occupationally exposed group varied considerably between individuals as well as between sites within the same individual.


Autonomic healing of polymer composites.
Structural polymers are susceptible to damage in the form of cracks, which form deep within the structure where detection is difficult and repair is almost impossible. Cracking leads to mechanical degradation of fibre-reinforced polymer composites; in microelectronic polymeric components it can also lead to electrical failure. Microcracking induced by thermal and mechanical fatigue is also a long-standing problem in polymer adhesives. Regardless of the application, once cracks have formed within polymeric materials, the integrity of the structure is significantly compromised. Experiments exploring the concept of self-repair have been previously reported, but the only successful crack-healing methods that have been reported so far require some form of manual intervention. Here we report a structural polymeric material with the ability to autonomically heal cracks. The material incorporates a microencapsulated healing agent that is released upon crack intrusion. Polymerization of the healing agent is then triggered by contact with an embedded catalyst, bonding the crack faces. Our fracture experiments yield as much as 75% recovery in toughness, and we expect that our approach will be applicable to other brittle materials systems (including ceramics and glasses).


Hematology of Swiss mice (Mus musculus) of both genders and different ages.
To describe the hematologic values of male and female, young and adult, Swiss mice (Mus musculus). Mus musculus (n=14) were randomly selected and separated by gender. The male and female, young and adult animals were sedation to obtain a blood sample, by intracardiac route at 30, 45, 60, 75, 90, 105 and 120 days after birth. The Swiss mouse hemogram values obtained, in relation to total eosinophils, basophils, and number of platelets, there was no statistical differences according to the genders or the age of the animals. Regarding the erythrocyte, hemoglobin and hematocrit values obtained, these were higher in females. The RDW-CD and MPV values were higher in the females than in the males. Lymphocytes are the predominant cells in the peripheral blood. The collection of 800 µL of blood by intracardiac route, every 15 days, did not affect the health of the animals. Analyses of the blood samples contribute to the experimental models provided by the Central Animal Facility of UFMS and used by professors.


Use of subsequent anticoagulants to increase the predictive value of Medicaid deep venous thromboembolism diagnoses.
Linked data bases that derive their information from health care administrative sources are increasingly being used to conduct pharmacoepidemiologic research. Computerized case ascertainment using these data would be highly advantageous in terms of time and cost considerations. For a study of oral-contraceptive-associated deep venous thromboembolism, we evaluated the utility of using anticoagulant treatment codes to validate diagnostic codes suggestive of deep venous thrombosis and pulmonary embolism. By requiring evidence of outpatient anticoagulant use within six months of hospitalization, the predictive value of case ascertainment increased from 42% to 65% for "probable" deep venous thromboembolism and from 70% to 97% for "possible" deep venous thromboembolism. In addition, use of anticoagulant treatment codes as a second marker of disease resulted in nondifferential outcome misclassification when the study base was restricted to current oral-contraceptive users. Use of confirmatory treatment claims may provide a rapid, cost-effective alternative to medical-record-based case ascertainment for pharmacoepidemiologic studies of selected outcomes conducted in Medicaid and other linked universal health care coverage populations.


Potential of resource recovery in UASB/trickling filter systems treating domestic sewage in developing countries.
This paper aims to present perspectives for energy (thermal and electric) and nutrient (N and S) recovery in domestic sewage treatment systems comprised of upflow anaerobic sludge blanket (UASB) reactors followed by sponge-bed trickling filters (SBTF) in developing countries. The resource recovery potential was characterized, taking into account 114 countries and a corresponding population of 968.9 million inhabitants living in the tropical world, which were grouped into three desired ranges in terms of cities' size. For each of these clusters, a technological arrangement flow-sheet was proposed, depending on their technical and economic viability from our best experience. Considering the population living in cities over 100, 000 inhabitants, the potential of energy and nutrient recovery via the sewage treatment scheme would be sufficient to generate electricity for approximately 3.2 million residents, as well as thermal energy for drying purposes that could result in a 24% volume reduction of sludge to be transported and disposed of in landfills. The results show that UASB/SBTF systems can play a very important role in the sanitation and environmental sector towards more sustainable sewage treatment plants.


Biomechanical Consequences of Anterior Femoral Notching in Cruciate-Retaining Versus Posterior-Stabilized Total Knee Arthroplasty.
Anterior femoral notching during total knee arthroplasty is a potential risk factor for periprosthetic supracondylar femur fracture. We conducted a study to determine if the design of the femoral implant changes the risk for periprosthetic supracondylar femur fractures after anterior cortical notching. An anterior cortical defect was created in 12 femoral polyurethane models. Six femora were instrumented with cruciate-retaining implants and 6 with posterior-stabilized implants. Each femur was loaded in external rotation along the anatomical axis. Notch depth and distance from anterior cortical notch to implant were recorded before loading, and fracture pattern was recorded after failure. There were no statistically significant differences in notch depth, distance from notch to implant, torsional stiffness, torque at failure, final torque, or fracture pattern between cruciate-retaining and posterior-stabilized femoral component designs. Periprosthetic fracture after anterior femoral notching is independent of the bone removed from the intercondylar notch. After notching, there likely is no significant difference in femoral strength in torsion between cruciate-retaining and posterior-stabilized designs.


Loss in connectivity among regions of the brain reward system in alcohol dependence.
A recently developed measure of structural brain connectivity disruption, the loss in connectivity (LoCo), is adapted for studies in alcohol dependence. LoCo uses independent tractography information from young healthy controls to project the location of white matter (WM) microstructure abnormalities in alcohol-dependent versus nondependent individuals onto connected gray matter (GM) regions. LoCo scores are computed from WM abnormality masks derived at two levels: (1) groupwise differences of alcohol-dependent individuals (ALC) versus light-drinking (LD) controls and (2) differences of each ALC individual versus the LD control group. LoCo scores based on groupwise WM differences show that GM regions belonging to the extended brain reward system (BRS) network have significantly higher LoCo (i.e., disconnectivity) than those not in this network (t = 2.18, P = 0.016). LoCo scores based on individuals' WM differences are also higher in BRS versus non-BRS (t = 5.26, P = 3.92 × 10(-6) ) of ALC. These results suggest that WM alterations in alcohol dependence, although subtle and spatially heterogeneous across the population, are nonetheless preferentially localized to the BRS. LoCo is shown to provide a more sensitive estimate of GM involvement than conventional volumetric GM measures by better differentiating between brains of ALC and LD controls (rates of 89.3% vs. 69.6%). However, just as volumetric measures, LoCo is not significantly correlated with standard metrics of drinking severity. LoCo is a sensitive WM measure of regional cortical disconnectivity that uniquely characterizes anatomical network disruptions in alcohol dependence.


Prior entry and temporal attention: cueing affects order errors in RSVP.
The law of prior entry states that attended objects come to consciousness more quickly than unattended ones. This has been well established in spatial cueing paradigms, where two task-relevant stimuli are presented near-simultaneously at two different locations. Here, we suggest that prior entry also plays a pivotal role in temporal attention paradigms, where stimuli appear at the same location but at distinct moments in time, in rapid serial presentation (RSVP). Specifically, we hypothesize that prior entry can explain temporal order reversals in reporting two targets from RSVP. In support of this, three experiments show that cueing attention toward either of the targets has a strong influence on order errors. We conclude that prior entry provides a viable explanation of the way in which relevant information is prioritized in RSVP.


Clinical, biopsy, and mass spectrometry findings of renal gelsolin amyloidosis.
Gelsolin amyloidosis is a rare type of amyloidosis typically involving the cranial and peripheral nerves, but rarely the kidney. Here we report the clinical, kidney biopsy, and mass spectrometry findings in 12 cases of renal gelsolin amyloidosis. Of the 12 patients, five were men and seven were women with mean age at diagnosis of 63.8 years. Gelsolin amyloidosis was most common in Caucasians (six patients) and Asians (four patients), and included one each African-American and Hispanic patients. Nephrotic syndrome was the most common cause of biopsy, although most patients also had progressive loss of kidney function. Hematological and serological evaluation was negative in 11 patients, while one patient had a monoclonal gammopathy. The renal biopsy showed large amounts of pale eosinophilic Congo red-positive amyloid deposits typically restricted to the glomeruli. Immunofluorescence studies were negative for immunoglobulins in nine cases with three cases of smudgy glomerular staining for IgG. Electron microscopy showed mostly random arrangement of amyloid fibrils with focally parallel bundles/sheets of amyloid fibrils present. Laser microdissection of the amyloid deposits followed by mass spectrometry showed large spectra numbers for gelsolin, serum amyloid P component, and apolipoproteins E and AIV. Furthermore, the p. Asn211Lys gelsolin mutation on mass spectrometry studies was detected in three patients by mass spectrometry, which appears to represent a renal-limited form of gelsolin amyloidosis. Thus, renal gelsolin amyloidosis is seen in older patients, presents with nephrotic syndrome and progressive chronic kidney disease, and histologically exhibits glomerular involvement. The diagnosis can be confirmed by mass spectrometry studies.


Acaricidal Activity of Tea Tree and Lemon Oil Nanoemulsions against Rhipicephalus annulatus.
Tick infestation is a serious problem in many countries since it has an impact on the health of animals used for food production and pets, and frequently affects humans. Therefore, the present study aimed to investigate the acaricidal effects of nanoemulsions of essential oils of Melaleuca alternifolia (tea tree, TT) and Citrus limon (lemon oil, CL) against the different stages (adult, eggs, and larvae) of deltamethrin-resistant Rhipicephalus annulatus ticks. Three forms of these oils were tested: pure oils, nanoemulsions, and a binary combination. Tea tree and lemon oil nanoemulsions were prepared, and their properties were assessed using a zeta droplet size measurement and a UV-Vis spectrophotometer. The results showed that TT and CL exhibited higher adulticidal effects in their pure forms than in their nanoemulsion forms, as demonstrated by the lower concentrations required to achieve LC50 (2.05 and 1.26%, vs. 12.8 and 11.4%, respectively) and LC90 (4.01% and 2.62%, vs. 20.8 and 19.9%, respectively). Significant larvicidal activity was induced by the TTCL combination, and LC50 was reached at a lower concentration (0.79%) than that required for the pure and nanoemulsion forms. The use of pure CL oil was found to have the most effective ovicidal effects. In conclusion, pure TT and CL have potent acaricidal effects against phenotypically resistant R. annulatus isolates. It is interesting that the activity levels of TT and CL EOs' binary and nanoemulsion forms were lower than those of their individual pure forms.


Immunoglobulins on the surface of blast cells in human acute leukemia.
By means of the direct fluorescent antibody technique it was shown that malignant cells in acute lymphoblastic leukemia do not, as a rule, bear immunoglobulins on the cell surgace (43 of 45 cases). During complete remission the number of Ig-positive cells corresponds to the number of Ig-positive cells in normal lymphocyte populations. During incomplete remission as well as during incomplete remission as well as during intensive chemotherapy, the lymphocyte-like cells are evidently malignant, since they do not contain a normal number of Ig-positive lymphocytes. In acute myeloblastic leukemia (AML) and acute myelomonoblastic leukemia (AMML), lymphocytes distribute normally according to the number of Ig-positive and Ig-negative in 34 of 38 cases. AMML blast cells were Ig-positive in nine of ten cases. The data are discussed in the light of current concepts about the presence of a common precursor cell of granulocytes and monocytes.


Myoglobin function in exercising skeletal muscle.
Short-term perfusion of the isolated dog gastrocnemius-plantaris muscle with hydrogen peroxide resulted in a decrease in steady-state muscle oxygen consumption and isometric tension generation. Hydrogen peroxide converted intracellular myoglobin to products incapable of combination with oxygen, but had no deleterious effect on neuromuscular transmission or on mitochondrial oxidative phosphorylation. It is concluded that functional intracellular myoglobin is important in maintaining oxygen consumption and tension generation in exercising skeletal muscle.


Appetitive, dietary and health effects of almonds consumed with meals or as snacks: a randomized, controlled trial.
Snacks contribute toward a significant proportion of human total daily energy intake. This study investigated the effects of almonds, a satiating and nutrient-rich, common snack, on postprandial glycemia, appetite, short-term body weight and fasting blood parameters when consumed with meals or alone as a snack. This was a 4-week randomized, parallel-arm study that entailed consuming almonds (43 g/day) with breakfast (BF) or lunch (LN), alone as a morning (MS) or afternoon (AS) snack or no almonds (CL). Participants (N=137) with increased risk for type 2 diabetes completed an oral glucose tolerance test (OGTT) and acute-feeding session at baseline, followed by almond consumption for 4 weeks before repeating the OGTT and acute-feeding trials. Anthropometric, biochemical and appetite responses were assessed. Almonds lowered serum glucose responses postprandially. Effects were most prominent in the snack groups. Almonds, consumed as snacks, also reduced hunger and desire to eat during the acute-feeding session. After 4 weeks, anthropometric measurements and fasting blood biochemistries did not differ from the control group or across intervention groups. Without specific guidance, daily energy intake was reduced to compensate for energy from the provided almonds. Dietary monounsaturated fat and α-tocopherol intakes were significantly increased in all almond groups. Almonds provide post-ingestive metabolic and appetitive benefits and did not increase the risk for weight gain. This suggests that almonds may be a healthful snack option.


Treatment for beta-blocker poisoning: a systematic review.
Introduction: Beta-adrenoreceptor antagonist (beta-blocker) poisoning is a common overdose which can lead to significant morbidity and mortality.Objective: To evaluate the effects of treatments for beta-adrenoreceptor antagonist poisoning.Methods: Searches were conducted across MEDLINE (1946-26 November 2019, Ovid); Embase (1974-26 November 2019, Ovid); and the Cochrane Central Register of Controlled Trials (CENTRAL, to 26 November 2019) utilising a combination of subject headings and free text. The search strategy identified 15, 553 citations. Two reviewers screened titles and abstracts prior to selecting 141 articles (Kappa on articles included = 0.982, 95% CI 0.980-0.985). Primary outcomes included mortality and improvement in haemodynamic parameters (e.g., heart rate, blood pressure or a composite measure able to quantitate a haemodynamic response).Results: The risk of bias was high for all interventions.Gastric decontamination: Fifteen case reports described the administration of activated charcoal and five detailed the use of gastric lavage. As there was concurrent utilisation of multiple interventions, it was difficult to draw definitive conclusions regarding the relative contribution of these interventions to mortality or survival.Catecholamines, inotropes and vasopressors: The use of catecholamines in treating beta-blocker toxicity was reported in 16 case reports, 3 case series and 2 animal studies. These agents most likely provided a survival benefit and improved haemodynamics.Atropine: Multiple intravenous boluses of atropine were associated with improvement in heart rate and blood pressure in one case report.Calcium: Intravenous calcium was associated with an improvement in haemodynamics in three out of six case reports but in association with multiple other therapies as well as in two animal studies.High-dose insulin euglycaemic therapy: The use of this therapy was associated with mortality benefit in 10 case series. Two case reports showed clear haemodynamic improvement in a timeframe consistent with insulin administration (bolus then continuous infusion). Maintenance dosing ranged from 1 to 10 units/kg/h of insulin. However, it is unclear whether high-dose insulin euglycaemic therapy improved haemodynamic response above catecholamines and other inotropic agents in humans. Hypoglycaemia and hypokalemia were commonly observed adverse effects.Glucagon: Glucagon was associated with minor improvements in haemodynamics through an increase in heart rate in two cases series, nine case reports and five animal studies.Methylthioninium chloride (methylene blue): Four case reports reported an association with improvement in haemodynamics following administration of methylene blue but in the setting of co-ingestion with amlodipine.Intravenous lipid emulsion therapy: There was variable response to intravenous lipid emulsion therapy reported in 10 case series, 5 animal studies and 21 case reports.Lignocaine: There were four case reports showing variable response to lignocaine in arrhythmias secondary to beta-blocker toxicity.Other treatments: Fructose diphosphate, levosimendan and amrinone did not provide a mortality or significant haemodynamic benefit in three animal studies and nine case reports. .Veno-arterial extracorporeal membrane oxygenation: Veno-arterial extracorporeal membrane oxygenation was associated with improved survival in patients with severe cardiogenic shock or cardiac arrest in an observational study and four cases series.Dialysis: The evidence of four case reports suggest haemodialysis may assist in the management of massive overdose of specific water-soluble beta-blockers (e.g., atenolol) by improving elimination; however, a survival or haemodynamic benefit was not established.Pacing: One case series and a single case report showed the utility of temporary overdrive cardiac pacing to prevent arrhythmias in sotalol toxicity.Conclusions: Catecholamines, vasopressors, high-dose insulin euglycaemic therapy and veno-arterial extracorporeal membrane oxygenation were associated with reduced mortality. However, it must be acknowledged that multiple treatments were often given simultaneously. Haemodynamic improvements in blood pressure and cardiac output were seen with the use of catecholamines, vasopressin and high-dose insulin euglycaemic therapy. Evidence for treatment recommendations is almost entirely drawn from very low- to low-quality studies and subject to bias. However, it is reasonable to have a graduated response to cardiovascular instability beginning with intravenous fluids, commencement of a single or a combination of catecholamine inotropes and vasopressors depending upon the type of haemodynamic compromise (bradycardia, left ventricular dysfunction, vasodilation). High-dose insulin euglycaemic therapy can be introduced as an adjunctive inotrope and lastly, more invasive methods such as veno-arterial extracorporeal membrane oxygenation should be considered in cases unresponsive to other therapies.


Transcriptional control of the bovine leukemia virus genome: role and characterization of a non-immunoglobulin plasma protein from bovine leukemia virus-infected cattle.
Using cloned bovine leukemia virus (BLV) DNA as a probe in the dot blot hybridization technique, we demonstrated that the expression of the BLV genome in infected lymphocytes is blocked in vivo at the transcriptional level. This blocking effect is due to a non-immunoglobulin protein present in the plasma but not in the serum of BLV-infected cattle. The plasma BLV-blocking protein also blocks the expression of the BLV genome in fibroblast cells of bovine and nonbovine origin infected with BLV in vitro. The plasma BLV-blocking factor has no inhibitory effect on the expression of Rauscher murine leukemia virus and feline leukemia virus in monolayer culture. The plasma BLV-blocking factor is not an interferon molecule. As determined by gel filtration chromatography, the plasma BLV-blocking factor has an apparent molecular weight of ca. 150,000.


[Tactics of treatment of the acute cholecystitis complicated by choledocholithiasis].
In this article is present the comparative analysis of the results of different surgical approaches of 201 patients with acute cholecystitis complicated by choledocholithiasis. In the 1st group of 70 (34.8%) patients in the first stage of treatment applied percutaneous cholecystostomies (PC). Retrograde endobiliary interventions endoscopic sphincterotomy (ES) were performed in the second stage before LC. In the 2nd group 131 (65.2%) patients underwent for treatment include preoperative endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy (ERCP/ES) followed by laparoscopic cholecystectomy (LC). The complications of retrograde interventions was higher by 3.5 times in the group of patients without prior decompression of the gallbladder. The surgical treatment was performed by 70 patients of the first group and by 79 (60.3%) patients of the second group. LC was performed by 66 (94.2%) patients with percutaneous cholecystostomies. Proved highly effective percutaneous cholecystostomy and low risk of complications stage treatment.


Evolutionary rates of commonly used nuclear and organelle markers of Arabidopsis relatives (Brassicaceae).
Recovering the genetic divergence between species is one of the major interests in the evolutionary biology. It requires accurate estimation of the neutral substitution rates. Arabidopsis thaliana, the first whole-genome sequenced plant, and its out-crossing relatives provide an ideal model for examining the split between sister species. In the study, rates of molecular evolution at markers frequently used for systematics and population genetics, including 14 nuclear genes spanning most chromosomes, three noncoding regions of chloroplast genome, and one intron of mitochondrial genome, between A. thaliana and four relatives were estimated. No deviation from neutrality was detected in the genes examined. Based on the known divergence between A. thaliana and its sisters about 8.0-17.6 MYA, evolutionary rates of the eighteen genes were estimated. Accordingly, the ratio of rates of synonymous substitutions among mitochondrial, chloroplast and nuclear genes was calculated with an average and 95% confidence interval of 1 (0.25-1.75): 15.77 (7.48-114.09): 74.79 (36.27-534.61). Molecular evolutionary rates of nuclear genes varied, with a range of 0.383-0.856×10(-8) for synonymous substitutions per site per year and 0.036-0.081×10(-9) for nonsynonymous substitutions per site per year. Compared with orthologs in Populus, a long life-span tree, genes in Arabidopsis evolved faster in an order of magnitude at the gene level, agreeing with a generation time hypothesis. The estimated substitution rates of these genes can be used as a reference for molecular dating.


Association study of cytochrome P450 1A1*2A polymorphism with prostate cancer risk and aggressiveness in Croatians.
Cytochrome P450 1A1 (CYP1A1) is an enzyme participating in the bioactivation of various endogenous and environmental reactive compounds that can bind to DNA and thus induce cancerogenesis. Gene encoding the enzyme is expressed in the prostate tissue and is polymorphic. CYP1A1*2A gene polymorphism is associated with elevated enzyme activity and/or inducibility which can lead to accumulation of genotoxic compounds and consequently to cancerogenesis. We examined the association of this polymorphism with prostate cancer (PCa) risk and aggressiveness. The case-control study consisted of 120 PCa patients and 120 benign prostatic hyperplasia (BPH) controls, in Croatian population. Regarding aggressiveness, PCa patients were grouped according to the Gleason score (GS), tumor stage (T) and existence of distant metastasis (M). The polymorphism was analyzed using real-time polymerase chain reaction (PCR). We did not observe association of mutated allele with PCa risk, neither with PCa aggressiveness. Furthermore, frequency of polymorphic genotype was slightly higher in BPH group (16.6% vs. 14.2%, respectively) and also in less aggressive form of PCa (20.4% vs. 9.6% for GS < 7; 15.6% vs. 9.1% for T < 3; 16.7% vs. 10.0% for no distant metastasis). Comparing our findings with other published results, we can assume that the ethnicity influence the genotype distribution and thus may affect the etiology of PCa, even possibly in the way to cause an opposite effect among different ethnic groups. Given the small number of participants, results should be validated on the larger sample size.


Gartland types IIB and III supracondylar fractures of the humerus in children: is Blount's method effective and safe?
Blount's method is controversial for the treatment of Gartland types IIB and III supracondylar fracture of the humerus (SCFH) in children. The purpose of this study was to evaluate the clinical and radiologic outcomes and the failure and complication rates. All types IIB and III SCFH treated with Blount's method from 2003-2013 were included in this retrospective single-center study. Clinical assessment was performed according to Flynn criteria. Baumann angle, anteversion angle, anterior humeral line, and humeroulnar angle were measured for radiographic assessment. Among 447 children with types IIB and III SCHF, 339 were treated according to Blount's method. There were 173 boys (51%), and the mean age was 6.3 years (1-14 years); 71% were type III. Mean time to surgery was 5.7 hours. According to Flynn criteria, results were satisfactory in 91% of cases. No compartment syndrome was encountered. There were 16 (4.7%) secondary displacements requiring surgical revision. Five (1.9%) children developed a cubitus varus deformity. At latest follow-up, the mean Baumann angle was 74.7° (95% confidence interval, 74.1-75.3), the mean anteversion angle was 39.9° (95% confidence interval, 39.5-40.3), the anterior humeral line was normal in 87.6% of cases, and the mean humeroulnar angle was 8.7°. Blount's method is appropriate to manage types IIB and III SCFH, provided anatomic and stable reduction is obtained.


Niche Differentiation among Three Closely Related Competibacteraceae Clades at a Full-Scale Activated Sludge Wastewater Treatment Plant and Putative Linkages to Process Performance.
Multiple clades within a microbial taxon often coexist within natural and engineered environments. Because closely related clades have similar metabolic potential, it is unclear how diversity is sustained and what factors drive niche differentiation. In this study, we retrieved three near-complete Competibacter lineage genomes from activated sludge metagenomes at a full-scale pure oxygen activated sludge wastewater treatment plant. The three genomes represent unique taxa within the Competibacteraceae A comparison of the genomes revealed differences in capacity for exopolysaccharide (EPS) biosynthesis, glucose fermentation to lactate, and motility. Using quantitative PCR (qPCR), we monitored these clades over a 2-year period. The clade possessing genes for motility and lacking genes for EPS biosynthesis (CPB_P15) was dominant during periods of suspended solids in the effluent. Further analysis of operational parameters indicate that the dominance of the CPB_P15 clade is associated with low-return activated sludge recycle rates and low wasting rates, conditions that maintain relatively high levels of biomass within the system.IMPORTANCE Members of the Competibacter lineage are relevant in biotechnology as glycogen-accumulating organisms (GAOs). Here, we document the presence of three Competibacteraceae clades in a full-scale activated sludge wastewater treatment plant and their linkage to specific operational conditions. We find evidence for niche differentiation among the three clades with temporal variability in clade dominance that correlates with operational changes at the treatment plant. Specifically, we observe episodic dominance of a likely motile clade during periods of elevated effluent turbidity, as well as episodic dominance of closely related nonmotile clades that likely enhance floc formation during periods of low effluent turbidity.


Caffeine ameliorates radiation-induced skin reactions in mice but does not influence tumour radiation response.
Intramuscular administration of caffeine at a dose of 80 mg kg(-1) body weight to the gastrocnemius muscles of Swiss mice 5 min prior to local irradiation (35 Gy) of the leg delayed the progression of radiation-induced skin reactions in such animals. While 90% epilation with reddening of the skin was noted in animals treated with radiation alone, animals pretreated with caffeine suffered only partial hair loss with slight reddening of the skin on the 16th and 20th days post-irradiation. Beyond the 28th day, damage scores in irradiated feet for both the groups were similar (score 3) and remained unchanged until the 32nd day and then decreased and disappeared completely in both treatment groups by the 40th day after irradiation. In addition, the effect of caffeine on the radiation response of a mouse fibrosarcoma was investigated. Results showed that intratumoral administration of caffeine at a dose of 80 mg kg(-1) body weight 5 min prior to local exposure of tumours to 10 Gy of 60Co gamma-rays did not influence the response of tumours to radiation. The present study thus showed that although caffeine ameliorated radiation-induced skin reactions in the mouse leg, it did not affect the tumour radiation response, indicating its potential application in cancer radiotherapy.


P2X7 Receptor Blockade Protects Against Acrolein-Induced Bladder Damage: A Potential New Therapeutic Approach for the Treatment of Bladder Inflammatory Diseases.
Inflammatory conditions of the urinary bladder have been shown to be associated with urothelial damage and loss of function. The purinergic P2X7 receptor has been implicated in several inflammatory conditions. The aim of this study was to investigate the role of the P2X7 receptor in acrolein-induced inflammatory damage using the porcine urinary bladder. For this purpose, an ex-vivo model of porcine urothelial damage induced by direct instillation of acrolein into the whole bladder lumen was used. To determine the role of the P2X7 receptor, the bladders were pre-incubated with a selective P2X7 receptor antagonist, A804598 (10 μM), for 1 h. The effects of the acrolein-induced urothelial damage on the bladder's function were assessed by examining the bladder wall contractile response, structure changes, apoptosis, and oxidative stress in the bladder tissues. The acrolein treatment led to significant damage to the urothelium histology, tight junction expression, and contractile responses. Acrolein also induced apoptosis in the mucosa layer. All these acrolein-induced responses were attenuated by pre-treatment with the P2X7 receptor antagonist A804598. Acrolein also significantly induced DNA oxidation in the submucosal layer; however, the P2X7 receptor antagonism did not show any protective effect towards the acrolein-induced oxidative stress. These findings suggested that the P2X7 receptor is involved in the acrolein-induced damage to the urothelium; therefore, the P2X7 receptor antagonists may be a new therapeutic option for the treatment of bladder inflammation.


Diabetes treatment for persons with severe mental illness: A registry-based cohort study to explore medication treatment differences for persons with type 2 diabetes with and without severe mental illness.
It has been argued that persons with severe mental illness (SMI) receive poorer treatment for somatic comorbidities. This study assesses the treatment rates of glucose-lowering and cardiovascular medications among persons with incident type 2 diabetes (T2D) and SMI compared to persons with T2D without SMI. We identified persons ≥30 years old with incident diabetes (HbA1c ≥ 48 mmol/mol and/or glucose ≥ 11.0 mmol/L) from 2001 through 2015 in the Copenhagen Primary Care Laboratory (CopLab) Database. The SMI group included persons with psychotic, affective, or personality disorders within five years preceding the T2D diagnosis. Using a Poisson regression model, we calculated the adjusted rate ratios (aRR) for the redemption of various glucose-lowering and cardiovascular medications up to ten years after T2D diagnosis. We identified 1,316 persons with T2D and SMI and 41,538 persons with T2D but no SMI. Despite similar glycemic control at diagnosis, persons with SMI redeemed a glucose-lowering medication more often than persons without SMI in the period 0.5-2 years after the T2D diagnosis; for example, the aRR was 1.05 (95% CI 1.00-1.11) in the period 1.5-2 years after the T2D diagnosis. This difference was mainly driven by metformin. In contrast, persons with SMI were less often treated with cardiovascular medications during the first 3 years after T2D diagnosis, e.g., in the period 1.5-2 years after T2D diagnosis, the aRR was 0.96 (95% CI 0.92-0.99). For people with SMI in addition to T2D, metformin is more likely to be used in the initial years after T2D diagnosis, while our results suggest potential room for improvement regarding the use of cardiovascular medications.


Impact of a health literacy intervention combining general practitioner training and a consumer facing intervention to improve colorectal cancer screening in underserved areas: protocol for a multicentric cluster randomized controlled trial.
Colorectal cancer (CRC) is a leading cause of cancer burden worldwide. In France, it is the second most common cause of cancer death after lung cancer. Systematic uptake of CRC screening can improve survival rates. However, people with limited health literacy (HL) and lower socioeconomic position rarely participate. Our aim is to assess the impact of an intervention combining HL and CRC screening training for general practitioners (GPs) with a pictorial brochure and video targeting eligible patients, to increase CRC screening and other secondary outcomes, after 1 year, in several underserved geographic areas in France. We will use a two-arm multicentric randomized controlled cluster trial with 32 GPs primarily serving underserved populations across four regions in France with 1024 patients recruited. GPs practicing in underserved areas (identified using the European Deprivation Index) will be block-randomized to: 1) a combined intervention (HL and CRC training + brochure and video for eligible patients), or 2) usual care. Patients will be included if they are between 50 and 74 years old, eligible for CRC screening, and present to recruited GPs. The primary outcome is CRC screening uptake after 1 year. Secondary outcomes include increasing knowledge and patient activation. After trial recruitment, we will conduct semi-structured interviews with up to 24 GPs (up to 8 in each region) and up to 48 patients (6 to 12 per region) based on data saturation. We will explore strategies that promote the intervention's sustained use and rapid implementation using Normalization Process Theory. We will follow a community-based participatory research approach throughout the trial. For the analyses, we will adopt a regression framework for all quantitative data. We will also use exploratory mediation analyses. We will analyze all qualitative data using a framework analysis guided by Normalization Process Theory. Limited HL and its impact on the general population is a growing public health and policy challenge worldwide. It has received limited attention in France. A combined HL intervention could reduce disparities in CRC screening, increase screening rates among the most vulnerable populations, and increase knowledge and activation (beneficial in the context of repeated screening). Registry: ClinicalTrials.gov. 2020-A01687-32 . Date of registration: 17th November 2020.


Abdominal aortic aneurysma with postoperative delayed paraparesis. Case report.
A 54-year-old man with an expanding abdominal aortic aneurysm was operated on with a straight aortic graft. A paraparesis ensued three days postoperatively. Possible causative mechanisms, including influence on spinal venous pressure and direct effects of extradurally injected local anesthetic, are discussed.


Assessment of dependency, agreeableness, and their relationship.
Agreeableness is central to the 5-factor model conceptualization of dependency. However, 4 meta-analyses of the relationship of agreeableness with dependency have failed to identify a consistent relationship. It was the hypothesis of the current study that these findings might be due in part to an emphasis on the assessment of adaptive, rather than maladaptive, variants of agreeableness. This hypothesis was tested by using experimentally altered NEO Personality Inventory-Revised (Costa & McCrae, 1992) items that were reversed with respect to their implications for maladaptiveness. The predicted correlations were confirmed with the experimentally altered version with measures of dependent personality disorder, measures of trait dependency (including 2 measures of adaptive dependency), and measures of dependency from alternative dimensional models of personality disorder. The theoretical implications of the findings and suggestions for future research are discussed.


Possibilities of chromium (III) separation from acid solution using the double-carrier supported liquid membrane (DCSLM).
This paper describes the problem of recovery and reusing chromium from aqueous solutions. The authors studied a novel double-carrier supported liquid membrane system (DCSLM) with di(2-ethylhexyl) phosphoric acid (D2EHPA) and bis(2,4,4-trimethyl) phosphinic acid (Cyanex272) as a carrier of Cr(III) ions as a method to separate chromium (III) from acid solutions. As a result, they confirmed that the presence of two carriers in the DCSLM with the most effective carrier concentration ratios, leads to approximately three times shorter pertraction, compared to a process conducted with the D2EHPA only. It was found that synergistic effect is independent of the initial concentration of chromium in the feed solution. Higher initial concentrations of Cr(III) ≥ 0.01 mol dm-3 cause high 'exhaustion' of active carrier molecules at the interface. Moreover, the authors observed the increase in viscosity in the membrane phase and process inhibition. It was found that efficiency of separation of chromium ions from aqueous solutions using a liquid membrane depends on the transport rate for these ions in the membrane (ions pertraction). Therefore, it was concluded that the pertraction stage of the Cr(III) ions limits the efficiency of the whole separation process.


[Chemotherapy of malignant brain tumours: principles, difficulties, results and strategies (author's transl)].
Long-lasting therapeutic results have not yet been reached in brain tumour chemotherapy. Mean survival rates in patients with malignant gliomas (glioblastoma multiforme, astrocytoma III-IV) can only be increased for a few months, even with the administration of alkylating nitrosourea derivatives which are in common use these days. In addition to general difficulties of chemotherapy, the well-protected site of the target organ, the brain, is responsible for that fact. This organ has special barrier mechanisms which reduce environmental influences; furthermore the kinetics of brain tumour cells and the interaction of pharmacological agents and tumourous cells are only scarcely known. Finally there are difficulties in the comparison of different samples because criteria of sampling are not always identical and an unequivocal terminology is not used in brain tumour classification. Nevertheless there has been some therapeutic progress after the introduction of urea derivatives into brain tumour chemotherapy, be it as single agent, combination or adjuvant chemotherapy. There is apparently an increase in long-time survivors indicating the effectiveness of the chemotherapeutic scheme in use. Own results with 5 different protocols confirm this tendency. Certain cases with correlations between Ct and post mortem findings are presented. Results and conclusions are discussed.


Generalizing Stepping Concepts To Non-Straight Walking.
People rarely walk in straight lines. Instead, we make frequent turns or other maneuvers. Spatiotemporal parameters fundamentally characterize gait. For straight walking, these parameters are well-defined for that task of walking on a straight path. Generalizing these concepts to non-straight walking, however, is not straightforward. People also follow non-straight paths imposed by their environment (store aisle, sidewalk, etc.) or choose readily-predictable, stereotypical paths of their own. People actively maintain lateral position to stay on their path and readily adapt their stepping when their path changes. We therefore propose a conceptually coherent convention that defines step lengths and widths relative to known walking paths. Our convention simply re-aligns lab-based coordinates to be tangent to a walker's path at the mid-point between the two footsteps that define each step. We hypothesized this would yield results both more correct and more consistent with notions from straight walking. We defined several common non-straight walking tasks: single turns, lateral lane changes, walking on circular paths, and walking on arbitrary curvilinear paths. For each, we simulated idealized step sequences denoting "perfect" performance with known constant step lengths and widths. We compared results to path- independent alternatives. For each, we directly quantified accuracy relative to known true values. Results strongly confirmed our hypothesis. Our convention returned vastly smaller errors and introduced no artificial stepping asymmetries across all tasks. All results for our convention rationally generalized concepts from straight walking. Taking walking paths explicitly into account as important task goals themselves thus resolves conceptual ambiguities of prior approaches.


Tree pattern matching in phylogenetic trees: automatic search for orthologs or paralogs in homologous gene sequence databases.
Comparative sequence analysis is widely used to study genome function and evolution. This approach first requires the identification of homologous genes and then the interpretation of their homology relationships (orthology or paralogy). To provide help in this complex task, we developed three databases of homologous genes containing sequences, multiple alignments and phylogenetic trees: HOBACGEN, HOVERGEN and HOGENOM. In this paper, we present two new tools for automating the search for orthologs or paralogs in these databases. First, we have developed and implemented an algorithm to infer speciation and duplication events by comparison of gene and species trees (tree reconciliation). Second, we have developed a general method to search in our databases the gene families for which the tree topology matches a peculiar tree pattern. This algorithm of unordered tree pattern matching has been implemented in the FamFetch graphical interface. With the help of a graphical editor, the user can specify the topology of the tree pattern, and set constraints on its nodes and leaves. Then, this pattern is compared with all the phylogenetic trees of the database, to retrieve the families in which one or several occurrences of this pattern are found. By specifying ad hoc patterns, it is therefore possible to identify orthologs in our databases.


Patients' access to 2018 FDA-approved drugs 1 year post approval.
To examine US commercial health plans' adoption of 2018 FDA-approved drugs. Database analysis. We identified novel drugs that the FDA approved in 2018 and categorized them as follows: cancer treatment, orphan drug, included in an expedited review program, and biosimilar. Using a data set of 17 large health plans' drug coverage policies and formularies, we examined coverage 1 year following FDA approval. The FDA approved 66 drugs in 2018 (5 were not yet marketed 1 year following approval). For 60 of 61 drugs, some plans issued coverage policies whereas other plans included the drug in their formularies. Plans imposed restrictions (eg, step therapy) in 37% (275/742) of coverage policies. Plans covered biosimilars, orphan drugs, and cancer treatments more generously than drugs not in those categories (P < .05). Plans imposed restrictions in their policies with different frequencies (range, 7%-52%). Plans imposed utilization management (UM) in 82% (3837/4697) of formulary entries. Of those entries, plans required prior authorizations in 98%, included drugs on the highest patient co-payment tier in 70%, and imposed step therapy in 3%. Plans most often placed orphan drugs and cancer treatments on the highest cost-sharing formulary tiers (68% and 64% of the time, respectively). Plans imposed UM in their formularies with different frequencies (range, 62%-100% of entries). Health plans imposed fewer coverage restrictions on cancer treatments, orphan drugs, and biosimilars than on drugs not in those categories. Some plans covered 2018 FDA-approved drugs more generously than others, which has implications for patients' access to innovative therapies.


Eclosion hormone provides a link between ecdysis-triggering hormone and crustacean cardioactive peptide in the neuroendocrine cascade that controls ecdysis behavior.
Three insect peptide hormones, eclosion hormone (EH), ecdysis-triggering hormone (ETH) and crustacean cardioactive peptide (CCAP), have been implicated in controlling ecdysis behavior in insects. This study examines the interactions between these three peptides in the regulation of the ecdysis sequence. Using intracellular recordings, we found that ETH is a potent activator of the EH neurons, causing spontaneous action potential firing, broadening of the action potential and an increase in spike peak amplitude. In turn, electrical stimulation of the EH neurons or bath application of EH to desheathed ganglia resulted in the elevation of cyclic GMP (cGMP) levels within the Cell 27/704 group (which contain CCAP). This cGMP production increases the excitability of these neurons, thereby facilitating CCAP release and the generation of the ecdysis motor program. Extracellular recordings from isolated nervous systems show that EH has no effect on nervous systems with an intact sheath. In desheathed preparations, in contrast, EH causes only the ecdysis motor output. The latency from EH application to ecdysis was longer than that after CCAP application, but shorter than that when ETH is applied to a whole central nervous system. These data, along with previously published results, support a model in which ETH causes pre-ecdysis behavior and at higher concentrations stimulates the EH neurones. EH release then facilitates the onset of ecdysis by enhancing the excitability of the CCAP neurons.