A cantilever torque magnetometry method for the measurement of Hall conductivity of highly resistive samples.
We present the first measurements of Hall conductivity utilizing a torque magnetometry method. A Corbino disk exhibits a magnetic dipole moment proportional to Hall conductivity when voltage is applied across a test material. This magnetic dipole moment can be measured through torque magnetometry. The symmetry of this contactless technique allows for the measurement of Hall conductivity in previously inaccessible materials. Finally, we calculate a low-temperature noise bound, demonstrate the lack of systematic errors, and measure the Hall conductivity of sputtered indium tin oxide.


Prevalence and Clinical Management of Non-malarial Febrile Illnesses among Outpatients in the Era of Universal Malaria Testing in Malawi.
Increasing access to rapid diagnostic tests for malaria (mRDTs) has raised awareness of the challenges healthcare workers face in managing non-malarial febrile illnesses (NMFIs). We examined NMFI prevalence, clinical diagnoses, and prescribing practices in outpatient clinics across different malaria transmission settings in Malawi. Standardized facility-based malaria surveillance was conducted at three facilities one of every 4 weeks over 2 years. Information on demographics, presenting symptoms, temperature, clinical diagnosis, and treatment were collected from outpatients presenting with malaria-like symptoms. Of the 25,486 patients with fever, 69% had NMFI. Non-malarial febrile illness prevalence was lower in 5- to 15-year-old patients (55%) than in children < 5 years (72%) and adults > 15 years of age (77%). The most common clinical diagnoses among febrile patients with negative mRDTs in all age-groups and settings were respiratory infections (46%), sepsis (29%), gastroenteritis (13%), musculoskeletal pain (9%), and malaria (5%). Antibiotic prescribing was high in all age-groups and settings. Trimethoprim-sulfamethoxazole (40%) and amoxicillin (29%) were the most commonly prescribed antibiotics and were used for nearly all clinical diagnoses. In these settings with minimal access to diagnostic tools, patients with fever and a negative mRDT received a limited number of clinical diagnoses. Many were likely to be inaccurate and were associated with the inappropriate use of the limited range of available antibiotics. Prescription and diagnostic practices for NMFIs in the facilities require research and policy input. Resource-limited malaria-endemic countries urgently need more point-of-care diagnostic tools and evidence-based diagnosis and treatment algorithms to provide effective and cost-efficient care.


Signatures of nanoemulsion jamming and unjamming in stimulated-echo NMR.
The unjamming of elastic concentrated nanoemulsions into viscous dilute nanoemulsions, through dilution with the continuous phase, offers interesting opportunities for a pulsed-field gradient (PFG) NMR, particularly if the nanoemulsion is designed to take advantage of the nuclear specificity offered by NMR. Here, we make and study size-fractionated oil-in-water nanoemulsions using a perfluorinated copolymer silicone oil that is highly insoluble in the aqueous continuous phase. By studying these nanoemulsions using ^{19}F stimulated-echo PFG-NMR, we avoid any contribution from the aqueous continuous phase, which contains a nonfluorinated ionic surfactant. We find a dramatic change in the ^{19}F PFG-NMR decays at high field-gradient strengths as the droplet volume fraction, ϕ, is lowered through dilution. At high ϕ, observed decays as a function of field-gradient strength exhibit decay-to-plateau behavior indicating the jamming of nanodroplets, which contain ^{19}F probe molecules, in an elastic material reminiscent of a nanoporous solid. In contrast, at lower ϕ, only a simple decay is observed, indicating that the nanodroplets have unjammed and can diffuse over much larger distances. Through a comparison with bulk mechanical rheometry, we show that this dramatic change coincides with the loss of low-frequency shear elasticity of the nanoemulsion.


[Antiphospholipid syndrome with only antiphosphatidylethanolamine antibodies: report of 20 cases].
The association of antiphosphatidylethanolamine antibodies (aPE) as the only antiphospholipid antibody with antiphospholipid syndrome (APS) is discussed. The aPE was described as the sole antibody in many cases suggesting APS. aPE was not included in the Sapporo criteria for the classification of APS. We investigated the clinical features of 20 patients with aPE only; 17 patients had symptoms potentially related to APS (group 1) and three had other manifestations (group 2). There were 15 women and five men, mean age was 35 +/- 12 years at the beginning. In group 1 (n = 17), ten patients presented arterial thrombosis, nine venous thrombosis (five had both), and six microvascular thrombosis (livedo reticularis, lacunar pathology). The aPE positivity was persistent in 13 patients. A subgroup of four patients (three women) presented arteriosclerosis with peripheral arteriopathy which started before 45 years of age. They had another atherosclerosis risk factor associated with aPE persistence. In group 2 (n = 3), there was no thrombotic event, one demyelinating pathology, one microvascular pathology, and one arterial dysplasia. The aPE positivity was never confirmed. Finally, 13 patients presented an APS with aPE only, confirmed at least 8 weeks later. Our study points out that testing for aPE would be of interest for patients when symptoms were potentially related to APS, particularly when other antiphospholipid antibodies were negative. This description questions the enlargement of the APS biological criteria defined in Sapporo. The role of aPE in atherosclerosis is considered.


Motor city blues.
With its safety net hospital in peril, Detroit had a choice: fundamentally reform its public health system or watch it collapse. Cities nationwide face a similar dilemma.


[The discovery of Tenebryl, the first French uro-angiographic iodized hydrosoluble product].
Ténébryl was perfected in 1931 by Marcel and André Guerbet. For the company which bore their name and after the discovery of Lipiodol, this was the opportunity to explore a new area in radiology: intravenous urography. The discovery of this product is exemplary in a greater sense, since it contributed to opening the way to a new class of contrast products of which the majority today are iodized products. All the ingredients of industrial research are present here, from risk-taking to successful commercialization.


Orbital Apex Metastasis from Adenoid Cystic Carcinoma: Acute Loss of Vision and Subsequent Recovery with the Radiation.
Orbital apex metastasis from adenoid cystic carcinoma (ACC) is rare. We present a patient with known metastatic ACC presented with a rapidly declining vision with visual acuity oculus dexter (OD) equal to counting fingers at two feet. On imaging, she was found to have a right orbital apex tumor causing compressive optic neuropathy. She received the intensity modulated radiation therapy (IMRT). After completion of the therapy, she had regained essentially a full vision with visual acuity OD of 20/30 without corrective lenses. The treatment rationale and pertinent literature are discussed in this article.


Temporal artery thermometry in children younger than 5 years: a comparison with rectal thermometry.
Temporal artery (TA) thermometry has come as one of the new methods for temperature measurement, especially in children in whom accurate temperature monitoring can save lives. The device which is convenient and simple to use is yet to gain popularity in several parts of the world, as there are conflicting reports of its accuracy. This study compares the accuracy of the TA thermometry in children younger than 5 years using the rectal thermometry as the gold standard. Temperature was measured simultaneously in eligible children younger than 5 years from the forehead and rectum using the TA thermometer (TAT-2000C Exergen, USA) and standard mercury in glass rectal thermometer, respectively. The difference between the mean temperatures obtained by the 2 thermometry methods was tested using the paired t test. Pearson correlation coefficient, linear regression, and Bland-Altman plot were also used to test the relationship and agreement between the 2 instruments. The sensitivity, specificity, and positive and negative predictive values were also calculated. Overall, the mean TA temperature (37.80°C ± 1.07°C) was significantly lower than the mean rectal temperature (38.07°C ± 0.95°C), P < 0.001. In neonates, however, the mean difference was not significant, 0.02 ± 0.59 (P = 0.810). There was a significant positive correlation between the rectal and the temporal temperatures (r = 0.80, P < 0.01). The Bland-Altman plot showed wide variation in the limit of agreement between the rectal and the TA temperatures which ranged from -1.02°C to +1.56°C. The sensitivity of the TA thermometer was 64.6% and 83.5%, respectively, at a TA fever cutoff of 38.0°C and 37.7°C. Temporal artery thermometer is not accurate enough for the measurement of core body temperature in children younger than 5 years. However, it may be used as a tool for screening for fever in very busy clinics and emergency room at a fever cutoff of 37.7°C.


Effect of synthetic gonadotrophin-releasing hormone (Gn-RH) on circulating luteinizing hormone (LH) and testosterone in young post-pubertal bulls.
The reproducibility of LH and testosterone responses after Gn-RH treatment in young post-pubertal bulls was tested. Ten bulls were injected im (250 mug) twice with an interval of 4 weeks. Blood samples were collected every 15 min for 21/2 h and then on the second occasion, every hour. LH increases very rapidly and reaches an initial peak by 30 min after Gn-RH injection. This increase over basal level was 25 to 30-fold. After a plateau of high levels lasting 40 to 50 min, a second peak of LH concentration occurs. LH then decreases and returns to basal levels by 6 to 7 h after treatment. The increase of plasma testosterone was more prolonged and of smaller magnitude than that of LH: 3 to 4-fold. There was a large and significant variation between bulls; but with LH, a given individual responded in a consistent manner on the two separate occasions. It is concluded that LH response to Gn-RH treatment might be useful and should be tested as a diagnostic value for clinical or breeding purposes. The testosterone response does not seem to be as valuable and reliable as that of LH.


Learning Experimental Design through Targeted Student-Centric Journal Club with Screencasting.
Knowledge and application of experimental design principles are essential components of scientific methodology, and experience with these skills is fundamental for participating in scientific research. However, undergraduates often enter the research laboratory with little training in designing and interpreting their own experiments. In the context of a research university laboratory, we designed a journal club training exercise to address this need. Students were instructed on methods for interpreting scientific literature using a screencast, a digital recording of a slide presentation narrated by an instructor. Students subsequently examined a series of research publications with a focus on the experimental designs and data interpretation in a two-session group discussion journal club format. We have found this approach to be an efficient and productive method for engaging students in learning about principles of experimental design and further preparing them for success in laboratory research.


Social and cognitive factors associated with children's secret-keeping for a parent.
This study examined children's secret-keeping for a parent and its relation to trust, theory of mind, secrecy endorsement, and executive functioning (EF). Children (N = 107) between 4 and 12 years of age participated in a procedure wherein parents broke a toy and asked children to promise secrecy. Responses to open-ended and direct questions were examined. Overall, secret-keeping increased with age and promising to keep the secret was related to fewer disclosures in open-ended questioning. Children who kept the secret in direct questioning exhibited greater trust and better parental ratings of EF than children who disclosed the secret. Findings highlight the importance of both social and cognitive factors in secret-keeping development.


Atrial Septal Defect as Unexpected Cause of Pulmonary Artery Hypertension.
Methamphetamine abuse is an increasingly prevalent cause of pulmonary artery hypertension in the United States. Conversely, an atrial septal defect rarely presents late as pulmonary artery hypertension. We present the case of a 44-year-old methamphetamine abuser who had a 3-month history of worsening fatigue and near-syncope. She had elevated cardiac enzyme levels and right-sided heart strain. Angiographic findings suggested methamphetamine-induced pulmonary artery hypertension; however, we later heard S2 irregularities that raised suspicion of an atrial septal defect. Ultimately, the diagnosis was pulmonary artery hypertension and a large secundum atrial septal defect with left-to-right flow. One year after defect closure, the patient was asymptomatic. In addition to discussing this unexpected case of a secundum atrial septal defect masquerading as methamphetamine-induced pulmonary artery hypertension, we briefly review the natural history of atrial septal defects and emphasize the importance of thorough examination in avoiding diagnostic anchoring bias.


Methylation-mediated silencing of the miR-124 genes facilitates pancreatic cancer progression and metastasis by targeting Rac1.
Previous studies have demonstrated that microRNA (miRNA) expression is altered in human cancer. However, the molecular mechanism underlying these changes in miRNA expression remains unclear. In this study, we investigated the epigenetic modification of miR-124 genes and the potential function of miR-124 in pancreatic cancer. Using pyrosequencing analysis, we found that miR-124 genes (including miR-124-1, miR-124-2 and miR-124-3) are highly methylated in pancreatic cancer tissues compared with in non-cancerous tissues. Hypermethylation mediated the silencing of miR-124, which was a frequent event in pancreatic duct adenocarcinoma (PDAC). Furthermore, miR-124 downregulation was significantly associated with worse survival of PDAC patients. Functional studies showed that miR-124 inhibited cell proliferation, invasion and metastasis. Furthermore, we characterized Rac1 as a direct target of miR-124, and miR-124 interacted with the 3'-untranslated region of Rac1, which we showed to be a putative tumor promoter in pancreatic cancer. Thus, the miR-124-mediated downregulation of Rac1 led to the inactivation of the MKK4-JNK-c-Jun pathway. Therefore, our study demonstrates that miR-124 is a tumor suppressor miRNA that is epigenetically silenced in pancreatic cancer. Our findings suggest a previously unidentified molecular mechanism involved in the progression and metastasis of pancreatic cancer.


Dietary intake of folate and risk of stroke in US men and women: NHANES I Epidemiologic Follow-up Study. National Health and Nutrition Examination Survey.
Few population-based studies have examined the relationship between dietary intake of folate and risk of stroke and cardiovascular disease (CVD). This study examines the association between dietary intake of folate and the subsequent risk of stroke and CVD. Study participants included 9764 US men and women aged 25 to 74 years who participated in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (NHEFS) and were free of CVD at baseline. Dietary intake of folate was assessed at baseline using a 24-hour dietary recall and calculated using ESHA software. Incidence data for stroke and CVD were obtained from medical records and death certificates. Over an average of 19 years of follow-up, 926 incident stroke events and 3758 incident CVD events were documented. The relative risk (RR) was 0.79 (95% confidence interval [CI], 0.63 to 0.99, P=0.03 for trend) for incident stroke events and 0.86 (95% CI: 0.78 to 0.95, P<0.001 for trend) for incident CVD events in the highest quartile of dietary folate intake (median, 405.0 microg/day) compared with those in the lowest quartile (median, 99.0 microg/day), after adjustment for established cardiovascular risk factors and dietary factors. Our findings indicate an inverse relationship between dietary intake of folate and subsequent risk of stroke and CVD. Increasing dietary intake of folate from food sources may be an important approach to the prevention of CVD in the US population.


Testicular torsion and climate changes in macroregions of São Paulo, Brazil.
To analyze the association between climate changes in the macroregions in the state of São Paulo and testicular torsion treated cases. The cases were selected in the Brazilian Public Health Data System Database from January 2008 to November 2016. All surgical procedure records were identified by the Hospital Admission Authorization document. Two codes were selected to process the search: testicular torsion (surgical cure code) and acute scrotum (exploratory scrototomy code). The macroregions were grouped in five areas linked to climate characteristics by International Köppen Climate Classification. A total of 2,351 cases of testicular torsion were registered in the period. For the areas B, C and E (testicular torsion n=2,130) there were statistical differences found in association of testicular torsion cases and decreased temperature (p=0.019, p=0.001 and p=0.006, respectively), however, in analyses for the areas A and D statistical differences were not observed (p=0.066 and p=0.494). Decrease in temperature was associated with testicular torsion in three macroregions of São Paulo. The findings support the theory of cold weather like a trigger in occurrence of testicular torsion in a tropical climate region.


BubR1 Is Essential for Thio-Dimethylarsinic Acid-Induced Spindle Assembly Checkpoint and Mitotic Cell Death for Preventing the Accumulation of Abnormal Cells.
Thio-dimethylarsinic acid (thio-DMA) was detected in human urine after exposure to inorganic arsenic and arsenosugars consumed by marine algae. Our previous studies have shown that thio-DMA disturbed the cell cycle progression and arrested cells in mitosis, though the biological significance or the mechanism by which thio-DMA-induced mitotic phase accumulation occurs is yet to be understood. In this study, we showed that thio-DMA promotes the phosphorylation of BubR1 protein, which is one of the constituents of the spindle assembly checkpoint (SAC) complex and accumulates in the cell in mitotic phase. Binding of Mad2 to CDC20, also known as the marker of the mitotic checkpoint complex (MCC) formation during the activation of SAC, was enhanced and mitotic associated cell death by apoptosis was promoted in HeLa cells but not in HepG2 cells. Basal BubR1 protein level in HepG2 was 10-times lower than that of HeLa cells. Consequently, BubR1 knockdown HeLa cells were generated by small interfering RNA (siRNA) technique. The MCC formation and mitotic arrest induced by thio-DMA were completely inhibited in BubR1 knockdown cells. Moreover, BubR1 knockdown cells could survive in the medium containing higher concentrations of thio-DMA with some abnormalities such as larger cell size, huge nucleus, multiple nuclei, and abnormal DNA contents. Especially, cyclin B1 negative tetraploid cells, which signify interphase cells with tetraploid, increased and survived after 48-72 h treatment with thio-DMA. Thus, these results suggest that BubR1-mediated SAC activation and MCC formation are one of the defense systems for preventing the accumulation and survival of abnormal cells induced by thio-DMA.


Idoxuridine in the treatment of herpes zoster.
An uncontrolled, double-blind, random-selection study of fifty consecutive patients with attacks of herpes zoster treated with one of two concentrations (5 per cent or 40 per cent) of idoxuridine (IDU) in dimethyl sulphoxide (DMSO) has shown that, over all, the patients fared better than would have been expected had they been treated only symptomatically. There was no apparent difference between the two concentrations of idoxuridine in regard to either side-effects or benefits. In 17 of the fifty patients the skin lesions healed more rapidly than would have been expected without treatment, and pain was relieved more rapidly than expected in 26 of the 47 patients in whom it was a feature of the attack. Side-effects, which included a transient stinging or burning sensation in 29 patients and acute sensitivity to idoxuridine (confirmed by patch-testing) in one, did not lead to withdrawal of any patient from the trial. Three patients complained of an unpleasant, garlicky taste during treatment. No significant abnormalities were noted in liver-function tests and in white-cell or platelet counts in patients in either treatment group. The solutions of idoxuridine in dimethyl sulphoxide were provided by W.B. Pharmaceutical Ltd.


Seed plant diversity of different forest types in Liangshui National Natural Reserve.
Thirty years ago, there was a monograph of vegetation and plant diversity in the region prepared by the Department of Forestry at the Northeast Forestry University (unpublished), but the variety of plants in the region has changed significantly over the past 30 years. In future years, the authors hope to publish a new monograph and this research is to prepare for this work. This study aimed at reporting the characteristics of plant diversity in five different forest types in Liangshui National Natural Reserve, China, each with three 25 × 25 m tree quadrats, twelve 5 × 5 m wide shrub quadrats and twelve 1 × 1 m wide herbaceous quadrats. Censuses of each forest type were conducted in 2016. The five main forest types presented differences in structure, diversity and species richness.


Cancer invasion and metastasis.
Metastasis is the transfer of malignant tumors from one organ to a distant organ. It is the most common cause of death in cancer patients. Different molecular mechanisms enable tumor cells to infiltrate the surrounding tissue, invade blood vessels and leave the blood stream at a different site. Tumor cell interaction with extracellular matrix components and epithelial-mesenchymal transition as well as angiogenesis are important factors in invasion and metastasis. Gene expression profiles of metastatic cells in various organs are different and not every tumor cell has the capacity to metastasize. The microenvironment in the organ influences formation of metastasis. Only 1% of micrometastases progress into macrometastases.


Programmed death-1/programmed death-L1 signaling pathway and its blockade in hepatitis C virus immunotherapy.
Chronic hepatitis C virus (HCV) infection is a public health issue that often progresses to life-threatening complications, including liver cirrhosis, fibrosis, and hepatocellular carcinoma. Impaired immune responses to HCV are key features of chronic HCV infection. Therefore, intervention strategies usually involve enhancing the immune responses against HCV. Cytotoxic CD8(+) T lymphocytes (CTLs) play a critical role in the control of HCV infection. However, their cytolytic function can be impaired by the expression of co-inhibitory molecules. Programmed death-1 (PD-1) receptor and its ligand PD-L1 function in a T cell co-inhibitory pathway, which either blocks the function of CTLs or the differentiation of CD8(+) T cells. During chronic HCV infection, the immune inhibitory receptor PD-1 is upregulated on dysfunctional HCV-specific CD8(+) T cells. As such, blockade of the PD-1/PD-L1 pathway in these CD8(+) T cells might restore their functional capabilities. Indeed, clinical trials using therapies to block this pathway have shown promise in the fostering of anti-HCV immunity. Understanding how chronic HCV infection induces upregulation of PD-1 on HCV specific T cells and how the PD-1/PD-L1 interaction develops HCV specific T cell dysfunction will accelerate the development of an efficacious prophylactic and therapeutic vaccination against chronic HCV infections, which will significantly improve HCV treatments and patient survival. In this review, we discuss the relationship between PD-1 expression and clinical responses and the potential use of PD-1 blockade for anti-HCV therapy.


The Significance of Inter-Eye Osmolarity Difference in Dry Eye Diagnostics.
The purpose of this study was to evaluate the diagnostic value of inter-eye osmolarity differences in relation to dry eye symptoms and other non-osmolar signs of dry eye disease. One hundred ninety one participants who attended a larger interventional study of dry eye disease prior to and after cataract surgery were analyzed for dry eye disease (DED). Dry eye diagnostics were performed for all subjects according to the DEWS II criteria: tear osmolarity was collected from both eyes with the TearLab system, non-invasive Tear film break up time (NIKBUT) was obtained on the test eye with Keratograph and ocular surface staining (OSS) was evaluated using the Oxford schema. The Ocular Surface Disease Index (OSDI) questionnaire was used to assess symptoms. Inter-eye osmolarity greater than 8, which is considered as a sign of DED according to the TearLab user manual, was evaluated and compared with other non-osmolar signs of DED. The 191 subjects were divided into three groups according to osmolarity measurements. Sixty-five subjects had normal osmolarity (below 308 mOsmol/L in both eyes and less than 9 mOsmol/L difference between the eyes), 107 had high osmolarity (308 mOsmol/L or higher in one of the eyes) and 19 had an inter-eye difference >8 mOsmol/L or higher, with neither eye having osmolarity higher than 307 mOsmol/L. Signs and symptoms in this last group were not correlated with the high osmolarity group or the normal group, though they appeared more similar to the normal group. The diagnostic value of inter-eye osmolarity difference in predicting symptoms or other non-osmolar signs of dry eyes appears weak. Our study suggests that the criterion of an inter-eye difference of 8 mOsmol/L is not a useful cut-off for diagnosing dry eyes based on osmolarity.


Impact of the COVID-19 Pandemic in Spain in the Successive Pandemic Waves on Hemodialysis Patients and Healthcare Personnel.
(1) Background: The impact of SARS-CoV-2 has been variable over the time course of the pandemic and in different populations. The aim was to analyze the impact of COVID-19 infection in a known population of hemodialysis (HD) patients and professionals in Spain at different times of the pandemic. (2) Methods: We conducted an observational, descriptive study with a follow-up from 3 March 2020 to 23 April 2022 (776 days), using in average of 414 professionals and 1381 patients from 18 HD units in Spain. The data from the positive PCR or the rapid antigen detection test (RADT) subject were analyzed and segmented into six periods (waves). (3) Results: Of 703 positive COVID-19 tests, 524 were HD patients (74.5%), and 179 were HD professionals (25.5%). Overall, 38% of staff and 43% of patients were affected. Differences were observed in regard to incidence (21% vs. 13%), mortality (3.5% vs. 0%), and symptomatology between the patients and professionals and throughout the pandemic. (4) Conclusions: COVID-19 severity varied during different pandemic waves, with a greater impact seen in the first wave. HD professionals and patients had similar infection rates, but patients had higher mortality rates. Community transmission was the primary route of infection.


Beta-lactam resistance and Enterobacteriaceae, United States.
Extended-spectrum cephalosporins (ESC) are an important drug class for treating severe Salmonella infections. We screened the human collection from the National Antimicrobial Resistance Monitoring System 2000 for ESC resistance mechanisms. Of non-Typhi Salmonella tested, 3.2% (44/1,378) contained blaCMY genes. Novel findings included blaCMY-positive Escherichia coli O157:H7 and a blaSHV-positive Salmonella isolate. CMY-positive isolates showed a ceftriaxone MIC > or =2 microg/mL.


Effect of pony morphology and hay feeding methods on back and neck postures.
The application of hay feeding devices, such as the use of hay nets or slow feeders, can help with the management of weight in ponies; however, there is still a lack of knowledge regarding their effect on equine posture. Therefore, the aim of the study was to assess the effect of different feeding devices on the posture of ponies using morphometric analysis. Two different breed types, Shetland type (SH, n = 5) versus Welsh Cob type (WC, n = 4), were fed the same forage in four different ways: on the ground (G), using a fully filled haynet (HF), using a partially filled haynet (HL) and using a slow-feeder hay box (HB). Video recordings were obtained and then geometric morphometric analysis was applied. Breed morphology was confirmed by body morphometric measurements. Data were analysed statistically using one-way ANOVA, canonical variate analysis (CVA), principal component analysis (PCA), partial least-squares (PLS) analysis and multivariate analysis of variance (MANOVA). Moreover, a mixed model was performed to study differences in mandibular angle. SH and WC ponies were shown to have significantly different body morphometric measurements. The geometric morphometric analysis results showed that ponies arch their back and modify their neck shape differently according to the feeding method and their morphological group. For the neck, the SH and WC ponies adapted similarly to the use of small-holed hay nets, but their posture varied when feeding from the ground or hay box. The back postures consistently differed according to the breed type and feeding method. The mandibular angle for both breed types was reduced with all the feeding devices compared to feeding from the ground. Further studies are needed to evaluate the long-term effects of slow-feeding devices on posture and mandibular angle, taking into consideration animals with different morphologies.


Fatigue in patients with neuromyelitis optica spectrum disorder and its impact on quality of life.
Fatigue is a prevalent symptom and major burden in neuroimmunological diseases. In neuromyelitis optica spectrum disorder (NMOSD), a severe autoimmune central nervous system (CNS) inflammatory disease with autoantibodies reactive to aquaporin-4, there are few reports about fatigue and quality of life (QOL). We aimed to evaluate the severity of fatigue and its relationship with QOL in patients with NMOSD. We prospectively studied patients with NMOSD who were in remission and seropositive for anti-aquaporin-4 antibody, and they were divided into 2 groups based on the presence of fatigue assessed using the Functional Assessment of Chronic Illness Therapy-fatigue score. Sleep quality, depression, pain, and QOL were also evaluated. A total of 35 patients were enrolled (mean age, 46.5 ± 14.1 years; female: male = 29:6), and the median Expanded Disability Status Scale (EDSS) score was 2.0 (range, 0 to 8.0). The patients with fatigue (N = 25, 71.4%) had poorer sleep quality and more severe depression than those without fatigue (p = 0.009 and p = 0.001). Both the physical and mental QOL scores were lower in patients with fatigue than in those without fatigue (p = 0.033 and p = 0.004). Multiple linear regression analyses showed that the degree of fatigue with EDSS score and pain were independent predictors of physical aspects of QOL (B = 0.382, p = 0.001), whereas depression was the only predictor of the mental components of QOL (B = -0.845, p = <0.001). Fatigue is a common symptom and an important predictor of QOL in patients with NMOSD.


Iron regulation of the cloned diphtheria toxin promoter in Escherichia coli.
Regulation of the diphtheria toxin promoter by iron was studied in Escherichia coli by using a galK transcriptional fusion. A fragment of the toxin (tox) operon containing the regulatory region was cloned from corynephage beta into a galK transcription vector such that expression of galK activity was controlled by the tox promoter. When E. coli N100 (a galK mutant) harboring this tox-galK fusion plasmid was grown in Luria broth, the specific activity of galactokinase remained constant throughout the exponential phase of growth. When bacteria were shifted from such high-iron medium into low-iron Luria broth, the specific activity of galactokinase increased rapidly, but induction of galactokinase was prevented by the addition of iron to the medium. Measurement of tox-specific mRNA by dot blot hybridization showed that this regulation occurred at the level of transcription. When the plasmid containing the tox-galK fusion was introduced into a fur mutant of E. coli, expression of galK was maximal in both high-iron and low-iron media; but repressibility of galK by iron in this strain was restored by complementation with the fur+ allele. The tox promoter has significant homology with the consensus sequence for other iron-regulated promoters of E. coli that are controlled by fur. These data indicate that the product of the fur gene can function in E. coli as an iron-dependent repressor for the tox promoter from corynephage beta.


Immediate and 30 days mortality in digoxin poisoning cases attended in the Hospital Emergency Services of Catalonia, Spain.
Digoxin poisoning is a frequent reason for seeking emergency care. This study aimed to assess mortality related to digoxin poisoning. Descriptive observational study of digoxin poisonings attended in the emergency departments of 4 hospitals in Catalonia from 2013 through 2015. We gathered data relevant to the poisonings and recorded immediate and 30-day mortality. Factors possibly related to mortality were explored. A total of 171 digoxin poisonings were attended. Seven (4.1%) were acute and 164 (95.9%) were chronic. The immediate and 30-day mortality rates were 6.4% and 13.4%, respectively. Bivariate analysis did not identify factors related to immediate mortality. However, the variables more often associated with 30-day mortality in this analysis were acute poisoning (after which 13% died vs 2.7% of those with chronic poisoning, P=.05), suicide attempts (8.7% of whom died vs 0.7%, P=.048), more compromised renal function (21.7% vs 9.5%, P=.037), fewer neurologic symptoms (4.3% vs 17.8% with more symptoms, P=.005), higher mean digoxin concentrations (4.7 mg/dL in those who died vs 3.7 mg/dL, P=.027), and a lower Barthel index (mean [SD] 49.1 [33.4] in those who died vs 70.3 [28.5]; P=.006). Logistic regression analysis identified serum digoxin concentration to be independently associated with immediate mortality. A lower Barthel index was associated with 30-day mortality. Immediate mortality is related to a high digoxin concentration in serum, and 30-day mortality to a low Barthel index.


Increased Mortality in HIV Infected Individuals with Tuberculosis: A Retrospective Cohort Study, Addis Ababa, Ethiopia.
Tuberculosis is one of the commonest coinfections and leading causes of death among people living with HIV in resource-limited countries. There is limited evidence on the short- and long-term mortality rate in people receiving antiretroviral therapy and coinfected by tuberculosis in sub-Saharan Africa, where the burden of coinfection is highest. This study aimed to compare mortality among HIV positives with and without tuberculosis coinfection receiving antiretroviral therapy in Addis Ababa, Ethiopia. HIV positives' medical records were reviewed between 2011 to 2018 and identified 7038 HIV-positive adults enrolled for antiretroviral therapy in Addis Ababa. The outcome of interest for this study was death. A parametric Gompertz regression model was applied to compare mortality between HIV with tuberculosis coinfection versus HIV without tuberculosis. Overall, 1123 (15.96%, 95% CI: 15.11-16.83%) individuals with HIV had tuberculosis coinfection at antiretroviral therapy enrollment. After adjusting for age, sex, education, marital status, cotrimoxazole therapy, body mass index, baseline CD4 cell count, and year in ART enrollment, HIV positives with tuberculosis coinfection had more than twice a higher overall mortality risk than HIV positives without tuberculosis coinfection (AHR: 2.53; 95% CI 1.63-3.91, p < 0.001). This large retrospective cohort study reveals significantly higher mortality in HIV and tuberculosis coinfected group. This suggests the need for enhanced utility of integrated HIV and tuberculosis health services in sub-Saharan Africa where tuberculosis prevalence is highest.


A targeting-and-extracting technique to enhance hearing in the presence of competing speech.
A targeting-and-extracting procedure of speech enhancement for hearing aids in the presence of background noise, especially competing speech, is proposed. The procedure is composed of two steps: targeting by a fixed (or deterministic) beamforming array, followed by a post-targeting extracting step. Emphasis is placed on the extracting step, which performs noise cancellation based on the acoustic difference between the desired speech and interfering speech. Either comb filtering or attenuation is applied to the signal in accordance with the current voiced/unvoiced/silence state of the desired signal. The comb filter design is based on the fundamental pitch frequency of the desired speech. Algorithms for deciding the voiced/unvoiced/silence state and determining the fundamental frequency are developed. The performance of the system is evaluated through computer simulation. The simulation results indicate significant noise cancellation and intelligibility improvement.


Evaluation of morphology, morphometry and follicular dynamics in FecGE genotyped ewes.
This study aimed to evaluate the effect of FecGE mutation on the development of ovarian follicles. To this end, 42 Santa Inês ewes were genotyped for FecGE mutation and classified as wild-type (FecG+/+), heterozygous (FecG+/E) or mutant homozygous (FecGE/E). Ovarian fragments were processed, and the follicles were analyzed with regard to the morphology and morphometry using classical histology. For the evaluation of follicular dynamics, ewes underwent oestrous synchronization and were monitored throughout an interovulatory period. A higher (P < 0.05) percentage of morphologically normal follicles in the primordial stage was identified in FecGE/E (90.0%) and FecG+/E (88.1%) ewes than in the FecG+/+ (73.0%) ewes. There was also a significantly greater (P < 0.05) number of morphologically normal follicles in the FecGE/E (87.3%) and FecG+/E (83.3%) ewes than in FecG+/+ (76.8%) ewes in the transitional stage. A smaller (P < 0.05) diameter was observed in the secondary follicles in FecGE/E (93.8 μm) ewes than in FecG+/E (171.8 μm) ewes. Regarding follicular dynamics, FecGE/E ewes showed a greater (P < 0.05) number of ovulations (2.5 ± 0.2) than FecG+/+ ewes (1.5 ± 0.3) ewes. Ovulatory follicles were smaller (P < 0.05) in the FecGE/E (5.1 mm) and FecG+/E (5.2 mm) ewes than in FecG+/+ (5.8 mm) ewes. Santa Inês nulliparous ewes carrying the FecGE mutation showed a greater proportion of morphologically normal follicles in the primordial and transitional stages than those not carrying the mutation. FecGE/E ewes demonstrated a higher number of ovulated follicles and that FecGE/E and FecG+/E ewes presented ovulatory follicles with a smaller diameter.


Novel polymer-based anion-exchangers with covalently-bonded functional layers of quaternized polyethyleneimine for ion chromatography.
For the first time novel pellicular anion-exchangers with functional layers of quaternized branched polyethyleneimine (PEI) covalently bonded to the surface of aminated poly(styrene-divinylbenzene) (PS-DVB) with 1,4-butanediol diglycidyl ether (1,4-BDDGE) as a linker are obtained and studied. The proposed method of synthesis includes alkylation of PS-DVB substrate containing secondary aminogroups with 1,4-BDDGE followed by amination with branched PEI containing primary, secondary, and tertiary amino groups. Quaternization of amino groups of PEI required for increasing ion-exchange capacity of the stationary phase is provided with two epoxides - glycidol and 1,4-BDDGE, which results in the considerable variations of ion-exchange selectivity. Chromatographic properties of the obtained anion-exchangers are evaluated using various model mixtures of anions (F-, HCOO-, CH3COO-, C2H5COO-, Cl-, BrO3-, NO2-, Br-, NO3-, ClO3-, S2O32-, C2O42-, CrO42-, SO42-, PO43-, I-, SCN-) in hydroxide and carbonate/bicarbonte eluents. All anion-exchangers show better selectivity toward the anions of weakly retained organic acids (acetate, formate, propionate) as compared with previously reported chemically derivatized anion-exchangers with monomeric functional sites in the ion-exchange layer. In terms of separation abilities, novel anion-exchangers with covalently-bonded PEI are not inferior to some commercial columns with grafted polymeric anion-exchange layer. Anion-exchanger quaternized with more hydrophilic glycidol packed in 10-cm long column enables the separation of 16 anions including weakly retained and highly retained polarizable ones within 26 min using gradient elution. Column efficiencies for both anion-exchangers with quaternized PEI are up to 32000 N/m and 37000 N/m in case of hydroxide and carbonate eluent, respectively, which is comparable with the values demonstrated by commercially available columns of related chemistry.


Human Rights Discourse in the Sustainable Development Agenda Avoids Obligations and Entitlements Comment on "Rights Language in the Sustainable Development Agenda: Has Right to Health Discourse and Norms Shaped Health Goals?".
Our commentary on Forman et al paper explores their thesis that right to health language can frame global health policy responses. We examined human rights discourse in the outcome documents from three 2015 United Nations (UN) summits and found rights-related terms are used in all three. However, a deeper examination of the discourse finds the documents do not convey the obligations and entitlements of human rights and international human rights law. The documents contain little that can be used to empower the participation of those already left behind and to hold States and the private sector to account for their human rights duties. This is especially worrying in a neoliberal era.


Study of static and dynamic first hyperpolarizabilities using time-dependent density functional quadratic response theory with local contribution and natural bond orbital analysis.
We apply time-dependent density-functional quadratic response theory to investigate the static and dynamic second-order polarizabilities (first hyperpolarizability) beta. A new implementation using Slater-type basis functions, numerical integration, and density fitting techniques is reported. The second order coupled perturbed Kohn-Sham equations are solved and the second-order perturbed charge density is obtained. It is useful to highlight atomic and bond contributions to understand the relation between molecular structure and properties. Four moderately sized molecules (para-nitroaniline and derivatives thereof) are investigated to assess the accuracy of the time-dependent density-functional theory computations and to investigate the distribution of the second-order charge density as well as the "beta density." Our results highlight the contributions from atoms and bonds on different functional groups to the total value of beta with Mulliken-type and natural bond orbital (NBO) analyses, and demonstrate in some cases how contributions from a particular bond may be identified easily by visual inspection of the beta density. In addition, the position of side group substitution on carbon-carbon bonds significantly affects the hyperpolarizability. A contribution analysis as performed here might be helpful for the design of new materials with desired properties.


Hepatic reperfusion injury following orthotopic liver transplantation in the rat.
At 24 hr following orthotopic transplantation, rat liver grafts were perfused in situ for 7 min with trypan blue, a vital dye that provides information on hepatic microcirculation and stains nuclei of nonviable cells. Spotty and uneven dye distribution was observed indicating that hepatic microcirculation was disturbed 24 hr following transplantation surgery. Under these conditions, 15-20% of the hepatocytes were nonviable as assessed from trypan blue staining and frank necrosis. In contrast, perfusion of livers from untransplanted rats or liver explants exposed to cold ischemia for 60 min were judged normal by the criteria of uniform distribution of dye in the organ and absence of necrosis and nuclear dye uptake. Thus the observed damage was associated with reintroduction of blood and can therefore be classified as a reperfusion injury. The altered microcirculation and cell death following the operation was reduced markedly by perfusion of the cold, ischemic explant with nitrogen-saturated but not with oxygen-saturated buffer for 5 min prior to the implantation operation. Protection was even greater if the perfusion medium contained verapamil (20 micrograms/ml), a Ca++ channel blocker. We conclude that reperfusion of the stored liver causes an oxygen-dependent alteration in hepatic microcirculation that leads to hypoxia and scattered hepatocellular necrosis in the implanted graft. Brief perfusion of the hypoxic implant under anaerobic conditions may remove substrates involved in oxygen radical generation and prevent reperfusion injury upon introduction of oxygen into the graft via the blood. Taken together, these results suggest that removal of Euro-Collins' solution under anaerobic conditions may be beneficial clinically in preventing injury of surgical explants.


Identification of a compound heterozygous mutation of ABCC2 in a patient with hyperbilirubinemia.
Bilirubin is the end product of heme catabolism, which is produced primarily from the breakdown of erythrocyte hemoglobin in the reticuloendothelial system. Hyperbilirubinemia is induced not only by increased bilirubin synthesis, but can also be caused by decreased bilirubin clearance. There are several disorders, which can contribute to hyperbilirubinemia, including Dubin‑Johnson syndrome (DJS). DJS is a rare autosomal recessive disorder, which is characterized by predominantly conjugated hyperbilirubinemia without progression to end‑stage liver disease. Previous studies have demonstrated that defects in multidrug resistance proteins ATP‑binding cassette C2 (ABCC2)/multidrug resistance‑associated protein 2 (MRP2) contribute to DJS. In the present study, a case of a patient with hyperbilirubinemia was examined and identified a compound heterozygous mutation in the ABCC2 gene (p.T435P and W442X). These were predicted to be deleterious by three bioinformatics programs (Polymorphism Phenotyping‑2, Sorting Intolerant From Tolerant and MutationTaster). These finding expand on the spectrum of ABCC2 mutations and provide additional evidence that ABCC2 is key in the development of DJS.


[The importance of relationship satisfaction and the questionnaire techniques of its measurement].
The quality of marriage or partnership has an impact on many areas of life. Consequently, a good working relationship can be a significant resource to cope with difficult life situations and stress, and may contribute to partners' well-being and healthy lifestyle. Therefore, its investigation has particular relevance. Relationship satisfaction is a complex concept which is confirmed by both diversity and multidimensionality of its definition. The aim of this study is to provide an overview of the importance of relationship satisfaction, inter- and intrapersonal factors influencing its development, its changes over family life cycles and the gender differences that may manifest in relationship satisfaction. In addition, this review summarizes the questionnaire techniques of measuring relationship satisfaction which are also reflected within the complexity and the diversity of the concept. Given the fact that the degree of relationship satisfaction plays a salient role in many aspects of life, the empirical research findings which emphasize the importance of this conception can serve as an alternative to aim the mobilization of its practical work.


A Cleverly Designed Novel Lipid Nanosystem: Targeted Retention, Controlled Visual Drug Release, and Cascade Amplification Therapy for Mammary Carcinoma in vitro.
To construct an ideal theranostic nanoplatform (LIP3); to clarify its physicochemical properties; to confirm its characteristics of dual-modality imaging, active-targeting, and cascade amplification therapy for mammary carcinoma; and to perform a preliminary exploration of the cytotoxicity mechanism. A self-prepared liposome nanosystem, LIP3, can actively target 4T1 cells because the surface is linked with C-RGD. Haematoporphyrin monomethyl ether (HMME), an excellent sonosensitizer entrapped in the lipid bilayer, can function in photoacoustic imaging. Low-intensity focused ultrasound (LIFU) of ultrasound-targeted microbubble destruction (UTMD) promotes localized drug delivery into tumours because PFH, a phase-change substance, is loaded in the LIP3 core, achieving visualization of targeted drug release, and sonodynamic therapy (SDT) can kill tumour cells. SDT provides a favourable environment for AQ4N, resulting in amplification of LIP3 treatment. Therefore, LIP3 shows targeted aggregation and targeted release, integrating dual-mode imaging and precise treatment. The self-prepared lipid nanosystem, LIP3, meets the above expectations and has ideal physicochemical properties, with a regular sphere with uniform distribution. Contrast-enhanced ultrasound (CEUS), photoacoustic imaging, and bimodal imaging were effective in vitro. In 4T1 cell experiments, the cell capacity was as high as 42.9%, and the cytotoxicity to 4T1 was more than 5 times that of LIP1 (containing AQ4N only) and more than 2 times that of LIP2 (containing only HMME), achieving comparable results as cascade therapy for mammary cancer. LIP3, a theranostic nanoplatform, was successfully constructed and conformed to the physicochemical characterization of ideal nanoparticles, with active-targeting, dual-modality imaging, visualized drug release, and precise treatment under the action of LIFU. SDT provides a favourable environment for AQ4N, resulting in amplification of LIP3 treatment. Therefore, LIP3 shows targeted aggregation and targeted release, integrating dual-mode imaging, and precise cascade treatment. This unique theranostic NPS with multiple capabilities is expected to be a favourable anti-cancer method in the future.


Complement resistance of capsulated strains of Aeromonas salmonicida.
The complement resistance of Aeromonas salmonicida strains grown under conditions promoting capsule formation was investigated using well characterized strains and their isogenic mutants. Complement resistance was previously studied using the same strains growing under non-capsulating conditions. The serum resistant strains were found to activate complement, but rapidly degrade C3b preventing productive formation of the lytic complex C5b-9. Isogenic lipopolysaccharide rough mutants grown under non-capsulating conditions were serum sensitive, binding a large amount of C3b and leading to productive formation of C5b-9. When grown under conditions promoting capsule formation, these mutants were partially resistant to complement because less C3b is bound to them and also partially degraded, with a concomitant reduction in lytic C5b-9.


The human pre-B cell receptor: structural constraints for a tentative model of the pseudo-light (psi L) chain.
In human pre-B cells, the mu chain is associated with a surrogate light chain composed of the lambda-like and Vpre-B gene products. This pre-B cell receptor presumably triggers early steps of B cell differentiation, We have determined the NH2-terminal amino acid sequence of the lambda-like chain, showing that the mature chain results from the cleavage of a leader segment of 44 residues, leaving a polypeptide of 169 amino acids having partial features of the Ig light chain domains, with the exception of the first 50 amino acid NH2-terminal region. We have completed the nucleotide sequence of the Vpre-B gene, which appears to contain 126 residues in its mature form of which the 24 COOH-terminal portion was not Ig-related. Analysis of transfectants has provided direct evidence that lambda-like and Vpre-B chains assemble together even in the absence of heavy chain, prompting the search for a structural basis of this interaction. Comparison with the domain organization of the regular Ig lambda chain suggests that most of the psi L chain can be accommodated within a CL-VL-like structure, with an extra "subdomain" contributed by the non-Ig-like portions of both the lambda-like and Vpre-B polypeptides.


Anti-HLA Antibodies Testing on Solid Phase: Comparative Evaluation of Different Kit Vendors Through Luminex Technology.
For decades, the detection of anti-HLA antibodies in candidates for solid-organ transplant has been performed with the traditional complement-dependent cytotoxicity method; this assay has been then integrated with the introduction of solid-phase assays. Over the past 20 years, the Luminex assay has become the most widely used in clinical laboratories due to both increased sensitivity and specificity versus enzyme-linked immunosorbent assay. However, even the Luminex technique has shown some critical issues, and choosing the most reliable method still remains challenging. In this study, we verified the concordance of the results obtained in detecting anti-HLA antibodies with 2 kit vendors that provide reagents for the Luminex platform. We used 314 serum samples from patients on wait lists for solid-organ transplant. Sera were tested with LABScreen Mixed-LSM12 (One Lambda-Thermo Fisher, Canoga Park, CA, USA) and LIFECODES LifeScreen Deluxe-LMX (Gen-Probe-Immucor, Stanford, CT, USA),which we indicated as vendor A and vendor B, respectively. Anti-HLA class I and class II antibody analyses were conducted by verifying the concordance of the results with Cohen kappa coefficient statistics and confidence interval. The kappa coefficient statistics showed "substantial" reliability for class I (0.61; confidence interval, 0.50-0.73) and "moderate" reliability for class II (0.56; confidence interval, 0.43-0.69). There were no considerable differences in results between the 2 kits regarding overall assignment of negativity or positivity of a sample. Discordant data between positive values for a test and negative for the other were found for samples with weak antibody positivity. Some discordant data were probably attributable to several factors such as the composition of the kits, the antibody titer in the serum, whether sera were diluted, different washing methods, and type of plate used.


Genetically Engineered Adipose Mesenchymal Stem Cells Using HIV-Based Lentiviral Vectors as Gene Therapy for Autoimmune Diseases.
The immunomodulatory and self-renewable features of human adipose-derived mesenchymal stem cells (hAD-MSCs) mark their importance in regenerative medicine. Interleukin (IL)-23 as a proinflammatory cytokine suppresses T regulatory cells and promotes the response of T helper 17 and T helper 1 cells. This pathway initiates inflammation and immunosuppression in several autoimmune diseases. The current study aimed at producing recombinant IL-23 decoy receptor (RIL-23R) using hAD-MSCs as a good candidate for ex vivo cell-based gene therapy purposes to reduce inflammation in autoimmune diseases. hAD-MSCs was isolated from lipoaspirate and then characterized by differentiation. RIL-23R was designed and cloned into a pCDH813A-1 lentiviral vector. The transduction of hAD-MSCs was performed at multiplicity of infection = 50 with pCDH-EFI α-RIL-23R-PGK copGFP. Expressions of RIL-23R and octamer-binding transcription factor 4 (OCT-4) were determined by real-time polymerase chain reaction. Self-renewing properties were assayed with OCT-4. Bioactivity of the designed RIL-23R was evaluated by IL-17 and IL-10 expression of mouse splenocytes. The results showed that the transducted hAD-MSCs/RIL-23R, expressing IL-23 decoy receptor, can provide a useful approach for a basic research on cell-based gene therapy for autoimmune disorders.


A real life cohort of Mepolizumab treatment in severe eosinophilic asthma.
Background. Mepolizumab, a monoclonal antibody that interacts with IL-5, was the first anti-IL-5 approved for uncontrolled severe eosinophilic asthma. In several randomised, placebo-controlled trials, treatment with mepolizumab has shown a significant improvement in asthma symptoms and the need to use of oral corticosteroids (OCS). Several studies have correlated blood levels of eosinophil cationic protein (ECP) with the degree of eosinophilic inflammation, which could make it an indirect marker of eosinophilic activity. Methods. This was a single-centre retrospective study that included all patients diagnosed with severe eosinophilic asthma under treatment with mepolizumab. We recorded the number of exacerbations, daily prednisone intake, asthma control test scores and forced expiratory volume in the first second. Results. We followed 22 patients, 14 of whom were OCS-dependent with a mean daily dose of 15.85 ± 15.62 mg prednisone. After 12 months, only five continued taking OCS and the mean daily dose was reduced by up to 2.50 ± 3.84 mg (p less than 0.007). The exacerbation rate at baseline was 2.91 ± 2.27 and decreased to 0.82 ± 1.14 in the following year (p less than 0.001). ACT scores increased significantly from 16.00 ± 5.85 to 20.71 ± 4.45 after six months (p = 0.003). We also observed a decrease in ECP from 81.46 ± 43.99 µg/L to 19.12 ± 18.80 µg/L (p > 0.001). Conclusions. These real-life results are consistent with previous clinical trials demonstrating the efficacy and safety of mepolizumab in routine clinical practice for severe uncontrolled eosinophilic asthma. We observed a significant decrease in blood eosinophil counts and in ECP levels, suggesting a reduction in eosinophil activity following mepolizumab treatment.


Therapist effects and the impacts of therapy nonattendance.
Although dropout from psychotherapy has received substantial attention, the impacts of nonattendance on client outcome across a course of psychotherapy have not been well researched. All in-person psychotherapy treatments require clients to actually attend sessions to generate positive symptomatic results, and missed sessions have at least a time and financial cost. Furthermore, it is plausible that therapist differences exist for client attendance rates. The present study examined impacts of nonattendance, particularly early in a course of treatment, comparing the effects of canceled and no-showed appointments on overall symptom reduction and rate of change while accounting for therapist effects. Using multilevel hierarchical regression, the impact of nonattendance on symptom reduction and rate of change was modeled on 5,253 clients (67.2% female, 72.3% white) across 83 therapists gathered from a practice research network. Results suggested that no-shows, but not cancellations, had negative impacts on the magnitude and rate of symptom change, with larger effects when occurring before the third session. Therapist effects on attendance also were identified; therapists varied greatly on nonattendance percentages of their clients after the third attended session. (PsycINFO Database Record


The inflammatory reaction to crystals.
Acute gout serves as a relatively well-defined paradigm for the review of the pathogenesis of acute microcrystal-induced inflammation. Inflammatory mediator systems activated directly or indirectly by urate crystals, the temporal events in a gouty paroxysm, and the possible factors responsible for the wide clinical variability of acute gout and other forms of crystal-induced inflammation are discussed.


Phase II trial of PCNU in advanced colorectal carcinoma. An Eastern Cooperative Oncology Group pilot study.
PCNU, a chloroethylnitrosourea with high alkylating activity, low carbamoylating activity, optimal octanol: water partition coefficient, and broad activity in animal systems was administered to 30 evaluable patients with measurable advanced colorectal carcinoma by brief intravenous infusions every 6 weeks. The initial dose was 75 or 100 mg/m2, with escalation or reduction for toxicity, and a total of 64 evaluable courses were given. Half of the patient population had received no prior chemotherapy. Two objective partial responses occurred. The response rate was 6.7% with a 95% confidence interval of 0.8-22.1%. Thrombocytopenia was dose-limited and leukopenia was relatively mild. Gastrointestinal toxicity was less severe than expected for clinically available nitrosoureas. In colorectal carcinoma, PCNU has limited clinical activity that does not appear to be superior to that of other nitrosoureas.


A novel explanation for the healing effect of the Er:YAG laser during skin rejuvenation.
The popularity of cutaneous laser resurfacing has soared in recent years. Ablative laser skin rejuvenation with carbon dioxide (CO₂) and erbium:yttrium-aluminum-garnet (Er:YAG) lasers has been popularized and their side effects individually reported. It has been suggested that initial collagen contraction and thermal damage modulate wound healing. Progress in laser technology permits precise tissue removal and minimal thermal damage. However, mechanisms for cosmetic improvement have not yet been completely determined. In the present short communication, we would like to suggest a possible mechanism for the healing effects exerted by the Er:YAG laser.


Ketogenic diet effects on cognition, mood, and psychosocial adjustment in children.
The ketogenic diet (KD) is increasingly used for the treatment of refractory epilepsy. The aim of this study was to evaluate possible adverse effects of the diet on cognition, behavior, psychosocial adjustment, and quality of life in school-aged children and adolescents. Fifteen subjects were assessed before diet initiation. After approximately 6 months, on diet treatment 11 patients (73%) were reassessed. We used a combination of individually administered psychological tests for the children and parent report questionnaires. Five of 15 patients had a seizure reduction of more than 50%. Cognition showed a small trend toward improvement in most patients. Psychosocial adjustment, on the other hand, showed small trends toward worsening. For mood, two areas showed a larger change, revealing more mood problems although this was not on a statistically significant level. In this small group of children, there is no indication that the KD has a negative impact on cognition or social adaptation at short term. There is a tendency toward an increase in mood problems.


Source level and vocalizing depth estimation of two blue whale subspecies in the western Indian Ocean from single sensor observations.
The source level (SL) and vocalizing source depth (SD) of individuals from two blue whale (BW) subspecies, an Antarctic blue whale (Balaenoptera musculus intermedia; ABW) and a Madagascar pygmy blue whale (Balaenoptera musculus brevicauda; MPBW) are estimated from a single bottom-mounted hydrophone in the western Indian Ocean. Stereotyped units (male) are automatically detected and the range is estimated from the time delay between the direct and lowest-order multiply-reflected acoustic paths (multipath-ranging). Allowing for geometric spreading and the Lloyd's mirror effect (range-, depth-, and frequency-dependent) SL and SD are estimated by minimizing the SL variance over a series of units from the same individual over time (and hence also range). The average estimated SL of 188.5 ± 2.1 dB re 1μPa measured between [25-30] Hz for the ABW and 176.8 ± 1.8 dB re. 1μPa measured between [22-27] Hz for the MPBW agree with values published for other geographical areas. Units were vocalized at estimated depths of 25.0 ± 3.7 and 32.7 ± 5.7 m for the ABW Unit A and C and, ≃20 m for the MPBW. The measurements show that these BW calls series are stereotyped in frequency, amplitude, and depth.


Heat stress interactions with protein, supplemental fat, and fungal cultures.
Cows that were subjected to hot environmental temperatures yielded less milk (3.1 kg/d) on a diet high in CP (18.4%) and of medium degradability (65%) than on diets high in CP of low degradability (59%) or medium in CP (16.1%). The high CP diets were associated with decreased DMI and higher water intake, ruminal NH4, and blood urea. Negative effects on yield from the high CP, medium degradability diet were not observed at moderate temperatures. Evaporative cooling of cows in hot weather resulted in a greater milk yield response to low versus medium rumen-undegradabale protein diets than for uncooled cows. Evaporative cooling of cows also affected response to protein quality. For cooled cows, high Lys diet (soybean, fish, and blood meals) increased milk yield 14% over that with low Lys diet (corn gluten meal), but, for uncooled cows, a high Lys diet only increased yield by 9%. Percentage of CP, degradability, and protein quality had no effect on body temperatures or respiration rates of lactating cows. Some, but not other, reports showed that supplementation of 2 to 2.5% fat to diets fed under hot summer conditions resulted in less yield response than when fat was added at moderate temperatures. In several studies, fungal cultures (3 to 5 g/d) in the diet decreased body temperatures and respiration rates in hot, but not cool, weather. Increased milk yields and cellulose digestibility also resulted from dietary fungal cultures in some, but not all, trials. The mechanism of action exerted by fungal cultures on body temperature and respiration rate is unclear.


Sham electroconvulsive therapy studies in depressive illness: a review of the literature and consideration of the placebo phenomenon in electroconvulsive therapy practice.
The gold standard for the establishment of therapeutic efficacy is the randomized placebo-controlled trial. In the case of electroconvulsive therapy (ECT), there is an older literature of a dozen so-called "sham ECT" trials. When cited, these trials are typically referred to as unequivocally demonstrating the superiority of ECT over sham ECT. However, there is an intriguingly high sham ECT response rate in some of the studies, and there is also some information regarding ECT response of depressive subtypes that informs the modern ECT practitioner. In this report, the sham ECT literature is reviewed in detail, and the author discusses possible mechanisms by which sham-treated patients improved.


[Foreign body aspiration in children: ten-years experience at the Ha'Emek Medical Center].
Foreign body aspiration is common in young children. Delay in treatment may lead to complications and an emergency bronchoscopy must be performed in suspicious cases. Prevention is the most critical element needed to reduce this morbidity. To examine the demographic data of children at high risk of foreign body aspiration in order to develop precautionary measures oriented to this population. A retrospective review was prepared of all the charts of children under 16 years old who underwent bronchoscopy for suspected foreign body aspiration in Ha'Emek Medical Center during the period 1994-2004. The review presented a total of 136 children who had undergone bronchoscopy. Foreign bodies were found in 73% of the cases. Two thirds of the patients were male and two thirds were children less then two years old. The incidence of bronchoscopies that were positive for foreign bodies was higher in children less then two years old (82.6%) compared with older children (57.1%), p = 0.001. The incidence of Arab children was higher when compared to Jewish children and significantly higher than their percentage in the general child population (p = 0.001). The rate of bronchoscopies was 11 procedures per 100,000 children per year. In the majority of cases food was aspirated (82%) especially nuts and seeds. We found that children under the age of two years, male children and Arab children were at the highest risk of foreign body aspiration. Nuts and seeds are particularly dangerous and it is recommended to prevent young children from eating them. Well-defined public education programs should achieve prevention.


Initiating and Managing Patients with Venous Thromboembolism on Anticoagulant Drugs: A Practical Overview.
Several new oral anticoagulants have recently been approved for the treatment of venous thromboembolism (VTE). In this review, we discuss the currently approved drugs and the factors that influence the choice of anticoagulant in a given patient. Once anticoagulation is initiated, periodic monitoring of adequacy of anticoagulation may be necessary depending on the choice of anticoagulant and patient-related factors, such as renal function. Situations that may warrant need for monitoring and the tests available for this purpose are discussed. We review reversal of anticoagulation in urgent/emergent situations as well as perioperative anticoagulation interruption in the elective setting. The data on use of direct oral anticoagulants in patients with compromised renal function, obesity and bariatric surgery, and in the treatment of cancer-associated thrombosis are discussed. The review aims to provide the clinician with the essential information to allow effective and safe use of anticoagulants for the treatment of VTE.


Secondary metabolites and insecticidal activity of Anemone pavonina.
The insecticidal properties of the crude extracts of the leaves and flowers of Anemone pavonina were evaluated on Pheidole pallidula ants and showed significant levels of activity. Bioassay-guided fractionations led to the isolation of the butenolide ranunculin (1) as the active principle. Chemical investigations of the extracts showed them to contain as major components the sitosterol glycopyranoside lipids 2-5 and the glycerides 6-8. The structures of the metabolites were elucidated, following acetylation and hydrolysis of the natural products, by interpretation of their NMR and mass spectral data. The uncommon lipid metabolites 2-8 were isolated for the first time from the genus Anemone and this is the first report of insecticidal activity of the Anemone metabolite ranunculin against ants.


How does prior health status (age, comorbidities and frailty) determine critical illness and outcome?
Critical illness has a significant impact on an individual's physical and mental health. However, it is less clear to what degree outcomes after critical illness are due to patients' preexisting characteristics, rather than the critical illness itself. In this review, we summarize recent findings regarding the role of age, comorbidity and frailty on long-term outcomes after critical illness. Age, comorbidity and frailty are all associated with an increased risk of critical illness. Although severity of illness drives the risk of acute mortality, recent data suggest that longer term outcomes are much more closely aligned with prior health status. There are growing data regarding the important role of noncardiovascular comorbidity, including psychiatric illness and obesity, in determining long-term outcomes. Finally, preadmission frailty is associated with poor long-term outcomes after critical illness; further data are needed to evaluate the attributable impact of critical illness on the health trajectories of frail individuals. Age, comorbidity and frailty play a critical role in determining the long-term outcomes of patients requiring intensive care.


Which domain of self-rated health best predicts medical care utilization among Taiwanese adults?
We attempted to identify the domain of self-rated health (SRH) that best predicts medical care utilization among Taiwanese adults. In addition, we examined the association between SRH and different measure of medical care utilization. We analyzed data on 11 987 community-dwelling adults aged 18 to 64 years from the 2005 Taiwan National Health Interview Survey (NHIS). NHIS data were linked to the 2006 National Health Insurance (NHI) administrative database. Then, medical care utilization in 2006, including all outpatient visits, hospitalizations, and mental health outpatient visits, was identified. Domain-specific health ratings were measured by using the Short Form-36 (SF-36) health survey questionnaire. Negative binominal models were used to estimate the contribution of the health domains to medical care utilization. Incidence rate ratios (IRRs) are presented. The IRR for the physical component scale showed that those with the highest scores had 77% of the outpatient visits of those with the lowest scores. The importance of mental health domains was markedly higher in estimating mental health outpatient visits. Those with mental health scores above the median had only 61% of mental health outpatient visits of those with scores below the median. A person's medical care utilization is reflected in the different domains of general health. Domain-specific measures of subjective health are not interchangeable with global general health ratings, because different domains have independent effects on medical care utilization. Our results are potentially important for medical resource allocation because they identify different health domain experiences that require improvement.


Perspective taking to assess topographical disorientation: Group study and preliminary normative data.
Difficulty in navigating in a well-known environment (i.e., topographical disorientation) is an incapacitating syndrome. Despite the relatively high frequency after a right cerebral lesion, there is currently a dearth of neuropsychological tests to assess it. We propose a completely new test, the third in a battery of three, which assesses perspective taking, a crucial process in spatial orientation. In this test, inspired from Piaget and Inhelder Three Mountains, the subject must imagine a change in perspective in two conditions: after a rotational or a linear displacement. This task was proposed to 63 patients with a right cerebral lesion and a control group (N = 112). Results show that a right cerebral lesion impairs perspective taking, more specifically when rotation is involved. In addition, the pattern of responses in patients indicates that they have a general deficit in the ability of decentering. Furthermore, we established preliminary normative data taking into account the effect of age and education (there was no effect of gender) on performance. These data indicate that this new test is a good tool in clinical practice for assessing spatial orientation and determining more precisely the symptoms underlying topographical disorientation.


[Nocardia brasiliensis leg ulcer and nodular lymphangitis in France].
Nocardia brasiliensis is a very rarely reported cause of chronic phagedenic ulcerations. We report the case of an elderly woman who developed such an infection after falling on her right leg on the road in the Bresse country (an essentially agricultural and bovine-cattle breading region) and developed a chronic phagedenic ulcer secondarily complicated by nodular lymphangitis of the thigh. A 75 year-old woman fell on her right leg on the side of the main road outside her hamlet in the Bresse country and secondarily developed a chronique phagedenic ulceration. We first considered her as suffering from pyoderma gangrenosum. A complete scanning only revealed an autoimmune thyroiditis and a rapidly healing gastric ulceration, and none of the treatments, either local or systemic, helped the skin condition to heal. After 3 weeks of application of a local corticoid ointment, the patient developed fever, general malaise, an exacerbation of her wound and an infiltration of the skin round her knee, together with nodular lymphangitic dissemination. A supplementary bacterial swab disclosed massive proliferation of a slow-growing Gram-positive bacillus, which proved to be Nocardia brasiliensis, together with a methicillino-sensitive Staphylococcus aureus. The treatment with sulfamethoxazole-trimetoprim gave a rash after 12 hours and was changed to amoxicillin and clavulanic acid, which rapidly proved to be permanently effective. The revelation of this particular slow-growing bacteria is difficult and requires bacterial swabs. Nocardia brasiliensis is relatively rare in primary skin ulcerations and we discuss the reasons why an elderly women should find this bacteria on the road outside her hamlet in the French countryside. This particular infectious condition requires general scanning, to make sure that the primary skin condition does not extend to other organs. We review the therapeutical options for patients who exhibit allergic reactions to the classically effective antibiotic drugs.


Purinergic signaling regulates neural progenitor cell expansion and neurogenesis.
Neural stem and progenitor cells typically exhibit a density-dependent survival and expansion, such that critical densities are required below which clonogenic progenitors are lost. This suggests that short-range autocrine factors may be critical for progenitor cell maintenance. We report here that purines drive the expansion of ventricular zone neural stem and progenitor cells, and that purine receptor activation is required for progenitor cells to be maintained as such. Neural progenitors expressed P2Y purinergic receptors and mobilized intracellular calcium in response to agonist. Receptor antagonists suppressed proliferation and permitted differentiation into neurons and glia in vitro, while subsequent removal of purinergic inhibition restored progenitor cell expansion. Real-time bioluminescence imaging of extracellular ATP revealed that the source of extracellular nucleotides are the progenitor cells themselves, which appear to release ATP in episodic burst events. Enzyme histochemistry of the adult rat brain for ectonucleotidase activity revealed that NTDPase, which acts to degrade active ATP and thereby clears it from areas of active purinergic transmission, was selectively localized to the subventricular zone and the dentate gyrus, regions in which neuronal differentiation proceeds from the progenitor cell pool. These data suggest that purine nucleotides act as proliferation signals for neural progenitor cells, and thereby serve as negative regulators of terminal neuronal differentiation. As a result, progenitor cell-derived neurogenesis is thus associated with regions of both active purinergic signaling and modulation thereof.


In Vivo GFP Knockdown by Cationic Nanogel-siRNA Polyplexes.
RNA interference (RNAi) is a powerful tool to treat diseases and elucidate target gene function. Prior to clinical implementation, however, challenges including the safe, efficient and targeted delivery of siRNA must be addressed. Here, we report cationic nanogel nanostructured polymers (NSPs) prepared by atom transfer radical polymerization (ATRP) for in vitro and in vivo siRNA delivery in mammalian models. Outcomes from siRNA protection studies suggested that nanogel NSPs reduce enzymatic degradation of siRNA within polyplexes. Further, the methylation of siRNA may enhance nuclease resistance without compromising gene knockdown potency. NSP-mediated RNAi treatments against Gapdh significantly reduced GAPDH enzyme activity in mammalian cell culture models supplemented with 10% serum. Moreover, nanogel NSP-mediated siRNA delivery significantly inhibited in vivo GFP expression in a mouse model. GFP knockdown was siRNA sequence-dependent and facilitated by nanogel NSP carriers. Continued testing of NSP/siRNA compositions in disease models may produce important new therapeutic options for patient care.


Metabolism of amyloid β peptide and pathogenesis of Alzheimer's disease.
The conversion of what has been interpreted as "normal brain aging" to Alzheimer's disease (AD) via transition states, i.e., preclinical AD and mild cognitive impairment, appears to be a continuous process caused primarily by aging-dependent accumulation of amyloid β peptide (Aβ) in the brain. This notion however gives us a hope that, by manipulating the Aβ levels in the brain, we may be able not only to prevent and cure the disease but also to partially control some very significant aspects of brain aging. Aβ is constantly produced from its precursor and immediately catabolized under normal conditions, whereas dysmetabolism of Aβ seems to lead to pathological deposition upon aging. We have focused our attention on elucidation of the unresolved mechanism of Aβ catabolism in the brain. In this review, I describe a new approach to prevent AD development by reducing Aβ burdens in aging brains through up-regulation of the catabolic mechanism involving neprilysin that can degrade both monomeric and oligomeric forms of Aβ. The strategy of combining presymptomatic diagnosis with preventive medicine seems to be the most pragmatic in both medical and socioeconomical terms.(Communicated by Kunihiko SUZUKI, M.J.A.).


Machine Learning Algorithms for Risk Prediction of Severe Hand-Foot-Mouth Disease in Children.
The identification of indicators for severe HFMD is critical for early prevention and control of the disease. With this goal in mind, 185 severe and 345 mild HFMD cases were assessed. Patient demographics, clinical features, MRI findings, and laboratory test results were collected. Gradient boosting tree (GBT) was then used to determine the relative importance (RI) and interaction effects of the variables. Results indicated that elevated white blood cell (WBC) count > 15 × 109/L (RI: 49.47, p < 0.001) was the top predictor of severe HFMD, followed by spinal cord involvement (RI: 26.62, p < 0.001), spinal nerve roots involvement (RI: 10.34, p < 0.001), hyperglycemia (RI: 3.40, p < 0.001), and brain or spinal meninges involvement (RI: 2.45, p = 0.003). Interactions between elevated WBC count and hyperglycemia (H statistic: 0.231, 95% CI: 0-0.262, p = 0.031), between spinal cord involvement and duration of fever ≥3 days (H statistic: 0.291, 95% CI: 0.035-0.326, p = 0.035), and between brainstem involvement and body temperature (H statistic: 0.313, 95% CI: 0-0.273, p = 0.017) were observed. Therefore, GBT is capable to identify the predictors for severe HFMD and their interaction effects, outperforming conventional regression methods.


Risk factors and digital interventions for anxiety disorders in college students: Stakeholder perspectives.
The worldwide prevalence of anxiety disorders among college students is high, which negatively affects countries, schools, families, and individual students to varying degrees. This paper reviews the relevant literature regarding risk factors and digital interventions for anxiety disorders among college students from the perspectives of different stakeholders. Risk factors at the national and societal levels include class differences and the coronavirus disease 2019 pandemic. College-level risk factors include the indoor environment design of the college environment, peer relationships, student satisfaction with college culture, and school functional levels. Family-level risk factors include parenting style, family relationship, and parental level of education. Individual-level risk factors include biological factors, lifestyle, and personality. Among the intervention options for college students' anxiety disorders, in addition to traditional cognitive behavioral therapy, mindfulness-based interventions, psychological counseling, and group counseling, digital mental health interventions are increasingly popular due to their low cost, positive effect, and convenient diagnostics and treatment. To better apply digital intervention to the prevention and treatment of college students' anxiety, this paper suggests that the different stakeholders form a synergy among themselves. The nation and society should provide necessary policy guarantees, financial support, and moral and ethical supervision for the prevention and treatment of college students' anxiety disorders. Colleges should actively participate in the screening and intervention of college students' anxiety disorders. Families should increase their awareness of college students' anxiety disorders and take the initiative to study and understand various digital intervention methods. College students with anxiety disorders should actively seek psychological assistance and actively accept and participate in digital intervention projects and services. We believe that in the future, the application of methods such as big data and artificial intelligence to improve digital interventions and provide individualized treatment plans will become the primary means of preventing and treating anxiety disorders among college students.


The Patient Experience of Waiting on the Deceased Donor Kidney Transplant List While Receiving Dialysis.
End stage renal disease (ESRD) is a global health problem, and the gold standard treatment is kidney transplantation. However, due to the global shortage of organs, many patients with ESRD rely on dialysis for survival while waiting several years for a kidney transplant. An integrative review of qualitative studies was conducted on the experience of patients with ESRD who require either peritoneal dialysis or hemodialysis while waiting for a deceased donor kidney transplant. Eight international studies were selected for review. Six themes were identified: 1) living in hope, 2) uncertainty, 3) mixed emotions, 4) coping with waiting, 5) restrictions on freedom, and 6) support network. Patients on dialysis and waiting for a kidney transplant have emotional, educational, and informational needs that need to be better understood and addressed by nurses and physicians.


Transfer Learning on Electromyography (EMG) Tasks: Approaches and Beyond.
Machine learning on electromyography (EMG) has recently achieved remarkable success on various tasks, while such success relies heavily on the assumption that the training and future data must be of the same data distribution. However, this assumption may not hold in many real-world applications. Model calibration is required via data re-collection and label annotation, which is generally very expensive and time-consuming. To address this issue, transfer learning (TL), which aims to improve target learners' performance by transferring knowledge from related source domains, is emerging as a new paradigm to reduce the amount of calibration effort. This survey assesses the eligibility of more than fifty published peer-reviewed representative transfer learning approaches for EMG applications. Unlike previous surveys on purely transfer learning or EMG-based machine learning, this survey aims to provide insight into the biological foundations of existing transfer learning methods on EMG-related analysis. Specifically, we first introduce the muscles' physiological structure, the EMG generating mechanism, and the recording of EMG to provide biological insights behind existing transfer learning approaches. Further, we categorize existing research endeavors into data based, model based, training scheme based, and adversarial based. This survey systematically summarizes and categorizes existing transfer learning approaches for EMG related machine learning applications. In addition, we discuss possible drawbacks of existing works and point out the future direction of better EMG transfer learning algorithms to enhance practicality for real-world applications.


Orbital floor fracture with entrapment: Imaging and clinical correlations in 45 cases.
Orbital floor fractures (OFF) with entrapment require prompt clinical and radiographic recognition for timely surgical correction. Correct CT radiographic interpretation of entrapped fractures can be subtle and thus missed. We reviewed the clinical, radiographic and intraoperative findings of 45 cases of entrapped OFF to correlate pre- and intraoperative findings with radiography. Retrospective review and statistical analysis of 45 patients with OFF using the chi squared and Kruskal-Wallis tests. Main outcome measures included patient demographics, clinical features, radiologic interpretation, intraoperative findings, and treatment outcomes. Twenty-one cases (47%) had radiologic evaluations of orbital CT scans that included commentary on possible entrapment. Intraoperatively, 16 (76%) of these patients had the inferior rectus muscle incarcerated in the fracture, while 5 (24%) patients had incarceration of the orbital fat. Possibility of entrapment was not commented on in the radiology reports of the remaining 24 (53%) cases. Intraoperatively, 13 (54%) of these patients had the inferior rectus muscle incarcerated in the fracture, while 11 (46%) patients had incarceration of the orbital fat. It is vital to assess the possibility of entrapment, especially in young patients, in the setting of OFF as a delay in diagnosis may lead to persistent diplopia, disfigurement, or bradycardia. Most radiology reports did not mention the possibility of entrapment in this cohort. A key concept is that entrapment occurs when any orbital tissue (muscle or fat) is trapped in the fracture site.


Pharmacokinetics of iloprost in patients with hepatic dysfunction.
In the present experiment the pharmacokinetics of iloprost was studied in eight hospitalized patients suffering from liver cirrhosis (mean age: 56 years, 3 females, 5 males, child-classification: A [n = 1], B [n = 5], C [n = 2]/mean 14C-aminopyrine breath test: 3.9% dose/2 h). Iloprost was administered as a 1 h-i.v. infusion with 1 ng/kg/min to all the test subjects. Steady state plasma levels of 93 +/- 31 pg/ml were observed at the end of infusion. The terminal half-life of iloprost was 28 +/- 24 min. From AUC values of 126 +/- 60 pg.h/ml a total clearance of 10 +/- 5 ml/min/kg was calculated. The study demonstrated that iloprost clearance was reduced by a factor of 2 in patients suffering from hepatic dysfunction compared with healthy subjects. Individual dose titration is the recommended dose regimen for iloprost therapy in all patients. Therefore, apart from a reduction of the starting dose (of approximately 50%) for titration, special recommendations are not necessary for patients with impaired liver function.


Night Monkey Hybrids Exhibit De Novo Genomic and Karyotypic Alterations: The First Such Case in Primates.
Using molecular chromosomal analyses, we discovered night monkey hybrids produced in captivity from matings between a female Aotus azarae boliviensis (2n = 50) and a male Aotus lemurinus griseimembra (2n = 53). The parents produced seven offspring in total, including one male and six females-a pattern consistent with Haldane's rule. Chromosomal studies were conducted on four of the hybrid offspring. Two of them showed relatively "simple" mixture karyotypes, including different chromosome numbers (2n = 51, 52), which were formed because of a heteromorphic autosome pair in the father (n = 26, 27). The other two hybrid monkeys exhibited de novo genomic and karyotypic alterations. Detailed analysis of the alterations revealed that one individual carried a mixture karyotype of the two parental species and an X chromosome trisomy (53,XXX). The second individual displayed trisomy of chromosome 18 (52,XX,+18) and a reciprocal translocation between autosomes 21 and 23 (52,XX,+18,t(21;23)). Interestingly, the second monkey exhibited mosaicism among blood cells (mos52,XX,+18[87]/52,XX,+18,t(21;23)[85]), but only a single karyotype (52,XX,+18) in skin fibroblast cells. The X- and 18-trisomies were derived from a doubling of the mother's chromosomes in early embryonic cell division, and the reciprocal translocation likely developed in the bone marrow of the offspring, considering that it was observed only in blood cells. Such occurrence of trisomies in hybrid individuals is a unique finding in placental mammals.


Glomerular targets of Heliothis subflexa male olfactory receptor neurons housed within long trichoid sensilla.
We used single-sensillum recordings to characterize male Heliothis subflexa antennal olfactory receptor neuron physiology in response to compounds related to their sex pheromone. The recordings were then followed by cobalt staining in order to trace the neurons' axons to their glomerular destinations in the antennal lobe. Receptor neurons responding to the major pheromone component, (Z)-11-hexadecenal, in the first type of sensillum, type-A, projected axons to the cumulus of the macroglomerular complex (MGC). In approximately 40% of the type-A sensilla, a colocalized receptor neuron was stained that projected consistently to the posterior complex 1 (PCx1), a specific glomerulus in an 8-glomerulus complex that we call the Posterior Complex (PCx). We found that receptor neurons residing in type-B sensilla and responding to a secondary pheromone component, (Z)-9-hexadecenal, send their axons to the dorsal medial glomerulus of the MGC. As in the type-A sensilla, we found a cocompartmentalized neuron within type-B sensilla that sends its axon to a different glomerulus of the PCx4. One neuron in type-C sensilla tuned to a third pheromone component, (Z)-11-hexadecenol, and a colocalized neuron responding to (Z)-11-hexadecenyl acetate projected their axons to the anteromedial and ventromedial glomeruli of the MGC, respectively.


Bovine leukemia virus transcription is controlled by a virus-encoded trans-acting factor and by cis-acting response elements.
Bovine leukemia virus (BLV) gene expression is exquisitely regulated at multiple levels, including a transcriptional control effected by virus-encoded trans-acting factors and cis-acting target sequences. Like the human T-cell leukemia viruses type I and type II, but unlike other RNA tumor viruses, BLV contains several open reading frames at the 3' end of its genome. A subgenomic mRNA which encodes two overlapping reading frames from this region could produce proteins of 38 and 18 kilodaltons (kDa). A series of cis-trans experiments using transfected virus gene constructs in different combinations revealed that expression of the 38-kDa protein was both necessary and sufficient to activate, in trans, the BLV promoter. This activation was specific for the BLV long terminal repeat, as a variety of related retroviral promoters were not responsive to the expression of the 38-kDa protein p38(XBL). Deletion analysis and construction of chimeric promoters identified a 75-base-pair long terminal repeat region which functions like a p38(XBL)-dependent enhancer element.


2: Recent advances in therapy of diabetes.
As suboptimal blood glucose control has a lasting harmful effect even if control improves later, intensive insulin therapy to minimise hyperglycaemia is now recommended for all patients with type 1 diabetes. The new rapid- and long-acting insulin analogues offer more physiological insulin profiles than traditional insulin preparations. Continuous insulin infusion ("pump therapy") may provide a solution for some patients with frequent hypoglycaemia or hypoglycaemic unawareness. Continuous blood glucose monitoring reveals postprandial hyperglycaemia and asymptomatic nocturnal hypoglycaemia and may be especially useful for programming overnight basal insulin rates for pump therapy. In type 2 diabetes, management should change with disease progression; introduction of insulin should not be delayed if metabolic control becomes suboptimal.


The effect on medication errors of pharmacists charting medication in an emergency department.
To determine the frequency and clinical significance of medication errors when (a) pharmacists elicit medication histories in the Emergency Department after medications have been prescribed by doctors and (b) pharmacists obtain and chart medication histories prior to doctors' approval. The Queen Elizabeth Hospital, a 350 bed South Australian teaching hospital, serving the local adult community. Emergency Department patients at risk of medication misadventure were recruited in two phases with a 'usual practice' arm (6 weeks) and a 'pharmacist medication charting' arm (5 weeks) reflecting an alternative intervention. In the 'usual care' arm, medication histories were compiled by a pharmacy researcher after a doctor had completed the medication chart. The researcher-elicited medication histories were compared with the doctors' medication charts and unintentional discrepancies were recorded. In the 'pharmacist medication charting' arm, the same process was followed except the researcher compiled the patients' medication histories at triage, prior to patients seeing a doctor. The medication history was then transcribed onto a medication chart for authorisation by a doctor. In addition, whether resolution of unintentional discrepancies for patients in the 'usual care' arm had occurred by discharge was determined by examining patients' medical records. Main outcome measure Frequency of unintentional discrepancies and medication errors. The study included 45 and 29 patients in the 'usual care' and intervention arms, respectively. In the 'usual care' arm, 75.6% of patients had one or more unintentional discrepancies compared with 3.3% in the 'pharmacist medication charting' arm. This resulted in an average of 2.35 missed doses per patient in the 'usual care' arm and 0.24 in the intervention arm. In addition, an average of 1.04 incorrect doses per patient were administered in the 'usual care' arm and none in the 'pharmacist medication charting' arm. The differences observed between the arms were statistically significant (P < 0.05) and deemed clinically significant by a multidisciplinary panel. This study provides evidence for pharmacists eliciting medication histories to prepare medication charts at the earliest possible opportunity following a patient's presentation to the Emergency Department.