Biallelic ERBB3 loss-of-function variants are associated with a novel multisystem syndrome without congenital contracture.
Gain-of-function pathogenic variants of the Erb-B2 receptor tyrosine kinase 3 (ERBB3) gene contribute to the occurrence and development of a variety of human carcinomas through activation of phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular signal-regulated kinase (ERK) signaling. ERBB3 gene homozygous germline variants, whose loss of function may cause autosomal recessive congenital contractural syndrome, were recently identified. This study aims to identify the disease-causing gene in a Chinese pedigree with variable phenotypes involving multiple systems, including developmental delay, postnatal growth retardation, transient lower limb asymmetry, facial malformations, atrioventricular canal malformation, bilateral nystagmus and amblyopia, feeding difficulties, immunodeficiency, anemia, and liver damage, but without congenital contracture. Trio-whole exome sequencing (WES) was performed to identify the disease-causing gene in a 24-month-old Chinese female patient. The pathogenicity of the identified variants was evaluated using in silico tools and in vitro functional studies. Trio-WES revealed compound heterozygous variants of c.1253 T > C (p.I418T) and c.3182dupA (p.N1061Kfs*16) in the ERBB3 gene. Functional studies showed that p.I418T resulted in normal expression of ERBB3, which was capable of interacting with ERBB2. However, the variant impaired ERBB3 phosphorylation, consequently blocking ERBB2 phosphorylation and AKT and ERK activation. The truncated protein resulting from the c.3182dupA variant also lacked the capacity to activate downstream signaling pathways. We report the first patient with a novel multisystem syndrome disorder without congenital contracture resulting from biallelic loss-of-function variants of ERBB3.


Human vitreous levels of selected antistaphylococcal antibiotics.
Staphylococcus epidermidis and S. aureus are the most common causes of bacterial endophthalmitis. A study of the penetration of selected antistaphylococcal antibiotics into human vitreous was undertaken in 58 patients. After 2-g intravenous doses of cephalothin, cefazolin, methicillin, oxacillin, or nafcillin were given to patients about to undergo vitreous surgery, mean vitreous levels for each antibiotic were as follows: cephalothin, 0.97 microgram/ml in diabetics and 0.69 microgram/ml in nondiabetics; cefazolin, 0.84 microgram/ml in diabetics and 1.6 microgram/ml in nondiabetics; methicillin, 2.56 micrograms/ml in diabetics and 2.64 micrograms/ml in nondiabetics; oxacillin, 0.62 microgram/ml in diabetics and 0.34 microgram/ml in nondiabetics; and nafcillin, 0.73 microgram/ml in diabetics and 0.75 microgram/ml in nondiabetics. Only cefazolin produced vitreous concentrations consistently above its minimum inhibitory concentration for 90% of S. epidermidis isolates. Staphylococcus aureus isolates were not similarly covered. There was a trend toward higher vitreous antibiotic concentrations in patients with proliferative vitreoretinopathy and rubeosis.


Treatment of uterine fibroids with agonist analogs of gonadotropin-releasing hormone.
Agonist analogs of GnRH were used to effect a "medical castration" in 14 patients with uterine fibroids, presenting with either an enlarged uterus, recurrent menometrorrhagia, and/or infertility. This study confirms prior reports of a reduction in uterine size and cessation of menometrorrhagia in patients with fibroids following treatment with GnRHa. Of interest, however, was the successful use of GnRHa as either the sole treatment for uterine fibroid-associated infertility, or as a preoperative adjunct in infertility patients scheduled for myomectomy. Three of the five infertility patients in this study achieved intrauterine pregnancies. Further study of the role of GnRHa treatment in infertility patients with uterine fibroids appears warranted.


Functional reorganization in the patient with progressing glioma of the pure primary motor cortex: a case report with special reference to the topographic central sulcus defined by somatosensory-evoked potential.
The concept of human brain reorganization due to slow-growing lesions, including low-grade glioma, has been gradually and generally accepted. However, few cases have been reported in which the reorganization, especially in the topographic pure primary motor cortex, was observed during brain surgery. We report a case of slow-growing oligodendroglioma located in the pure primary motor cortex, as detected by magnetic resonance imaging that could be resected in part thanks to the brain plasticity. In addition, we describe a pitfall of topographic guidance using somatosensory-evoked potential (SEP) monitoring. A 36-year-old right-handed patient underwent resection of a gradually growing oligodendroglioma located in the right primary motor cortex, with no other adjacent lesions, 8 years after the initial biopsy. The central sulcus was defined with intraoperative SEP monitoring in both operations. Based on the findings of the intraoperative direct electrical stimulation under awake craniotomy, we suspect that motor function shifted posteriorly and reorganized beyond the central sulcus. Pure primary motor cortex could be reorganized by its own lesion. In reorganized brain, topographic central sulcus defined based on SEP findings may be an inappropriate guidance to estimate true functional area. In such a condition, intraoperative direct electrical stimulation under awake craniotomy makes it feasible to resect pure primary motor cortex invaded by tumors.


Single-leg mechanical performance and inter-leg asymmetries during bilateral countermovement jumps: A comparison of different calculation methods.
The possibility to selectively assess the force exerted by each leg during bilateral jumps has allowed sport scientists to explore inter-leg asymmetries, this metric being a rich source of research due to its potential applications to improve sports performance and reduce the risk of injury. The purpose of this study was to explore the reliability and agreement of single-leg mechanical performance and inter-leg asymmetry variables obtained by two procedures of analysis (Synchronous [simultaneous jump detection for both legs] and Asynchronous [specific jump detection for each leg]) during bilateral countermovement jumps (CMJs). During a single testing session, 74 participants performed 5 maximal height bilateral CMJs on dual force platforms (Kistler, model 9260AA6, Winterthur, Switzerland), and the 2 trials that differed the least in terms of squat depth and jump height were considered for statistical analyses. The following mechanical variables were calculated separately for each leg using the Synchronous and Asynchronous procedures: mean force, peak force, and propulsive impulse. The procedures showed comparable reliability, except for mean force and propulsive impulse of the left leg (higher for the Asynchronous procedure). The agreement between the procedures was very high, while the most reliable mechanical variable was mean force (CV≈2.9%, ICC≈0.98), followed by peak force (CV≈4.4%, ICC≈0.96) and propulsive impulse (CV≈6.4%, ICC≈0.91). Reliability of inter-leg asymmetries was greater using mean and peak force (ICC range=0.74-0.82) than using propulsive impulse (ICC range = 0.65-0.66). Both Synchronous and Asynchronous procedures can be used to evaluate single-leg mechanical performance (mean force, peak force, and propulsive impulse) and asymmetries, whereas mean force should be used to evaluate single-leg mechanical performance and mean or peak force to assess asymmetries.


Number versus distribution in classifying regional lymph node metastases from colon cancer.
Metastasis to regional lymph nodes from colon cancer is an important prognostic factor. In the TNM classification, node metastases are classified into three grades based on the number of metastatic nodes. In the Japanese General Rules for Clinical and Pathologic Studies on Cancer of the Colon, Rectum, and Anus (JGR), node metastases are classified into four grades based on the distribution of metastatic nodes. Based on the findings of node metastases in 164 patients with colon cancer obtained by the clearing method, node classifications by the JGR and TNM classifications were compared. The case distribution by the JGR grading was 41.5% in n (-), 29.3% in n1 (+), 18.3% in n2 (+), and 11.0% in n3 (+) disease. In the TNM classification, the distribution was 23.8% in pN1 and 34.8% in pN2 disease. The 5-year survival rate by the JGR was 98.4% in n (-), 74.3% in n1 (+), 51.2% in n2 (+), and 30.0% in n3 (+) disease; in TNM classification, this rate was 76.0% in pN1 and 45.0% in pN2 disease. In the classification of regional node metastases from colon cancer, the JGR classification showed a wider range in distribution and 5-year survival rate compared with the TNM system.


Mediastinal and axillar lymphadenopathy in patients with rheumatoid arthritis: prevalence and clinical significance.
With recent advances of biological disease-modifying antirheumatic drugs, chest CT has been increasingly performed in rheumatoid arthritis (RA) patients, and mediastinal/axillar lymphadenopathy is being detected. To determine the prevalence of mediastinal and axillar lymph node enlargements on chest CT in RA patients at the initial diagnosis, and to assess its clinical significance. We retrospectively reviewed the medical records and chest CT findings of 78 consecutive RA patients. The short axis of the most enlarged lymph nodes (SLN) on CT was measured for the mediastinal and axillar regions separately. The SLN was classified into two groups: Group 1, 10 mm or less; and Group 2, larger than 10 mm. Group 2 was observed in 13 of 78 patients (17%) for the mediastinum, and in 29 (37%) for the axilla; 11 patients (14%) showed Group 2 for both regions. The Group 2 patients (n = 31), either mediastinum or axilla, showed significantly higher simple disease activity index (SDAI) (mean, 36.0) than the patients of Group 1 (n = 47; mean SDAI, 23.0) (p < 0.001). For the mediastinal SLN, the RA-related lung disease was more frequently observed in the Group 2 patients than in the Group 1 (p = 0.036). The mediastinal and/or axillar lymphadenopathy on chest CT may reflect the activity of RA. The mediastinal lymphadenopathy also seems to relate to the RA-related lung disease.


Maintenance of peripheral tolerance to islet antigens.
Reestablishment of immune tolerance to the insulin-producing beta cells is the desired goal for type 1 diabetes (T1D) treatment and prevention. Immune tolerance to multiple islet antigens is defective in individuals with T1D, but the mechanisms involved are multifaceted and may involve loss of thymic and peripheral tolerance. In this review we discuss our current understanding of the varied mechanisms by which peripheral tolerance to islet antigens is maintained in healthy individuals where genetic protection from T1D is present and how this fails in those with genetic susceptibility to disease. Novel findings in regards to expression of neo-islet antigens, non-classical regulatory cell subsets and the impact of specific genetic variants on tolerance induction are discussed.


Extremely discrepant mutation spectrum of SLC26A4 between Chinese patients with isolated Mondini deformity and enlarged vestibular aqueduct.
Mutations in SLC26A4 cause Pendred syndrome (hearing loss with goiter) or DFNB4 (non-syndromic hearing loss with inner ear malformation, such as enlarged vestibular aqueduct or Mondini deformity). The relationship between mutations in SLC26A4 and Mondini deformity without enlarged vestibular aqueduct has not been studied in any Chinese deaf population. The purpose of this study was to assess whether mutations in the SLC26A4 gene cause Mondini deformity without an enlarged vestibular aqueduct (isolated Mondini deformity) in a Chinese population. In total, 144 patients with sensorineural hearing loss were included and subjected to high-resolution temporal bone CT. Among them, 28 patients with isolated Mondini dysplasia (MD group), 50 patients with enlarged vestibular aqueduct with Mondini dysplasia (EVA with MD group), 50 patients with enlarged vestibular aqueduct without Mondini dysplasia (EVA group), and 16 patients with other types of inner ear malformations (IEM group) were identified. The coding exons of SLC26A4 were analyzed in all subjects. DNA sequence analysis of SLC26A4 was performed in all 144 patients. In the different groups, the detection rate of the SLC26A4 mutation differed. In the isolated MD group, only one single allelic mutation in SLC26A4 was found in one patient (1/28, 3.6%). In the EVA with MD group, biallelic and monoallelic SLC26A4 mutations were identified in 46 patients (46/50, 92.0%) and three patients (3/50, 6.0%), respectively. Also, in the EVA group, biallelic and monoallelic SLC26A4 mutations were identified in 46 patients (46/50, 92.0%) and three patients (3/50, 6.0%), respectively. These percentages were identical to those in the EVA plus MD group. Only two patients carried monoallelic mutations of the SLC26A4 gene in the IEM group (2/16, 12.5%). There were significant differences in the frequency of SLC26A4 mutation among the groups (P<0.001). The detection rate of SLC26A4 mutation in the isolated MD group was significantly lower than in the EVA group (with or without MD; P<0.001), and there was no significant difference in the detection rate of SLC26A4 between the MD group and IEM group (P>0.5). Although mutations in the SLC26A4 gene were frequently found in Chinese EVA patients with and without MD, there was no evidence to show a relationship between isolated MD and the SLC26A4 gene in the Chinese population examined. Hearing impairment in patients with isolated MD may be caused by factors other than mutations in the SLC26A4 gene.


A qualitative study of physicians' perceptions of three decision aids.
The study objective was to investigate physicians' perceptions of three patient decision aids (DA). Semi-structured telephone interviews were conducted with 20 family physicians and 12 gynecologists about a DA for women considering long-term hormone replacement therapy; with 16 respirologists about a DA for the use of intubation and mechanical ventilation for patients with severe chronic obstructive pulmonary disease; and with 19 physicians (geriatricians, gastroenterologists, internists) about a DA for long-term placement of feeding tubes in the elderly. Participants were identified by a snowball sampling technique. The interviews were analyzed using standard qualitative methods. Most participants (81%) indicated some willingness to use the DAs. The characteristics of the DA viewed positively included it being: balanced, well organized, a useful tool, evidence-based, improves decision making process and multimedia. Some of the negative characteristics were stated as: too complex, the cost, the availability, only appropriate for certain groups of patients, and time consuming. The DAs were acceptable to most participants. Perceived positive and negative factors were similar for all DAs. Uptake of decision aids may be facilitated if physicians have an opportunity to examine and try them, and if they can have unfettered access to them for distribution purposes.


Validation of difficulty scoring system for laparoscopic liver resection in patients who underwent laparoscopic left lateral sectionectomy.
A difficulty scoring system (DSS) based on the extent of liver resection, tumor location, liver function, tumor size, and tumor proximity to major vessels was recently developed to assess the difficulty of various laparoscopic liver resection procedures. We validated DSS in patients who underwent laparoscopic left lateral sectionectomy (LLS). We reviewed the clinical data of 124 patients who underwent laparoscopic LLS between July 2003 and November 2015 and validated the DSS in 90 patients who underwent laparoscopic LLS for tumor according to their surgical outcomes. We also developed and evaluated the modified DSS in 34 patients who underwent LLS for intrahepatic duct (IHD) stones. The DSS score ranged from 3 to 6 in laparoscopic LLS for tumors. The median blood loss (P = 0.002) was significantly different among patients divided into subgroups by DSS score. We made modified DSS for IHD stones using factors influencing longer operation time, including stone location (P = 0.002), atrophy of liver parenchyma (P = 0.012), ductal stricture <1 cm from the bifurcation (P = 0.047), and combined choledochoscopic examination for remnant IHD (P < 0.001). The modified DSS score for IHD stones ranged from 3 to 7. Blood loss (P = 0.02) and operation time (P < 0.001) were significantly different among subgroups of patients divided by their difficulty scores. The median hospital stay (P = 0.004) and operation time (P = 0.039) were significantly longer and the complication rate (P = 0.025) and complication grade (P = 0.021) were significantly greater in patients with IHD stones than in patients with tumors. The surgical difficulty varies among patients undergoing the same laparoscopic LLS procedure. The modified DSS developed here can also be applied to patients with IHD stones.


Correlation analysis between body composition, serological indices and the risk of falls, and the receiver operating characteristic curve of different indexes for the risk of falls in older individuals.
This study assessed the risk factors for falls and evaluated the correlation between body composition, serological indices, and the risk of falls in older individuals. This cross-sectional study included 387 individuals ≥60 years of age in the cadre ward of the First Hospital of Jilin University. The information used in this study was obtained from the comprehensive geriatric assessment database of the cadre ward. The body composition of the individuals was measured by bioelectrical impedance analysis using an InBody S10 device. We assessed fall risk using the fall risk assessment tool. Individuals with ≤2 points were placed in the low-risk group, those with 3-9 points were placed in the medium-risk group, and those with ≥10 points were placed in the high-risk group. Differences in age, educational background, height, cognitive impairment, malnutrition, ability of daily living, depression, diastolic blood pressure, heart rate, intracellular water, total body moisture, water ratio, limb moisture (right and left, upper and lower), trunk moisture, fat-free weight, arm girth, body cell mass, skeletal muscle mass, limb muscle (right and left, upper and lower), appendicular skeletal muscle mass index (ASMI), sarcopenia, hemoglobin level, hematocrit level, aspartate aminotransferase level, albumin level, anemia, and hypoproteinemia were observed among the three groups (p < 0.001, p = 0.002, p = 0.006, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.008, p = 0.010). Ordinal logistic regression analysis showed that the probability of the fall risk increasing by one level was 1.902 times higher for each unit of decrease in educational background, respectively. In addition, the probability of the fall risk increasing by one level was 2.971, 3.732, 3.804, 1.690 and 2.155 times higher for each additional unit of age, cognitive impairment, lower limb edema, decreased skeletal muscle mass, and sarcopenia, respectively. Our findings suggest that educational background, age, cognitive impairment, lower limb edema, decreased skeletal muscle mass, and sarcopenia were associated with falls in older individuals. Body composition and serological indices can assist in the early identification of falls in the older people.


Outpatient learning perspectives at a UK hospital.
Undergraduate students spend much of their training in the clinical workplace, increasingly in hospital outpatient settings; however, they report that this does not always yield the educational value that they expect. This study investigates ways in which outpatient learning can be enhanced from the perspectives of students and teachers, exploring which approaches may be most appropriate in different circumstances. We conducted 14 semi-structured interviews with medical students from one UK medical school and consultants (specialists) at a single teaching hospital. We explored their experiences and perceptions of clinical teaching and learning in this outpatient setting. Transcripts were analysed through a consensual qualitative research approach. An evaluation of established frameworks for outpatient teaching was conducted and strategies were matched to stakeholder needs. A total of 24 core ideas were identified, which were categorised into: individual factors (student, doctor and patient), interpersonal factors, team factors and organisational factors. Teaching strategies that address stakeholder needs included: student-led clinics, case-based discussions, one-minute preceptor, the SNAPPS tool (summarize, narrow differential, analyse, probe preceptor, plan and select issues for self-learning), advanced organisers and supplementing. There is a complex interplay between personal, interpersonal, team and organisational factors that contribute to the effectiveness of the outpatient setting as a learning environment. Strategies at the personal and interpersonal levels are unlikely to be successful or sustained without organisational resourcing and support. Further research is needed to implement and evaluate these suggested strategies.


Orexin pathway in Parkinson's disease: a review.
Parkinson's disease (PD) is a progressive neurodegenerative disease (NDD) caused by dopaminergic neuron degeneration in the substantia nigra (SN). Orexin is a neuropeptide that plays a role in the pathogenesis of PD. Orexin has neuroprotective properties in dopaminergic neurons. In PD neuropathology, there is also degeneration of orexinergic neurons in the hypothalamus, in addition to dopaminergic neurons. However, the loss of orexinergic neurons in PD began after the degeneration of dopaminergic neurons. Reduced activity of orexinergic neurons has been linked to developing and progressing motor and non-motor symptoms in PD. In addition, the dysregulation of the orexin pathway is linked to the development of sleep disorders. The hypothalamic orexin pathway regulates various aspects of PD neuropathology at the cellular, subcellular, and molecular levels. Finally, non-motor symptoms, particularly insomnia and disturbed sleep, promote neuroinflammation and the accumulation of neurotoxic proteins as a result of defects in autophagy, endoplasmic reticulum (ER) stress, and the glymphatic system. As a result, this review aimed to highlight the potential role of orexin in PD neuropathology.


Expansion of the evolutionarily conserved network of J-domain proteins in the Arabidopsis mitochondrial import complex.
We report that discriminate interaction between the expanded mitochondrial chaperone network and variability in their expression might determine their functional specificities and impart robustness to mitochondrial import processes in plants. Mitochondrial Hsp70 (mtHsp70), the central component of the pre-sequence associated motor (PAM) complex, is crucial for the import of proteins to the mitochondrial matrix. Activity of mtHsp70 is regulated by a heterodimeric complex of two J-domain proteins (JDPs), Pam18 and Pam16. Compared to other eukaryotes, plants harbor multiple copies of these JDPs, which posit that plants have an increasingly complex mtHsp70: JDP network in their mitochondrial matrix. Here, we show that although highly similar in sequence, some of the plant JDPs are functionally different. Protein: protein interaction studies including yeast two-hybrid and Bimolecular Fluorescence Complementation revealed that while all the AtPam18s interacted with AtPam16s, the strengths of these promiscuous interactions are variable. Further, down-regulation of AtPAM16L affected seed germination, even in the presence of its seemingly identical paralog, AtPAM16. Knockdown of AtPAM16L caused reduction in mitochondrial number and deregulation of several mitochondrial genes, suggesting towards a specific role of AtPam16L in maintaining mitochondrial homeostasis, especially under stress conditions. Our findings suggest that variations in the spatio-temporal expression, accompanied by discriminate interactions between the JDPs, might be defining the functional specificity of the mtHsp70 co-chaperone machinery and providing resilience to mitochondrial import processes in plants, especially under stress conditions.


Effect of hydrazine sulfate on glucose-regulating enzymes in the normal and cancerous rat.
Glucokinase, hexokinase, fructose 1,6-bisphosphatase and phosphoenolpyruvate carboxykinase specific activities were monitored in liver cytosol from rats that had been made cancerous with 1,2-dimethylhydrazine and then treated with hydrazine sulfate. The presence of intestinal cancer, specifically, was confirmed by laparotomy and by histological analysis. Sustained changes in hexokinase and glucokinase specific activities were first evident during the latter weeks that the carcinogen was being administered. Upon subsequent treatment with hydrazine sulfate, glucokinase activity further decreased, and liver cytosolic phosphoenolpyruvate carboxykinase activity increased. Liver cytosolic hexokinase and fructose 1,6-bisphosphatase specific activities were not appreciably affected by the hydrazine sulfate treatment. These results indicate that hydrazine sulfate may influence carbohydrate metabolism at the level of selected liver enzymes not only with respect to gluconeogenesis, but also in terms of glucose uptake.


Ubiquitin Tunes Hedgehog in Matters of the Heart.
Oligogenic inheritance makes the etiology of developmental diseases challenging to determine. In this issue of Developmental Cell, Kong et al., 2020 identify members of a membrane-tethered ubiquitin complex that attenuates Hedgehog signaling strength and genetically interact to regulate digit number, body patterning, and cardiac development.


Impact of weather changes on hospital admissions for hypertension.
Blood pressure (BP) shows a seasonal variation with higher levels at lower temperatures. Many hypertensives, however, report on BP disturbances rather in association with acutely changing weather conditions than with absolute temperatures. To date, the impact of changing meteorological parameters on hypertensive episodes remains elusive. We performed a retrospective time series regression analysis on 203,703 patients in three hospitals in Germany between 2010 and 2018, of whom 7362 patients were admitted for hypertensive disease. Numbers of daily admissions for hypertension were associated with metereological data obtained from three nearby weather stations. Data comprised temperature (mean, maximal, minimal and range within 24 h), athmospheric pressure, and precipitation. Changes of these parameters were calculated over a two and three day period. There was an inverse correlation between maximal daily temperature and the number of admissions for hypertensive disease, which remained significant both after adjustment for seasonality and week day in a spline model and in a constrained distributed lag model. A decrease of maximal temperature by 5 °C was associated with a 3% increase of risk for admission for hypertension and vice versa. There were no significant effects of precipitation and athmospheric pressure on the number of admissions. With regard to all observed metereological parameters, neither the change within two, nor within three days was consistently associated with the number of daily admissions. High temperatures are associated with lower numbers of hypertensive episodes requiring hospital admission. In contrast to the subjective perception of many hypertensive patients, however, acutely changing weather conditions are not associated with a higher risk of hypertensive emergency.


Network meta-analysis of comparative efficacy of animal-assisted therapy vs. pet-robot therapy in the management of dementia.
This network meta-analysis aimed to compare and rank the efficacy of animal-assisted therapy (AAT) and pet-robotic therapy (PRT) in the management of dementia. Relevant studies were identified by searching PubMed, EMBASE, the Cochrane Library, SCOPUS, and Web of Science (WoS) until October 13, 2022. Traditional meta-analysis was first conducted based on the random-effects model, then random network meta-analysis was conducted to determine the relative efficacy and rank probability of AAT and PRT. Nineteen randomized controlled trials (RCTs) were included in this network meta-analysis. Network meta-analysis revealed that PRT marginally benefited agitation alleviation compared with control (standard mean difference [SMD]: -0.37, 95% confidence interval [95%CI]: -0.72 to -0.01) although both AAT and PRT did not improve cognitive function, reduce depression, and improve Quality of Life (QoL). The SUCRA probabilities indicated that PRT ranked better than AAT in agitation, cognitive function, and QoL, although there were no differences between the two therapies. The present network meta-analysis reveals that PRT may help alleviate agitated behaviors in people with dementia. However, future studies are warranted to establish evidence of the effectiveness of PRT and further evaluate the differences between different robot types in managing dementia.


Utility of ultrasound after a negative CT abdomen and pelvis in the emergency department.
The purpose of this study is to assess the utility of an abdominal and/or pelvic ultrasound (US) performed within 24 h after a negative CT of the abdomen and pelvis (CTAP) in the emergency department (ED). The secondary endpoint is to assess whether there is a significant increase in length of stay (LOS) in the ED due to immediate US reimaging. We reviewed the imaging reports of 335 patients over the course of 3 years in our ED who had an US within 24 h after a negative CTAP. We then assessed type of US and whether the US showed any acute findings. We also evaluated LOS in the ED. Out of 335 patients, there were only three US cases suspicious for acute surgical pathology (3/335 or 0.9%). On 30-day clinical follow-up, only one of the three cases was confirmed as cholecystitis on pathology. The most common non-surgical findings on US not initially reported on CTAP were ovarian cysts (29/83) and gallstones (9/83). Additionally, the LOS for patients who received both a CTAP and US was 119 min longer than patients who only received a CTAP. US abdomen and/or pelvis reimaging within 24 h following a negative CTAP is unlikely to change surgical management in the acute setting. US reimaging can still be useful in diagnosing non-surgical pathology, which could serve to explain the patient's pain. US reimaging after negative CTAP is associated with an average increase in the ED LOS.


Novel function of transglutaminase 2 in extracellular histone-induced acute lung injury.
Extracellular histones induce endothelial damage, resulting in lung haemorrhage; however, the underlying mechanism remains unclear. Factor XIII, as a Ca2+-dependent cross-linking enzyme in blood, mediates fibrin deposition. As another isozyme, transglutaminase 2 (TG2) has a catalytic activity distributing in most tissues. Herein, we investigated whether TG2 promotes fibrin deposition and mediates the adhesion of platelets to ECs in histone-induced acute lung injury (ALI). We evaluated the lung histology and the adhesion of platelets to endothelial cells (ECs) after injecting histones to wild-type (WT) C57BL/6J and TG2 knockout (TG2-/-) mice, and administered a TG2 inhibitor (NC9) to WT mice. Pulmonary haemorrhage was more severe in TG2-/- mice than that in WT mice. The area of fibrin deposition and the proportion of CD41+CD31+ cells were lower in TG2-/- mice than in WT mice. Pre-treatment of NC9 decreased the area of fibrin deposition and the proportion of CD41+CD31+ cells in WT mice. These results suggest that TG2 prevents from pulmonary haemorrhage in ALI by promoting the adhesion of platelets to ECs and the fibrin deposition.


Disseminated strongyloidiasis in a immunocompromised host.
Strongyloidiasis in an immunocompromised patient has the potential to be life threatening. We describe a boy who was on steroids for acute demyelinating myelitis and receiving antibiotics for E. coli UTI and meningitis. He developed anasarca, malabsorption, malnutrition and left ventricular failure. Duodenal biopsy revealed abundant rhabditiform larvae of Strongyloides stercoralis. The diagnosis went unsuspected and proved fatal. This emphasizes the need to have a high index of suspicion and early intervention for S. stercoralis in immunosuppressed persons who present with refractory gastrointestinal symptoms.


Sleep actigraphy in hypertensive patients with the 'non-dipper' blood pressure profile.
Several prospective studies have demonstrated a higher cardiovascular complication rate in patients with a non-dipping compared with a dipping blood pressure profile. However, the extent of blood pressure reduction during sleep can be highly variable in an individual patient, and a repeat ambulatory blood pressure study commonly shows a change in category. The reasons for this variability are not clear. In general, hypertensive patients with a non-dipper blood pressure profile have higher actigraphy-measured activity during time in bed than dipper hypertensive patients but no analysis of actigraphy-determined sleep parameters has been published. We therefore prospectively studied 52 hypertensive patients who were off antihypertensive drugs for at least 3 weeks and who underwent simultaneous ambulatory and wrist actigraphy monitoring. All patients were clinically free of any sleep-related disorder. The blood pressure profile was labelled dipper when the change in mean awake blood pressure to sleep blood pressure was 10% or higher and non-dipper if less than 10%. Overall activity levels were higher during the time in bed in the non-dipper group compared with the dipper group. An inverse relationship of daytime activity with age was seen in men (r = -0.54, P = 0.001) but not in women (r = -0.06, P = 0.79). Both groups of hypertensive patients had a similar total time in bed (458 +/- 92 min, in dippers and 433 +/- 106 min in non-dippers, P = 0.39). Sleep latency (time to onset of sleep after getting into bed) was a median of 7 min in dippers and 15 min in non-dippers (P = 0.10). In addition, dipper hypertensives spent more of the time in bed asleep than non-dippers (87% vs 76%, P = 0.004). Logistic regression analysis revealed that body mass index, kg/m(2) (OR, 1.3), and night-time activity (units/min) (OR, 1.1) were predictive of a non-dipping blood pressure profile. These data show a possible disturbance of sleep in non-dipper hypertensive patients.


Substance P as an excitatory transmitter of primary afferent neurons in guinea-pig sympathetic ganglia.
Electrophysiological and neurochemical experiments were carried out to examine a possible transmitter role substance P in the prevertebral ganglia of the guinea-pig. When potentials were recorded intracellularly from neurons of the isolated ganglia, stimulation of the pre- or postganglionic nerves elicited a non-cholinergic slow excitatory postsynaptic potential (EPSP). This synaptic potential was compared with the effects of substance P. Brief application of substance P caused a depolarization of the ganglion cells with a similar time course to that of the non-cholinergic slow EPSP. Changes in membrane resistance during the substance P-induced depolarization resembled those associated with the non-cholinergic slow EPSP. During the substance P-induced depolarization the non-cholinergic slow EPSP was markedly depressed. Attempts were made to determine the origin of the fibers eliciting the non-cholinergic slow EPSP. In the inferior mesenteric ganglia isolated together with preganglionic nerves that retained intact connections with spinal nerve roots, dorsal root stimulation evoked a non-cholinergic slow EPSP but not a cholinergic fast EPSP in the ganglion cells, whereas ventral root stimulation caused only cholinergic fast EPSPs. Following the prolonged treatment with capsaicin, the non-cholinergic slow EPSP was greatly depressed or abolished. Radioimmunoassay revealed that after ligation or section of pre- or postganglionic nerves an accumulation of substance P occurred in the proximal stumps of the interrupted nerves. Stimulation with high potassium medium evoked a release of immunoreactive substance P from the prevertebral ganglia and the release was calcium-dependent. The present findings suggests that axon collaterals of certain visceral primary efferents form synapses with principal cells in the prevertebral ganglia and release substance P as a transmitter for the non-cholinergic slow EPSP.


Differential effect of multiple kinesin motors on run length, force and microtubule binding rate.
The in vitro transport of cargo by motor proteins constitutes a model system to understand mechanisms of vesicle trafficking inside cells. Here we apply the classic bead assay with a short, stiff kinesin protein to test the effect of multiple motors on essential transport parameters: distance, force and microtubule binding rate. Measurements of unloaded run length show that the transition from single- to multiple-motor behavior can be characterized by the appearance of extended runs, in accordance with a recently proposed model that quantifies the probability of multiple-motor engagement. In this transition, application of mechanical load using optical tweezers allows us to register maximum force values above single kinesin levels (8 pN). Yet, averages of run length and maximum force undergo little change as the probability of multiple-motor participation increases. In contrast, the measured rate of bead binding to microtubules scales linearly with the average number of motors per bead. These observations suggest that multiple motors bound randomly to the same cargo mainly increase the probability of attachment of these cargoes to the cytoskeletal filament network.


Training mode-dependent changes in motor performance in neck pain.
To determine whether changes in motor performance after a course of exercise in patients with mechanical neck pain (MNP) were dependent on the primary behavioral demand of the exercise performed. Randomized controlled trial. University laboratory. Volunteers (N=60; 35 women, 25 men; mean age, 37.9y) with chronic MNP participated in the study. Exercise targeted to improve cervical motor performance including endurance training (ETr; n=20), coordination training (CTr; n=20), and active mobility training (n=20). Changes in the cervical motor performance domains of strength, endurance, coordination, and active mobility were evaluated immediately after the 10-week training program, and at a 26-week follow-up. Between-group comparisons revealed significantly greater gains in endurance (P<.02) by the ETr group, and significantly greater gains in coordination (P<.01) by the CTr group. All 3 groups had improvement in pain (P<.01) and disability (P<.01). Changes in motor performance in individuals with MNP in response to an exercise program were dependent on the specific mode of exercise performed, with minimal improvement in other domains of motor performance.


Attention-deficit hyperactivity disorder and communication disorders. Issues and clinical practices.
Attention-deficit hyperactivity disorder (ADHD) is reviewed from the perspective of speech-language pathology, and various characteristics of the communicative process that co-occur with ADHD are presented. Incorporating Barkley's "inhibition model" with a systems theory approach and a functionality component, implications for service delivery and intervention are discussed. Five specific types of interventions are presented to encourage collaboration.


The efficacy of telephone counseling for health promotion in people with multiple sclerosis: a randomized controlled trial.
To determine if motivational interviewing-based telephone counseling increases health promotion activities and improves other health outcomes in people with multiple sclerosis (MS). Randomized controlled trial with wait-list controls and single-blinded outcome assessments conducted at baseline and at 12 weeks. MS research and training center in the Pacific Northwest. Community-residing persons (N=130) with physician confirmed MS aged 18 or older who were able to walk unassisted at least 90 m (300 ft). A single in-person motivational interview followed by 5 scheduled telephone counseling sessions to facilitate improvement in 1 of 6 health promotion areas: exercise, fatigue management, communication and/or social support, anxiety and/or stress management, and reducing alcohol or other drug use. Health Promotion Lifestyle Profile II plus fatigue impact, subjective health, and objective measures of strength, fitness, and cognition. Intent-to-treat analyses of change scores were analyzed using nonparametric tests. Seventy persons were randomized to treatment and 60 to the control condition. The treatment group reported significantly greater improvement in health promotion activities, including physical activity, spiritual growth, and stress management as well as in fatigue impact and mental health compared with controls. In addition, the exerciser subgroup showed greater improvement than controls in self-selected walking speed. A less intensive, more accessible approach to health promotion based on telephone counseling and motivational interviewing shows promise and merits further study.


Avoiding and nonexpressing: coping styles of patients with paragangliomas.
Paraganglioma (PGL) patients and succinate dehydrogenase (SDH) gene mutation carriers at risk for PGLs have a decreased quality of life (QoL). QoL may be affected by the strategy an individual uses when dealing with a stressful situation, ie, specific coping styles. Understanding the various approaches to coping may allow the development of targeted interventions to improve patient QoL. The objective of the study was to assess coping styles in PGL patients and SDH mutation carriers. This was a cross-sectional study. The study was conducted at a tertiary referral center. Coping styles were assessed using the Utrecht Coping List. The results from the study cohort were compared with a control group and data derived from the literature. Potential differences in coping styles between the various SDH mutation carriers and PGL patients without an SDH mutation were explored. Of the 174 patients who responded, 122 were SDHD, 25 SDHB, and 2 SDHC mutation carriers. An additional 25 patients lacked an SDH mutation. They recruited 100 peers as controls. Compared with the general population, the study cohort was more avoidant of problems (P < .001) and reported less expression of emotion (P < .01). Compared with patients with other conditions, they sought more social support (P < .001). There were no significant differences in coping styles between the various categories of mutation carriers or PGL patients lacking a mutation. Coping styles of PGL patients and SDH mutation carriers differ from those of control and reference groups and include an avoidant coping style and a lack of emotional expression.


Different associations of estrogen receptor β isoforms, ERβ1 and ERβ2, expression levels with tumor size and survival in early- and late-onset breast cancer.
In breast cancer, little is known about the consequences of co-expression of ERα with the second estrogen receptor, ERβ, and its isoforms in light of their joint prognostic value. Previously reported correlations have been based mostly on independent ERα and ERβ expression levels in breast tumors. To address whether the expression ratio of ERα and ERβ and its isoforms may be a more important parameter than their absolute levels, we analyzed relative mRNA expression ratios of ERβ1 to ERβ2 and ERα in 74 clinical samples of invasive breast cancer including 39 early-onset and 35 late-onset breast cancers. Expression levels were correlated with clinical and histopathological parameters and disease-free interval. A specific correlation of ERβ1 expression levels with tumor size was detected in early-onset breast cancer patients and of ERβ2 levels with tumor size in late-onset patients. Expression of both ERβ isoforms inversely correlated with expression of the two estrogen regulated genes, progesterone receptor and pS2 in both groups. Higher levels of ERβ2 than ERβ1 isoform were associated with a better outcome in late-onset patients. Our results suggest that different isoforms of ERβ may be involved in suppression of tumor growth in young and elder patients and may have different prognostic values.


Bedaquiline inhibits the yeast and human mitochondrial ATP synthases.
Bedaquiline (BDQ, Sirturo) has been approved to treat multidrug resistant forms of Mycobacterium tuberculosis. Prior studies suggested that BDQ was a selective inhibitor of the ATP synthase from M. tuberculosis. However, Sirturo treatment leads to an increased risk of cardiac arrhythmias and death, raising the concern that this adverse effect results from inhibition at a secondary site. Here we show that BDQ is a potent inhibitor of the yeast and human mitochondrial ATP synthases. Single-particle cryo-EM reveals that the site of BDQ inhibition partially overlaps with that of the inhibitor oligomycin. Molecular dynamics simulations indicate that the binding mode of BDQ to this site is similar to that previously seen for a mycobacterial enzyme, explaining the observed lack of selectivity. We propose that derivatives of BDQ ought to be made to increase its specificity toward the mycobacterial enzyme and thereby reduce the side effects for patients that are treated with Sirturo.


Tuberculosis among drug users and homeless persons: impact of voluntary X-ray investigation on active case finding.
Illicit drug use and homelessness are major contributors to the incidence of tuberculosis (TB) among inhabitants of major cities. The primary objective of this study was to establish a sustainable low-threshold chest X-ray screening programme for pulmonary TB among illicit drug users and homeless persons and to integrate this into the existing public health programme for active case finding. A secondary objective was to estimate the coverage of the programme, assess other risk factors and determine TB rates and treatment outcome in these two groups. Illicit drug users and homeless persons were asked to voluntarily participate in an X-ray screening programme. The coverage of the intervention, total number and characteristics of cases and the follow-up of treatment were assessed. A total of 4,529 chest radiographs were made from 3,477 persons, of whom 66% were homeless and 34% were illicit drug users, between May 2002 and April 2007. Coverage for screening once every 2 years ranged between 18 and 26%. Thirty-nine TB cases (14 drug users, 25 homeless persons) were identified, representing 8.7% of the total case load of 448 notified cases of pulmonary TB in Frankfurt during this period. Among the drug users, human immunodeficiency virus coinfection (10/14) seemed to play a key role in the development of TB. The case-finding rate of 861/100,000 radiographs (1,122/100,000 persons) is as high as that in routine contact investigations (1,078/100,000). Among all individuals with TB, 76% completed treatment. A novel targeted TB screening approach with voluntary radiographic examination of illicit drug users and homeless persons can be integrated into the existing public TB prevention programme and provides a high case-finding rate.


Nucleotide sequence of the sacS locus of Bacillus subtilis reveals the presence of two regulatory genes.
The nucleotide sequence of 3 kb of Bacillus subtilis chromosomal DNA, including sacS, reveals that the regulatory locus for levansucrase synthesis consists of two genes, sacX and sacY. The sacX gene product is remarkably similar to sucrose-specific enzyme II of the B. subtilis phosphoenolpyruvate-dependent phosphotransferase system. The product of sacY is similar, both in amino acid sequence and most probably in its function, to BglG, an Escherichia coli transcriptional antitermination factor.


Analysis of the evolutionarily conserved repeat motifs in the genome of the highly endangered central Indian swamp deer Cervus duvauceli branderi.
We have analyzed the genome of central Indian swamp deer Cervus duvauceli branderi, an inhabitant of the Kanha National Park, a wildlife conservatory in Central India, with a view to provide a genetic basis for their extinction. Evolutionarily conserved repeat sequence motifs (GATA)3.75, TA(GATA)4, (GACA)3.75, (TGG)6 and a set of mouse beta-actin primers were used to uncover the sequence variation within and between related species by employing techniques of hybridization and AP-PCR amplification. The oligo probe carrying the GACA and TGG repeat motifs was found to be positive with Cervus genome, whereas (GATA)3.75, TA(GATA)4 and beta-actin probes did not cross-hybridize with the same. AP-PCR amplification with (GACA)3.75, unlike the (TGG)6 primer, generated distinct bands in the range of 0. 37-2.10kb amongst different genomes including Cervus. A comparative genome analysis of other species using the AP-PCR approach with (GACA)3.75 primer revealed the phylogenetic status of Cervus duvauceli branderi. From the analysis of a very limited number of Cervus DNA samples, we observed a high level of genetic homogeneity that may be a prime reason for the extinction of this species. This study has implications in the context of conservation of this endangered Cervus duvauceli branderi species.


Identification of sequence mutations in Phytophthora cactorum genome associated with mefenoxam resistance and development of a molecular assay for the mutant detection in strawberry (F. × ananassa).
Phytophthora crown rot (PhCR) caused by Phytophthora cactorum is one of the most damaging diseases of strawberry worldwide. Mefenoxam is one of the major fungicides currently used to manage PhCR. However, the emergence and spread of resistant isolates have made controlling the pathogen in the field problematic. In the present study, using whole genome sequencing analysis, mutations associated with mefenoxam-resistant isolates were identified in six different genomic regions of P. cactorum. The 95.54% reads from a sensitive isolate pool and 95.65% from a resistant isolate pool were mapped to the reference genome of P. cactorum P414. Four point mutations were in coding regions while the other two were in noncoding regions. The genes harboring mutations were functionally unknown. All mutations present in resistant isolates were confirmed by sanger sequencing of PCR products. For the rapid diagnostic assay, SNP-based high-resolution melting (HRM) markers were developed to differentiate mefenoxam-resistant P. cactorum from sensitive isolates. The HRM markers R3-1F/R3-1R and R2-1F/R2-1R were suitable to differentiate both sensitive and resistant profiles using clean and crude DNA extraction. None of the mutations associated with mefenoxam resistance found in this study were in the RNA polymerase subunit genes, the hypothesized target of this compound in oomycetes. Our findings may contribute to a better understanding of the mechanisms of resistance of mefenoxam in oomycetes since serves as a foundation to validate the candidate genes as well as contribute to the monitoring of P. cactorum populations for the sustainable use of this product.


Protective effect of Euterpe oleracea Mart (açaí) extract on programmed changes in the adult rat offspring caused by maternal protein restriction during pregnancy.
This study examined the effect of açaí (Euterpe oleracea Mart.) seed extract (ASE) on cardiovascular and renal alterations in adult offspring, whose mothers were fed a low-protein (LP) diet during pregnancy. Four groups of rats were fed: control diet (20% protein); ASE (200 mg/kg per day); and LP (6% protein); LP + ASE (6% protein + ASE) during pregnancy. After weaning, all male offspring were fed a control diet and sacrificed at 4 months old. We evaluated the blood pressure, vascular function, serum and urinary parameters, plasma and kidney oxidative damage, and antioxidant activity and renal structural changes. Hypertension and the reduced acetylcholine-induced vasodilation in the LP group were prevented by ASE. Serum levels of urea, creatinine and fractional excretion of sodium were increased in LP and reduced in LP + ASE. ASE improved nitrite levels and the superoxide dismutase and glutathione peroxidase activity in LP, with a corresponding decrease of malondialdehyde and protein carbonyl levels. Kidney volume and glomeruli number were reduced and glomerular volume was increased in LP. These renal alterations were prevented by ASE. Treatment of protein-restricted dams with ASE provides protection from later-life hypertension, oxidative stress, renal functional and structural changes, probably through a vasodilator and antioxidant activity.


The membrane-permeabilizing effect of avenacin A-1 involves the reorganization of bilayer cholesterol.
Avenacin A-1 is a member of a group of naturally occurring compounds called saponins. It is found in oat plants, where it protects against fungal pathogens. A combined electrical and optical chamber was used to determine the interaction of avenacin A-1 with Montal-Mueller planar lipid bilayers. This system allowed simultaneous measurement of the effect of avenacin A-1 on the fluorescence and lateral diffusion of a fluorescent lipid probe and permeability of the planar lipid bilayer. As expected, cholesterol was required for avenacin A-1-induced bilayer permeabilization. The planar lipid bilayers were also challenged with monodeglucosyl, bis-deglucosyl, and aglycone derivatives of avenacin A-1. The results show that the permeabilizing activity of the native avenacin A-1 was completely abolished after one, two, or all three sugar residues are hydrolyzed (monodeglucosyl, bis-deglucosyl, and aglycone derivatives, respectively). Fluorescence recovery after photobleaching (FRAP) measurements on cholesterol-containing planar lipid bilayers revealed that avenacin A-1 caused a small but significant reduction in the lateral diffusion of the phospholipid probe N-(7-nitrobenzoyl-2-oxa-1,3-diazol-4-yl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (NBD-PE). Similarly, with the sterol probe (22-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3beta-ol (NBD-Chol), avenacin A-1, but not its derivatives, caused a more pronounced reduction in the lateral diffusion than that observed with the phospholipid probe. The data indicate that an intact sugar moiety of avenacin A-1 is required to reorganize membrane cholesterol into pores.


Transgenic animal models to explore and modulate the blood brain and blood retinal barriers of the CNS.
The unique environment of the brain and retina is tightly regulated by blood-brain barrier and the blood-retinal barrier, respectively, to ensure proper neuronal function. Endothelial cells within these tissues possess distinct properties that allow for controlled passage of solutes and fluids. Pericytes, glia cells and neurons signal to endothelial cells (ECs) to form and maintain the barriers and control blood flow, helping to create the neurovascular unit. This barrier is lost in a wide range of diseases affecting the central nervous system (CNS) and retina such as brain tumors, stroke, dementia, and in the eye, diabetic retinopathy, retinal vein occlusions and age-related macular degeneration to name prominent examples. Recent studies directly link barrier changes to promotion of disease pathology and degradation of neuronal function. Understanding how these barriers form and how to restore these barriers in disease provides an important point for therapeutic intervention. This review aims to describe the fundamentals of the blood-tissue barriers of the CNS and how the use of transgenic animal models led to our current understanding of the molecular framework of these barriers. The review also highlights examples of targeting barrier properties to protect neuronal function in disease states.


Nucleotide sequence of the pnd gene in plasmid R483 and role of the pnd gene product in plasmolysis.
The pnd gene of R plasmid R483, like the srnB gene of the F plasmid, increases the degradation of stable RNA in Escherichia coli. The nucleotide sequence of the pnd locus was determined and compared with that of the srnB locus. The genes have open reading frames that are 54% homologous, and both have an upstream inverted repeat sequence. The pnd gene expression seems to decrease the osmotic barrier of the cytoplasmic membrane, since no plasmolytic vacuoles were formed in the cells carrying the gene when the cells were exposed to hypertonic sucrose solution. This result suggests that RNase I in the periplasm passes through the altered membrane to degrade stable RNA in the cytoplasm.


Gingival squamous cell carcinoma mimicking a non-neoplastic proliferative lesion in an older patient.
To report a case of gingival squamous cell carcinoma (SCC) in an elderly patient mimicking a non-neoplastic proliferative lesion. Oral SCC is a well-recognised malignancy of the oral cavity that may mimic benign reactive proliferative processes. An excisional biopsy was performed, and the diagnosis was gingival SCC. It is essential that both the clinician and pathologist to be aware of such a presentation to allow for proper diagnosis and treatment.


Structure and function of lineage-specific sequence insertions in the bacterial RNA polymerase beta' subunit.
The large beta and beta' subunits of the bacterial core RNA polymerase (RNAP) are highly conserved throughout evolution. Nevertheless, large sequence insertions in beta and beta' characterize specific evolutionary lineages of bacteria. The Thermus aquaticus RNAP beta' subunit contains a 283 residue insert between conserved regions A and B that is found in only four bacterial species. The Escherichia coli RNAP beta' subunit contains a 188 residue insert in the middle of conserved region G that is found in a wide range of bacterial species. Here, we present structural studies of these two beta' insertions. We show that the inserts comprise repeats of a previously characterized fold, the sandwich-barrel hybrid motif (as predicted from previous sequence analysis) and that the inserts serve significant roles in facilitating protein/protein and/or protein/nucleic acid interactions.


Author Correction: TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells.
In the original version of this Article, financial support was not fully acknowledged. The PDF and HTML versions of the Article have now been corrected to include the following: "This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001144), the UK Medical Research Council (FC001144), and the Wellcome Trust (FC001144)." https://doi.org/10.1038/s41467-018-05370-7 .


Medication safety improvements during care transitions in an Australian intensive care unit following implementation of an electronic medication management system.
For patients requiring admission to the Intensive Care Unit (ICU), transfers of care (TOC) during admission to and discharge from the ICU are particularly high-risk periods for medication errors. In the Australian setting, commonly general wards and the ICU do not share an integrated Electronic Medical ecord (EMR) and specifically an Electronic Medication Management System (EMMS) as part of the EMR. To evaluate the effect of a hospital wide integrated EMMS on medication error rates during ICU admission and at TOC. A 6-month historical control study was performed before and after implementation of the EMMS in the ICU of a tertiary hospital. Prescribing errors detected by pharmacists in the study period were divided into phase 1, (pre-EMMS, 6months), phase 2 (3 months post implementation after shakedown stage) and phase 3 (next 3 months of post implementation). They were categorized as prescribing error types under system or clinical intervention. Chi square statistics and interrupted time series analysis were used to determine if there was significant change in the proportion of patients who had an error at TOC during each phase. Logistics regression was used to determine the relationship between the dependent (error type) and the independent variable (study phase) for errors that occurred during TOC. Errors occurred during TOC in 42 %, 64 % and 19 % of patients in phase 1, 2 and 3 respectively. There was a significant decline in the proportion of patients with an error between phase 1 and 3 (p < 0.01). During a patient's ICU admission, at least one medication error occurred in 28.3 %, 62.6 % and 25.1 % in phase 1, 2 and 3 respectively. Besides procedural errors, the likelihood of an error occurring was greatest in phase 1, compared to phase 2 and 3 across system-related error categories. Medication errors during TOC reduced following implementation of the integrated ICU EMMS. EMMS safety features facilitated reduced system related prescribing errors as well as the severity of errors made.


Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates.
Although biochemical analysis of HIV-1 integrase enzyme suggested the use of integrase inhibitors (INIs) against HIV-1C, different viral subtypes may favor different mutational pathways potentially leading to varying levels of drug resistance. Thus, the aim of this study was to search for the occurrence and natural evolution of integrase polymorphisms and/or resistance mutations in HIV-1C Ethiopian clinical isolates prior to the introduction of INIs. Plasma samples from chronically infected drug naïve patients (N = 45), of whom the PR and RT sequence was determined previously, were used to generate population based sequences of HIV-1 integrase. HIV-1 subtype was determined using the REGA HIV-1 subtyping tool. Resistance mutations were interpreted according to the Stanford HIV drug resistance database ( http://hivdb.stanford.edu ) and the updated International Antiviral Society (IAS)-USA mutation lists. Moreover, rates of polymorphisms in the current isolates were compared with South African and global HIV-1C isolates. All subjects were infected with HIV-1C concordant to the protease (PR) and reverse transcriptase (RT) regions. Neither major resistance-associated IN mutations (T66I/A/K, E92Q/G, T97A, Y143HCR, S147G, Q148H/R/K, and N155H) nor silent mutations known to change the genetic barrier were observed. Moreover, the DDE-catalytic motif (D64G/D116G/E152 K) and signature HHCC zinc-binding motifs at codon 12, 16, 40 and 43 were found to be highly conserved. However, compared to other South African subtype C isolates, the rate of polymorphism was variable at various positions. Although the sample size is small, the findings suggest that this drug class could be effective in Ethiopia and other southern African countries where HIV-1C is predominantly circulating. The data will contribute to define the importance of integrase polymorphism and to improve resistance interpretation algorithms in HIV-1C isolates.


[Myoclonus and epilepsy: diagnosis and pathophysiology].
Myoclonus presents as a sudden brief involuntary jerk triggered by the central nervous system. Electromyographic studies enable determining whether the jerk is caused by a muscular contraction, i.e. positive myoclonus, or by an interruption of muscular activity, i.e. negative myoclonus. Many classifications have been proposed, reflecting our lack of understanding about myoclonus. Myoclonus is a symptom and should never be considered as a diagnosis. Clinical history and physical examination are the basis to diagnosis. Clinical neurophysiology testing can reveal a neuroanatomical localization and certain patterns have some etiological specificity. Etiological hypotheses can be put forward on the basis of clinical and neurophysiological data. The cortex is the most commonly identified source of myoclonus, but the subcortical area and spinal area can also be involved. Myoclonus is considered epileptic when it is combined with an epileptiform discharge on the EEG. The International Classification of Epileptic Syndromes should be applied in this situation. Myoclonic epilepsies are a collection of syndromes in which myoclonic seizures are a prominent feature. Myoclonus can occur as one among several seizure components, as the only manifestation of seizure, or as one of multiple seizure types within an epileptic syndrome. Neurophysiological studies are needed to investigate the pathophysiological mechanisms of the myoclonus. Electrophysiological studies report that myoclonic seizures are produced through a cortical generator via a polysynaptic mechanism acting on muscles. Apparently, the epileptiform discharges stimulate the motor cortex resulting in myoclonus jerk. Despite recent progress, advances are still needed to achieve a better understanding of the pathophysiological mechanisms involved in myoclonus. In myoclonic epileptic syndromes, more useful information can probably be obtained from studies grouping several patients with a same epileptic syndrome than from single case reports.


Trastuzumab, non-pegylated liposomal-encapsulated doxorubicin and paclitaxel in the neoadjuvant setting of HER-2 positive breast cancer.
Neoadjuvant treatment based on the combination of trastuzumab plus chemotherapy is the standard of care in patients with HER2-positive early or locally advanced breast cancer. The concurrent use of trastuzumab, anthracyclines and taxanes is frequently used in this setting despite the potential cardiotoxicity of both anthracyclines and trastuzumab. However, not much information is available about this chemotherapy scheme. We wanted to evaluate the efficacy and safety profile of the combination of trastuzumab, liposome-encapsulated doxorubicin and paclitaxel as neoadjuvant scheme. We also tried to establish predictive factors of pathologic complete response. The study was carried out in a tertiary University Hospital of Spain. This is a descriptive study of the clinical practice performed in our hospital. Efficacy was measured in terms of pathologic complete response, which was defined as the absence of invasive cancer cells in the breast and the axilla after neoadjuvant treatment. Thirty patients were included, the median age was 48. Seventeen (56.7 %) were hormonal receptor (HR) positive, 14 (46.6 %) had IIIa-b clinical stage and one of them had inflammatory breast cancer. 12 patients (40 %) achieved pCR. Patients with HR-negative BC achieved a higher pCR rate than those ones with HR-positive BC (61.5 % and 23.5 %, respectively; p value = 0.035). 21 patients (70 %) underwent breast conservative surgery. The treatment was in general well tolerated, most frequent grade 3-4 adverse events were neutropenia (20 %), asthenia and liver enzyme alteration (10 %) and febrile neutropenia (6.7 %). No patient developed heart failure, but one (3.3 %) presented a 10 % asymptomatic absolute reduction in left ventricular fraction ejection. The studied treatment for the neoadjuvant setting of HER2 positive breast cancer seems to be an effective therapeutic option. Despite the expected high rate of cardiotoxicity of this regimen, the study results shows that this treatment regimen appears to be safe. The combination of trastuzumab, non-pegylated liposomal-encapsulated doxorubicin and paclitaxel should be considered for the treatment of HER2-overexpressing breast cancer.


A comparative study of the effect of refining on physical and electrokinetic properties of various cellulosic fibres.
The aim of this work was to study the influence of refining on various pulp properties such as freeness, specific surface area, specific volume, surface charge, total charge and elastic modulus. The results indicated that specific surface area of the pulps increased with increased refining, and at the same freeness level the pine pulp exhibited higher surface charge, surface area, and specific volume than the eucalyptus pulps. Also, the eucalypt pulps were much easier to beat than the pine pulps. The total fibre charge, as determined by conductometric titrations, was not affected by refining. However, the surface charge, as determined by titrations with poly-DADMAC, increased with refining. Increasing the specific surface area by refining resulted in a higher fibre surface charge and better fibre-fibre bonding. The change of the fibre surface charge during refining could be monitored using the FTIR characteristic bands within 1700-1300cm(-1).


Ultrasound, cavitation bubbles and their interaction with cells.
This article reviews the basic physics of ultrasound generation, acoustic field, and both inertial and non-inertial acoustic cavitation in the context of localized gene and drug delivery as well as non-linear oscillation of an encapsulated microbubble and its associated microstreaming and radiation force generated by ultrasound. The ultrasound thermal and mechanical bioeffects and relevant safety issues for in vivo applications are also discussed.


Effect of Fe2+ ions on gypsum precipitation during bulk crystallization of reverse osmosis concentrates.
In reverse osmosis desalination, the concentrate is a saline solution that may become supersaturated. Heterogeneous nucleation of salts occurs at the membrane surface, resulting in the buildup of inorganic deposits on the membrane. The inorganic nucleation process, however, is complex in natural waters. Most studies focused primarily on single salt fouling of membranes, and related treatment for single solute systems. However, scale formation, especially gypsum, is affected by the presence of different salts and metals. In this wok, for the first time, we investigate the mixed precipitation of iron oxides and gypsum. The role of citric acid in the inhibition of precipitation was studied for different concentrations in both the absence and the presence of Fe2+. Conductivity and ion concentration measurements were used to estimate the formation time of gypsum. Scanning electron microscopy, X-Ray Diffraction (XDR) analysis, and Infra-Red spectroscopy analysis were used to provide structural information. Collected data showed that the presence of Fe2+ accelerates gypsum precipitation and shortens its induction time. Analytic results showed that gypsum crystals are greatly affected by the presence of Fe2+ ions, which generated needle shaped crystals. Citric acid can delay the induction time of gypsum precipitation. It also affects the morphology of gypsum crystals through adsorption mechanism. XDR diagrams revealed that the presence of citric acid (20 mg/L) can stabilize the bassanite phase (CaSO4·½H2O) for much longer periods. In the presence of Fe2+ ions, citric acid extends the induction time of calcium sulfate and minimizes the acceleration effect of Fe2+ ions. SEM images showed that the presence of ferrous ions during the chemical inhibition generates the β-hemihydrate form of calcium sulfate.


Muscular endurance training and motor unit firing patterns during fatigue.
With muscular training, the central nervous system may regulate motor unit firing rates to sustain force output and delay fatigue. The aims of this study were to investigate motor unit firing rates and patterns of the adductor pollicis (AdP) muscle in young, able-bodied adults throughout a sustained submaximal isometric fatiguing contraction and postactivation potentiation pre-post 4 weeks of muscular endurance training. Fifteen participants (training group: N = 10; control group: N = 5) performed maximal voluntary contractions (MVCs) and a sustained isometric 20 % MVC fatigue task pre-post training. Single-motor-unit potentials were recorded from the AdP during the fatigue task with intramuscular fine-wire electrodes. Twitch force potentiation was measured during single-pulse electrical stimulation of the ulnar nerve before and after MVCs. The training group endurance trained their AdP muscle at 20 % MVC for 4 weeks. Mean motor unit firing rates were calculated every 5 % of endurance time (ET). ET increased by 45.2 ± 8.7 % (p < 0.001) following muscular endurance training. Although ET increased, mean motor unit firing rates during the fatigue task did not change significantly with training. The general motor unit firing pattern consisted of an initial slowing followed by an increase in firing rate late in fatigue and remained consistent pre-post training. Potentiation did not change following training. These data suggest that the ability of the neuromuscular system to sustain motor unit firing rate may serve as a mechanism to augment the duration of submaximal muscle performance and delay muscular fatigue.


Analysis of biogenic amines in the brain of the American cockroach (Periplaneta americana) by gas chromatography-negative ion chemical ionisation mass spectrometry.
Biogenic amines in the brain of the American cockroach have been identified and quantified by an extraction-derivatisation procedure involving their reaction with ditrifluoromethylbenzoyl chloride (DTFMB) in the aqueous phase followed by extraction into an organic solvent, hydrolysis of phenolic esters and conversion of free hydroxyl groups to trimethylsilyl (TMS) ethers and subsequent analysis by gas chromatography-negative ion chemical ionisation mass spectrometry. The molecular ion of these DTFMB-TMS derivatives carried most of the ion current which made the method highly specific and gave a potential limit of detection below the picogram level. This method establishes unequivocally that the principal amines in cockroach brain are tyramine, p-octopamine, dopamine, 5-hydroxytryptamine and noradrenaline. In contrast to mammalian nervous tissue, the other positional isomers of octopamine, together with the isomeric synephrines, are absent.


Are You Threatening Me? Asian-American Panethnicity in the Trump Era.
This study explores the effect of Donald Trump's candidacy, and first year in office, on Asian-American linked fate. We argue that the use of anti-Asian and anti-immigrant messaging during the 2016 election, and the enactment of discriminatory policies once elected, increased feelings of panethnic linked fate among Asian Americans. To test our hypotheses, we assess Asian Americans' levels of linked fate before the 2016 election, immediately after the 2016 election, and one year after the 2016 election with several time-series surveys. We find that Asian-American linked fate is higher after the election and remains high one year later. Qualitative data collected through open-ended survey responses suggest that the increase in panethnic linked fate can be at least partially attributed to Trump's discriminatory rhetoric. The results have implications for Asian-American political behavior, particularly mobilization, by invoking collective action through panethnic linked fate.


Linking the geographical, the medical and the political in analysing health care delivery systems.
The models and methodologies used by medical geographers for analysing health care delivery systems are critically reviewed. As a result, it is argued that an intellectual cul-de-sac has been reached because of the lack of linkage in these models and methodologies that explicitly recognize the socio-cultural and political-economic influences in the environment, where the health care delivery system under study exists. Using the example of abortion services in Canada in general, and Ontario specifically for illustrative purposes, a general model for linking the geographical, the medical and the political aspects of health care delivery is proposed.


PH dependence of the Adair constants of human hemoglobin. Nonuniform contribution of successive oxygen bindings to the alkaline Bohr effect.
In order to solve the problem of an apparent discrepancy between the pH variance of oxygen equilibrium curve and the linear relation between the number of released Bohr protons and the degree of ligation, precise oxygen equilibrium curves of human hemoglobin were determined at a number of pH values from 6.5 to 8.8. From the equilibrium data individual steps (Adair constants), ki (i equals 1, 2, 3, 4), were obtained and the number of Bohr protons (deltaHi+) released on the ith stage of oxygenation was estimated. The pH dependence of k4 was very small, while the other ks strongly depended on pH over the pH range examined. As a consequence, the contribution of each step of oxygen binding to the alkaline Bohr effect nonuniform: deltaH4 was very small compared with deltaH1+, deltaH2+, and deltaH3+. In spite of this, calcuation has shown that the fractional number of released protons is essentially proportional to fractional oxygen saturation because of cooperative effects in hemoglobin. Thus, the present study indicates that the linear relationship between the fractional number of released protons and the degree of ligation, as obtained from titration experiments, is not necessarily incompatible with the pH variance of the shape of the oxygen equilibrium curve. The nonuniform pH depencence of the Adair constants implies that the two-state allosteric model of Monod, J., Wyman, J., and Changeus, J.P. (1965) J. Mol. Biol. 12, 88-118 is not adequate to describe the heterotropic effect caused by protons.


An updated approach to correcting impotence in elderly men.
A myth about transurethral prostatectomy is that it renders the patient unable to achieve an erection. There is no evidence that this is so, nor any evidence that prostatic hypertrophy itself causes impotence. It is imperative that the patient understand what the prosthesis will and will not do for him. All currently available devices provide a penile shaft rigid enough for intromission, but because all devices occupy only the corpora cavernosa, the erect penis will not be as long or as great in circumference as the patient's physiologic erections once were.


Antibiotic prophylaxis for transrectal prostate biopsy: a prospective randomized study of tosufloxacin versus levofloxacin.
To assess the efficacy of tosufloxacin as a prophylactic agent for transrectal biopsy of the prostate (TBP), we conducted a randomized prospective study comparing tosufloxacin versus levofloxacin. A randomized prospective study comparing tosufloxacin versus levofloxacin was performed. In group A, 124 patients received 300 mg tosufloxacin tosilate (including 204 mg tosufloxacin) twice daily for 2 days, with the initial dose being 2 h prior to biopsy. In group B, 119 patients received 200 mg levofloxacin in the same manner. Infectious complications were reported equally in six cases in each group (4.8% in group A and 5.0% in group B). Each group included five cases of acute prostatitis and one of cystitis. Six patients suffering from prostatitis required hospitalization, while those with symptomatic urinary tract infection were treated as outpatients. Tosufloxacin was as effective as levofloxacin when administered twice daily for 2 days as prophylaxis for TBP, which suggests that this regimen is useful for reducing the clinical and febrile infection rate following TBP.


A second look at efficacy criteria for onychomycosis: clinical and mycological cure.
Approval of topical onychomycosis drugs by regulatory agencies may be negatively impacted by an overly stringent definition of complete cure, which includes nail clearing plus mycological cure. In this position paper, we discuss interpretation of mycological outcome and clinical trial length. We reviewed data from seven international onychomycosis trials that enrolled subjects with positive KOH and dermatophyte-positive culture at screening followed by 48 weeks of treatment. Further, we examined 94 KOH-positive/culture-negative week 52 follow-up samples for morphological hyphal damage. From 3054 samples collected at week 52 follow-up visits, 2360 were culture-negative. However, a significant percentage (78.7%) of these subungual samples (n = 1857) remained KOH-positive. From the subset of follow-up samples examined for morphological changes, we identified hyphal breakage or distortion in 56 direct smears (60%), which may indicate nonviability. Reassessment of the definition of onychomycosis cure is critical. For clinical trials of topical agents, length of treatment should be re-examined. Further, in our experience, a high rate of subungual debris samples remained direct smear-positive while converting to negative culture. Evidence of morphological hyphal damage suggests that late-visit microscopic results may be false-positives. Therefore, the absence of clinical signs following an adequate washout period, coupled with a negative culture, with or without negative microscopy, should be considered the definition of onychomycosis cure.


Exploring the Effects of Near Infrared Light on Resting and Evoked Brain Activity in Humans Using Magnetic Resonance Imaging.
We explore whether near infrared light can change patterns of resting (task-negative) and/or evoked (task-positive; eg finger-tapping) brain activity in normal, young human subjects using fMRI (functional magnetic resonance imaging). To this end, we used a vielight transcranial device (810 nm) and compared the scans in subjects after active- and sham-light sessions. Our fMRI results showed that, while light had no effect on cerebral blood flow and global resting state brain activity (task-negative), there were clear differences between the active- and sham-light sessions in the patterns of evoked brain activity after finger-tapping (task-positive). The evoked brain regions included the putamen, primary somatosensory and parietal association cortex, and the overall effect of the light was to suppress or reduce their activity. We also found that while light had no effect on the resting functional connectivity of the putamen and primary somatosensory cortex and the rest of the brain, it did have an effect on the functional connectivity of parietal association cortex. In summary, our fMRI findings indicated that transcranially applied light did have a major impact on brain activity in normal subjects, but only when the brain region was itself functionally active, when undertaking a particular task. We suggest that these light-induced changes, particularly those in parietal association cortex, were associated with attention and novelty, and served to deactivate the so-called default mode network. Our results lay the template for our planned fMRI explorations into the effects of light in both Alzheimer's and Parkinson's disease patients.


The effects of 6-week low glycemic load diet based on low glycemic index foods in overweight/obese children--pilot study.
To evaluate the effectiveness of a 6-week low Glycemic Load (GL) diet intervention based on low Glycemic Index (GI) foods on body weight, body composition, metabolic risk factors and satiety in overweight/obese pre-pubertal children. Following a pediatric examination 8 healthy, average age 11 year old, Caucasian, pre-pubertal overweight/obese (BMI = 24, 7 +/- 3.8 kg/m(2)) children participated in the study. The Low GL diet intervention was based on the replacement of at least 50% of the high GI foods with Low-GI foods. The children with one of their parents participated in weekly nutrition consultations. Body composition, fasting glucose, insulin, cholesterol and triglyceride were measured before and after the study. Dietary changes were made based on weekly 4-day food-diaries. Despite no change in body weight, there was a significant (p < 0.05) reduction in % body fat (29.4 +/- 4.2 vs. 25.4 +/- 5.3), Waist-to-Hip Ratio (WHR 0.87 +/- 0.053 vs. 0.86 +/- 0.05), decrease in self-reported hunger level (4.37 +/- 0.74 vs. 1.75 +/- 0.75) and the total number of risk factors (28 vs. 15). There was a strong negative correlation between fasting glucose and insulin levels at baseline and in the magnitude of change after the study (r = -0.93 and r = -0.85 respectively; p < 0.01). A 6 week study demonstrated the practicality and effectiveness of this Low GL dietary approach. Despite of the unchanged body weight, Low GL diet consultations positively modified body fat content and cardiovascular risk factors in overweight or obese children.


Oral health of dental assistants and patients receiving maintenance--an investigation based on a district of Thuringia, Germany.
The aim of the study was to assess data for the oral health behaviour and oral health of dental assistants (DAs) and patients (PTs) who regularly received preventive dental care. One-hundred DAs (38.8 years) and 100 PTs (44 years) participated in the study conducted in the Unstrut-Hainich region of Thuringia, Germany. A questionnaire established oral hygiene and smoking habits. The dental examination included the caries index DMF-T, evaluation of the periodontal situation (PSI) as well as gingival inflammation [papilla bleeding index (PBI)]. Seventy-seven DAs and 46 PTs used dental floss regularly. Twenty-four DAs and 27 PTs were smokers. The mean DMF-T of DAs was 12.5, which was significantly lower than the DMF-T of PTs (17.0) (P < 0.001). The main reason for this difference was the number of missing teeth (DAs: 0.9, PTs: 4.8; P < 0.001). In both groups, several participants required periodontal treatment. Nevertheless, the number of DAs with PSI scores 3 or 4 was significantly lower (9%) than the corresponding number of PTs (63%) (P < 0.001). The PBI showed a significant difference between the groups (DAs = 0.1, PTs = 0.3; P < 0.01). Although the oral health of the participating DAs clearly exceeded the results found for PTs, it was concluded that DAs did not avail themselves of their job-related knowledge and skills and so failed to optimize their personal oral health behaviour.


Measuring Community Prevalence of Trichomonas vaginalis Infection to Guide Local Screening Practices: A Process Improvement Project.
The Centers for Disease Control and Prevention suggests screening for Trichomonas vaginalis infection might be considered in high-prevalence populations. High asymptomatic infection rates and poor sensitivity of clinical diagnosis make it difficult to estimate local prevalence. Testing of ThinPrep samples can provide an estimate of local Trichomonas vaginalis infection rates and guide screening practices.


Effects of hexoprenaline on the lecithin/sphingomyelin ratio and pressure-volume relationships in fetal rabbits.
A placebo-controlled, double-blind trial was carried out on 74 New Zealand White rabbit fetuses from 15 does to assess the effect of a fetal injection of hexoprenaline on surfactant release. After the uterus was exposed, half the fetuses received 0.1 ml (0.25 microgram) of hexoprenaline injected intraperitoneally through the intact uterine wall; the other half received an equivalent volume of placebo. After 3 hours, the abdomen was reopened, and the fetuses were surgically delivered and killed before breathing. The lecithin/sphingomyelin (L/S) ratios, obtained from lung washings, revealed a mean of 1.59:1 for the placebo group and 1.92:1 for the hexoprenaline group (p less than 0.001). Pressure/volume curves were generated from the lungs of 24 fetuses from 10 does, and the volume of air in the lungs for each pressure was analyzed in four ways: total volume, volume per gram of fetal body weight, volume per gram of dry lung weight, and as a percentage of total lung capacity at a pressure of 40 cm H2O. A first and second inflation-deflation curve was obtained for each experiment. The lungs from the hexoprenaline-treated group retained significantly more air than those from the placebo group. The most significant comparison was obtained when lung volume was expressed per gram of dry lung weight. The possibility of administering a beta 2-sympathomimetic drug to the mother in advanced preterm labor, specifically to release surfactant in the fetal lung, is suggested.


Changing analytical approaches in European epidemiology -- a short comment on a recent article.
Multilevel analysis is today considered a more appropriate way to monitor health care performance, as it allows a less biased estimation of uncertainty, and can also separate and quantify contextual (as opposed to individual) effects. Multilevel analysis should be applied as the standard methodology for hospital comparisons. A greater awareness of this question in future Journal articles may be in order.


Association between Florida's smoke-free policy and acute myocardial infarction by race: A time series analysis, 2000-2013.
Racial disparities in acute myocardial infarctions (AMIs) are increasing over time. Previous studies have shown that the implementation of smoke-free policies is associated with reduced AMI rates. The objective of this study was to determine the association between smoke-free policy and AMI hospitalization rates and smoking by race. Healthcare Cost and Utilization Project data from Florida from 2000-2013 were analyzed using interrupted time series analysis to determine the relationship between Florida's smoke-free restaurant and workplace laws and AMI among the total adult population (aged ≥18years), by age, race, and gender. Behavioral Risk Factor Surveillance System data from Florida from 2000 to 2010 were analyzed using logistic regression to determine the association between policy and the adult smoking prevalence. After implementation of the smoke-free policy, no statistically significant associations between AMI hospitalization rates or smoking prevalence were detected in the total population. In the subgroup analysis, the policy was associated with declines in AMI hospitalization rates among non-Hispanic white adults aged 18-44years (β=-0.001 per 10,000, p-value=0.0083). No other relationships with AMI hospitalization rates and smoking prevalence were found in the subgroup analysis. More comprehensive smoke-free and tobacco control policies are needed to further reduce AMI hospitalization rates, particularly among minority populations. Further research is needed to understand and address how the implementation of smoke-free policies affects secondhand smoke exposure among racial and ethnic minorities.


Multimorbidity: prevalence, effect on quality of life and daily functioning, and variation of this effect when one condition is a rheumatic disease.
To examine the prevalence and effect of multimorbidity on health-related quality of life (HRQoL) and daily functioning in the general population, and to analyze the influence on HRQoL and daily functioning of multimorbidity including a rheumatic disease. A national health survey was conducted on 2192 randomly selected adults in Spain. Multimorbidity was defined as the co-occurrence of at least 2 chronic diseases, as defined by self-report. All subjects completed the 12-item short form (SF-12) health survey and the Health Assessment Questionnaire (HAQ). Estimates and 95% confidence intervals (CI) of the prevalence of multimorbidity were obtained. The effect on HAQ and SF-12 scores is presented as beta-coefficients obtained from multiple linear regressions. The estimated prevalence of multimorbidity was 30% (95% CI 25 to 34), and the prevalence of multimorbidity including a rheumatic disease was 17% (95% CI 13 to 20). Multimorbidity was associated with impaired daily functioning [HAQ beta = 0.07 (95% CI 0.02 to 0.11)], and lower HRQoL [SF-12(physical component) beta = -4.2 (95% CI -5.2 to -3.22); SF-12(mental dimension) beta = -3.3 (95% CI -4.5 to -2.2)]. Subjects with multimorbidity including a rheumatic disease reported worse scores than those without a rheumatic disease: HAQ beta 0.13 (95% CI 0.07 to 0.18) versus -0.03 (95% CI -0.08 to 0.02), and SF-12(physical component) beta -6.5 (95% CI -5.2 to -3.2) versus 0.5 (95% CI -0.7 to 1.7). Multimorbidity is frequent in the general population and can considerably impair daily functioning and HRQoL. Having a rheumatic disease worsens these outcomes.


A self-powered UV photodetector based on TiO2 nanorod arrays.
Large-area vertical rutile TiO2 nanorod arrays (TNAs) were grown on F/SnO2 conductive glass using a hydrothermal method at low temperature. A self-powered ultraviolet (UV) photodetector based on TiO2 nanorod/water solid-liquid heterojunction is designed and fabricated. These nanorods offer an enlarged TiO2/water contact area and a direct pathway for electron transport simultaneously. By connecting this UV photodetector to an ammeter, the intensity of UV light can be quantified using the output short-circuit photocurrent without a power source. A photosensitivity of 0.025 A/W and a quick response time were observed. At the same time, a high photosensitivity in a wide range of wavelength was also demonstrated. This TNA/water UV detector can be a particularly suitable candidate for practical applications for its high photosensitivity, fast response, excellent spectral selectivity, uncomplicated low-cost fabrication process, and environment-friendly feature.


Localization of avian LHRH-immunoreactive neurons in the hypothalamus of the domestic fowl, Gallus domesticus, and the Japanese quail, Coturnix coturnix.
The localization of LHRH-containing perikarya and nerve fibers in the hypothalami of the domestic fowl and Japanese quail was investigated by means of the specific immunoperoxidase ABC method, using antisera against chicken LHRH-I ([Gln8]-LHRH), chicken GnRH-II ([His5-Trp7-Tyr8]-LHRH[2-10]) and mammalian LHRH ([Arg8]-LHRH). Chicken LHRH-I-immunoreactive perikarya were sparsely scattered in the nucleus preopticus periventricularis (POP), nucleus filiformis (FIL) and nucleus septalis medialis (SM), and in bilateral bands extending from these nuclei into the septal area in both species. A few reactive perikarya were also observed in the nucleus accumbens (Ac) and lobus parolfactorius (LPO). Numerous cLHRH-I-immunoreactive fibers were widely scattered in the preoptic, septal and tuberal areas, and were densely concentrated in the external layer of the median eminence and in organum vasculosum of the lamina terminalis (OVLT) in both species. Anti-mammalian LHRH serum cross-reacted weakly with perikarya and fibers immunoreactive to anti-cLHRH-I serum in normal chicken and quail. Anti-cGnRH-II[2-10] serum immunoreacted with magnocellular neurons distributed in the rostral end of the mesencephalon along the midline close to the nervus oculomotorius (N III). These perikarya were apparently different from cLHRH-I immunoreactive neurons. No immunoreactive cells and fibers against anti-cGnRH-II[2-10] were observed in the hypothalamus and median eminence of the chicken or quail. Anti-cGnRH-II[2-10] bound specifically with cGnRH-II.(ABSTRACT TRUNCATED AT 250 WORDS)


External carotid endarterectomy: indications, technique, and late results.
In the past 14 years, 22 patients (25 operated sides), with occlusion of the internal carotid artery (ICA), underwent ipsilateral external carotid artery (ECA) endarterectomy at our institution. Operative indications were amaurosis fugax in 13 sides and nonlateralizing transient ischemic attacks in the remaining 12. There were no operative deaths. One patient suffered a minor stroke after operation. Follow-up ranged from 6 to 110 months (median 36 months). In 16 cases, simple endarterectomy with or without vein patch closure was performed (type I). In two cases the ostium of the ICA was occluded with interrupted sutures after endarterectomy (type II). In the remaining seven cases the ICA was transposed as a patch over the endarterectomized ECA after endarterectomy (type III). All but six patients (six sides) underwent duplex scanning or angiography during follow-up. Four of nine patients with previous nonlateralizing symptoms had persistent symptoms after operation, whereas none of those with previous amaurosis fugax did. Recurrent occlusive disease was more common in type I reconstructions (p less than 0.05). Proper ECA reconstruction results in long-term patency. In the patient with ipsilateral ICA occlusion, transposition of the ICA as a patch over the endarterectomized ECA offers a valid hemodynamic solution. Objective parameters are needed to identify patients with nonlateralizing symptoms who will benefit from operation.


A double-blind, randomised, placebo-controlled, dose-finding trial of the novel tuberculosis vaccine AERAS-402, an adenovirus-vectored fusion protein, in healthy, BCG-vaccinated infants.
Several novel tuberculosis vaccines are currently in clinical trials, including AERAS-402, an adenovector encoding a fusion protein of Mycobacterium tuberculosis antigens 85A, 85B, and TB10.4. A multicentred trial of AERAS-402 safety and immunogenicity in healthy infants was conducted in three countries in sub-Saharan Africa, using an adaptive design. In a double-blind, randomised, placebo-controlled, dose-finding trial, we enrolled BCG-vaccinated, HIV-uninfected infants aged 16-26 weeks. Infants in the safety/dose-finding phase received two doses of AERAS-402 across three dose levels, or placebo, intramuscularly on days 0 and 28. Infants in the expanded safety phase received three doses of the highest dose level, with the 3rd dose at day 280. Follow up for safety and immunogenicity was for up to two years. We enrolled 206 infants (52 placebo and 154 AERAS-402 recipients) into the dose-finding phase and 281 (141 placebo and 140 AERAS-402 recipients) into the expanded safety phase. Safety data were acceptable across all dose levels. No vaccine-related deaths were recorded. A single serious adverse event of tachypnoea was deemed related to study vaccine. Antibodies directed largely against Ag85A and Ag85B were detected. Low magnitude CD4+ and CD8+ polyfunctional T cell responses were observed at all dose levels. The addition of a third dose of AERAS-402 at the highest dose level did not increase frequency or magnitude of antibody or CD8+ T cell responses. AERAS-402 has an acceptable safety profile in infants and was well tolerated at all dose levels. Response rate was lower than previously seen in BCG vaccinated adults, and frequency and magnitude of antigen-specific T cells were not increased by a third dose of vaccine.


Amino acid sequence of chicken gizzard smooth muscle SM22 alpha.
The complete amino acid sequence of SM22 alpha, a novel and abundant 22-kDa protein from chicken gizzard smooth muscle, was determined by a combination of automated and manual Edman degradation methods on fragments produced by suitable chemical and proteolytic cleavages. The protein consists of a single polypeptide chain of 197 residues, has a Mr of 21, 978, and a net charge of +4.5 at neutral pH. The pattern of alternating hydrophilic and hydrophobic regions throughout the length of SM23 alpha is typical of a globular protein. The overall secondary structural analysis, using several algorithms based on the sequence, predicts approximately 31% alpha-helix, 24% beta-sheet, 18% beta-turn, and 27% random coil. A search against the National Biomedical Research Foundation Protein Sequence Databank (Washington) and GenBank (Los Alamos) failed to demonstrate significant similarity with any other protein of known sequence.