Black Nurse, White Milk: Breastfeeding, Slavery, and Abolition in 19th-Century Brazil.
Brazil imported more enslaved Africans than any other slave-owning society in the Americas, and it was the last country in the western hemisphere to abolish the institution. Whereas many enslaved persons toiled on plantations and in mines, urban slavery was also prominent, with enslaved men carrying coffee through the streets and enslaved women washing clothes. One gendered aspect of urban slavery in 19th-century Brazil included slave owners renting out enslaved women as wet nurses to breastfeed the children of elite families. This article reviews medical dissertations, debates, and journal articles, as well as advertisements for wet nurses, showing that physicians believed that enslaved women's milk was both nutritionally and morally inferior to white women's milk. In the latter half of the 19th century, physicians viewed abolition as the only answer to what they deemed the increasingly "dangerous" practice of enslaved wet nursing, which they believed was the root cause of high infant mortality rates across races and classes. Readers should consider the ethical dilemmas of the practice of enslaved wet nursing, which often resulted in the violent separation of mother and child.


Patterns of spread and persistence of foot-and-mouth disease types A, O and Asia-1 in Turkey: a meta-population approach.
Despite significant control efforts, foot-and-mouth disease (FMD) persists in Turkey, and new strains of serotypes A, O and Asia-1 are periodically reported to enter the country from the east. The status of FMD in Turkey is important regionally because the country forms a natural bridge between Asia where the disease is endemic, and Europe which has disease-free status. This study analysed spatial and temporal patterns of FMD occurrence in Turkey to explore factors associated with the disease's persistence and spread. Annual records of FMD distribution in Turkish provinces throughout 1990-2002, grouped by serotype (O, A and Asia 1), were analysed using geostatistical techniques to explore their spatial and temporal patterns. A meta-population model was used to test how disease status, expressed in terms of presence/absence, extinction, and colonization, and measured at the province level throughout the periods 1990-1996 and 1997 2002, could be predicted using province-level data on: ruminant livestock numbers; meat production-demand discrepancy (as a surrogate measure of animal and animal products marketing, i.e. long-distance contagion through the traffic of mainly live animals to urban centres); and the disease prevalence distribution as recorded for the previous year. A drastic overall reduction in FMD occurrence was observed from the period 1990-1996 to 1997-2002 when the disease was shown to retract into persistence islands. FMD occurrence was associated with host abundance, short distance contagion from adjacent provinces, and meat production-demand discrepancies. With FMD retracting into identified provinces, a shift in predictors of FMD occurrence was observed with a lower contribution of short-distance contagion, and a relatively higher association with meat production-demand discrepancies leading to live animal transport over long distances, and hence presenting opportunities for identifying critical-control points. The pattern of persistence differed according to serotype groups and is discussed in relation to their differential affinity to cattle and small ruminant hosts.


Protein-tyrosine phosphatases and cancer.
Tyrosine phosphorylation is an important signalling mechanism in eukaryotic cells. In cancer, oncogenic activation of tyrosine kinases is a common feature, and novel anticancer drugs have been introduced that target these enzymes. Tyrosine phosphorylation is also controlled by protein-tyrosine phosphatases (PTPs). Recent evidence has shown that PTPs can function as tumour suppressors. In addition, some PTPs, including SHP2, positively regulate the signalling of growth-factor receptors, and can be oncogenic. An improved understanding of how these enzymes function and how they are regulated might aid the development of new anticancer agents.


Flavour formation by lactic acid bacteria and biochemical flavour profiling of cheese products.
Flavour development in dairy fermentations, most notably cheeses, results from a series of (bio)chemical processes in which the starter cultures provide the enzymes. Particularly the enzymatic degradation of proteins (caseins) leads to the formation of key-flavour components, which contribute to the sensory perception of dairy products. More specifically, caseins are degraded into peptides and amino acids and the latter are major precursors for volatile aroma compounds. In particular, the conversion of methionine, the aromatic and the branched-chain amino acids are crucial. A lot of research has focused on the degradation of caseins into peptides and free amino acids, and more recently, enzymes involved in the conversion of amino acids were identified. Most data are generated on Lactococcus lactis, which is the predominant organism in starter cultures used for cheese-making, but also Lactobacillus, Streptococcus, Propionibacterium and species used for surface ripening of cheeses are characterised in their flavour-forming capacity. In this paper, various enzymes and pathways involved in flavour formation will be highlighted and the impact of these findings for the development of industrial starter cultures will be discussed.


Infection with Streptococcus agalactiae in a London hospital.
Streptococcus agalactiae is presently the commonest beta-haemolytic streptococcus isolated from clinical material in this hospital. Between October 1974 and March 1975, 81 patients with such infections were seen. Seventeen had urinary tract infections, six had septicaemia, and one neonate had meningitis. Three of those with septicaemia were neonates and two died. The organism was also found to be a cause of pyogenic skin conditions in five patients. Isolates from throat swabs in 12 patients, from sputum in four, and from the female genital tract in 18 were considered part of the normal flora. Human strains of Str. agalactiae were found to be biochemically different from animal strains.


Comparison of a neurothesiometer and vibration in measuring vibration perception thresholds and relationship to nerve conduction studies.
To compare vibration perception thresholds (VPTs) obtained with two different instruments, a neurothesiometer and a vibratron, and to characterize variability of repeat measures and correlation with sural nerve conduction parameters. A total of 152 patients with diabetic peripheral neuropathy received electrodiagnostic evaluation and quantitative VPT testing with the Vibratron II and the Horwell Neurothesiometer. Of the patients, 42 returned for repeat nerve conduction studies and VPT testing with both types of equipment on three separate occasions. The variability of repeat testing for the vibratron was 34 and 31% in the right and left first toes, respectively. Variability for neurothesiometer was 8 and 6% for the right and left toes. This variability compares with that of sural nerve conduction velocity of 2% and that of sural nerve amplitude of 8% in this series of patients. We conclude that VPT determined with the neurothesiometer is less variable than with the vibratron and more reflective of peripheral nerve function. Our results indicate that the neurothesiometer can be used reliably in clinical research trials.


In vivo measurements of electrical conductivity of porcine organs at low frequency: new method of measurement.
Calculations of the induced currents created in the human body by external electromagnetic fields would be more accurate provided that more realistic experimental values of the electrical properties of the body were available. The purpose of this work is to experimentally obtain values for the conductivity of living organs in conditions close to the real situation. Two-electrode in vivo measurements of the bioimpedance of some porcine organs have been performed. From these measurements and taking into account geometrical considerations, the electrical conductivity for the kidney, liver, heart, and spinal cord has been obtained and were found to be higher than the values reported in the literature. Furthermore, a new experimental procedure is proposed where the conductivity is determined from the values of the electrical potential and currents that are induced by an external electromagnetic field created by a coil placed close to the organ under study.


Intratesticular islet allografts in the spontaneously diabetic BB/W rat.
Thirty-three male BB/W rats with diabetes of 11-145 days duration were divided into 3 groups: six received abdominal, intratesticular islet allografts and no immunosuppression posttransplantation; 15 were similarly grafted and in addition were given four injections of ALS regularly at 10-day intervals for 30 days after transplantation; and 12 rats received scrotal, intratesticular islet allografts and four injections of ALS. in the absence of immunosuppression all six of the rats with abdominal, intratesticular islet allografts became normoglycemic within 2 days after transplantation but in none did graft survival exceed 17 days; a marked prolongation of graft survival of greater than 65-441 days occurred in 13 of the 15 animals with identical intratesticular allografts; sustained immunosuppression was not needed for prolonged islet allograft survival in rats with cryptorchid islet allografts; and (4) only one of the 12 rats with scrotal, intratesticular allografts became normoglycemic whereas 11 remained severely glycosuric. However, on surgical translocation of the grafted testes from the scrotum into the abdominal cavity, the rats promptly became normoglycemic in the absence of any additional therapy.


Radiofrequency Lesions through Deep Brain Stimulation Electrodes in Movement Disorders: Case Report and Review of the Literature.
Although there are few reports of radiofrequency lesions performed through deep brain stimulation (DBS) electrodes in patients with movement disorders, experience with this method is scarce. We present 2 patients who had been previously treated with DBS of subthalamic nuclei (STN) and the ventral intermediate (VIM) nucleus of the thalamus for Parkinson's disease and essential tremor, respectively, and underwent a radiofrequency lesion through their DBS electrodes after developing a hardware infection. The authors conduct a review of the literature regarding this method. Both patients had a good clinical outcome after 20 and 8 months, respectively, as assessed by a reduction in Fahn-Tolosa-Marin Scale and Unified Parkinson's Disease Rating Scale scores. The second patient underwent a second DBS system implantation surgery after his radiofrequency treatment to optimize his management, achieving optimal clinical control with lower current and drug requirements than before the radiofrequency intervention. No adverse effects were observed. Radiofrequency lesions through DBS electrodes allow the creation of small and localized lesions. Its effectiveness and low-risk profile, in addition to its low cost, make this procedure suitable and a possible alternative in the therapeutic repertoire for the surgical treatment of movement disorders.


The effect of the Accreditation Council for Graduate Medical Education Duty Hours Policy on plastic surgery resident education and patient care: an outcomes study.
The Accreditation Council for Graduate Medical Education (ACGME) Work-Hours Duty Policy became effective on July 1, 2003, mandating the reduction of resident duty work hours. The Baylor College of Medicine Multi-Institutional Integrated Plastic Surgery Program instituted a resident duty work-hours policy on July 1, 2002 (1 year ahead of the national mandate). Outcomes data are needed to facilitate continuous improvements in plastic surgical residency training while maintaining high-quality patient care. To assess the effect of this policy intervention on plastic surgery resident education as measured through the six core competencies and patient/resident safety, the investigators surveyed all categorical plastic surgery residents 6 months after implementation of the policy. This work represents the first empiric study investigating the effect of duty hours reduction on plastic surgery training and education. The categorical plastic surgery residents at the Baylor College of Medicine Multi-Institutional Integrated Plastic Surgery Program completed a 68-item survey on a five-point Likert scale (1 = strongly disagree to 5 = strongly agree). Residents were asked to rate multiple parameters based on the ACGME six core competencies, including statements on patient care and clinical/operative duties, resident education, resident quality of life, and resident perceptions on this policy. All surveys were completed anonymously. The sample size was n = 12 (program year 3 through program year 6), with a 100 percent response rate. Univariate and bivariate statistical analysis was conducted with SPSS version 10.0 statistical software. Specifically, interquartile deviations were used to find consensus among resident responses to each statement. Descriptive statistics indicated higher percentages of agreement on a majority of statements in three categories, including patient care and clinical/operative duties, academic duties, and resident quality of life. Using interquartile deviation, the highest levels of consensus among the residents were found in positive statements addressing resident alertness (both in and out of the operative environment), time to read/prepare for cases/conferences, efficacy of the didactic curriculum, and overall satisfaction with this policy for surgery resident education. Residents also felt that their patients favored this work hours policy. In addition, there was high consensus that this policy improved overall patient care. The majority of residents identified a negative effect of this policy through an increase in cross-coverage responsibilities, however, and half of the residents perceived that faculty negatively viewed their unavailability postcall. In addition, no consensus among the residents was achieved regarding perceptions on overall weekly operative experience. Plastic surgery residents perceived that the reduction of resident work hours through adherence to the ACGME guidelines has beneficial effects on patient care and clinical/operative duties, academic duties, and resident quality of life. Residents felt, however, that these benefits may increase cross-coverage workloads. Furthermore, residents were concerned about faculty perception of their changes in postcall duties. In contrast to previously published findings in the general surgery literature, the current results indicate that residents do not believe that this policy negatively affects continuity of patient care. In fact, the current findings suggest that adherence to this policy improves patient care on multiple levels. The effect on the operative experience remains to be elucidated. Further large-scale and longitudinal research design and analysis is warranted to better assess the results of the ACGME resident duty work-hours policy in plastic surgery resident education.


Limbic neurochemical changes in patients with functional motor symptoms.
To assess by magnetic resonance spectroscopy (MRS) the N-acetylaspartate, myo-inositol, choline, sum of glutamate and glutamine (Glx), and creatine (Cr) content in the anterior cingulate cortex (ACC)/medial prefrontal cortex (mPFC) and in the occipital cortex (OCC) (control region) in patients with functional motor symptoms (FMS) and healthy controls, and to determine whether neurochemical limbic changes as estimated by MRS correlate with FMS-related motor symptom severity, alexithymia, anxiety, depression, and quality of life. This case-control study enrolled 10 patients with FMS and 10 healthy controls. Participants underwent MRS and were tested with the Mini-Mental State Examination, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, 20-Item Toronto Alexithymia Scale, and EuroQol 5D. In patients with FMS, MRS showed increased Glx/Cr in the ACC/mPFC but normal content in the control OCC. All the other metabolites tested were normal in both regions. The increased Glx/Cr content in the ACC/mPFC correlated with alexithymia, anxiety, and severity of symptoms. The abnormal limbic Glx increase could have a crucial pathophysiologic role in FMS, possibly by altering limbic-motor interactions, ultimately leading to abnormal movements.


The role of automated feedback in training and retaining biological recorders for citizen science.
The rapid rise of citizen science, with lay people forming often extensive biodiversity sensor networks, is seen as a solution to the mismatch between data demand and supply while simultaneously engaging citizens with environmental topics. However, citizen science recording schemes require careful consideration of how to motivate, train, and retain volunteers. We evaluated a novel computing science framework that allowed for the automated generation of feedback to citizen scientists using natural language generation (NLG) technology. We worked with a photo-based citizen science program in which users also volunteer species identification aided by an online key. Feedback is provided after photo (and identification) submission and is aimed to improve volunteer species identification skills and to enhance volunteer experience and retention. To assess the utility of NLG feedback, we conducted two experiments with novices to assess short-term (single session) and longer-term (5 sessions in 2 months) learning, respectively. Participants identified a specimen in a series of photos. One group received only the correct answer after each identification, and the other group received the correct answer and NLG feedback explaining reasons for misidentification and highlighting key features that facilitate correct identification. We then developed an identification training tool with NLG feedback as part of the citizen science program BeeWatch and analyzed learning by users. Finally, we implemented NLG feedback in the live program and evaluated this by randomly allocating all BeeWatch users to treatment groups that received different types of feedback upon identification submission. After 6 months separate surveys were sent out to assess whether views on the citizen science program and its feedback differed among the groups. Identification accuracy and retention of novices were higher for those who received automated feedback than for those who received only confirmation of the correct identification without explanation. The value of NLG feedback in the live program, captured through questionnaires and evaluation of the online photo-based training tool, likewise showed that the automated generation of informative feedback fostered learning and volunteer engagement and thus paves the way for productive and long-lived citizen science projects.


Empirically supported treatments in pediatric psychology: nocturnal enuresis.
To review the medical and psychological literature concerning enuresis treatments in light of the Chambless criteria for empirically supported treatment. A systematic search of the medical and psychological literature was performed using Medline and Psychlit. Several review studies and numerous well-controlled experiments have clearly documented the importance of the basic urine alarm alone as a necessary component in the treatment of enuresis or combined with the "Dry-Bed Training" intervention, establishing them as "effective treatments." Other multicomponent behavioral interventions that also include the urine alarm such as "Full Spectrum Home Training" have further improved the outcome for bed-wetters, but are classified as "probably efficacious" at this time because independent researchers have not replicated them. Less rigorously examined approaches that focus on improving compliance with treatment or include a "cognitive" focus (i.e., hypnosis) warrant further study. We recommend a "biobehavioral" perspective in the assessment and treatment of bed-wetting and suggest that combining the urine alarm with desmopressin offers the most promise and could well push the already high success rates of conditioning approaches closer to 100%. Much important work is yet to be completed that elucidates the mechanism of action for the success of the urine alarm and in educating society about its effectiveness so that its availability is improved.


Spatial and temporal attention modulate the early stages of face processing: behavioural evidence from a reaching paradigm.
A presently unresolved question within the face perception literature is whether attending to the location of a face modulates face processing (i.e. spatial attention). Opinions on this matter diverge along methodological lines - where neuroimaging studies have observed that the allocation of spatial attention serves to enhance the neural response to a face, findings from behavioural paradigms suggest face processing is carried out independently of spatial attention. In the present study, we reconcile this divide by using a continuous behavioural response measure that indexes face processing at a temporal resolution not available in discrete behavioural measures (e.g. button press). Using reaching trajectories as our response measure, we observed that although participants were able to process faces both when attended and unattended (as others have found), face processing was not impervious to attentional modulation. Attending to the face conferred clear benefits on sex-classification processes at less than 350ms of stimulus processing time. These findings constitute the first reliable demonstration of the modulatory effects of both spatial and temporal attention on face processing within a behavioural paradigm.


Changes in fatty acid composition of the single platelet phospholipids induced by pantethine treatment.
In a single-blind cross-over study the effect of oral treatment with pantethine on plasma and platelet lipid composition was evaluated in 20 patients with dyslipidaemia (7 IIa, 7 IIb and 6 Iv type). In plasma significant decreases of total cholesterol and triglycerides with increase of high density lipoprotein-cholesterol were observed. In platelets pantethine treatment significantly reduced phospholipid and cholesterol content. In addition gas-chromatographic analysis showed a reduction of saturated and monounsaturated and a relative increase of polyunsaturated fatty acid content of platelet phospholipids. A selective relative increase was observed of some n-3 polyunsaturated fatty acids like eicosapentaenoic and docosahexaenoic acid whereas arachidonic acid decreased. The present study indicates a favourable influence of pantethine not only on plasma but also on platelet lipids which could be of value in delaying the development of atherosclerosis in dyslipidaemic patients.


Disease burden of herpes zoster in Sweden--predominance in the elderly and in women - a register based study.
The herpes zoster burden of disease in Sweden is not well investigated. There is no Swedish immunization program to prevent varicella zoster virus infections. A vaccine against herpes zoster and its complications is now available. The aim of this study was to estimate the herpes zoster burden of disease and to establish a pre-vaccination baseline of the minimum incidence of herpes zoster. Data were collected from the Swedish National Health Data Registers including the Patient Register, the Pharmacy Register, and the Cause of Death Register. The herpes zoster burden of disease in Sweden was estimated by analyzing the overall, and age and gender differences in the antiviral prescriptions, hospitalizations and complications during 2006-2010 and mortality during 2006-2009. Annually, 270 per 100,000 persons received antiviral treatment for herpes zoster, and the prescription rate increased with age. It was approximately 50% higher in females than in males in the age 50+ population (rate ratio 1.39; 95% CI, 1.22 to 1.58). The overall hospitalization rate for herpes zoster was 6.9/100,000 with an approximately three-fold increase for patients over 80 years of age compared to the age 70-79 group. A gender difference in hospitalization rates was observed: 8.1/100,000 in females and 5.6/100,000 in males. Herpes zoster, with a registered complication, was found in about one third of the hospitalized patients and the most common complications involved the peripheral and central nervous systems. Death due to herpes zoster was a rare event. The results of this study demonstrate the significant burden of herpes zoster disease in the pre-zoster vaccination era. A strong correlation with age in the herpes zoster- related incidence, hospitalization, complications, and mortality rates was found. In addition, the study provides further evidence of the female predominance in herpes zoster disease.


Neuroendocrine Tumors of the Breast.
A small but increasingly recognized and studied subset of breast carcinomas are characterized by neuroendocrine (NE) differentiation. As with nearly all forms of breast neoplasia, NE tumors are characterized by considerable heterogeneity in microscopic appearance and clinical aggressiveness. About half of NE breast carcinomas recapitulate the histological spectrum typical of their counterparts in other organ systems, varying from "carcinoid-like" to small cell carcinoma, with most representing intermediate grade tumors. Despite NE morphology, these tumors have a high frequency of estrogen receptor expression. Clinical outcomes of women with NE breast carcinomas are reliably grade and stage dependent. Tumors associated with "solid papillary" differentiation comprise the remaining cases of NE breast neoplasia. Solid papillary carcinoma is an intrinsically low grade/favorable prognosis class of breast neoplasia that usually presents in post-menopausal age groups. About half of solid papillary carcinoma present as a distinctive pattern of ductal carcinoma in situ that may be difficult to recognize owing to its close resemblance to florid proliferative lesions. Invasive solid papillary carcinomas are characterized by a variety of histological patterns and often show mucinous differentiation. Future studies are necessary to better define the histogenesis, optimal classification, and improved directed therapies for NE breast neoplasia.


Lowering calcium in the nucleus tractus solitarius causes hypotension and bradycardia.
It has been shown that saline microinjected into the region of the nucleus tractus solitarius (NTS) causes, but artificial cerebrospinal fluid (CSF) in the same volume does not cause, hypotension and bradycardia. This study was done to examine the possibility that the difference in effects between saline and artificial CSF may be due to the lack of calcium ions in saline. In anesthetized rats, saline or artificial CSF with or without calcium ions was microinjected into the region of the NTS. Saline microinjected in volumes of 0.2 and 0.5 microliter produced the volume-dependent decreases in arterial pressure and heart rate. Saline with added calcium ions and artificial CSF did not elicit the hypotensive and bradycardic response, but artificial CSF without calcium ions produced hypotension and bradycardia. These results suggest that the lack of calcium ions in the injected solutions is the factor that determines the hypotensive and bradycardic response. These results suggest that lowering the local availability of calcium to the NTS neurons results in hypotension and bradycardia.


Molecular epidemiology and distribution of serotypes, surface proteins, and antibiotic resistance among group B streptococci in Italy.
Group B streptococci (GBS) comprising three different sets of isolates (31 invasive, 36 noninvasive, and 24 colonizing isolates) were collected in Italy during the years 2002 to 2005. Clonal groups were established by pulsed-field gel electrophoresis (PFGE), and selected isolates were studied by multilocus sequence typing (MLST). GBS isolates were also characterized by classical and molecular techniques for serotyping and protein gene and antibiotic resistance profiling. Some serotypes were significantly associated with a particular isolate population: serotype Ia more frequently corresponded to invasive strains than other strains, serotype V was more frequently encountered among noninvasive strains, and nontypeable strains were more common among isolates from carriers. Four major clonal groups accounted for 52.7% of all isolates: PFGE type 1/clonal complex 1 (CC1) comprised mainly serotype V isolates carrying the alp3 gene, PFGE type 2/CC23 encompassed serotype Ia isolates with the alp1 or alpha gene, PFGE type 3/CC17 comprised serotype III isolates carrying the rib gene, and PFGE type 4/CC19 consisted mainly of serotype II isolates possessing the rib gene. The same serotypes were shared by isolates of different clonal groups, and conversely, isolates belonging to the same clonal groups were found to be of different serotypes, presumably due to capsular switching by the horizontal transfer of capsular genes. Erythromycin resistance (prevalence, 16.5%; 15 resistant isolates of 91) was restricted to strains isolated from patients with noninvasive infections and carriers, while tetracycline resistance was evenly distributed (prevalence, 68.1%; 62 resistant isolates of 91). Most erythromycin-resistant GBS strains were of serotype V, were erm(B) positive, and belonged to the PFGE type 1/CC1 group, suggesting that macrolide resistance may have arisen both by clonal dissemination and by the horizontal transfer of resistance genes.


Crystallization in supercooled liquid Cu: Homogeneous nucleation and growth.
Homogeneous nucleation and growth during crystallization of supercooled liquid Cu are investigated with molecular dynamics simulations, and the microstructure is characterized with one- and two-dimensional x-ray diffraction. The resulting solids are single-crystal or nanocrystalline, containing various defects such as stacking faults, twins, fivefold twins, and grain boundaries; the microstructure is subject to thermal fluctuations and extent of supercooling. Fivefold twins form via sequential twinning from the solid-liquid interfaces. Critical nucleus size and nucleation rate at 31% supercooling are obtained from statistical runs with the mean first-passage time and survival probability methods, and are about 14 atoms and 10(32) m(-3)s(-1), respectively. The bulk growth dynamics are analyzed with the Johnson-Mehl-Avrami law and manifest three stages; the Avrami exponent varies in the range of 1-19, which also depends on thermal fluctuations and supercooling.


Consequences of cytotoxic T-lymphocyte escape: common escape mutations in simian immunodeficiency virus are poorly recognized in naive hosts.
Cytotoxic T lymphocytes (CTL) are associated with control of immunodeficiency virus infection but also select for variants that escape immune recognition. Declining frequencies of epitope-specific CTL frequencies have been correlated with viral escape in individual hosts. However, escape mutations may give rise to new epitopes that could be recognized by CTL expressing appropriate T-cell receptors and thus still be immunogenic when escape variants are passed to individuals expressing the appropriate major histocompatibility complex class I molecules. To determine whether peptide ligands that have been altered through escape can be immunogenic in new hosts, we challenged naïve, immunocompetent macaques with a molecularly cloned simian immunodeficiency virus (SIV) bearing common escape mutations in three immunodominant CTL epitopes. Responses to the altered peptides were barely detectable in fresh samples at any time after infection. Surprisingly, CTL specific for two of three escaped epitopes could be expanded by in vitro stimulation with synthetic peptides. Our results suggest that some escape variant epitopes evolving in infected individuals do not efficiently stimulate new populations of CTL, either in that individual or upon passage to new hosts. Nevertheless, escape variation may not completely abolish an epitope's immunogenicity. Moreover, since the mutant epitope sequences did not revert to wild type during the study period, it is possible that low-frequency CTL exerted enough selective pressure to preserve epitope mutations in viruses replicating in vivo.


Metal-free carbonaceous electrocatalysts and photocatalysts for water splitting.
Water splitting driven by sunlight or renewable resource-derived electricity has attracted great attention for sustainable production of hydrogen from water. Current research interest in this field is focused on the development of earth-abundant photo- or electrocatalytic materials with high activity and long-term stability for hydrogen and/or oxygen evolution reactions. Due to their unique properties and characteristics, carbon and related carbon-based materials show great potential to replace some of the existing precious metal catalysts in water splitting technology. This tutorial review summarizes the recent significant progress in the fabrication and application of metal-free carbonaceous materials as photo- or electrocatalysts for water splitting. Synthetic strategies and applications of various carbonaceous materials, including graphitic carbon nitride (g-C3N4), graphene, carbon nanotubes (CNTs) as well as other forms of carbon-containing materials, for electrochemical or photochemical water splitting are presented, accompanied by a discussion of the key scientific issues and prospects for the future development of metal-free photo- and electrocatalysts.


Video-rate centimeter-range optical coherence tomography based on dual optical frequency combs by electro-optic modulators.
Imaging speed and range are two important parameters for optical coherence tomography (OCT). A conventional video-rate centimeter-range OCT requires an optical source with hundreds of kHz repetition rate and needs the support of broadband detectors and electronics (>1 GHz). In this paper, a type of video-rate centimeter-range OCT system is proposed and demonstrated based on dual optical frequency combs by leveraging electro-optic modulators. The repetition rate difference between dual combs, i.e. the A-scan rate of dual-comb OCT, can be adjusted within 0~6 MHz. By down-converting the interference signal from optical domain to radio-frequency domain through dual comb beating, the down-converted bandwidth of the interference signal is less than 22.5 MHz which is at least two orders of magnitude lower than that in conventional OCT systems. A LabVIEW program is developed for video-rate operation, and the centimeter imaging depth is proved by using 10 pieces of 1-mm thick glass stacked as the sample. The effective beating bandwidth between two optical comb sources is 7 nm corresponding to ~108 comb lines, and the axial resolution of the dual-comb OCT is 158 µm. Dual optical frequency combs provide a promising solution to relax the detection bandwidth requirement in fast long-range OCT systems.


[The use of nitatsid and gipozol'-N in the combined treatment of acute inflammatory diseases of the maxillofacial area].
Combined drugs with a hydrophilic base, nitacide and hyposol-n, were used in combined therapy of acute purulent inflammations of the maxillofacial area. Time course of clinical parameters and changes in microflora were studied in patients administered different local treatments with different inflammatory reactions. The data indicate a high efficiency of the drugs, which optimized local therapy of suppurative wounds and are recommended for wide practical use.


Cardiac diagnostic test results and outcomes in 44 dogs naturally infected with Trypanosoma cruzi.
The protozoal parasite Trypanosoma cruzi causes myocarditis in dogs. To describe the cardiac diagnostic test results and outcomes of dogs naturally infected with T. cruzi. Forty-four client-owned dogs. Medical records were retrospectively reviewed to identify dogs with an indirect fluorescent antibody test result for T. cruzi ≥1 : 80. Data collected included signalment, cardiac diagnostic test results (ECG, echocardiography, cardiac troponin I) and outcome. Outcomes were categorized as alive, dead (cardiac or noncardiac) or lost to follow up. ECG abnormalities were present in 41 dogs with ventricular arrhythmias (n = 28) and atrioventricular block (AVB) (n = 15) most commonly identified. Echocardiographic chamber enlargement was present in 28 dogs and most often included the right ventricle (RV) (n = 15) and left atrium (n = 12). Troponin was ≥2 times the reference range in 20/36 (56%) dogs. In univariate analysis using nonparametric Kaplan-Meier, ventricular arrhythmias with a modified Lown score ≥2 (P = .02), presence of AVB (P = .04), and RV enlargement (P = .006) were associated with decreased survival times. Right ventricular enlargement (HR 3.6; 95% confidence interval [CI] 1.4-9.3; P = .007) and higher body weight at presentation (HR 1.0; 95% CI 1.0-1.1; P = .04) were associated with decreased time to death in the final explanatory multivariable model. Cardiac abnormalities were common and variable, and RV enlargement was associated with shorter survival time. A diagnostic evaluation that includes screening for arrhythmias, echocardiography, and cTnI can provide useful information related to the characterization of heart disease in dogs seropositive for T. cruzi.


Stereotactic body radiation therapy for primary and metastatic liver tumors.
The full potential of stereotactic body radiation therapy (SBRT), in the treatment of unresectable intrahepatic malignancies, has yet to be realized as our experience is still limited. Thus, we evaluated SBRT outcomes for primary and metastatic liver tumors, with the goal of identifying factors that may aid in optimization of therapy. From 2005 to 2010, 62 patients with 106 primary and metastatic liver tumors were treated with SBRT to a median biologic effective dose (BED) of 100 Gy (42.6-180). The majority of patients received either three (47%) or five fractions (48%). Median gross tumor volume (GTV) was 8.8 cm(3) (0.2-222.4). With a median follow-up of 18 months (0.46-46.8), freedom from local progression (FFLP) was observed in 97 of 106 treated tumors, with 1- and 2-year FFLP rates of 93% and 82%. Median overall survival (OS) for all patients was 25.2 months, with 1- and 2-year OS of 81% and 52%. Neither BED nor GTV significantly predicted for FFLP. Local failure was associated with a higher risk of death [hazard ratio (HR) = 5.1, P = .0007]. One Child-Pugh Class B patient developed radiation-induced liver disease. There were no other significant toxicities. SBRT provides excellent local control for both primary and metastatic liver lesions with minimal toxicity. Future studies should focus on appropriate selection of patients and on careful assessment of liver function to maximize both the safety and efficacy of treatment.


Constructive feedforward ART clustering networks. I.
Part I of this paper proposes a definition of the adaptive resonance theory (ART) class of constructive unsupervised on-line learning clustering networks. Class ART generalizes several well-known clustering models, e.g., ART 1, improved ART 1, adaptive Hamming net (AHN), and Fuzzy ART, which are optimized in terms of memory storage and/or computation time. Next, the symmetric Fuzzy ART (S-Fuzzy ART) network is presented as a possible improvement over Fuzzy ART. As a generalization of S-Fuzzy ART, the simplified adaptive resonance theory (SART) group of ART algorithms is defined. Gaussian ART (GART), which is found in the literature, is presented as one more instance of class SART. In Part II of this work, a novel SART network, called fully self-organizing SART (FOSART), is proposed and compared with Fuzzy ART, S-Fuzzy ART, GART and other well-known clustering algorithms. Results of our comparison may easily extend to the ARTMAP supervised learning framework.


Increased Src activity disrupts cadherin/catenin-mediated homotypic adhesion in human colon cancer and transformed rodent cells.
Src has been implicated in the development and progression of human colon cancer. Because the capacity for tumor cells to dissociate from the primary tumor is a critical step in the development of metastases, the effect of a naturally occurring, activated Src-531 on intercellular adhesion was examined. Homotypic adhesion was assessed using dissociation assays on Src-transformed rat fibroblasts and human colon cancer cell lines. The data indicate that both rodent and human cells expressing the mutant Src protein display up to 7-fold less homotypic adhesion than do wild-type cells (P < 0.01). Experiments demonstrated that cadherin was phosphorylated in cells transfected with activated Src and that cadherin/catenin complexes were disrupted as a result. Experiments using dominant negative (DN) Src or an Src-specific inhibitor (PD 180970), demonstrated that adhesion was restored when Src activity was inhibited in Src-531 transfectants, confirming that Src is a causal factor in the decreased homotypic adhesion observed. In addition, DN Ras, DN focal adhesion kinase (FAK), but not Stat3beta, restored intercellular adhesion, which suggested that Ras and FAK may be downstream effectors of Src-mediated homotypic adhesion. Collectively, these data support a role for Src, Ras, and FAK in the regulation of intercellular adhesion, which may in turn regulate metastatic potential of human colon cancer cells.


Maternal Mortality in Georgia: Incidence, Causes and Level of Underreporting: A National Reproductive Age Mortality Study 2014.
Accurate data on maternal mortality are essential for assessing progress towards Sustainable Development Goals (SDG).The aim of the study was to determine the incidence and causes of maternal deaths in Georgia, then explore the potential for improvement of quality of maternal health care. The study's secondary aims were to identify the level of underreporting of maternal deaths in Georgian vital statistics over 1 year (2012) and to compare these results with previous data from 2006. The study findings allow to support the country in developing evidence-based policies and tracking progress towards meeting SDG targets. A national Reproductive Age Mortality Survey (RAMOS) was conducted in Georgia in 2014-15. Multiple data sources were used to identify deaths of women aged 15-49 years between January and December 2012. All deaths in women of reproductive age were investigated through verbal autopsy (VA) diagnoses. Deaths in women during pregnancy or one-year postpartum were further investigated by conducting interviews and medical record reviews at the last medical facility which provided health care for the woman during her fatal condition. A specialist panel reviewed these cases and assigned underlining causes of deaths. We found that 98% of deaths among women of reproductive age were registered by Georgia's civil registration and vital statistics system (CRVS). A total of 918 deaths met the study inclusion criteria. Thirty-six (4.1%) women died during pregnancy or within one-year postpartum. Among these 36 deaths, 23 (63.8%) were maternal deaths, 15 early (either during pregnancy or 42 days postpartum) and eight late (43-365 days postpartum) deaths (65.2% vs 34.8%). The remaining 13 of 36 deaths were coincidental deaths. Fourteen maternal deaths were reported by official statistics and nine deaths were not included in these statistics. Thus, the underreporting rate was 39%. Direct obstetric causes accounted for 73.9% (n=17) of maternal deaths, whereas 26.1% (n=6) were indirect. The leading causes of direct maternal deaths were infection (21.7%), hemorrhage (17.4%), pulmonary embolism (13.0%), and pregnancy-induced hypertension (8.7%). The RAMOS study calculated a maternal mortality ratio (early maternal deaths) of 26.3 per 100,000 live births compared with the official figure of 22.8 per 100,000 live births. Registration of early maternal deaths significantly improved since last survey in 2008, while indirect and late maternal deaths continue to be unrecognized, as reflected in official Georgian statistics. The difference between RAMOS study findings and officially reported maternal mortality rates is minimal, showing improvements in detection of maternal deaths by the national maternal mortality surveillance system. The greatest number of direct obstetric deaths occur in the first week postpartum, which likely reflects deficiencies in quality of care.


Children's metamemorial judgments in an event recall task.
Two studies were conducted in which two different indicators of metacognitive monitoring were investigated in a complex everyday memory task. In the first phase of each experiment, 8- and 10-year-olds as well as adults were shown a short event (video) and gave judgments of learning, that is, rated their certainty that they would later be able to recall specific details correctly. In the second phase of the experiments, participants underwent a memory interview about the event and in Study 2 also gave confidence judgments, that is, rated their certainty that the provided answers to the memory questions were correct. Results revealed significant influences of memory characteristics on monitoring in that delaying judgments and monitoring judgments concerning irretrievable information affected judgments of learning. From 8 years of age onward, there were relatively appropriate metamemorial monitoring abilities in both indicators. Moderate intraindividual consistency was found across the two measures of metacognitive monitoring, with a tendency toward higher consistency in older age groups. The results are discussed in terms of the adequacy of the underlying theoretical construct.


The dangers of conditioning on the time of occurrence of one demographic process in the analysis of another.
In studies of the fertility of migrants in which the data are confined to the migrants only, estimation bias will normally appear in comparisons of childbearing before and after migration. The same issue arises in studies of union formation before and after first birth, marriage formation before and after home purchase, and in any other comparison of behaviour before and after an index event if one confines the study only to those who have experienced the index event. It is normally better to avoid analysis of behaviour before the index event because such analysis actually conditions on the later arrival of the index event. In this paper, we provide graphical and mathematical representations of this problem and show how one can get a meaningful (unconditional) comparison of behaviour before and after the index event provided the data contain enough information for both sub-periods. Otherwise, the analyst should refrain from making a comparison of this nature.


Design teams: a promising organizational intervention for improving turnover rates in the child welfare workforce.
This purpose of this article is to describe results from a quasi-experimental study investigating the effects of an intervention designed to address organizational causes of turnover in public child welfare. Much of the previous research in this area has used proxy measures for turnover while the current study measures both worker intent to leave and actual turnover rates. This study adds to the knowledge base by (1) describing an organizational intervention aimed at addressing the organizational causes of turnover; (2) analyzing quantitative changes in actual turnover rates as well as organizational factors; and (3) analyzing supplemental qualitative data to provide a deeper understanding of the organizational changes that occurred through the course of the intervention.


Patients with uterine papillary serous cancers may benefit from adjuvant platinum-based chemoradiation.
The coexistence of minimal uterine disease and extrauterine metastases is common in patients with uterine papillary serous carcinoma (UPSC). Only complete surgical staging accurately depicts the extent of this disease. The purpose of this study was to evaluate different therapeutic options in surgically staged patients. We retrospectively reviewed all patients with UPSC histologically limited in the uterus to the endometrium treated at our institution between 1987 and 2002. Twenty-three (45%) cases were International Federation of Gynecology and Obstetrics (FIGO) stage IA, seven (15%) were stage IIIA, one (2%) was stage IIIC, and nine (18%) stage IV. Additionally, 11 of these 51 patients (21%) were diagnosed with two cancers: a stage IA UPSC and concomitant advanced stage serous cancer of the ovary, fallopian tube, or peritoneum. Stage IA patients with no cancer in the hysterectomy specimen (defined as no residual uterine disease) had no recurrences (n = 10) regardless of treatment. There was a trend toward increased survival in stage IA patients with residual uterine disease who were treated with chemoradiation (concomitant vaginal brachytherapy and platinum-based chemotherapy). There were no recurrences in patients with locoregional disease (stages IA-IIIA) who received chemoradiation. All patients with advanced stage UPSC (stage IIIC or IV or two primary cancers) did poorly regardless of treatment. Our findings suggest that stage IA patients with no residual uterine disease may be observed. Stage IA patients with residual uterine disease may benefit from chemoradiation. More effective treatment needs to be identified for advanced stage UPSC.


Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.
Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.


Biomechanical comparison of fixation techniques in midshaft clavicular fractures.
The purpose of this study is to evaluate the biomechanical properties and the stability among a locking clavicle plate (LCP), a dynamic compression plate (DCP) and an external fixator (Ex-fix) in an unstable displaced clavicle fracture model under torsional and three-point bending loading. Forty-eight human adult formalin-fixed clavicles were paired according to their bone mineral density homogeneously into three groups: LCP, DCP, and Ex-fix. Each specimen was osteotomized at the midshaft. Torsional and three-point bending forces were performed for 1000 cycles with stiffness recorded at 10 cycles (initial) and then at 100-cycle intervals thereafter. Initial stiffness, failure loads, and the percentage of initial stiffness at the various intervals were compared using analysis of variance. The mean initial stiffness values (Nmm/deg) for torsion were 703.2 (LCP), 448.1 (DCP), and 365.2 (Ex-fix). The mean failure moments (Nmm) for torsion were 7671.7 (LCP), 4370.3 (DCP), and 2999.7 (Ex-fix). The mean initial stiffness (Nmm) for bending were 32.6 (LCP), 23.4 (DCP), and 20.6 (Ex-fix). The mean failure loads (N) for bending were 213.2 (LCP), 131.1 (DCP), and 102.7 (Ex-fix). For both torsion and bending, an overall significant difference among the three constructs in terms of failure loads and also a significant difference between the locking plate and the other two models only in terms of initial stiffness was seen. For torsion and bending, at all cyclic intervals, there was a significant difference between the locking plate and the other two models. After 700 cycles, a significant difference was also detected between the DCP and Ex-fix in torsion, but no difference was found between these groups at any cyclic interval in bending. The locking plate is significantly more stable than DCP and Ex-fix under torsional and bending cyclic loading in a displaced fracture clavicle model.


Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials.
Several meta-analyses of randomized clinical trials (RCTs) have demonstrated the many health benefits of intermittent fasting (IF). However, there has been little synthesis of the strength and quality of this evidence in aggregate to date. To grade the evidence from published meta-analyses of RCTs that assessed the associations of IF (zero-calorie alternate-day fasting, modified alternate-day fasting, the 5:2 diet, and time-restricted eating) with obesity-related health outcomes. PubMed, Embase, and Cochrane database of systematic reviews were searched from database inception to January 12, 2021. Data analysis was conducted from April 2021 through July 2021. Meta-analyses of RCTs investigating effects of IF in adults were included. The effect sizes of IF were recalculated using a random-effects model. We assessed the quality of evidence per association by applying the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluations) as high, moderate, low, and very low. A total of 11 meta-analyses comprising 130 RCTs (median [IQR] sample size, 38 [24-69] participants; median [IQR] follow-up period, 3 [2-5] months) were included describing 104 unique associations of different types of IF with obesity-related health outcomes (median [IQR] studies per association, 4 [3-5]). There were 28 statistically significant associations (27%) that demonstrated the beneficial outcomes for body mass index, body weight, fat mass, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting plasma glucose, fasting insulin, homeostatic model assessment of insulin resistance, and blood pressure. IF was found to be associated with reduced fat-free mass. One significant association (1%) supported by high-quality evidence was modified alternate-day fasting for 1 to 2 months, which was associated with moderate reduction in body mass index in healthy adults and adults with overweight, obesity, or nonalcoholic fatty liver disease compared with regular diet. Six associations (6%) were supported by moderate quality evidence. The remaining associations found to be significant were supported by very low (75 associations [72%]) to low (22 associations [21%]) quality evidence. In this umbrella review, we found beneficial associations of IF with anthropometric and cardiometabolic outcomes supported by moderate to high quality of evidence, which supports the role of IF, especially modified alternate-day fasting, as a weight loss approach for adults with overweight or obesity. More clinical trials with long-term follow-up are needed to investigate the effects of IF on clinical outcomes such as cardiovascular events and mortality.


The role of persistence in chemical evaluations.
The initial stage in the assessment and priority setting of chemicals for their potential to cause harm to humans and the environment is usually a hazard assessment employing metrics for persistence, bioaccumulation, and inherent toxicity. This hazard assessment is followed, when necessary, by the more demanding task of risk assessment. Hazard assessment of data and processes influencing persistence are discussed, leading to a number of suggestions for more effective evaluation. These include 1) an initial focus on accurate data for intensive chemical partitioning and reaction half-life properties that are universally applicable as distinct from extensive properties that can be included later on a location-specific basis; 2) separate treatments of near-field and far-field exposures; 3) a focus on persistence and its effect on levels of exposure, especially for substances for which "time to exposure" is less than "time to degradation" and have been termed "pseudo-persistent." We show that "continuously present" is a better descriptor of this concern. Case studies illustrate and support these suggestions. Data on the intensive properties and on exposure pathways are best combined in evaluative multimedia mass balance models that can provide a clear depiction of the likely chemical fate, exposure routes, and levels. The information generated by the mass balance models can serve to justify and direct a full risk assessment that includes region-specific information on chemical quantities, estimates of exposure, and potential for adverse effects.


Endoscopic identification of the pharyngeal (palatovaginal) canal: an overlooked area.
Objective The pharyngeal or palatovaginal canal (PC) is a small tunnel that lies between the sphenoid process of the palatine bone and the vaginal process of the sphenoid bone. Currently, little endoscopic information is available about this region. Design and Setting Endoscopic endonasal cadaveric study. Subjects and Methods Twenty sides in 10 adult cadaver heads were studied endoscopically. The sphenopalatine foramen (SPF) and the adjacent pterygopalatine fossa were exposed. Dissection medial to the vidian canal demonstrated a tunnel that runs posteromedially in the sphenoid floor. Endoscopic data were documented. Additionally, canal measurements were obtained on 20 sides from coronal CT scans of paranasal sinuses. Results The PC was identifiable in 85% of the sides, although thickness of its bony wall was variable. The endoscopic relationship of the canal and its artery with other landmarks is described. Radiologically, the diameter of the PC averaged 1.7 mm, and the mean distance from the PC to the vidian canal was 3.78 mm. Conclusion The current study provides a novel endoscopic identification of an overlooked canal. The pharyngeal artery can be a source of bleeding during extended endoscopic procedures. The PC itself could be a place for finger-like projections of anatomically related neoplasms.


Use of infrared thermography to detect early alterations of peripheral perfusion: evaluation in a porcine model.
This study aimed to evaluate the variations of infrared thermography according to rapid hemodynamic changes, by measuring the peripheral skin temperature in a porcine model. Eight healthy piglets were anesthetized and exposed to different levels of arterial pressure. Thermography was performed on the left forelimb to measure carpus and elbow skin temperature and their associated gradient with the core temperature. Changes in skin temperature in response to variations of blood pressure were observed. A negative correlation between arterial pressure and temperature gradients between peripheral and core temperature and a negative correlation between cardiac index and these temperature gradients were observed. Thermography may serve as a tool to detect early changes in peripheral perfusion.


Nanoparticulate cellular patches for cell-mediated tumoritropic delivery.
The targeted delivery of therapeutics to tumors remains an important challenge in cancer nanomedicine. Attaching nanoparticles to cells that have tumoritropic migratory properties is a promising modality to address this challenge. Here we describe a technique to create nanoparticulate cellular patches that remain attached to the membrane of cells for up to 2 days. NeutrAvidin-coated nanoparticles were anchored on cells possessing biotinylated plasma membrane. Human bone marrow derived mesenchymal stem cells with nanoparticulate patches retained their inherent tumoritropic properties as shown using a tumor model in a 3D extracellular matrix. Additionally, human umbilical vein endothelial cells with nanoparticulate patches were able to retain their functional properties and form multicellular structures as rapidly as unmodified endothelial cells. These results provide a novel strategy to actively deliver nanostructures and therapeutics to tumors utilizing stem cells as carriers and also suggest that nanoparticulate cellular patches may have applications in tissue regeneration.


Crystallographic structure of porcine adenovirus type 4 fiber head and galectin domains.
Adenovirus isolate NADC-1, a strain of porcine adenovirus type 4, has a fiber containing an N-terminal virus attachment region, shaft and head domains, and a C-terminal galectin domain connected to the head by an RGD-containing sequence. The crystal structure of the head domain is similar to previously solved adenovirus fiber head domains, but specific residues for binding the coxsackievirus and adenovirus receptor (CAR), CD46, or sialic acid are not conserved. The structure of the galectin domain reveals an interaction interface between its two carbohydrate recognition domains, locating both sugar binding sites face to face. Sequence evidence suggests other tandem-repeat galectins have the same arrangement. We show that the galectin domain binds carbohydrates containing lactose and N-acetyl-lactosamine units, and we present structures of the galectin domain with lactose, N-acetyl-lactosamine, 3-aminopropyl-lacto-N-neotetraose, and 2-aminoethyl-tri(N-acetyl-lactosamine), confirming the domain as a bona fide galectin domain.


Detection of recombinant growth hormone by evanescent cascaded waveguide coupler on silica-on-silicon.
An evanescent wave based biosensor is developed on the silica-on-silicon (SOS) with a cascaded waveguide coupler for the detection of recombinant growth hormone. So far, U -bends and tapered waveguides are demonstrated for increasing the penetration depth and enhancing sensitivity of the evanescent wave sensor. In this work, a monolithically integrated sensor platform containing a cascaded waveguide coupler with optical power splitters and combiners designed with S -bends and tapper waveguides is demonstrated for an enhanced detection of recombinant growth hormone. In the cascaded waveguide coupler, a large surface area to bind the antibody with increased penetration depth of evanescent wave to excite the tagged-rbST is obtained by splitting the waveguide into multiple paths using Y splitters designed with s -bends and subsequently combining them back to a single waveguide through tapered waveguide and combiners. Hence a highly sensitive fluoroimmunoassay sensor is realized. Using the 2D FDTD (Finite-difference time-domain method) simulation of waveguide with a point source in Rsoft FullWAVE, the fluorescence coupling efficiency of straight and bend section of waveguide is analyzed. The sensor is demonstrated for the detection of fluorescently-tagged recombinant growth hormone with the detection limit as low as 25 ng/ml.


Mortality and Morbidity in Infants <34 Weeks' Gestation in 25 NICUs in China: A Prospective Cohort Study.
Objectives: To describe the rates and variability of mortality and morbidity of preterm infants born in China. Methods: This prospective cohort study included infants born at <34 weeks' gestation and admitted to 25 NICUs within 7 days of birth between May 1st, 2015 and April 30th, 2016. Infants were followed until death or NICU discharge. The primary outcome was a composite of mortality or any major morbidity (sepsis, necrotizing enterocolitis, intraventricular/periventricular leukomalacia, retinopathy of prematurity, and bronchopulmonary dysplasia) in infants who received complete care following medical advice. Secondary outcomes included rate of discharge against medical advice, mortality and individual morbidities. Results: Of the 8,065 infants, 6,852 (85%) received complete care and 1,213 (15%) were discharged against medical advice. Among infants who received complete care, the rate of the composite outcome was 27% (1,827/6,852), mortality 4% (248/6,852), sepsis 14% (990/6,852), necrotizing enterocolitis 3% (191/6,550), intraventricular hemorrhage/periventricular leukomalacia 7% (422/6,307), retinopathy of prematurity 2% (67/3,349), and bronchopulmonary dysplasia 9% (616/6,852). There were significant variations between NICUs for all outcomes. Conclusions: Discharged against medical advice, mortality, and morbidity rates for preterm infants <34 weeks' gestation are high in China with significant variations between NICUs.


Influence of the mineral content and morphological pattern of artificial root caries lesion on composite resin bond strength.
Dentine substrates with different mineral contents and morphological patterns were created by submitting root slabs to the following treatments: (A) immersion in artificial saliva during the experimental period (control), (B) demineralization for 32 h to induce caries lesion (demineralized group), and (C) demineralization for 32 h followed by remineralization for 8 d (remineralized group). The slabs were longitudinally sectioned, the mineral content was determined by cross-sectional microhardness, and the bond strength of an adhesive system/composite resin was assessed using a microtensile bond strength test. The dentine morphology after the treatments as well as the failure pattern of the debonded specimens was examined by scanning electron microscopy. Statistically significant differences were found in mineral content. Morphological analysis showed marked differences between the patterns of demineralized and remineralized substrates. The bond strength mean value of the control A did not differ from the group B, but was statistically higher than the group C. Since no linear relationship was found between dentine mineral content and bond strength values, it could be suggested that the morphological pattern may be more relevant than the mineral content to explain the bond strength of composite resin to dentine.


Detection and quantification of inbreeding depression for complex traits from SNP data.
Quantifying the effects of inbreeding is critical to characterizing the genetic architecture of complex traits. This study highlights through theory and simulations the strengths and shortcomings of three SNP-based inbreeding measures commonly used to estimate inbreeding depression (ID). We demonstrate that heterogeneity in linkage disequilibrium (LD) between causal variants and SNPs biases ID estimates, and we develop an approach to correct this bias using LD and minor allele frequency stratified inference (LDMS). We quantified ID in 25 traits measured in [Formula: see text] participants of the UK Biobank, using LDMS, and confirmed previously published ID for 4 traits. We find unique evidence of ID for handgrip strength, waist/hip ratio, and visual and auditory acuity (ID between -2.3 and -5.2 phenotypic SDs for complete inbreeding; [Formula: see text]). Our results illustrate that a careful choice of the measure of inbreeding combined with LDMS stratification improves both detection and quantification of ID using SNP data.


Comparison of perioperative outcomes of robotic-assisted versus video-assisted thoracoscopic right upper lobectomy in non-small cell lung cancer.
Robotic-assisted thoracic surgery (RATS) has been widely used in the treatment of lung cancer. The perioperative outcomes of right upper lobectomy (RUL) using RATS and video-assisted thoracic surgery (VATS) were retrospectively investigated and compared. We aimed to summarize a single-center experience of RATS and 4-port unidirectional VATS in RUL, and to discuss the safety and the essentials of the surgery. We retrospectively analyzed the 685 with non-small cell lung cancer (NSCLC) patients who underwent minimally invasive RUL in our center by the same surgical group from January 2015 to December 2019. Both RATS and VATS were performed with three ports with utility incision. The 685 participants were divided into RATS (335 cases) and VATS (350 cases) groups according to surgical method. Baseline characteristics and perioperative outcomes including dissected lymph nodes, postoperative duration of drainage, postoperative hospital stay, and incidence of postoperative complications were compared between the groups. In the 685 patients enrolled, the baseline characteristics were comparable, and no postoperative 30-day mortality or intraoperative blood transfusion were observed. Compared with VATS, RATS had less surgical duration (90.22±12.16 vs. 92.68±12.26 min, P<0.001), less length of stay (4.71±1.37 vs. 5.26±1.56 days, P<0.001), and decreased postoperative duration of drainage (3.49±1.15 vs. 4.09±1.57 days, P<0.001). No significant difference was observed in the lymph nodes dissection, blood loss, conversion rate and morbidities. The cost of RATS was much higher than VATS (85,329.41±12,893.44 vs. 68,733.43±14,781.32 CNY, P<0.001). Robot assisted RUL had similar perioperative outcomes compared to VATS RUL lobectomy using similar three port with utility incision technique. The advantages of RATS included finer dissection of lymph node, relatively less operation time, earlier chest tube removal and discharge.


The CRL4Cdt2 ubiquitin ligase mediates the proteolysis of cyclin-dependent kinase inhibitor Xic1 through a direct association with PCNA.
During DNA polymerase switching, the Xenopus laevis Cip/Kip-type cyclin-dependent kinase inhibitor Xic1 associates with trimeric proliferating cell nuclear antigen (PCNA) and is recruited to chromatin, where it is ubiquitinated and degraded. In this study, we show that the predominant E3 for Xic1 in the egg is the Cul4-DDB1-XCdt2 (Xenopus Cdt2) (CRL4(Cdt2)) ubiquitin ligase. The addition of full-length XCdt2 to the Xenopus extract promotes Xic1 turnover, while the N-terminal domain of XCdt2 (residues 1 to 400) cannot promote Xic1 turnover, despite its ability to bind both Xic1 and DDB1. Further analysis demonstrated that XCdt2 binds directly to PCNA through its C-terminal domain (residues 401 to 710), indicating that this interaction is important for promoting Xic1 turnover. We also identify the cis-acting sequences required for Xic1 binding to Cdt2. Xic1 binds to Cdt2 through two domains (residues 161 to 170 and 179 to 190) directly flanking the Xic1 PCNA binding domain (PIP box) but does not require PIP box sequences (residues 171 to 178). Similarly, human p21 binds to human Cdt2 through residues 156 to 161, adjacent to the p21 PIP box. In addition, we identify five lysine residues (K180, K182, K183, K188, and K193) immediately downstream of the Xic1 PIP box and within the second Cdt2 binding domain as critical sites for Xic1 ubiquitination. Our studies suggest a model in which both the CRL4(Cdt2) E3- and PIP box-containing substrates, like Xic1, are recruited to chromatin through independent direct associations with PCNA.


Identification of microRNAs during rat liver regeneration after partial hepatectomy and modulation by ursodeoxycholic acid.
New gene regulation study tools such as microRNA (miRNA or miR) analysis may provide unique insights into the remarkable ability of the liver to regenerate. In addition, we have previously shown that ursodeoxycholic acid (UDCA) modulates mRNA levels during liver regeneration. Bile acids are also homeotrophic sensors of functional hepatic capacity. The present study was designed to determine whether miRNAs are modulated in rats following 70% partial hepatectomy (PH) and elucidate the role of UDCA in regulating miRNA expression during liver regeneration (LR). Total RNA was isolated from livers harvested at 3-72 h following 70% PH or sham operations, from both 0.4% (wt/wt) UDCA and control diet-fed animals. By using a custom microarray platform we found that several miRNAs are significantly altered after PH by >1.5-fold, including some previously described as modulators of cell proliferation, differentiation, and death. In particular, expression of miR-21 was increased after PH. Functional modulation of miR-21 in primary rat hepatocytes increased cell proliferation and viability. Importantly, UDCA was a strong inducer of miR-21 both during LR and in cultured HepG2 cells. In fact, UDCA feeding appeared to induce a sustained increase of proliferative miRNAs observed at early time points after PH. In conclusion, miRNAs, in particular miR-21, may play a significant role in modulating proliferation and cell cycle progression genes after PH. miR-21 is additionally induced by UDCA in both regenerating rat liver and in vitro, which may represent a new mechanism behind UDCA biological functions.


TRIM14 regulates melanoma malignancy via PTEN/PI3K/AKT and STAT3 pathways.
Melanoma is one of the most aggressive cancers with poor overall survival. To date, there are still few effective methods for the treatment of melanoma. TRIM14 was previously reported to be an important oncogene in many tumors. Nevertheless, the roles of TRIM14 in melanoma remain unknown. In this study, we found that TRIM14 was abnormally upregulated in melanoma cell lines. Knockdown of TRIM14 suppressed melanoma cell proliferation, migration, invasion, epithelial-mesenchymal transition, and melanin synthesis. Overexpression of TRIM14 had opposite effects on the cellular functions of melanoma cell lines. Further study revealed that TRIM14 knockdown increased PTEN protein levels, which in turn inactivated AKT and STAT3 pathways. Moreover, blocking AKT or STAT3 pathway with a specific inhibitor could partially reverse the promotion of melanoma malignancy mediated by TRIM14 overexpression. In addition, in vivo assay also supported the above findings. These results indicated that TRIM14 might be a promising target for melanoma treatment.


Enzymatic and antigenic characterization of immunoglobulin A1 proteases from Bacteroides and Capnocytophaga spp.
Bacteroides and Capnocytophaga species have been implicated as periodontal pathogens. Some of these species possess immunoglobulin A1 (IgA1) proteases that are capable of cleaving the human IgA1 molecule in the hinge region, leaving intact Fc alpha and Fab alpha fragments. The purpose of this study was to characterize this activity. In addition to IgA1 protease activity in already known species, IgA1 protease activity was a feature of Bacteroides buccalis, Bacteroides oralis, Bacteroides veroralis, Bacteroides capillus, and Bacteroides pentosaceus. Results of immunoelectrophoretic and sodium dodecyl sulfate-polyacrylamide gel electrophoretic analyses suggested that all species cleave the alpha-chain at the same peptide bond, i.e., the prolyl-seryl bond between residues 223 and 224 in the hinge region. The Bacteroides proteases could be classified as thiol proteases, which were at the same time dependent on metal ions, while the Capnocytophaga proteases were metallo enzymes. None of the proteases were inhibited by the physiologic proteases inhibitors alpha 2-macroglobulin and alpha 1-proteinase inhibitor. Investigations with enzyme-neutralizing antibodies raised in rabbits against protease preparations from the respective type strains revealed that, despite otherwise identical characteristics, the IgA1 protease of each Bacteroides species was antigenically distinct. Bacteroides buccae and the two later synonymous species B. capillus and B. pentosaceus produced identical proteases. In contrast, IgA1 proteases from Capnocytophaga ochracea and Capnocytophaga sputigena strains were apparently identical, while Capnocytophaga gingivalis had a protease that differed from those of the other Capnocytophaga species.


Clerocidin alkylates DNA through its epoxide function: evidence for a fine tuned mechanism of action.
Clerocidin (CL) is an effective topoisomerase II-poison, which has been shown to produce DNA depurination and strand breaks per se at the guanine (G) level. To elucidate the roles played by the different functional groups of CL in the reactivity towards nucleic acids, we investigated CL derivatives with key structural modifications. The derivatives were reacted with plasmid, single-/double-stranded DNA and isolated 2'-deoxy-guanosines (dG). We show here that an intact oxirane ring is essential to achieve DNA modification and depurination. Through HPLC/MS and MS/MS techniques we were able to unambiguously characterize adducts obtained by reacting isolated dG and single-/double-stranded DNA with the drugs, indicating beyond reasonable doubt that the structure of a typical adduct is formed by epoxide alkylation at N7 of G with subsequent loss of the pentose unit. Further, we showed that reduction of vicinal carbonyl functions affect drug activity to a large extent. Our findings demonstrate that the characteristic DNA-alkylating properties of CL arise from mutual action of the functional groups present in this molecule. Its oxidation state seems crucial to modulate the rates of reactivity by finely tuning the strain applied on the oxirane ring.


Effect of the chloride ion as a hole scavenger on the photocatalytic conversion of CO2 in an aqueous solution over Ni-Al layered double hydroxides.
The photocatalytic conversion of CO2 into useful chemical compounds in water without using organic sacrificial reagents is a promising method to overcome environmental and energy problems. Various synthesized layered double hydroxides (LDHs) are capable of reducing CO2 to CO in an aqueous solution under UV light irradiation. However, it is difficult to oxidize H2O to O2 in a photocatalytic system using LDHs as photocatalysts. In this study, we investigated the photocatalytic conversion of CO2 using a Ni-Al LDH in an aqueous solution of NaCl. Hypochlorous acid (HClO) was produced as an oxidation product of Cl(-) with the formation of reduction products such as CO and H2 under photoirradiation. We propose the inclusion of Cl(-) in the reaction solution to be one of the most promising ways for obtaining a hole scavenger, an approach that would enable the construction of an artificial photosynthesis system for the conversion of CO2.


The rate of intravenous cocaine administration determines susceptibility to sensitization.
The potential for addiction is thought to be greatest when drugs of abuse reach the brain rapidly, because this produces intense subjective pleasurable effects. However, the ability of drugs to induce forms of cellular plasticity related to behavioral sensitization may also contribute to addiction. Therefore, we studied the influence of rate of intravenous cocaine delivery on its ability to induce psychomotor sensitization. In one experiment, rotational behavior in rats with a unilateral 6-hydroxydopamine lesion was used as an index of psychomotor activation, and in a second experiment, locomotor activity in neurologically intact rats was used. Rapid (5-16 sec) intravenous infusions of cocaine induced robust psychomotor sensitization at all doses tested (0.5-2.0 mg/kg). Treatments given over 25 sec failed to induce sensitization at all doses tested. Treatments given over 50 or 100 sec induced sensitization only at the highest dose tested. Thus, the rate of intravenous cocaine delivery has profound effects on the ability of cocaine to induce psychomotor sensitization. This suggests that the temporal dynamics of drug delivery to the brain is a critical factor in the ability of cocaine to induce forms of neuronal plasticity that may contribute to addiction.


Genome-wide identification and expression profile of YABBY genes in Averrhoa carambola.
Members of the plant-specific YABBY gene family are thought to play an important role in the development of leaf, flower, and fruit. The YABBY genes have been characterized and regarded as vital contributors to fruit development in Arabidopsis thaliana and tomato, in contrast to that in the important tropical economic fruit star fruit (Averrhoa carambola), even though its genome is available. In the present study, a total of eight YABBY family genes (named from AcYABBY1 to AcYABBY8) were identified from the genome of star fruit, and their phylogenetic relationships, functional domains and motif compositions, physicochemical properties, chromosome locations, gene structures, protomer elements, collinear analysis, selective pressure, and expression profiles were further analyzed. Eight AcYABBY genes (AcYABBYs) were clustered into five clades and were distributed on five chromosomes, and all of them had undergone negative selection. Tandem and fragment duplications rather than WGD contributed to YABBY gene number in the star fruit. Expression profiles of AcYABBYs from different organs and developmental stages of fleshy fruit indicated that AcYABBY4 may play a specific role in regulating fruit size. These results emphasize the need for further studies on the functions of AcYABBYs in fruit development.


[The assesment of diastolic function in patients with rheumatoid arthritis].
Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune chronic disease. In comparison with the overall population, mortality and morbidity of RA patients are increased due to cardiovascular diseases. There is increasing evidence that autoimmunity mechanisms are included in pathogenesis of cardiovascular diseases. Isolated disorder of diastolic function can, even with normal heart contractility, lead to heart failure. The aim of this study was to assess diastolic function in RA patients and determine factors causing diastolic dysfunction. The study included 88 patients with RA treated at Rheumatology Department, Clinical Hospital Centre, Zemun. All the patients were thoroughly examined (clinical findings, laboratory and echocardiographic examination). All parameters of diastolic function (mitral and pulmonary flow) were measured. In RA patients 98.9% had diastolic function disorder. This parameter had been changed prior to clinical signs of heart failure and decrease of ejection fraction. Indicators of diastolic function, velocities E, A and their ratio V(E)/V(A), as well as velocities S, D and their ratio V(S)/V(D) were lower in patients with positive rheumatoid factor. The patients' age (p < 0.01), duration of the disease (p < 0.05), high level of cholesterol (p < 0.05), triglycerides (p < 0.05) and arterial hypertension (p < 0.05) were significant factors considerably affecting diastolic function. These findings suggest subclinical myocardial disorder in a great number of RA patients. Apart from early and aggressive treatment of the chronic inflammatory process, it is also necessary to prevent further heart complications by timely recognition and treatment of "standard" risk factors fbr cardiovascular diseases.


Metastatic carcinoid presenting as a breast lesion.
Metastasis to the breast is a rare occurrence, constituting fewer than 2% of all breast tumours. Of all metastatic tumours in the breast, most arise from contralateral breast primaries. Other reported primary solid tumour sites include melanoma; lung, gastric, and renal cancers; and approximately 29 cases of carcinoid tumour.Ambiguous presentations and an absence of carcinoid syndrome features make accurate radiographic and histologic assessment of breast carcinoids challenging. Here, we report the case of a 52-year-old woman who presented with a mammographic abnormality in the left breast. Excisional biopsy revealed histopathology consistent with carcinoid. After an exhaustive work-up, carcinoid within the terminal ileum was ultimately identified, and the woman was diagnosed with metastatic breast carcinoid, an exceedingly rare entity. This paper describes the common mammographic, cytologic, and immunohistochemical features typical of metastatic breast carcinoid tumours, together with their common clinical features, prognosis, and treatment options.


Soil fungal networks moderate density-dependent survival and growth of seedlings.
Pathogenic and mutualistic fungi have contrasting effects on seedling establishment, but it remains unclear whether density-dependent survival and growth are regulated by access to different types of mycorrhizal fungal networks supported by neighbouring adult trees. Here, we conducted an extensive field survey to test how mycorrhizal and pathogenic fungal colonization of arbuscular mycorrhizal (AM) and ectomycorrhizal (ECM) seedlings in a subtropical forest respond to density of neighbouring adult trees. In addition, we undertook a hyphal exclusion experiment to explicitly test the role of soil fungal networks in driving density-dependent effects on seedling growth and survival. Conspecific adult density was a strong predictor for the relative abundance of putative pathogens, which was greater in roots of AM than of ECM seedlings, while mycorrhizal fungal abundance and colonization were not consistently affected by conspecific adult density. Both ECM and AM fungal networks counteracted conspecific density-dependent mortality, but ECM fungi were more effective at weakening the negative effects of high seedling density than AM fungi. Our findings reveal a critical role of common fungal networks in mitigating negative density-dependent effects of pathogenic fungi on seedling establishment, which provides mechanistic insights into how soil fungal diversity shapes plant community structure in subtropical forests.


Interactions between septal and entorhinal inputs to the rat dentate gyrus: facilitation effects.
We examined facilitation effects between the medial septum and perforant path inputs to the dentate gyrus for the four possible combinations of paired-pulse activation. Facilitation effects occurred in all cases. The largest facilitation effects occurred when the septal pulse served as the conditioning pulse for the population spike subsequently evoked by a perforant path pulse. Using 3 pulses, we also examined the influence of septal activation on paired-pulse facilitation of the perforant path-granule cell population spike. A septal stimulation pulse, applied 6-10 ms prior to the onset of the population spike evoked by a perforant path conditioning pulse, did not affect the perforant path-dentate test response at any interpulse interval. If the septal pulse occurred immediately prior to population spike onset, however, there was a significantly greater depression of the test response from 70-3000 ms, but no effect at early intervals (20-50 ms). The effect of the septal pulse appears more consistent with a direct action of the septal terminals on granule cells than with an indirect action via the recurrent inhibitory interneurons.


Xenopus laevis lectin is localized at several sites in Xenopus oocytes, eggs, and embryos.
The endogenous lectin of Xenopus laevis oocytes, unfertilized eggs, and blastula-stage embryos was immunohistochemically localized using a highly specific antiserum. Each tissue was examined with several techniques, including paraformaldehyde or glutaraldehyde fixation, frozen or plastic sections, and immunofluorescence or immunoperoxidase staining. In oocytes and unfertilized eggs, lectin was detected in association with yolk platelets, cortical granules, and the vitelline envelope. In embryos, cortical granules had disappeared and lectin was found in the cleavage furrows between the embryonic cells. The distribution of the lectin suggests that it plays more than one role in this developing system.


POINT: a database for the prediction of protein-protein interactions based on the orthologous interactome.
One possible path towards understanding the biological function of a target protein is through the discovery of how it interfaces within protein-protein interaction networks. The goal of this study was to create a virtual protein-protein interaction model using the concepts of orthologous conservation (or interologs) to elucidate the interacting networks of a particular target protein. POINT (the prediction of interactome database) is a functional database for the prediction of the human protein-protein interactome based on available orthologous interactome datasets. POINT integrates several publicly accessible databases, with emphasis placed on the extraction of a large quantity of mouse, fruit fly, worm and yeast protein-protein interactions datasets from the Database of Interacting Proteins (DIP), followed by conversion of them into a predicted human interactome. In addition, protein-protein interactions require both temporal synchronicity and precise spatial proximity. POINT therefore also incorporates correlated mRNA expression clusters obtained from cell cycle microarray databases and subcellular localization from Gene Ontology to further pinpoint the likelihood of biological relevance of each predicted interacting sets of protein partners.


Managing the Severe Cavus Foot Deformity in Global Humanitarian Programs.
The cavus foot represents a complex spectrum of deformity ranging from the subtle idiopathic to the severe sensorimotor neuropathy and other neuromuscular deformities. The successful surgical treatment of the cavus foot depends on a fundamental understanding of the underlying multiplanar deformity, inherent muscle balance, and the rigidity of the hindfoot. The location of the deformity is described and understood according to its multiple apices. These deformities are addressed with osteotomies or arthrodesis directed at the apices of deformity. Simultaneously, correction of muscular imbalances with appropriate tendon transfers must also be performed to prevent recurrent deformity. With these principles in mind, the surgical correction of the cavus foot becomes simplified and algorithmically driven.


Complexes of adenosine deaminase with two potent inhibitors: X-ray structures in four independent molecules at pH of maximum activity.
Adenosine deaminase, which catalyzes the irreversible hydrolytic deamination of adenosine nucleosides to inosine nucleosides and ammonia, is a key enzyme in purine metabolism and lymphoid development. The X-ray structures of murine adenosine deaminase with bound potent inhibitors (Ki values approximately 10(-13) M) (8R)-hydroxyl-2'-deoxycoformycin (pentostatin), a transition state analogue, and (6S)-hydroxyl-1,6-dihydropurine riboside, a reaction coordinate analogue, have been determined and refined to resolutions of 2.6 and 1.95 A, respectively. Crystals of both complexes were obtained at pH 7, where the enzyme is fully active, in an identical space group with the asymmetric unit containing four molecules. In addition to the very high degree of similarity between the four independent molecules in each complex structure, there is also considerable structural similarity of the complex with the dihydropurine riboside with that of an identical complex previously determined at pH 4.2 where the enzyme is 20% active. The interactions between the enzyme and the two analogues are extremely similar. These include the coordination of the 8R- or 6S-hydroxyl group of the analogues to the Zn2+ which mainly contributes to the strong potency and very high degree of stereospecificity of inhibition by these analogues. The interactions are further indicative of the structural and chemical requirements of substrates. These structures and recent site-directed mutagenesis have further shed light on the catalytic mechanism of the enzyme.


Association of Rad9 with double-strand breaks through a Mec1-dependent mechanism.
Rad9 is required for the activation of DNA damage checkpoint pathways in budding yeast. Rad9 is phosphorylated after DNA damage in a Mec1- and Tel1-dependent manner and subsequently interacts with Rad53. This Rad9-Rad53 interaction has been suggested to trigger the activation and phosphorylation of Rad53. Here we show that Mec1 controls the Rad9 accumulation at double-strand breaks (DSBs). Rad9 was phosphorylated after DSB induction and associated with DSBs. However, its phosphorylation and association with DSBs were significantly decreased in cells carrying a mec1Delta or kinase-negative mec1 mutation. Mec1 phosphorylated the S/TQ motifs of Rad9 in vitro, the same motifs that are phosphorylated after DNA damage in vivo. In addition, multiple mutations in the Rad9 S/TQ motifs resulted in its defective association with DSBs. Phosphorylation of Rad9 was partially defective in cells carrying a weak mec1 allele (mec1-81), whereas its association with DSBs occurred efficiently in the mec1-81 mutants, as found in wild-type cells. However, the Rad9-Rad53 interaction after DSB induction was significantly decreased in mec1-81 mutants, as it was in mec1Delta mutants. Deletion mutation in RAD53 did not affect the association of Rad9 with DSBs. Our results suggest that Mec1 promotes association of Rad9 with sites of DNA damage, thereby leading to full phosphorylation of Rad9 and its interaction with Rad53.


Admissions to Canadian hospitals for acute asthma: a prospective, multicentre study.
Asthma exacerbations constitute one of the most common causes of emergency department (ED) attendance in most developed countries. While severe asthma often requires hospitalization, variability in admission practices has been observed. To describe the factors associated with admission to Canadian hospitals for acute asthma after ED treatment. Subjects 18 to 55 years of age treated for acute asthma in 20 Canadian EDs prospectively underwent a structured ED interview (n=695) and telephone interview two weeks later. The median age of the patients was 30 years, and the majority were women (62.8%). The admission rate was 13.1% (95% CI 10.7% to 15.8%). Admitted patients were older, more often receiving oral or inhaled corticosteroids at presentation, and more frequently receiving systemic corticosteroids and magnesium sulphate in the ED. Similar proportions received beta-2 agonists and/or ipratropium bromide within 1 h of arrival. On multivariable analyses, factors associated with admission included age, previous admission in the past two years, more than eight beta-2 agonist puffs in the past 24 h, a Canadian Triage and Acuity Score of 1 to 2, a respiratory rate of greater than 22 breaths/min and an oxygen saturation of less than 95%. The admission rate for acute asthma from these Canadian EDs was lower than reported in other North American studies. The present study provides insight into practical factors associated with admission for acute asthma and highlights the importance of history and asthma severity markers on ED decision making. Further efforts to standardize ED management and expedite admission decision-making appear warranted.


Systems collaborate for a healthier community. A Community Health Advisory Board focuses on immunization.
The Community Health Advisory Board (CHAB), Pierce County, WA, involves four healthcare systems--Franciscan Health System, MultiCare Medical Center, Group Health Cooperative of Puget Sound, and Good Samaritan Hospital--that have joined forces with other providers in an innovative attempt to better serve their community. An evaluation by representatives of New York University's Hospital Community Benefit Standard Program prompted St. Joseph Medical Center, Tacoma, WA, to bring major providers together in a coordinated effort that could reach community residents in need. At their first meeting in November 1992, CHAB members agreed on a purpose: to facilitate collaboration between healthcare providers throughout the county to develop programs and services that improve the health status of community residents. In January 1993 CHAB members selected a "quick success" project: a program aimed at increasing immunization levels to 90 percent for two-year-old children in the county. In February 1993 CHAB members committed the "best and brightest" to the Immunization Task Force, naming experts in planning, nursing, community health, education, and marketing. When the Immunization Task Force assessed the project, they realized that the "quick success" program would not be accomplished so quickly. CHAB has had to address underlying problems to make higher immunization levels sustainable. In March 1994 members will evaluate the immunization program's process, status, and structure; data on immunization levels; and the group's demonstrated ability to cooperate.


Comparison of Macintosh, Truview EVO2, Glidescope, and Airwayscope laryngoscope use in patients with cervical spine immobilization.
The purpose of this study was to evaluate the effectiveness of the Pentax AWS, Glidescope, and the Truview EVO2, in comparison with the Macintosh laryngoscope, when performing tracheal intubation in patients with neck immobilization using manual in-line axial cervical spine stabilization. One hundred and twenty consenting patients presenting for surgery requiring tracheal intubation were randomly assigned to undergo intubation using a Macintosh (n=30), Glidescope (n=30), Truview EVO2 (n=30), or AWS (n=30) laryngoscope. All patients were intubated by one of the three anaesthetists experienced in the use of each laryngoscope. The Glidescope, AWS, and Truview EVO2 each reduced the intubation difficulty score (IDS), improved the Cormack and Lehane glottic view, and reduced the need for optimization manoeuvres, compared with the Macintosh. The mean IDS was significantly lower with the Glidescope and AWS compared with the Truview EVO2 device, and the IDS was lowest with the AWS. The duration of tracheal intubation attempts was significantly shorter with the Macintosh compared with the other devices. There were no differences in success rates between the devices tested. The AWS produced the least haemodynamic stimulation. The Glidescope and AWS laryngoscopes required more time but reduced intubation difficulty and improved glottic view over the Macintosh laryngoscope more than the Truview EVO2 laryngoscope when used in patients undergoing cervical spine immobilization.


UpGene: Application of a web-based DNA codon optimization algorithm.
Although DNA codon optimization is a standard molecular biology strategy to overcome poor gene expression, to date no public software exists to facilitate this process. Among the uses of codon optimization, human immunodeficiency virus (HIV) vaccine development represents one of the most difficult challenges. A key obstacle to an effective DNA-based vaccine is the low-level expression of HIV genes in mammalian cells, which is due primarily to the instability of HIV mRNAs resulting from AU-rich elements and rare codon usage. In this report we describe the development of a DNA optimization algorithm integrated with a PCR primer design program to redesign specific coding sequences for maximal gene expression. Using this algorithm combination, together with PCR-based gene assembly, we have successfully optimized gene sequences for simian immunodeficiency virus (SIV) strain mac239 structural antigenic proteins gag and env, resulting in high-level gene expression in eukaryotic cells. Our findings demonstrate that our user-friendly algorithm is a valuable tool for DNA-based HIV vaccine development. Moreover, it can be used to optimize any other genes of interest and is freely available online at http://www.vectorcore.pitt.edu/upgene.html.