Correlates of Female-Perpetrated Intimate Partner Violence in Kano, Northern Nigeria.
Women are by no means the exclusive victims of intimate partner violence (IPV). This study assessed the lifetime prevalence and predictors of female-perpetrated IPV among public servants in Kano, Nigeria. Using a descriptive cross-sectional design and systematic sampling, pre-tested structured self-administered questionnaires were used to assess prevalence, types, and predictors of IPV among 302 married men. The lifetime prevalence of IPV was 66.8% (n = 177; 95% confidence interval [CI] = [60.7, 72.4]). Of surveyed men who have ever experienced violence, 78.0% (n = 138), 81.4% (n = 144), and 16.4% (n = 29) encountered physical assault, psychological aggression, and sexual coercion, respectively. After controlling for confounders, having ≥5 children, adjusted odds ratio (aOR) [95% CI] = 3.93 [1.16, 13.29], p = .027, and childhood experience of violence, aOR [95% CI] = 0.14 [0.05, 0.39], p = .0001, remained significant predictors of female-perpetrated IPV. In conclusion, female-perpetrated IPV is prevalent in northern Nigeria. Addressing IPV will require comprehensive violence prevention measures, including counseling and support for victims and exposed children.


Mitochondrial porin of Neurospora crassa: cDNA cloning, in vitro expression and import into mitochondria.
cDNA encoding porin of Neurospora crassa, the major protein component of the outer mitochondrial membrane, was isolated and the nucleotide sequence was determined. The deduced protein sequence consists of 283 amino acids (29,979 daltons) and shows sequence homology of around 43% to yeast porin; however, no significant homology to bacterial porins was apparent. According to secondary structure predictions, mitochondrial porin consists mainly of membrane-spanning sided beta-sheets. Porin was efficiently synthesized in vitro from the cDNA; this allowed us to study in detail its import into mitochondria. Thereby, three characteristics of import were defined: (i) import depended on the presence of nucleoside triphosphates; (ii) involvement of a proteinaceous receptor-like component on the surface of the mitochondria was demonstrated; (iii) insertion into the outer membrane was resolved into at least two distinct steps: specific binding to high-affinity sites and subsequent assembly to the mature form.


Effect of Patient Education on Reducing Medication in Spinal Cord Injury Patients With Neuropathic Pain.
To determine whether providing education about the disease pathophysiology and drug mechanisms and side effects, would be effective for reducing the use of pain medication while appropriately managing neurogenic pain in spinal cord injury (SCI) patients. In this prospective study, 109 patients with an SCI and neuropathic pain, participated in an educational pain management program. This comprehensive program was specifically created, for patients with an SCI and neuropathic pain. It consisted of 6 sessions, including educational training, over a 6-week period. Of 109 patients, 79 (72.5%) initially took more than two types of pain medication, and this decreased to 36 (33.0%) after the educational pain management program was completed. The mean pain scale score and the number of pain medications decreased, compared to the baseline values. Compared to the non-response group, the response group had a shorter duration of pain onset (p=0.004), and a higher initial number of different medications (p<0.001) and certain types of medications. This study results imply that an educational pain management program, can be a valuable complement to the treatment of spinal cord injured patients with neuropathic pain. Early intervention is important, to prevent patients from developing chronic SCI-related pain.


Keratocystic odontogenic tumor: a retrospective study of 183 cases.
In 2005, the WHO Working Group considered odontogenic keratocyst (OKC) to be a tumor and recommended the term keratocystic odontogenic tumor (KCOT), separating the lesion from the orthokeratinizing variant, which is now considered an odontogenic cyst. We analyzed the clinicopathological features of KCOTs encountered over a period of 28 years at Meikai University Hospital. The diagnosis was confirmed by reevaluation of hematoxylin and eosin-stained slides on the basis of the 2005 WHO Classification. Clinical history was also taken into consideration. A total of 183 KCOTs were found, and the two genders were affected almost evenly (51.3% male; 48.7% female; male to female ratio 1.05 to 1). Patient age at the time of diagnosis ranged from 6 to 78 years, with a peak in the third decade of life (mean age: 32.8 years). The mandible was the site of occurrence of 70.5% of tumors; 16.4% occurred in the maxilla and 13.1% in both. Association with the nevoid basal cell carcinoma syndrome (NBCCS) was found in 6.0% of all tumors, and recurrence was found in 13.1% of patients. We found that tumors that initially appeared in the maxilla alone had a higher recurrence rate than those that first appeared in the mandible alone. Pathological examination of KCOT is important to avoid misdiagnosis and provide appropriate treatment and follow-up.


Cortical representation of swallowing: a modified dual task paradigm.
It is unclear whether the cortical representation of swallowing is lateralized to the left cerebral hemisphere, right hemisphere, or bilaterally represented. As dysphagia is common in acute stroke, it is important to elucidate swallowing lateralization to facilitate earlier detection of stroke patients who may be at greater risk for dysphagia and aspiration. In this study, a modified dual task paradigm was designed to study laterality of swallowing in a group of 14 healthy, young, right-handed, male adults. The subjects were studied at baseline and with interference. Baseline conditions, performed separately, were continuous swallowing, finger tapping using the right and left index fingers, and word repetition. Interference tasks, including tapping with the right index finger, tapping with the left index finger, and word repetition, were completed with and without swallowing. Finger-tapping rate was measured, and x-ray samples of the swallowing task were taped to measure swallowing rate and volume swallowed. At baseline, the rate of tapping the right index finger was significantly faster than that of the left index finger. There was a significant decline in the tapping rates of both left and right index fingers with swallowing interference. The volume per swallow was significantly reduced during the interfering language task of silent repetition. These results offer partial support for a bilateral representation of swallowing as well as suggest an important left hemispheric contribution to swallowing. However, it cannot be concluded that the left hemisphere is more important than the right, as a comparable right hemisphere task was not studied.


Comparing Outcomes of Flap-Based Salvage Reconstructions in the Radiated Breast.
Chest wall irradiation significantly decreases the strength and quality of breast tissue supporting prostheses, increasing the risk of skin breakdown and implant or tissue expander extrusion. Autologous tissue, including the latissimus dorsi (LD) or abdominal-based flaps, including the muscle-sparing transverse rectus abdominis myocutaneous or deep inferior epigastric perforator flaps, may be used to salvage reconstructions. However, data comparing outcomes of the two flap options remains limited. We compare postoperative outcomes from both flap types after autologous salvage reconstruction in irradiated breasts. Charts were retrospectively reviewed from patients who underwent either chest wall radiation or postmastectomy radiation therapy followed by salvage autologous reconstruction with either a LD and an implant or an abdominal-based flap (muscle-sparing transverse rectus abdominis myocutaneous or deep inferior epigastric perforator flaps). Patients with a history of tissue expander or implant failure requiring autologous salvage as part of 2-staged or delayed-immediate breast reconstruction that were operated on between January 2005 and November 2015 were included. Basic demographics, comorbidities, and recipient site complications (infection, wound dehiscence, seroma, hematoma, fat necrosis, and flap failure) were collected. A total of 72 patients met the inclusion criteria which included 72 flaps; 35 LD and 37 abdominally based flaps. Demographics and comorbidities did not vary significantly between patient groups. Mean follow-up was 767.6 weeks, and all reconstructions were unilateral. Nineteen (26.4%) patients had at least one complication, most commonly minor infections (9.7%). Overall complication rates were not significantly different between flap groups (P = 0.083). Wound dehiscence was significantly higher in the abdominal group (P = 0.045), and fat necrosis also trended higher in this group (P = 0.085). Major infection trended higher in the latissimus group (P = 0.069). When comparing outcomes of salvage flap-based reconstruction in radiated breast tissue, overall complication rates were similar when comparing postoperative outcomes between the LD- and abdominal-based flaps. Wound dehiscence was significantly higher when salvage reconstruction used an abdominal flap. Understanding the complications after salvage procedures can help inform decision making and optimize patient care to improve outcomes after breast reconstruction in the radiated breast.


Occupational Radiation Exposure and Deaths From Malignant Intracranial Neoplasms of the Brain and CNS in U.S. Radiologic Technologists, 1983-2012.
Childhood exposure to acute, high-dose radiation has consistently been associated with risk of benign and malignant intracranial tumors of the brain and CNS, but data on risks of adulthood exposure to protracted, low-to-moderate doses of radiation are limited. In a large cohort of radiologic technologists, we quantified the association between protracted, low-to-moderate doses of radiation and malignant intracranial tumor mortality. The study population included 83,655 female and 26,642 male U.S. radiologic technologists who were certified for at least 2 years as of 1982. The cohort was followed from the completion date of the first or second survey (1983-1989 or 1994-1998) to the date of death, loss to follow-up, or December 31, 2012, whichever was earliest. Occupational brain doses through 1997 were based on work history, historical data, and, for most years after the mid 1970s, individual film badge measurements. Radiation-related excess relative risks (ERRs) and 95% CIs were estimated from Poisson regression models adjusted for attained age and sex. Cumulative mean absorbed brain dose was 12 mGy (range, 0-290 mGy). During follow-up (median, 26.7 years), 193 technologists died of a malignant intracranial neoplasm. Based on models incorporating a 5-year lagged cumulative brain dose, cumulative brain dose was not associated with malignant intracranial tumor mortality (overall ERR per 100 mGy, 0.1; 95% CI, < -0.3 to 1.5). No effect modification was observed by sex or birth cohort. In this nationwide cohort of radiologic technologists, cumulative occupational radiation exposure to the brain was not associated with malignant intracranial tumor mortality.


Polyol concentrations in serum during hemodialysis.
Polyol concentrations were determined by selected-ion monitoring in 10 sample sets taken before dialysis and hourly for 4 h during dialysis. Predialysis concentrations (mumol/L) exceeding the upper limit of normal (mean + 2 SD; n = 33) were found for erythritol (25.4-59.0), threitol (11.5-46.7), and arabinitol (21.0-49.3) in all 10 cases; mannitol (2.7-62.0) in nine cases; and xylitol (0.7-1.3) in eight cases. Concentrations of adonitol, galactitol, and sorbitol were all within normal limits. During dialysis, the concentration of six polyols decreased by approximately 50%, but there were no significant changes for xylitol and adonitol. Erythritol, threitol, and arabinitol concentrations remained more than double the upper limit of normal in all patients after 4 h of dialysis. High residual concentrations were found for mannitol (seven cases) and xylitol (six cases). The results suggest fundamental differences in the homeostasis as well as the dialyzability of different polyols. The potential toxic significance of the high residual concentrations after a 4-h dialysis needs to be investigated.


Geologic storage of radioactive waste: field studies in Sweden.
Access to a granitic rock mass in an iron ore mine in Sweden provided a unique opportunity for underground experiments related to the geologic disposal of radioactive waste. These field tests demonstrated the importance of hydrogeology and the difficulties in predicting the thermomechanical behavior of fractured granitic rocks. To characterize a site fully, measurements made from the surface must be supplemented by extensive subsurface measurements and experiments. Much effort is needed at this stage to generate the technology required for the development of waste repositories.


Evidence that eukaryotic translation elongation factor 1A (eEF1A) binds the Gcn2 protein C terminus and inhibits Gcn2 activity.
The eukaryotic elongation factor 1A (eEF1A) delivers aminoacyl-tRNAs to the ribosomal A-site during protein synthesis. To ensure a continuous supply of amino acids, cells harbor the kinase Gcn2 and its effector protein Gcn1. The ultimate signal for amino acid shortage is uncharged tRNAs. We have proposed a model for sensing starvation, in which Gcn1 and Gcn2 are tethered to the ribosome, and Gcn1 is directly involved in delivering uncharged tRNAs from the A-site to Gcn2 for its subsequent activation. Gcn1 and Gcn2 are large proteins, and these proteins as well as eEF1A access the A-site, leading us to investigate whether there is a functional or physical link between these proteins. Using Saccharomyces cerevisiae cells expressing His(6)-eEF1A and affinity purification, we found that eEF1A co-eluted with Gcn2. Furthermore, Gcn2 co-immunoprecipitated with eEF1A, suggesting that they reside in the same complex. The purified GST-tagged Gcn2 C-terminal domain (CTD) was sufficient for precipitating eEF1A from whole cell extracts generated from gcn2Δ cells, independently of ribosomes. Purified GST-Gcn2-CTD and purified His(6)-eEF1A interacted with each other, and this was largely independent of the Lys residues in Gcn2-CTD known to be required for tRNA binding and ribosome association. Interestingly, Gcn2-eEF1A interaction was diminished in amino acid-starved cells and by uncharged tRNAs in vitro, suggesting that eEF1A functions as a Gcn2 inhibitor. Consistent with this possibility, purified eEF1A reduced the ability of Gcn2 to phosphorylate its substrate, eIF2α, but did not diminish Gcn2 autophosphorylation. These findings implicate eEF1A in the intricate regulation of Gcn2 and amino acid homeostasis.


Novel biophysical determination of miRNAs related to prostate and head and neck cancers.
In this study we have chosen a new approach and characterized three miRNAs (miR-23a, miR-34a and miR-320a) related to prostate cancer and head and neck cancer by spectral (circular dichroic and UV-absorption spectra) and electrochemical (voltammetry at graphite and mercury electrodes) methods. The spectral and voltammetric results, reflecting different nucleotide sequences of miRNAs, were complemented by the results of DNAs(U) having the same oligonucleotide sequences as miRNAs. The effect of the substitution of ribose for deoxyribose was shown and structural diversity was confirmed. The stability of RNA and DNA(U) was studied using CD and UV-absorption spectroscopy and melting points were calculated. MiRNA-320a with the highest content of guanine provided the highest melting point. With respect to the rapid progress of miRNA electrochemical sensors, our results will be useful for the research and development of sensitive, portable and time-efficient miRNA sensors, which will be able to diagnose cancer and other diseases.


Engineering a cleavable disulfide bond into a natural product siderophore using precursor-directed biosynthesis.
An analogue of the bacterial siderophore desferrioxamine B (DFOB) containing a disulfide motif in the backbone was produced from Streptomyces pilosus cultures supplemented with cystamine. Cystamine competed against native 1,5-diaminopentane during assembly. DFOB-(SS)1[001] and its complexes with Fe(iii) or Ga(iii) were cleaved upon incubation with dithiothreitol. Compounds such as DFOB-(SS)1[001] and its thiol-containing cleavage products could expand antibiotic strategies and Au-S-based nanotechnologies.


The impact of electroencephalography, pressure, and pO2 monitoring on the risk of stroke during cardiopulmonary bypass.
Currently it is possible to account for an incidence of perfusion-related perioperative stroke of about 1%. The sources of stroke over which cardiac surgeons have some control relate to the perfusion circuit, the conducting of coronary pulmonary bypass, the operative approach to the patient with intracardiac clot, maneuvers that eliminate air during left heart procedures, control of biochemical factors such as hyperglycemia, and to the choice of anesthetic agents and drugs given during the procedure. The availability of equipment that allows in-line continuous monitoring of arterial and venous O2 saturations, control of physiologic parameters within certain limits, selective use of encephalographic monitoring for high-risk patients, along with careful attention to the details of the procedure, may allow the surgeon to alter favorably the numbers of patients suffering neurologic complications as a consequence of cardiac surgery. We have limited our investigation in this study to those neurologic events occurring from the onset of anesthesia through the recovery from anesthesia when the patient can be neurologically examined.


Homology and molecular dynamics models of toll-like receptor 7 protein and its dimerization.
Toll-like receptor protein 7 is a transmembrane protein playing a crucial role in the signaling pathways involved in innate immunity. Its crystal structure is not yet available, but there are several proteins possessing domains of sufficiently high homology, which enabled us to build a model of the toll-like receptor protein 7 monomer and gain insights into dimer formation. To obtain a reliable structure prediction, we subjected this model to equilibration using molecular dynamics simulations. Furthermore, the equilibrated monomer structure was used to construct models of dimerization and to predict binding sites for small ligands. Docking studies were performed for some of the known toll-like receptor protein 7 ligands. We determined that a new homology model generated by the LOOPP server provides a good alternative to a previously reported model. Our docking results indicate that the addition of either imiquimod or 1V209 to a toll-like receptor protein 7 dimer changes an unfavorable interaction into a favorable one. We found that eight small molecules docked to two pockets in toll-like receptor protein 7 bind to both pockets at pH 7 and at pH 5.5. This work provides a realistic model that could be used for drug discovery aimed at finding toll-like receptor protein 7 dimerization activators, with potential clinical applications to a host of diseases, including cancer.


A mouse model of naturally occurring age-related cognitive impairment.
Age-related cognitive impairment (ARCI) is a neurological condition that affects millions of older people, but little is known about the increased risk of developing more severe neurodegeneration and dementia. Preclinical research is needed to understand the mechanisms of the impairment and the neuropathology associated with it. We have characterized a model of naturally occurring ARCI in the C57BL/6J mouse strain that shows an age-dependent development of cognitive impairment. As in people, some mice have little cognitive impairment while others have more severe cognitive impairment. Therefore, mice can be categorized as resistant or susceptible and the two groups can be studied for behavioral and neuropathology differences. Preliminary observations show no difference in strength and agility test scores between ARCI resistant and susceptible mice of either sex suggesting the cognitive impairment in ARCI susceptible mice is not accompanied by impairment in daily living activities, similar to ARCI in humans. The hippocampal area of the brain from ARCI susceptible mice shows evidence of an increase in the inflammatory cytokine MCP-1 compared to ARCI resistant mice, suggesting inflammation may be associated with ARCI. These preliminary observations suggest that ARCI in C57BL/6J mice could be a high-impact model to study how resilience to brain aging may predict resilience to dementia associated with Alzheimer's disease and other age-related neurological conditions.


Atmospheric dry deposition of persistent organic pollutants to the Atlantic and inferences for the global oceans.
Atmospheric deposition to the oceans is a key process affecting the global dynamics and sinks of persistent organic pollutants (POPs). A new methodology that combines aerosol remote sensing measurements with measured POP aerosol-phase concentrations is presented to derive dry particulate depositional fluxes of POPs to the oceans. These fluxes are compared with those due to diffusive air-water exchange. For all polychlorinated biphenyl (PCB) congeners and lower chlorinated dibenzo-p-dioxins and furans (PCDD/Fs), air-water exchange dominates the dry deposition mechanism. However, this tendency reverses in some areas, such as in marine aerosol influenced areas and dust outflow regions, consistent with the important variability encountered for the depositional fluxes. Seasonal variability is mainly found in mid-high latitudes, due to the important influence of wind speed enhancing dry deposition fluxes and temperature as a driver of the gas-particle partitioning of POPs. The average dry aerosol deposition flux of sigmaPCBs and sigmaPCDD/Fs to the Atlantic Ocean is calculated to be in the order of 66 ng m(-2) yr(-1) and 9 ng m(-2)yr(-1) respectively. The total dry aerosol deposition of sigmaPCBs and sigmaPCDD/Fs to the Atlantic Ocean is estimated to be 2200 kg yr(-1) and 500 kg yr(-1), respectively, while the net air-water exchange is higher, 22000 kg sigmaPCBs yr(-1) for PCBs and 1300 kg sigmaPCDD/Fs yr(-1). Furthermore, it is suggested that marine aerosol plays an important role in scavenging atmospheric contaminants.


[Risk stratification in heart surgery].
Risk scores have been important in patient assessment, such as, age, severity of heart disease, and comorbidity in patients undergoing heart surgery. Several risk scores have been developed to predict mortality after heart surgery. This paper analyzes data of the world, cardiac surgery reporting system, which contains information on cardiac preoperative risk factors, and postoperative complications.


Tumor size as a predictive factor.
Is tumor size a predictive factor in carcinoma of the pancreas? In order to answer this question, the data of the Japan Pancreatic Cancer Registry from 1981 to 1987 were retrospectively analyzed. Of the 7687 cases that were registered, 5826 cases (75.7%) were laparotomized. Out of the 5826, 2311 (39.7%) underwent resection. Postoperative deaths within 1 mo among resected cases numbered 104, and the operative mortality rate was 4.5%. The postoperative survival rates were calculated by Kaplan-Meier's method. They clearly showed that the rates for small carcinomas (greater than 2 cm [T1]) were significantly higher than those for the tumors larger than 2 cm (T2, T3, T4) according to the Greenwood formula. Although the survival-rate calculation excluded operative deaths and deaths of causes other than pancreatic cancer, and included islet cell carcinoma, cystadenocarcinoma, and acinar cell carcinoma, it seems that tumor size may be a predictive factor for postoperative prognosis. However, our previous study on long-term survivors (more than 5 yr) after resection on the exocrine pancreatic cancer) revealed that there was no relation between the size of tumor and the postoperative prognosis. In those long-term survivors, there was no definite or severe cancerous invasion of either the retroperitoneal tissue or the portal venous system. It is concluded that a tumor 2 cm or smaller has a significantly better prognosis after resection than does a tumor larger than 2 cm, and it seems, in general, that tumor size may be a predictive factor. However, if the tumor does not invade the retroperitoneal tissue or the portal venous system, tumor size per se is not always a predictive factor.


[The right to complain under the BOPZ Act (Formal Admissions to Psychiatric Hospitals): experiences in psychogeriatrics].
The Act on Formal Admissions to Psychiatric Hospitals (BOPZ) enables psychogeriatric patients to complain. According to a BOPZ evaluation study concerning the right to complain, which was held in 1995 and 1996, the current procedure to complain appears to be inadequate for psychogeriatric patients. The Act on the right to complain, which came into force recently, didn't improve this procedural inadequacy. We suggest to improve the right to complain both at the level of government as at the institutional level. The right to complain could thus contribute substantially to the legal position of the psychogeriatric patient and the quality of health care. The introduction of a client informant is recommended.


Autobiologies on YouTube: Narratives of Direct-to-Consumer Genetic Testing.
Despite a growing personal genomics market, little is known about how people engage with the possibilities offered by direct-to-consumer (DTC) genetic testing. In order to help address this gap, this study deploys narrative analysis of YouTube videos posted by individuals who have purchased DTC genetic testing for disease. Genetic testing is said to be contributing to new states of illness, where individuals may become "patients-in-waiting." In the videos analyzed, we found a new form of storytelling about this ambiguous state of illness, which we refer to as autobiology. Autobiology - the study of, and story about, one's own biology - concerns narratives of sense-making through forms of biological practice, as well as wayfaring narratives which interweave genetic markers and family histories of disease. These autobiologies - part of a broader shift toward public stories about genetics and other healthcare technologies - exhibit playfulness, as well as being bound with consumerist practices.


Prolonged suppression of a corticotropin-producing bronchial carcinoid by oral bromocriptine.
The addition of orally administered bromocriptine mesylate to cyproheptadine hydrochloride therapy completely normalized urinary-free cortisol levels for three months in a 21-year-old woman with Cushing's syndrome in whom results from standard dexamethasone suppression and metyrapone stimulation tests as well as baseline corticotropin levels were originally compatible with a diagnosis of an occult pituitary adenoma. When transsphenoidal exploration of the sella turcica was unsuccessful and hypercortisolism persisted, the source of corticotropin was discovered using petrosal sinus and venal caval catheterization. A 1 X 1.5-cm carcinoid tumor of the lung was identified and removed, thereby correcting the hypercortisolism. The tumor was demonstrated by immunoperoxidase staining to contain corticotropin. Orally administered bromocriptine, with or without cyproheptadine therapy, may be useful in the palliative treatment of some patients with carcinoid or other ectopic corticotropin-producing tumors. We postulate that bromocriptine therapy acted directly on carcinoid tumor cells to directly inhibit corticotropin production by a dopaminergic mechanism.


A survey of the practice of nurses' skills in Wenchuan earthquake disaster sites: implications for disaster training.
To determine nursing skills most relevant for nurses participating in disaster response medical teams; make recommendations to enhance training of nurses who will be first responders to a disaster site; to improve the capacity of nurses to prepare and respond to severe natural disasters. Worldwide, nurses play a key role in disaster response teams at disaster sites. They are often not prepared for the challenges of dealing with mass casualties; little research exists into what basic nursing skills are required by nurses who are first responders to a disaster situation. This study assessed the most relevant disaster nursing skills of first responder nurses at the 2008 Wenchuan earthquake disaster site. Data were collected in China in 2008 using a self-designed questionnaire, with 24 participants who had been part of the medical teams that were dispatched to the disaster sites. The top three skills essential for nurses were: intravenous insertion; observation and monitoring; mass casualty triage. The three most frequently used skills were: debridement and dressing; observation and monitoring; intravenous insertion. The three skills performed most proficiently were: intravenous insertion; observation and monitoring; urethral catheterization. The top three ranking skills most important for training were: mass casualty transportation; emergency management; haemostasis, bandaging, fixation, manual handling. The core nursing skills for disaster response training are: mass casualty transportation; emergency management; haemostasis, bandaging, fixation, manual handling; observation and monitoring; mass casualty triage; controlling specific infection; psychological crisis intervention; cardiopulmonary resuscitation; debridement and dressing; central venous catheter insertion; patient care recording.


Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study.
Approximately 40,000 men die each year of hormone-refractory prostate cancer (HRPC). The results of treatment with chemotherapy have been disappointing to date, with no trials demonstrating a benefit with respect to survival duration. Corticosteroids and mitoxantrone each have been shown to be active agents in this disease. The purpose of this study was to demonstrate an advantage of mitoxantrone and hydrocortisone (M+H) over hydrocortisone alone with respect to survival duration. Two hundred forty-two patients with HRPC were randomized to receive either M+H or hydrocortisone alone. Patients were monitored for survival, time to disease progression, time to treatment failure, response, and quality-of-life (QOL) parameters. Treatment in both arms was well tolerated. Although there was a delay in time to treatment failure and disease progression in favor of M+H over hydrocortisone alone, there was no difference in overall survival (12.3 months for M+H v 12.6 months for hydrocortisone alone). There was an indication that QOL was better with M+H, in particular with respect to pain control. M+H generated more frequent responses and a delay in both time to treatment failure and disease progression compared with hydrocortisone alone. In addition, there was a possible benefit of M+H with respect to pain control over hydrocortisone alone. No improvement in survival was observed. Although M+H could be viewed as a palliative option for patients with HRPC, new drugs and novel strategies are needed to improve survival for this disease.


Electrical activity alterations induced by chronic absorption of lindane (gamma-hexachlorocyclohexane) trace concentrations in adult rat heart.
The heart of adult rat offspring, born to mothers treated with trace concentrations of lindane (0.5 to 2 ppb) through a beverage and to mothers chronically treated with lindane (CL-T) with the same trace concentration, also through a beverage, during lactation and growth has a round shape and accumulates lindane. The left ventricle (LV) presents a hypertrophied area, atrophied papillary muscles, and unorganized collagen bundles and layers. These observations led us to study the electrical activity of their left ventricle papillary muscles (LVPM) by recording action potential using intracellular microelectrodes. CL-T shortened LVPM action potential duration (APD): 1 ppb shortened the plateau; 2 ppb shortened the plateau and the slow repolarizing phase. In CL-T (2 ppb) and untreated groups, low temperature (22 degrees C) decreased the resting potential and prolonged APD. TEA (tetraethylammonium; 1-2 mmol/L) partially lengthened CL-T (2 ppb lindane) APD. Quinidine (0.2 mmol/L) and E-4031 (10 nmol/L) prolonged CL-T APD, suggesting that the rapid delayed outward K+ current (IKr) was increased. Our results indicate the silent effects of chronic exposure to trace concentrations of lindane on the morphological and electrical activity of heart muscle. They demonstrate that chronic lindane treatment of female rats alters the tissue integrity and electrical activity in the LV of their offspring.


Sediment ingestion rates in waterfowl (Anatidae) and their use in environmental risk assessment.
When waterfowl (Anatidae) ingest sediment as they feed, they are exposed to the environmental contaminants in those sediments. The rate of ingestion may be key to assessing environmental risk. Rates of sediment ingestion were estimated as from <2% to 22% in 16 species of waterfowl collected in the northeastern United States. The piscivorous red-breasted merganser (Mergus serrator) ingested sediment at the lowest rate and the benthos-feeding canvasback (Aythya valisineria) at the highest rate. Sediment ingestion rates were related to diet and to the sediments where waterfowl fed. Waterfowl ingested the least sediment from hard-bottomed habitats with fast-moving water and ingested the most sediment from soft-bottomed areas with slow-moving water. Understanding the greater hazards from contaminants associated with low-flow habitats may help in prioritizing sites to be remediated. The tundra swan (Cygnus columbianus), which ingests sediment at an estimated 8.4% of its diet, dry weight, is suggested as a potential generic model for use in environmental risk assessments designed to protect waterfowl.


Heterotypic gap junctions between two neurons in the drosophila brain are critical for memory.
Gap junctions play an important role in the regulation of neuronal metabolism and homeostasis by serving as connections that enable small molecules to pass between cells and synchronize activity between cells. Although recent studies have linked gap junctions to memory formation, it remains unclear how they contribute to this process. Gap junctions are hexameric hemichannels formed from the connexin and pannexin gene families in chordates and the innexin (inx) gene family in invertebrates. Here we show that two modulatory neurons, the anterior paired lateral (APL) neuron and the dorsal paired medial (DPM) neuron, form heterotypic gap junctions within the mushroom body (MB), a learning and memory center in the Drosophila brain. Using RNA interference-mediated knockdowns of inx7 and inx6 in the APL and DPM neurons, respectively, we found that flies showed normal olfactory associative learning and intact anesthesia-resistant memory (ARM) but failed to form anesthesia-sensitive memory (ASM). Our results reveal that the heterotypic gap junctions between the APL and DPM neurons are an essential part of the MB circuitry for memory formation, potentially constituting a recurrent neural network to stabilize ASM.


Salivary cortisol: a better measure of adrenal cortical function than serum cortisol.
Salivary cortisol concentration was found to be directly proportional to the serum unbound cortisol concentration both in normal men and women and in women with elevated cortisol-binding globulin (CBG). The correlation was excellent in dynamic tests of adrenal function (dexamethasone suppression, ACTH stimulation), in normals and patients with adrenal insufficiency, in tests of circadian variation and randomly collected samples. Women in the third trimester of normal pregnancy exhibited elevated salivary cortisol throughout the day. The relationship between salivary and serum total cortisol concentration was markedly non-linear with a more rapid increase in salivary concentration once the serum CBG was saturated. The rate of equilibrium of cortisol between blood and saliva was very fast, being much less than 5 minutes. These data, combined with a simple, stress-free, non-invasive collection procedure, lead us to suggest that salivary cortisol is a more appropriate measure for the clinical assessment of adrenocortical function than is serum cortisol.


Temporal regulation of cytokine mRNA expression by tristetraprolin: dynamic control by p38 MAPK and MKP-1.
Cytokines drive many inflammatory diseases, including asthma. Understanding the molecular mechanisms responsible for cytokine secretion will allow us to develop novel strategies to repress inflammation in the future. Harnessing the power of endogenous anti-inflammatory proteins is one such strategy. In this study, we investigate the p38 MAPK-mediated regulatory interaction of two anti-inflammatory proteins, mitogen-activated protein kinase phosphatase 1 (MKP-1) and tristetraprolin (TTP), in the context of asthmatic inflammation. Using primary cultures of airway smooth muscle cells in vitro, we explored the temporal regulation of IL-6 cytokine mRNA expression upon stimulation with TNF-α. Intriguingly, the temporal profile of mRNA expression was biphasic. This was not due to COX-2-derived prostanoid upregulation, increased expression of NLRP3 inflammasome components, or upregulation of the cognate receptor for TNF-α-TNFR1. Rather, the biphasic nature of TNF-α-induced IL-6 mRNA expression was regulated temporally by the RNA-destabilizing molecule, TTP. Importantly, TTP function is controlled by p38 MAPK, and our study reveals that its expression in airway smooth muscle cells is p38 MAPK-dependent and its anti-inflammatory activity is also controlled by p38 MAPK-mediated phosphorylation. MKP-1 is a MAPK deactivator; thus, by controlling p38 MAPK phosphorylation status in a temporally distinct manner, MKP-1 ensures that TTP is expressed and made functional at precisely the correct time to repress cytokine expression. Together, p38 MAPK, MKP-1, and TTP may form a regulatory network that exerts significant control on cytokine secretion in proasthmatic inflammation through precise temporal signaling.


[Principal results of physiological experiments with mammals aboard biosatellite "Cosmos-936"].
The program of the 18.5-day flight of the biosatellite Cosmos-936 included studies of physiological effects of prolonged weightlessness (20 rats) and artificial gravity (10 rats). The latter produced a normalizing effect on the function of the myocardium, musculo-skeletal system and excretory system. Simultaneously, artificial gravity exerted an adverse effect on the functions dependent on several sensors, primarily optic, vestibular and motor sensors. It is postulated that the adverse effects are associated with a relatively high rate of rotation and a short arm of the centrifuge.


Comparison of the function of the beta(C) and beta(E) subunits of activin in AML12 hepatocytes.
To investigate the function of the beta(C) and beta(E) subunits of activin, we overexpressed these subunits in AML12 cells, a normal hepatocyte cell line, using adenovirus vector. Overexpression of the beta(C) subunit increased [3H]thymidine incorporation and the cell number. In contrast, both [3H]thymidine incorporation and the cell number were reduced in the beta(E) overexpressing cells. When AML cells overexpressing the beta(E) subunit were cultured in medium containing 1% serum for 48 h, many of the cells died by apoptosis, whereas cells overexpressing the beta(C) subunit or beta-galactosidase survived in the same condition. To examine dimer formation, the beta(C) and beta(E) subunits were expressed in AML12 cells. In these cells, the beta(C) homodimer, the beta(E) homodimer and the beta(C)-beta(E) heterodimer were detected. When the expression level of the beta(E) subunit was increased, formation of the beta(E) homodimer was increased, while formation of the beta(C)-beta(E) heterodimer was slightly reduced. Overexpression of the beta(E) subunit did not significantly affect the formation of the beta(C) homodimer. These results indicate that the beta(C) and beta(E) subunits form homo- and heterodimers, and that the functions of the two subunits are quite different.


Psychopathological features of anorectic patients who dropped out of inpatient treatment as assessed by the Minnesota multiphasic personality inventory.
Anorexia nervosa often requires inpatient treatment that includes psychotherapeutic intervention in addition to physical and nutritional management for severe low body weight. However, such patients sometimes terminate inpatient treatment prematurely because of resistance to treatment, poor motivation for treatment, unstable emotions, and problematic behaviors. In this study, the psychopathological factors related to the personality of anorexic patients that might predict discontinuation of inpatient treatment were investigated using the Minnesota Multiphasic Personality Inventory (MMPI). Subjects were 75 consecutive anorectic inpatients who received cognitive behavioral therapy with a behavior protocol governing privileges in a university hospital based general (not psychiatric) ward. The MMPI was done on admission for all patients. A comparison was done of patients who completed the process of inpatient treatment, including attainment of target body weight (completers), and patients who dropped out of inpatient treatment (dropouts). No significant differences between completers (n = 51) and dropouts (n = 24) were found in the type of eating disorder, age of onset, duration of illness, age, or BMI at admission. Logistic regression analysis found the MMPI scales schizophrenia (Sc), hypomania (HYP), deviant thinking and experience, and antisocial attitude to be factors predicting completion or dropout. Dropouts have difficulty adapting to inpatient treatment protocols such as our behavior protocol governing privileges because they have social and emotional alienation, a lack of ego mastery (Sc), emotional instability (HYP) and an antisocial attitude. As a result, they have decreased motivation for treatment, leave the hospital without permission, attempt suicide, or shoplift, which leads them to terminate inpatient treatment prematurely. Treatments based on cognitive behavioral therapy with a behavior protocol governing privileges should be carefully adopted for anorectic patients who exhibit the psychopathological elements identified in this study.


Genetic, Maternal, and Environmental Risk Factors for Cryptorchidism: An Update.
Unilateral or bilateral cryptorchidism is an isolated anomaly in the majority of cases, with evidence to date suggesting that it is a complex disorder resulting from interactions between genetic and environmental factors. Population, family, and limited genome-wide association data suggest moderate genetic risk, multiple susceptibility loci, and a role for the maternal environment. Epidemiologic studies have identified low birth weight or intrauterine growth retardation as factors most strongly associated with cryptorchidism, with additional evidence suggesting that maternal smoking and gestational diabetes increase risk. Animal studies have shown that the testis regulates its own descent by secretion of hormones that stimulate differentiation of the gubernaculum, and that endocrine-disrupting chemicals (EDCs) exhibit antiandrogenic and/or estrogenic activity that alters testicular function or gubernacular response to hormonal stimulation. However, we have yet to determine the degree to which EDCs contribute to cryptorchidism risk in humans, in part due to the varying methodology used in epidemiological and exposure studies. Large populations will be required to define the gene-environment interactions that predispose to cryptorchidism, in view of multiple small effect genetic susceptibility loci, ubiquitous exposure to mixtures of EDCs, and possible epigenetic effects. The present review provides an update of potential genetic and environmental risk factors for cryptorchidism, and future work required to better understand the etiology of this common and complex disease.


acal is a long non-coding RNA in JNK signaling in epithelial shape changes during drosophila dorsal closure.
Dorsal closure is an epithelial remodeling process taking place during Drosophila embryogenesis. JNK signaling coordinates dorsal closure. We identify and characterize acal as a novel negative dorsal closure regulator. acal represents a new level of JNK regulation. The acal locus codes for a conserved, long, non-coding, nuclear RNA. Long non-coding RNAs are an abundant and diverse class of gene regulators. Mutations in acal are lethal. acal mRNA expression is dynamic and is processed into a collection of 50 to 120 bp fragments. We show that acal lies downstream of raw, a pioneer protein, helping explain part of raw functions, and interacts genetically with Polycomb. acal functions in trans regulating mRNA expression of two genes involved in JNK signaling and dorsal closure: Connector of kinase to AP1 (Cka) and anterior open (aop). Cka is a conserved scaffold protein that brings together JNK and Jun, and aop is a transcription factor. Misregulation of Cka and aop can account for dorsal closure phenotypes in acal mutants.


Biomechanical study of 4-hole pubic symphyseal plating: locked versus unlocked constructs.
To the authors' knowledge, no published studies have examined the use of locking plates on injuries of the anterior pelvic ring. The purpose of this study was to determine whether locked plates provide enhanced stability in the treatment of pubic symphyseal disruptions. Completely unstable pelvic injuries were simulated in pelvic Sawbones (model 1301; Pacific Research Laboratories, Vashon, Washington) and 2 different fixation constructs used for anterior fixation (4-hole, 3.5-mm pubic symphysis plate with all locked or all unlocked screws). Adjunctive sacroiliac screw fixation with a single 7.3-mm screw placed into S1 was used in all specimens. Specimens were analyzed for motion at the pubic symphysis and sacroiliac joints using a Material Testing System (MTS Systems Corporation, Eden Prairie, Minnesota). Each specimen was subjected to compressive loading in a single-limb stance. Side loading was also examined. The main outcome measurement was motion at the pubic symphysis and sacroiliac joints and overall construct stiffness. No significant difference existed in overall construct stiffness between the 2 methods of pubic symphysis fixation. The motions at the pubic symphysis or injured sacroiliac joints were not significantly different. In addition, motion at the pubic symphysis joint with lateral load was not improved with a locking construct.No significant difference existed between 4-hole locked or unlocked constructs used for fixation of the pubic symphysis. No apparent advantage of locking screws exists for disruptions of the pubic symphysis, and recent reports have questioned the possibility of catastrophic failure.


Apical Reference Stimulation: A Possible Solution to Facial Nerve Stimulation.
Postimplantation facial nerve stimulation is a common side-effect of intracochlear electrical stimulation. Facial nerve stimulation occurs when electric current intended to stimulate the auditory nerve, spread beyond the cochlea to excite the nearby facial nerve, causing involuntarily facial muscle contractions. Facial nerve stimulation can often be resolved through adjustments in speech processor fitting but, in some instances, these measures exhibit limited benefit or may have a detrimental effect on speech perception. In this study, apical reference stimulation mode was investigated as a potential intervention to facial nerve stimulation. Apical reference stimulation is a bipolar stimulation strategy in which the most apical electrode is used as the reference electrode for stimulation on all the other intracochlear electrodes. A person-specific model of the human cochlea, facial nerve and electrode array, coupled with a neural model, was used to predict excitation of auditory and facial nerve fibers. These predictions were used to evaluate the effectiveness in reducing facial nerve stimulation using apical reference stimulation. Predictions were confirmed in psychoacoustic tests by determining auditory comfort and threshold levels for the apical reference stimulation mode while capturing electromyography data in two participants. Models predicted a favorable outcome for apical reference stimulation, as facial nerve fiber thresholds were higher and auditory thresholds were lower, in direct comparison to conventional monopolar stimulation. Psychophysical tests also illustrated decreased auditory thresholds and increased dynamic range during apical reference stimulation. Furthermore, apical reference stimulation resulted in lower electromyography energy levels, compared to conventional monopolar stimulation, which suggests a reduction in facial nerve stimulation. Subjective feedback corroborated that apical reference stimulation alleviated facial nerve stimulation. Apical reference stimulation may be a viable strategy to alleviate facial nerve stimulation considering the improvements in dynamic range and auditory thresholds, complemented with a reduction in facial nerve stimulation symptoms.


Fish oil ameliorates renal injury and hyperlipidemia in the Milan normotensive rat model of focal glomerulosclerosis.
Rats of the Milan normotensive rat strain (MNS) spontaneously develop severe proteinuria and excessive glomerular thromboxane (Tx)A2 production at a young age. These abnormalities are accompanied by podocyte alterations, progressive focal glomerulosclerosis (FGS), and interstitial fibrosis, resembling human FGS. Since it has been shown that pharmacologic Tx-synthase inhibition protects MNS rats from these changes, it was hypothesized that a fish oil (FO) enriched diet, by enhancing TxA3 production instead of TxA2, might afford similar protection, compared with diets enriched in safflower oil (SO) or lard (LD). Rats were pair-fed 11% fat diets from age of 1 to 11 months. Glomerular TxA2 at 11 months was significantly lower in PO-fed rats than in SO- and LD-fed rats (11 +/- 3.0, 69 +/- 3.0, 59 +/- 19.0 nanograms per min/mg, respectively; P < 0.001). At 3 months, urinary albumin excretion was similar among the groups. Over the course of the study, rats fed FO developed significantly less albuminuria than the SO and LD groups (P < 0.001 by analysis of variance for repeated measures), such that the values at 11 months were 25 +/- 5.8, 49 +/- 8.7, and 68 +/- 13.0 mg/24h, respectively. Serum cholesterol and triglycerides were also significantly lower in FO-fed rats than in SO- and LD-fed rats. The extent of FGS was similar in the three groups, but FO-fed rats had less interstitial injury than the other groups. It was observed that a fish-oil diet substantially alleviated albuminuria, normalized nephrotic hyperlipidemia, and reduced interstitial injury, but did not prevent the development of FGS in the MNS model.


Robotic System for Inspection by Contact of Bridge Beams Using UAVs.
This paper presents a robotic system using Unmanned Aerial Vehicles (UAVs) for bridge-inspection tasks that require physical contact between the aerial platform and the bridge surfaces, such as beam-deflection analysis or measuring crack depth with an ultrasonic sensor. The proposed system takes advantage of the aerodynamic ceiling effect that arises when the multirotor gets close to the bridge surface. Moreover, this paper describes how a UAV can be used as a sensor that is able to fly and touch the bridge to take measurements during an inspection by contact. A practical application of the system involving the measurement of a bridge's beam deflection using a laser tracking station is also presented. In order to validate our system, experiments on two different bridges involving the measurement of the deflection of their beams are shown.


Pharmacogenetics in Europe: barriers and opportunities.
This paper reviews the current situation in the field of pharmacogenetics/pharmacogenomics (PGx) in Europe. High expectations surrounding the clinical application of PGx remain largely unmet, as only a limited number of such applications have actually reached the market and clinical practice. Thus, the potential impact of PGx-based diagnostics on healthcare and its socio-economic implications are still unclear. With the aim of shedding some light on these uncertainties, the Institute for Prospective Technological Studies (IPTS) of the European Commission's Joint Research Centre (JRC) has conducted a review of the 'state of the art' and a further analysis on the use of pharmacogenetics diagnostics for preventing toxic drug reactions and improving drug efficacy in Europe. The paper presents highlights from the JRC-IPTS studies and discusses possibilities for improving translation of PGx research in Europe by comparing some experiences in the USA. We also illustrate the related barriers for the clinical uptake of PGx in Europe with specific case-studies. Most of the barriers identified extend beyond the European context. This reflects the global problems of scarcity of data demonstrating proven clinical validity or utility and favorable cost-effectiveness studies to support the clinical application of PGx diagnostic tests in the clinical setting. Another key barrier is the lack of incentives for the private sector to invest in the development and licensing of PGx diagnostic tests for improving the safety and efficacy of out-of-patent drugs. It therefore seems that one key aspect where policy can affect the clinical uptake of PGx is via sustaining large-scale industry-academia collaborations for developing and proving the utility of PGx diagnostics.


Safety and efficacy of Trans-warmer mattress for preterm neonates: results of a randomized controlled trial.
To compare the admission temperatures, incidence of hypothermia and discharge outcomes of preterm neonates managed with Trans-warmer mattress (TWM) initiated in the delivery room (DR) and controls. A prospective quasi-randomized controlled trial was performed between January and November 2009 on preterm neonates <32 weeks gestation. Infants in the intervention group were resuscitated and transported to neonatal intensive care unit (NICU) on a TWM, in addition to other measures recommended by the Neonatal Resuscitation Program. The mean (s.d.) gestational age 28.7 (3) vs 28.7 (2.4) weeks and birth weight 1151 (407) vs 1175 (413) g) were comparable in the intervention (n=53) and control (n=49) groups. Temperature of the DR, maternal temperature, 5 min Apgar score, mode of delivery, cord pH and need for resuscitation were similar in both groups. Temperature of neonates in the DR (36.3 vs 36.0 °C) was also similar. Admission temperature in the NICU was significantly higher 36.2 °C (0.8) vs 35.7 °C (0.8) and incidence of hypothermia (temperatures <36 °C) lower in the intervention group (34 vs 57%, P<0.05). TWM use was not associated with any adverse effects. On logistic regression, low birth weight, lack of use of TWM and low DR temperature were independently associated with admission hypothermia. In this quasi-randomized controlled trial, the admission temperatures of preterm neonates on whom TWM was used were significantly higher compared to controls with a reduction in the incidence of hypothermia. A TWM initiated in the DR may be a simple efficacious method of reducing hypothermia in preterm neonates.


An in-silico approach to design potential siRNAs against the ORF57 of Kaposi's sarcoma-associated herpesvirus.
Kaposi's sarcoma-associated herpesvirus (KSHV) is one of the few human oncogenic viruses, which causes a variety of malignancies, including Kaposi's sarcoma, multicentric Castleman disease, and primary effusion lymphoma, particularly in human immunodeficiency virus patients. The currently available treatment options cannot always prevent the invasion and dissemination of this virus. In recent times, siRNA-based therapeutics are gaining prominence over conventional medications as siRNA can be designed to target almost any gene of interest. The ORF57 is a crucial regulatory protein for lytic gene expression of KSHV. Disruption of this gene translation will inevitably inhibit the replication of the virus in the host cell. Therefore, the ORF57 of KSHV could be a potential target for designing siRNA-based therapeutics. Considering both sequence preferences and target site accessibility, several online tools (i-SCORE Designer, Sfold web server) had been utilized to predict the siRNA guide strand against the ORF57. Subsequently, off-target filtration (BLAST), conservancy test (fuzznuc), and thermodynamics analysis (RNAcofold, RNAalifold, and RNA Structure web server) were also performed to select the most suitable siRNA sequences. Finally, two siRNAs were identified that passed all of the filtration phases and fulfilled the thermodynamic criteria. We hope that the siRNAs predicted in this study would be helpful for the development of new effective therapeutics against KSHV.


Long-acting nanoformulated antiretroviral therapy elicits potent antiretroviral and neuroprotective responses in HIV-1-infected humanized mice.
Long-acting nanoformulated antiretroviral therapy (nanoART) with improved pharmacokinetics, biodistribution and limited systemic toxicities will likely improve drug adherence and access to viral reservoirs. Atazanavir and ritonavir crystalline nanoART were formulated in a poloxamer-188 excipient by high-pressure homogenization. These formulations were evaluated for antiretroviral and neuroprotective activities in humanized NOD/scid-IL-2Rgc (NSG) mice. NanoART-treated NSG mice were evaluated for drug biodistribution, pharmacodynamics and toxicity. CD34 human hematopoietic stem cells were transplanted at birth in replicate NSG mice. The mice were infected with HIV-1ADA at 5 months of age. Eight weeks later, the infected animals were treated with weekly subcutaneous injections of nanoformulated ATV and RTV. Peripheral viral load, CD4 T-cell counts and lymphoid and brain histopathology and immunohistochemistry tests were performed. NanoART treatments by once-a-week injections reduced viral loads more than 1000-fold and protected CD4 T-cell populations. This paralleled high ART levels in liver, spleen and blood that were in or around the human minimal effective dose concentration without notable toxicities. Importantly, examination of infected brain subregions showed that nanoART elicited neuroprotective responses with detectable increases in microtubule-associated protein-2, synaptophysin and neurofilament expression when compared to untreated virus-infected animals. Therapeutic interruptions produced profound viral rebounds. Long-acting nanoART has translational potential with sustained and targeted efficacy and with limited systemic toxicities. Such success in drug delivery and distribution could improve drug adherence and reduce viral resistance in infected people.


Anomalies of the TGF-beta postreceptor signaling pathway in ovarian cancer cell lines.
Transforming growth factor-beta (TGF-beta) can cause cell cycle arrest, terminal differentiation, or apoptosis in most normal epithelial cells, whereas most malignant cell lines are resistant to TGF-beta. Mechanisms of resistance to TGF-beta caused by modulation of cell cycle regulators and/or inactivation of components of the TGF-beta signaling transduction pathway such as C-myc and Smad4 have been demonstrated in human pancreatic cancer and squamous cell carcinoma cell lines. But, this has not been shown in ovarian cancer. To investigate the potential association between loss of sensitivity to TGF-beta and expression status of transforming growth factor receptor II (T beta RII), Smad4, CDC25A and C-myc in fourteen cell lines derived from ovarian cancer, the expression levels of these genes were examined by semi-quantitative RT-PCR. Normal ovarian surface tissues were used as controls. Expression of T beta RII was detectable in all of fourteen cell lines. Expression of Smad4 was decreased in ten cell lines and nine cell lines overexpressed CDC25A, compared to normal controls. CDC25A gene was overexpressed in 88% (8/9) of tumorigenic cell lines as determined by xenografts in nude mice, and only in 20% (1/5) of non-tumorigenic cell lines (P < 0.05). C-myc was not overexpressed in any of these cell lines. The loss of sensitivity to TGF-beta of cell lines derived from ovarian cancers may be related to (1) a decreased expression of Smad4, which mediates TGF-beta induced growth inhibition; and/or (2) an overexpression of CDC25A. This overexpression correlates with increased tumorigenicity of ovarian cancer cell lines. The loss of sensitivity to TGF-beta is not associated with a lack of T beta RII.


Effect of cyproterone acetate on pituitary-adrenocortical function in man.
Recent literature (1973-1976) suggests suppression of pituitary-adrenal function in patients (eg with pubertas praecox) who are treated with cyproterone acetate in high doses for prolonged periods. Therefore we investigated in our metabolic ward the effects of administration of 200 mg cyproterone acetate per day during 20 days to 4 healthy male volunteers. Baseline plasma cortisol and ACTH levels, repeated diurnal plasma cortisol and ACTH profiles and the results of tetracosactide (Synacthen) stimulation tests and single-dose metyrapone (Metopiron) tests proved to be comparable before, during and after treatment. Moreover, a slight gradual increase in urinary cortisol excretion during the observation period indicated that cyproterone acetate in the given dose during 20 days certainly does not reduce the pituitary-adrenal function of 4 healthy male volunteers. Long-term administration (during 1 to 7 years) of the combination of cyproterone acetate and ethinyloestradiol did not suppress serum levels of cortisol, prolactin, thyroxine and TSH in 18 female patients with hirsutism and/or acne.


Considerable escape of SARS-CoV-2 Omicron to antibody neutralization.
The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1-3. It has since spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development4, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose.


Patient-centered care and distal radius fracture outcomes: a prospective cohort study analysis.
Prospective cohort. Effects of patient-centered care on distal radius fracture recovery lacks evidence. To understand from the perspective of a patient with a distal radius fracture: if the Patient Perception of Patient-Centeredness Questionnaire (PPPC) subscales apply to distal radius fracture populations; the strongest and weakest areas of patient-centered care; changes in patient perceptions of patient-centeredness during recovery; and, correlations between aspects of patient-centered care and patient reported pain and disability. Patients with distal radius fractures (n = 129; mean age = 54.03, SD = 14.63) completed the Patient Rated Wrist Evaluation (PRWE) and PPPC, at baseline (less than 10 days post-fracture) and at three months post-injury. Outcome measure responses were factor analyzed and tested for correlations. Factors identified were titled Clinician-Patient Dialogue, representing communication components of patient-centered care, and Clinician-Patient Alliance, representing partnership components of patient-centered care. Small significant correlations (r = 0.22) between PRWE and PPPC responses were observed with Clinician-Patient Alliance more correlated at baseline and Clinician-Patient Dialogue at follow-up. Important aspects of the patient-clinician dynamic were identified. Communication between clinician and patient was perceived most favorably at baseline; and partnership improved by three months. 1b.


Perinatal mortality: clinical value of postmortem magnetic resonance imaging compared with autopsy in routine obstetric practice.
To compare postmortem magnetic resonance imaging (MRI) with autopsy in perinatal deaths. To determine the acceptance and feasibility of postmortem perinatal MRI. Cohort study. Large teaching hospital. Fetuses and neonates from 16 weeks gestational age until 28 days after birth, stillbirths as well as intrapartum and neonatal deaths. MRI was performed prior to autopsy in a consecutive cohort of perinatal deaths after full parental consent. Agreement between MRI and autopsy was calculated. The consent rate for both examinations was recorded separately, as well as the time between the perinatal death and the MRI. Full agreement between MRI and autopsy. Of 58 cases, 26 parents consented to both examinations (45%). Autopsy showed 18 major malformations, of which 10 were detected with MRI. The positive predictive value of MRI was 80% (4/5) and the negative predictive value was 65% (13/20). Additional consent for MRI was given in eight cases (14%). In 84%, the MRI could be performed within 48 hours. MRI is of value if autopsy is refused, but diagnostic accuracy is insufficient to recommend substitution of full autopsy. The acceptance rate of MRI only is better than that of autopsy.


Calbindin D28K gene transfer via herpes simplex virus amplicon vector decreases hippocampal damage in vivo following neurotoxic insults.
Increases in cytoplasmic Ca2+ concentration ([Ca2+]i) can lead to neuron death. Preventing a rise in [Ca2+]i by removing Ca2+ from the extracellular space or by adding Ca2+ chelators to the cytosol of target cells ameliorates the neurotoxicity associated with [Ca2+]i increases. Another potential route of decreasing the neurotoxic impact of Ca2+ is to overexpress one of the large number of constitutive calcium-binding proteins. Previous studies in this laboratory demonstrated that overexpression of the gene for the calcium-binding protein calbindin D28K, via herpes simplex virus (HSV) amplicon vector, increases the survival of hippocampal neurons in vitro following energetic or excitotoxic insults but not following application of sodium cyanide. We now report that in vivo hippocampal infection with the calbindin D28K HSV vector increases neuronal survival in the dentate gyrus after application of the antimetabolite 3-acetylpyridine and increases transsynaptic neuronal survival in area CA3 following kainic acid neurotoxicity. The protective effects of infection with the calbindin D28K vector in an intact brain may prove to be beneficial during changes in Ca2+ homeostasis caused by neurological trauma associated with aging and certain neurological diseases.


Characterization and in vitro phase I microsomal metabolism of designer benzodiazepines: An update comprising flunitrazolam, norflurazepam, and 4'-chlorodiazepam (Ro5-4864).
The number of newly appearing benzodiazepine derivatives on the new psychoactive substances (NPS) drug market has increased over the last couple of years totaling 23 'designer benzodiazepines' monitored at the end of 2017 by the European Monitoring Centre for Drugs and Drug Addiction. In the present study, three benzodiazepines [flunitrazolam, norflurazepam, and 4'-chlorodiazepam (Ro5-4864)] offered as 'research chemicals' on the Internet were characterized and their main in vitro phase I metabolites tentatively identified after incubation with pooled human liver microsomes. For all compounds, the structural formula declared by the vendor was confirmed by gas chromatography-mass spectrometry (GC-MS), liquid chromatography-tandem mass spectrometry (LC MS/MS), liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS) analysis and nuclear magnetic resonance (NMR) spectroscopy. The metabolic steps of flunitrazolam were monohydroxylation, dihydroxylation, and reduction of the nitro function. The detected in vitro phase I metabolites of norflurazepam were hydroxynorflurazepam and dihydroxynorflurazepam. 4'-Chlorodiazepam biotransformation consisted of N-dealkylation and hydroxylation. It has to be noted that 4'-chlorodiazepam and its metabolites show almost identical LC-MS/MS fragmentation patterns to diclazepam and its metabolites (delorazepam, lormetazepam, and lorazepam), making a sufficient chromatographic separation inevitable. Sale of norflurazepam, the metabolite of the prescribed benzodiazepines flurazepam and fludiazepam, presents the risk of incorrect interpretation of analytical findings.


Epidural and subcutaneous morphine, meperidine (pethidine), fentanyl and sufentanil in the rat: analgesia and other in vivo pharmacologic effects.
The experiments examined the characteristics of analgesia produced by different doses of morphine, meperidine (pethidine), fentanyl, and sufentanil after epidural and subcutaneous injection in rats. The specificity of the analgesia was also determined; other in vivo pharmacologic activities (i.e., blockade of pinna and cornea reflexes and production of skeletal muscle rigidity) were monitored as pharmacologic indices of opiate drug activity in the brain. After subcutaneous injection, the opiates produced dose-dependent analgesia, blocked the pinna and cornea reflexes, and induced muscle rigidity. After epidural injection, all four compounds produced dose-dependent analgesia and had greater potency, earlier onset, shorter duration, and greater specificity of analgesic action than was the case after subcutaneous injection. Specificity is defined here as the ratio of the ED50 dose that blocked the pinna reflex to the ED50 dose that produced analgesia. The gains in potency and specificity, but not the gains in onset time and the losses in duration of analgesia, differed considerably among the compounds that were examined. The subcutaneous-to-epidural potency ratio related in a linear manner with the lipid-to-water partition coefficient. The gain in specificity also appeared to be related to lipid solubility. The microgram X kg-1 doses at which the opiates produced analgesia in rats correlate well with the potency of these compounds in producing analgesia after epidural injection in humans. The rat epidural preparation reflected the doses, onset, and specificity, but not the duration, of analgesia produced by epidural opiates in humans.


Sphene: uranium-lead ages.
Uranium-lead ages were measured on 14 samples of sphene from rocks aged from 1000 to 2750 x 10(6) years. All samples gave concordant or nearly concordant ages, the maximum difference between the Pb(206)-U(238) and Pb(207)-Pb(206) ages being 10 percent. Sphene has more concordant ages than has the coexisting zircon in each of seven rocks in which they were compared. Sphene sometimes has greater ages than does coexisting biotite, although in two metamorphic rocks, in which metamorphism was sufficiently intense to cause redistribution of radiogenic strontium-87 between various mineral phases, sphene dates the time of metamorphism rather than of original crystallization of the rocks.


Strokelets: A Learned Multi-Scale Mid-Level Representation for Scene Text Recognition.
In this paper, we are concerned with the problem of automatic scene text recognition, which involves localizing and reading characters in natural images. We investigate this problem from the perspective of representation and propose a novel multi-scale representation, which leads to accurate, robust character identification and recognition. This representation consists of a set of mid-level primitives, termed strokelets, which capture the underlying substructures of characters at different granularities. The Strokelets possess four distinctive advantages: 1) usability: automatically learned from character level annotations; 2) robustness: insensitive to interference factors; 3) generality: applicable to variant languages; and 4) expressivity: effective at describing characters. Extensive experiments on standard benchmarks verify the advantages of the strokelets and demonstrate the effectiveness of the text recognition algorithm built upon the strokelets. Moreover, we show the method to incorporate the strokelets to improve the performance of scene text detection.


A news-based climate policy uncertainty index for China.
Climate policies can have a significant impact on the economy. However, these policies have often been associated with uncertainty. Quantitative assessment of the socioeconomic impact of climate policy uncertainty is equally or perhaps more important than looking at the policies themselves. Using a deep learning algorithm-the MacBERT model-this study constructed indices of Chinese climate policy uncertainty (CCPU) at the national, provincial and city levels for the first time. The CCPU indices are based on the text mining of news published by a set of major newspapers in China. A clear upward trend was found in the indices, demonstrating increasing policy uncertainties in China in addressing climate change. There is also evidence of clear regional heterogeneity in subnational indices. The CCPU dataset can provide a useful source of information for government actors, academics and investors in understanding the dynamics of climate policies in China. These indices can also be used to investigate the empirical relationship between climate policy uncertainty and other socioeconomic factors in China.


Renal mitochondrial restoration by gymnemic acid in gentamicin-mediated experimental nephrotoxicity: evidence from serum, kidney and histopathological alterations.
Background: Nephrotoxicity refers to the toxigenic impact of compounds and medications on kidney function. There are a variety of drug formulations, and some medicines that may affect renal function in multiple ways via nephrotoxins production. Nephrotoxins are substances that are harmful to the kidneys. Purpose: This investigation examines the renoprotective effect of gymnemic acid (GA) on Wistar rats in gentamicin-induced nephrotoxicity by analyzing serum, kidney, and histopathological markers. Study-design/methods: The current study investigated the protective effect of GA at doses of 20, 40, and 60 mg/kg against gentamicin-induced nephrotoxicity in rats. Vitamin E was administered to compare the antioxidant capacity and efficacy of GA. In addition to the treatment groups, 100 mg/kg of gentamicin was administered intraperitoneal for 14 days. At the end of the study protocol, kidney homogenate, blood, and serum were evaluated biochemically. Serum creatinine, blood urea, glomerular filtration rate (GFR), mitochondrial dysfunctions, inflammatory cytokines, and renal oxidative stress were examined to assess gentamicin-induced nephrotoxicity. In addition, the impact of GA on the above-mentioned nephrotoxic markers were evaluated and further confirmed by histological analysis. Results: This study establishes a correlation between antibiotic use, especifically aminoglycosides and acute renal failure. The research demonstrates the nephrotoxic effects of aminoglycosides, inducing mitochondrial ETC-complex dysfunction, and renal tissue inflammation in experimental rats. GA's antioxidant properties restored renal oxidative stress markers, reducing kidney inflammation and injury. Histopathological analysis revealed a significant reduction in renal injury with GA treatment. Additionally, GA demonstrated greater efficacy than Vitamin E in restoring antioxidant potential and mitochondrial enzymes. Conclusion: Consequently, our findings imply that long-term use of GA may be a suitable therapeutic strategy for reducing aminoglycoside toxicity. The current study suggests GA's potential in treating gentamicin-induced nephrotoxicity and acute renal failure, meriting further investigation using advanced techniques.


Role of cytoplasm-specific introgression in the evolution of the polyploid wheats.
Studies of N-banded mitotic and meiotic karyotypes of Triticum turgidum L. (2n = 28; AABB) and Triticum timopheevii Zhuk. (2n = 28; AAGG) and hybrids between them, along with observations of meiotic pairing between telocentrics of the AB-genome chromosomes and their respective homologues and homeologues in T. timopheevii, showed that chromosome 4 (m4) of Triticum monococcum L. is present (as 4A(t)) in T. timopheevii but is lacking in T. turgidum. Neither 4A nor 4B pairs with 4A(t), but 4A pairs with 4G and, for this reason and because of its banding pattern, must be considered a B-genome chromosome. T. timopheevii chromosomes 4A(t) and 3A(t) are involved in a reciprocal translocation, and 2A(t), 1G, 2G, and 5G are also involved in translocations. Chromosome arm 4BL occasionally pairs with 7G. The satellites are on the short arms of chromosomes 6A(t) and 6G of T. timopheevii and 1B and 6B of T. turgidum. It is suggested that (i) T. timopheevii orginated as an allotetraploid of Aegilops speltoides Tausch/T. monococcum and (ii) T. turgidum was derived from T. timopheevii by introgressive hybridization with an unknown diploid species, which contributed its distinctive cytoplasm, chromosome 4B or a substantial portion of it, and additional chromosome segments. Rapid fixation of 4B in T. turgidum was ensured by cytoplasm-specific transmission.


Isolation and characterization of phosphorylated bovine prolactin.
Quantitative isolation of bovine prolactin was accomplished by immunoaffinity chromatography using clonal antibody as the stationary ligand. The phosphorylated and non-phosphorylated (native) prolactins contained in the immunopurified preparations were separated by chromatofocusing. Isolates from individual pituitaries revealed that phosphorylated prolactin represented between 20 and 80% of the total prolactin. The stoichiometry of phosphate in phosphorylated prolactin was 1.4:1 when determined by amino acid analysis after preparation of the S-ethylcysteine derivative. One major phosphorylation site, serine-90, and two minor sites, serine-26 and -34, were determined by mapping and sequencing studies. Serine-90 was conserved in prolactins, growth hormones and placental lactogens. Serine-26 and -34 were conserved in prolactins, but were not found in growth hormones or placental lactogens. Absorption spectroscopy of the aromatic amino acid residues indicated that phosphorylation of prolactin was associated with a unique structural conformation.


Damage to Aspergillus fumigatus and Rhizopus oryzae hyphae by oxidative and nonoxidative microbicidal products of human neutrophils in vitro.
Our previous studies established that human neutrophils could damage and probably kill hyphae of Aspergillus fumigatus and Rhizopus oryzae in vitro, primarily by oxygen-dependent mechanisms active at the cell surface. These studies were extended, again quantitating hyphal damage by reduction in uptake of (14)C-labeled uracil or glutamine. Neither A. fumigatus nor R. oryzae hyphae were damaged by neutrophils from patients with chronic granulomatous disease, confirming the importance of oxidative mechanisms in damage to hyphae. In contrast, neutrophils from one patient with hereditary myeloperoxidase deficiency damaged R. oryzae but not A. fumigatus hyphae. Cell-free, in vitro systems were then used to help determine the relative importance of several potentially fungicidal products of neutrophils. Both A. fumigatus and R. oryzae hyphae were damaged by the myeloperoxidase-hydrogen peroxide-halide system either with reagent hydrogen peroxide or enzymatic systems for generating hydrogen peroxide (glucose oxidase with glucose, or xanthine oxidase with either hypoxanthine or acetaldehyde). Iodide with or without chloride supported the reaction, but damage was less with chloride alone as the halide cofactor. Hydrogen peroxide alone damaged hyphae only in concentrations >/=1 mM, but 0.01 mM hypochlorous acid, a potential product of the myeloperoxidase system, significantly damaged R. oryzae hyphae (a 1 mM concentration was required for significant damage to A. fumigatus hyphae). Damage to hyphae by the myeloperoxidase system was inhibited by azide, cyanide, catalase, histidine, and tryptophan, but not by superoxide dismutase, dimethyl sulfoxide, or mannitol. Photoactivation of the dye rose bengal resulted in hyphal damage which was inhibited by histidine, tryptophan, and 1,4-diazobicyclo(2,2,2)octane. Lysates of neutrophils or separated neutrophil granules did not affect A. fumigatus hyphae, but did damage R. oryzae hyphae. Similarly, three preparations of cationic proteins purified from human neutrophil granules were more active in damaging R. oryzae than A. fumigatus hyphae. This damage, as with the separated granules and whole cell lysates, was inhibited by the polyanion heparin. Damage to R. oryzae hyphae by neutrophil cationic proteins was enhanced by activity of the complete myeloperoxidase system or by hydrogen peroxide alone in subinhibitory concentrations. These data support the importance of oxidative products in general and the myeloperoxidase system in particular in damage to hyphae by neutrophils. Cationic proteins may also contribute significantly to neutrophil-mediated damage to R. oryzae hyphae.


Weight suppression predicts weight change over 5 years in bulimia nervosa.
Recent studies suggest that weight suppression (WS), defined as the discrepancy between current and highest past weight, predicts short-term weight gain in bulimia nervosa (BN) during treatment. The current study was designed to build on this preliminary work by examining the relation between WS and long-term weight change in BN. Treatment-seeking women (N=97) with DSM-IV BN participated in a naturalistic longitudinal follow-up study of eating disorders. At intake, height and weight were measured and highest past weight was assessed. Self-reported weights were collected every 6 months for 5 years. Hierarchical Linear Modeling (HLM) estimated growth curves for weight change over time. Significant inter-person variability was detected for intercepts and slopes (P<0.001) so both were treated as random effects. Participants' weights increased over the study course, moderated by baseline WS (P<0.001), such that higher WS predicted more rapid weight gain. Weight change was not associated with entry weight, height, or highest-ever weight, suggesting that WS per se predicted weight change. These findings complement previous short-term studies in BN by demonstrating that WS predicts weight gain over 5 years. Because weight gain could spur radical dieting that maintains BN, these results have important treatment implications.


Providers' reflections on infrastructure and improvements to promote access to care for Veterans experiencing housing instability in rural areas of the United States: A qualitative study.
Veterans in rural areas of the United States face barriers to accessing healthcare and other services, which are intensified for those experiencing housing instability. Recent legislative acts have the potential to address obstacles faced by rural patients in the U.S. This study explores how infrastructure-including features related to the physical and digital environment-impacts the ability of rural Veterans experiencing housing instability to access healthcare and related services from the perspective of homeless service providers within the Veterans Health Administration (VHA). We conducted semi-structured telephone interviews (n = 22) with providers in high/low performing and/or resourced communities across the U.S. in May and June 2021 and analysed transcripts using template analysis. Themes described by providers highlight how infrastructure limitations in rural areas can exacerbate health disparities for Veterans experiencing housing instability, the impact of COVID-19 on service access, and recommendations to enhance service delivery. Providers suggested that VHA reconfigure where and how staff work, identify additional resources for transportation and/or alternative transportation models, and increase Veterans' access to technology and broadband Internet. Federal infrastructure investments should address challenges faced by Veterans experiencing housing instability in rural areas and the concerns of providers connecting them with care.


The Neutralizing Monoclonal Antibodies against SFTS Group Bandaviruses Suggest New Targets of Specific or Broad-Spectrum Antivirals.
Severe fever with thrombocytopenia syndrome virus (SFTSV), Heartland virus (HRTV) and Guertu virus (GTV) belong to the severe fever with thrombocytopenia syndrome/Heartland group of genus Bandavirus in the family Phenuiviridae of order Bunyavirales. Severe fever with thrombocytopenia syndrome virus and HRTV, identified from ticks from Asia and America, respectively, are important pathogens causing severe febrile diseases in humans. Guertu virus, closely related to these two viruses, is a potential pathogen, but no confirmed infection has been identified. So far, human-derived neutralizing monoclonal antibodies (mAbs) against SFTSV have been identified as having a great potential to be developed as antivirals; however, there is still a lack of neutralizing mAbs to GTV and HRTV. In this study, five neutralizing the mAbs against GTV and HRTV were obtained by hybridoma screening technology, four of which (14B4, 14D8, and 20D4 derived from GTV, and 27C8 derived from HRTV) showed cross reactivity and neutralization to all three viruses, and one derived from HRTV (10D6) neutralized HRTV specifically. The possible mechanisms of mAbs cross neutralization among the three viruses are discussed by analyzing their glycoprotein (GP) sequences and structures. Generating these neutralizing mAbs provides important antiviral candidates against GTV, HRTV, and SFTSV despite their differential activities, and their protective effect could be further evaluated in virus-infected mice. Their differential neutralizing efficiency and specificity further suggested that the three viruses share common mechanisms on the basis of GP functioning, and that HRTV poses a unique mechanism that differs from the other viruses. These findings shed light on developing broad-spectrum antiviral strategies against bandaviruses and promoting an understanding of the bandavirus infection process.


Blastomycosis and opportunistic infections in patients with acquired immunodeficiency syndrome. An autopsy study.
Patients with acquired immunodeficiency syndrome (AIDS) are subject to a host of opportunistic infections, but to our knowledge a predisposition to blastomycosis has not previously been established. Autopsies of two patients with AIDS revealed disseminated blastomycosis with massive pulmonary involvement, Blastomyces meningoencephalitis, and widespread dissemination. The massive systemic involvement and rapid terminal course in both cases may reflect the state of acquired immunodeficiency. An analysis of an autopsy series showed that the incidence of blastomycosis was increased in patients with AIDS, although some other opportunistic organisms were more common (eg, Pneumocystis carinii, Mycobacterium avium-intracellulare, and Candida species). Thus, the diagnosis and treatment of blastomycosis must be pursued in patients with AIDS. Additional data are needed to further determine the incidence of blastomycosis in the population of patients with AIDS.


[Update on medical therapies of nasopharyngeal carcinomas].
Nasopharyngeal carcinomas (NPC) are predominantly of undifferentiated type (UCNT or undifferentiated carcinoma of nasopharyngeal type), rare (<1/100,000) and sporadic in occidental countries, but endemic in the Mediterranean area of intermediate incidence (2 to 10/100,000) and highly frequent (>10/100,000) in South East Asia. NPC staging is based on TNM UICC 2002 that has a prognostic and therapeutic orientation impact. Irradiation of the primitive tumor and its extensions remains the standard loco-regional treatment. The recent introduction of primary and concomitant chemotherapy leads to an improvement in terms of overall and disease-free survival, specially for for high-risk-patients (T3-4 and N2-3 disease). Prognosis remain linked to T, N, histologic type and quality of response to chemotherapy and radiotherapy.


Mechanisms of ALA-D inhibition by lead and of its restoration by zinc and dithiothreitol.
To induce the inhibition of ALA-D (delta-aminolaevulinic acid dehydratase) activity by lead in vitro, it is necessary to preincubate the enzyme fraction with lead ions and the Hb fraction (factors) together. The combination of two of the three (ALA-D fraction, lead acetate, and Hb fraction) in the preincubation has only a small effect on the activity. Lead preincubated with ALA-D and Hb fractions does not alter the affinity of the enzyme for the substrate, suggesting that the substrate can bind to the enzyme molecules (non-competitive inhibition). The restoration of activity by zinc with dithiothreitol is associated with the removal of lead from ALA-D fraction proteins to which it has bound in vivo and in vitro. The mode of the inhibitory action of tin on ALA-D is similar to that of lead because the inhibition is intensified by the addition of Hb fraction and is restored by heating. The inhibition concentration is, however, higher than that of lead. Of the three methods recovering decreased activity, heating is the most specific to detect inhibition by lead.


Motion of a nano-spheroid in a cylindrical vessel flow: Brownian and hydrodynamic interactions.
We study the motion of a buoyant or a nearly neutrally buoyant nano-sized spheroid in a fluid filled tube without or with an imposed pressure gradient (weak Poiseuille flow). The fluctuating hydrodynamics approach and the deterministic method are both employed. We ensure that the fluctuation-dissipation relation and the principle of thermal equipartition of energy are both satisfied. The major focus is on the effect of the confining boundary. Results for the velocity and the angular velocity autocorrelations (VACF and AVACF), the diffusivities and the drag and the lift forces as functions of the shape, the aspect ratio, the inclination angle and the proximity to the wall are presented. For the parameters considered, the boundary modifies the VACF and AVACF such that three distinct regimes are discernible - an initial exponential decay followed by an algebraic decay culminating in a second exponential decay. The first is due to the thermal noise, the algebraic regime is due both to the thermal noise and the hydrodynamic correlations, while the second exponential decay shows the effect of momentum reflection from the confining wall. Our predictions display excellent comparison with published results for the algebraic regime (the only regime for which earlier results exist). We also discuss the role of the off-diagonal elements of the mobility and the diffusivity tensors that enable the quantifications of the degree of lift and margination of the nanocarrier. Our study covers a range of parameters that are of wide applicability in nanotechnology, microrheology and in targeted drug delivery.


Interaction of steroid--peroxidase conjugates with cellulose immunosorbents in aqueous and micellar media.
In 0.1 M bicarbonate buffer (pH 9.0) and in microemulsions of aerosol OT (AOT) and its mixture with Triton X-45 in heptane, antibodies against cortisol (anti-COR) and progesterone (anti-PROG) were covalently immobilized on fine-porous cellulose filters (0.6 cm diameter) after sodium periodate oxidation. Immunosorbents obtained in different media were characterized in terms of antibody-bound density and antigen-binding capacity with respect to peroxidase--steroid conjugates HP--COR-11 and HP--PROG-4 containing 11 molecules of cortisol and four progesterone molecules, respectively. For all immunosorbents antigen-binding capacity expressed as peroxidase activity of immune complexes formed on the solid cellulose phase in aqueous and micellar media was determined. Dissociation constants of immunocomplexes on the cellulose formed in aqueous and micellar media were determined using ELISA. In all cases Kd values in aqueous media were approximately 10-8 M and were significantly lower than corresponding values of dissociation constants of immune complexes in mixed microemulsions of AOT and Triton X-45.


Aqueous zymography screening of matrix metalloproteinase activity and inhibition based on colorimetric gold nanoparticles.
An optical gold nanoparticles (AuNPs)-based method was fabricated for the rapid detection of matrix metalloproteinase (MMP) activity and screening potential MMP inhibitors without sophisticated instruments. The diagnosis platform was composed of AuNPs, particular MMP substrates and 6-mercapto-1-hexanol (MCH). The functionalized AuNPs were subjected to specific MMP digestion, and the MMP found the substrate on AuNPs, such that the AuNPs lost shelter and MCH increased the attraction force between AuNPs. Consequently, AuNPs aggregation and a color change from red to purple with increasing MMP concentration were observed. The surface plasmon resonance (SPR) of the formed AuNPs allowed for the quantitative detection of MMP activity. A sensitive linear correlation existed between the absorbance and the activity of the MMPs, which ranged from 10 ng/mL to 700 ng/mL in NTTC buffer and plasma samples. The proposed colorimetric method could be accomplished in a homogeneous solution with one-step operation in 30 min and has been successfully applied to the determination of particular MMP activity in plasma samples, in which the results are consistent with substrate zymography. This technology may become a simple platform for parallel screening a number of inhibitors and offer an alternative method to studying the efficiency of inhibitors for suppressing MMP activity. The absorbance ratio at 625 nm and 525 nm (A(625)/A(525)) confirmed the efficiency of the inhibitors as observed in substrate zymography. The IC(50) of ONO-4817 and galardin for MMP-1, MMP-2 and MMP-7 determined by the proposed colorimetric method was similar to the results of substrate zymography.


Distribution of epilepsy syndromes in a cohort of children prospectively monitored from the time of their first unprovoked seizure.
To assess the distribution of epilepsy syndromes and their stability in children. A cohort of 407 children with a first unprovoked seizure was prospectively recruited and followed up for a mean of 9.4 years. Etiology and epilepsy syndromes were classified by using the International League Against Epilepsy (ILAE) guidelines in the 182 children with two or more seizures. Classification was done both at time of second seizure and at last follow-up. Two-year terminal remission also was analyzed by etiology and epilepsy syndrome. Etiology of epilepsy syndromes was idiopathic in 45 (25%), cryptogenic in 89 (49%), and remote symptomatic in 48 (26%). In the initial classification, 114 (63%) children had a localization-based epilepsy syndrome including idiopathic in 26, cryptogenic in 34, and symptomatic based on localization or etiology in 54. Twenty-one (12%) children had a generalized epilepsy syndrome, including 19 with primary generalized epilepsy. Forty-seven (26%) cases were in the category of undetermined if focal or generalized. At last follow-up, there was a change in either etiology (n = 16) or the final epilepsy syndrome classification (n = 33) or both (n = 15) in 34 (19%) cases. At time of last follow-up, 144 (79%) of the children with epilepsy were in 2-year terminal remission, and 108 (59%) were in 2-year terminal remission without medications. Factors associated with a favorable prognosis included an idiopathic or cryptogenic etiology and having a localization-based idiopathic epilepsy syndrome. After two seizures, childhood-onset epilepsy can be classified by etiology and epilepsy syndrome. Prognosis is favorable in the majority of cases. However, the apparent syndrome may change with longer follow-up. The ability to classify these cases early in the clinical course is important if they are to be used for prognostic purposes.


Escherichia coli bacteremia in the squirrel monkey. I. Effect of cobra venom factor treatment.
Squirrel monkeys were significantly depleted of complement by a nontoxic protein constituent of cobra venom, and the influence of cobra factor (CoF) treatment on the course of Escherichia coli bacteremia was studied. Striking neutropenia occurred rapidly in control animals while the rate of occurrence of neutropenia was 20 to 30 times slower in the CoF-treated animals, suggesting that the E. coli-induced neutropenia was at least partially a complement-mediated response. In the CoF-treated monkeys, the initial rate of clearance of the E. coli from the circulation tended to be slower and the resultant levels of bacteremia were higher than in control animals. These observations are consistent with a hypothesis that complement-mediated neutrophilic leucocyte function is an important host defense mechanism in gram-ngeative bacillary bacteremia.