Radiographic and pathologic correlation of coal workers' pneumoconiosis.
The relationships between chest radiographs (CXR) and corresponding pathology were investigated in 430 autopsied coal miners from West Virginia. Whole-lung sections were reviewed and graded on four-point severity scales for the following lesions of coal workers' pneumoconiosis (CWP): macules, micro- and macronodules (small and large fibrotic nodules), and progressive massive fibrosis (PMF). Antemortem CXR were classified by three B readers using the 1971 International Labor Office (ILO) U/C classification (6). On pathologic examination, 96% of miners had macules, 70% micronodules, 45% macronodules, 15% silicosis, and 28% PMF. By CXR, 69% of the miners had small, rounded opacity profusions of category > or = 0/1. Data analysis revealed increasing odds that small opacities of category > or = 0/1 would be detected with increasing grade of nodules. Profusion category 0/0 was often reported for cases with macules of mild to moderate grade and mild levels of micronodules. Overall, q-type opacities were associated with macules and micronodules, whereas the large r-type opacities were associated with macronodules. By CXR, large opacities showed good correlation with pathologic PMF. However, about one-third of cases identified as having large opacities by CXR were not substantiated as PMF by pathology. One-fourth of these cases could be explained by lung lesions such as Caplan's nodules, tuberculosis scars, and tumors. Similarly, 22% of cases classified as PMF on pathology had no large opacities by CXR. In half of these cases, the radiologists had noted other abnormalities (cancer, tuberculosis) by CXR as large opacities. Overall, the study showed good agreement (Somer's d = 0.64) between the predicted probabilities and observed responses of a profusion category > or = 0/1 for pathologic CWP lesions. However, the study also showed that CXR were insensitive for detecting minimal CWP lesions, and were unreliable indicators in the presence of concomitant pulmonary pathology.


An experimental study of jejunal pouch replacements following total gastrectomy.
The nutritional effects of pouch replacement after total gastrectomy remain clinically controversial. Two previous experiments failed to show any nutritional benefit. However, the pouches applied clinically and examined experimentally so far were all of anti-peristaltic type. Male 7- or 8-week-old Wistar rats were divided into 3 experimental groups after total gastrectomy. For group 1 and 2 rats, Roux-en-Y reconstructions and Hunt-Lawrence pouches, i.e., anti-peristaltic type, were performed, respectively. Group 3 rats underwent a new type of iso-peristaltic pouch replacement. Food intake was recorded daily and all rats were weighed once a week. At the end of the 12-week experimental period, there were 9 rats in group 1, 10 in group 2, and 8 in group 3. The volumes of the gastric reservoirs were measured, and blood samples were taken. Five 20-week-old rats served as control of weight, food intake, and laboratory data. The volumes of the gastric reservoirs in group 2 and 3 rats were significantly larger than in group 1 animals. However, there were no intergroup differences in weight change or food intake. The weights and the food intakes of the 3 experimental groups were significantly lower than those of the control rats. No superiority in the results of blood samples was observed among the experimental groups. Correlations between weight gain and food intake were shown in all groups. But, a correlation between the volume of the gastric reservoir and food intake was observed only for group 3 rats. The present study showed no nutritional benefits of an iso- as well as an anti-peristaltic pouch replacement.


"A lot of them have scary tears during childbirth…" experiences of healthcare workers who care for genitally mutilated females.
Despite concerted efforts to curb Female Genital Mutilation/Cutting (FGM/C), it is still a contributor to the high morbidity and mortality rates among females in Africa. According to available literature, the experiences of healthcare workers who care for the genitally mutilated females in Nigeria have not been described, hindering efforts towards ending this procedure through evidence-based, community-led interventions. This qualitative study described the experiences of healthcare workers caring for the genitally mutilated females in South-Eastern Nigeria. In-depth interviews conducted with 17 participants resulted in two themes and five sub-themes. The participants faced major challenges in caring for these females as the complications of FGM/C resulted in situations requiring advanced skills for which they were ill-prepared. Irrespective of this complex situation, the participants believed FGM/C was an age-old cultural practice; some even supported its continuation. The solution to this problem is not simple. However, educational programmes involving all cadres of healthcare workers could assist with eradicating this practice. Also, enforcing the anti-FGMC law could enhance the eradication of this procedure.


Confirmatory factor analysis of ITPA models with language-impaired children.
The major objective of the current investigation was to provide an evaluation of the validity of the ITPA for language-impaired children using confirmatory factor analysis. In addition to an examination of the validity of the traditional ITPA models, a new model is tested. The new model is based on considerations of the structural complexity of the ITPA subtests. and allows one to interpret ITPA results in processing terms. The results suggest that four-factor models provided the best representation of the ITPA scores in language-impaired children. Compared with the traditional ITPA models, the new model showed either an improved or equal goodness of fit. Language-impaired children tested with the ITPA (n = 100) exhibited a profile pattern suggesting that subtests with low processing demands are "easier" than tests with high processing demands. Thus, the present study supports the contention that language-impaired children suffer from constraints on information processing.


Disequilibrium mapping: composite likelihood for pairwise disequilibrium.
The pattern of linkage disequilibrium between a disease locus and a set of marker loci has been shown to be a useful tool for geneticists searching for disease genes. Several methods have been advanced to utilize the pairwise disequilibrium between the disease locus and each of a set of marker loci. However, none of the methods take into account the information from all pairs simultaneously while also modeling the variability in the disequilibrium values due to the evolutionary dynamics of the population. We propose a Composite Likelihood (CL) model that has these features when the physical distances between the marker loci are known or can be approximated. In this instance, and assuming that there is a single disease mutation, the CL model depends on only three parameters, the recombination fraction between the disease locus and an arbitrary marker locus, theta, the age of the mutation, and a variance parameter. When the CL is maximized over a grid of theta, it provides a graph that can direct the search for the disease locus. We also show how the CL model can be generalized to account for multiple disease mutations. Evolutionary simulations demonstrate the power of the analyses, as well as their potential weaknesses. Finally, we analyze the data from two mapped diseases, cystic fibrosis and diastrophic dysplasia, finding that the CL method performs well in both cases.


Diurnal changes in liver and plasma lipids of choline-deficient rats.
Early effects of choline deficiency were studied in rats. Nonphospholipid ("neutral lipid") and phospholipid were measured in plasma and in three fractions of a liver homogenate: sediment, supernatant fraction, and "floating fat." A single choline-deficient meal caused significant aberrations from the typical diurnal changes observed in the lipid fractions of the controls. These changes occurred in the following sequence: (a) failure of phospholipid to increase, after feeding, in the sediment fraction; (b) increase of neutral lipid, compared with controls, exclusively in the floating fraction; and (c) failure of neutral lipid to return to control levels. The rate of accumulation of neutral lipid increased during the first 4 days of deficiency. The occurrence of NADH-cytochrome c dehydrogenase in the floating fat and the absence of succinate dehydrogenase activity point to microsomal origin of the floating fat. Early effects of choline deficiency on plasma lipids were limited to phospholipid, and occurred later than changes in the liver. Plasma nonphospholipid levels were unchanged during the first 2 days; this does not support impaired secretion or transportation of glyceride as the cause of fatty liver in the early stages of choline deficiency.


Acute effects of the very low carbohydrate diet on sleep indices.
We compared the effect of short-term consumption of a very low carbohydrate (VLC) diet over 48 h to a control mixed diet on sleep indices in healthy, non-obese men. This study employed a repeated-measure design where subjects were given isocaloric (2400 kcal) diets and matching evening test meals (4 h before usual bed-time), which were either mixed low-fat, high carbohydrate (15.5%, 12.5% and 72% of energy from protein, fat and carbohydrate, respectively) or VLC (38%, 61% and < 1% of energy from protein, fat and carbohydrate, respectively). Polysomnographic testing was performed on the familiarization and control night, 4 h after the first VLC test meal (acute phase) and 48 h (ketosis phase) following commencement of the VLC diet. Fourteen healthy, non-obese men (aged 18-35 years; body mass index 23.4 +/- 1.9 kg/m(2)) who were good sleepers took part in the study. Objective sleep was recorded using a computerized sleep system. Urine ketone level was monitored with reagent strips before the evening test meals and at bed-time on the control night, during the VLC acute and ketosis phases. Blood glucose level was measured with a glucometer before the evening test meal until 120 min following the meal. Hunger and fullness were assessed immediately after the meal until bed-time with Likert scales. The proportion of rapid-eye movement (REM) sleep to total sleep time was significantly reduced at the VLC acute and VLC ketosis when compared to the control night (P = 0.006; n = 11 and P = 0.05; n = 14, respectively). The percentage of slow wave sleep (SWS) significantly increased for both the VLC acute (17.7 +/- 6.7) and ketosis (17.8 +/- 6.1) phases compared to control (13.9 +/- 6.3), P = 0.02 for both phases. In healthy, good sleepers, the VLC diet over the short-term promotes increases in the percentage of SWS (deep sleep stage 4) and a reduction in the percentage of REM sleep ('dreaming' sleep) compared to the control mixed diet. The sleep changes may be linked to the metabolism of the fat content of the VLC diet.


Vitamin D Status in a Bulgarian Population With Type 2 Diabetes and Diabetic Foot Ulcers.
The aim of this study was to assess vitamin D status in patients with type 2 diabetes and diabetic foot ulcers (DFU). A total of 242 participants with type 2 diabetes, mean age 59.1 ± 10 years, mean body mass index 31.4 ± 6.3 kg/m2, and estimated glomerular filtration rate ≥45 mL/min/1.73m2, were divided into 2 groups: 73 with DFU (35 with and 38 without active infection) and 169 without DFU (106 with diabetic peripheral neuropathy, 63 without complications). Neuropathy was assessed by 10 g monofilament, Rydel-Seiffer 128 Hz tuning fork, and temperature discrimination. Serum 25(OH)D (25-hydroxy vitamin D) was assessed by ECLIA (electro-chemiluminescence immunoassay) method. Median 25(OH)D level was 12.6 ng/mL (IQR [interquartile range] 9.3-17.6 ng/mL) in the studied cohort. The DFU group presented with lower 25(OH)D level as compared with diabetic patients without foot ulcers (non-DFU group): 11.6 ng/mL (IQR 8.5-15.8 ng/mL) versus 13.5 ng/mL (IQR 9.6-18.6 ng/mL), P = .001; the diabetic peripheral neuropathy subgroup demonstrated lower 25(OH)D level in comparison with participants without complications: 12.5 ng/mL (IQR 9-17.2 ng/mL) versus 15.9 ng/mL (IQR 10.4-20.8 ng/mL), P = .031. This remained significantly different even after correction for age and duration of diabetes. There was no difference in 25(OH)D level between the subgroups according to the presence of active infection. In conclusion, vitamin D deficiency may play a role in the development of diabetes complications.


Change-Point Analysis of Eye Movement Characteristics for Female Drivers in Anxiety.
Driver hazard perception is highly related to involvement in traffic accidents, and vision is the most important sense with which we perceive risk. Therefore, it is of great significance to explore the characteristics of drivers' eye movements to promote road safety. This study focuses on analyzing the changes of drivers' eye-movement characteristics in anxiety. We used various materials to induce drivers' anxiety, and then conducted the real driving experiments and driving simulations to collect drivers' eye-movement data. Then, we compared the differences between calm and anxiety on drivers' eye-movement characteristics, in order to extract the key eye-movement features. The least squares method of change point analysis was carried out to detect the time and locations of sudden changes in eye movement characteristics. The results show that the least squares method is effective for identifying eye-movement changes of female drivers in anxiety. It was also found that changes in road environments could cause a significant increase in fixation count and fixation duration for female drivers, such as in scenes with traffic accidents or sharp curves. The findings of this study can be used to recognize unexpected events in road environment and improve the geometric design of curved roads. This study can also be used to develop active driving warning systems and intelligent human⁻machine interactions in vehicles. This study would be of great theoretical significance and application value for improving road traffic safety.


Shunaoxin pills improve the antihypertensive effect of nifedipine and alleviate its renal lipotoxicity in spontaneous hypertension rats.
Shunaoxin pills (SNX) have been used to treat cerebrovascular diseases in China since 2005. Hypertension is a major risk factor for cerebrovascular disease. This study aimed to explore the synergistic antihypertensive effect of SNX and nifedipine and whether SNX could alleviate nifedipine-induced renal lipotoxicity. During administration, systolic blood pressure was measured weekly. After 5 weeks administration, we examined pathological changes of kidney, renal function, the lipid metabolism index, and adipogenesis genes expression in the kidney tissues, and explored its underlying mechanism. Finally, network pharmacology was used for supplement and verification. As a result, SNX improved the antihypertensive effect of nifedipine and apparently improved nifedipine-induced renal pathological changes, dyslipidemia and the levels of adipogenesis gene expression in kidney tissues. SNX reduced the levels of interleukin-6 and interleukin-1β in renal tissues, down-regulated the production of malondialdehyde, and increased superoxide dismutase activity and the protein expression of heme oxygenase-1 in kidney tissues. Network pharmacology also showed that SNX could improve nifedipine-induced renal lipotoxicity. The combination of SNX and nifedipine had certain benefits in the treatment of hypertension.


Evaluation of arch width variations among different skeletal patterns in South Indian population.
Anterior cranial base can be taken as a reference line (SN) to determine the steepness of mandibular plane. Subjects with high mandibular plane angle tend to have a long face and one with low MP-SN angle has a shorter face. This study was done to investigate if dental arch widths correlated with vertical facial types and if there are any differences in arch widths between untreated male and female adults in South Indian population. Lateral cephalogram and dental casts were obtained from 180 untreated South Indian adults (90 males and 90 females) above 18 year old with no cross bite, minimal crowding and spacing. The angle between the anterior cranial base and the mandibular plane was measured on lateral cephalogram of each patient. Dental casts were used to obtain comprehensive dental measurements including maxillary and mandibular inter canine, inter premolar and inter molar widths, as well as amount of crowding or spacing. The results showed that male arch widths were significantly larger than those of females (P < 0.05) and there was a significant decrease in inter arch width as the MP-SN angle increased in untreated adult South Indian population. The results obtained in our study when compared with studies done in other population groups showed that there is difference in inter arch widths according to ethnicity and race. It was concluded that the dental arch width is associated with gender, race and vertical facial morphology. Thus using individualized arch wires according to each patient's pre treatment arch form and width is suggested during orthodontic treatment.


Integrins modulate the infection efficiency of West Nile virus into cells.
The underlying mechanisms allowing West Nile virus (WNV) to replicate in a large variety of different arthropod, bird and mammal species are largely unknown but are believed to rely on highly conserved proteins relevant for viral entry and replication. Consistent with this, the integrin αvβ3 has been proposed lately to function as the cellular receptor for WNV. More recently published data, however, are not in line with this concept. Integrins are highly conserved among diverse taxa and are expressed by almost every cell type at high numbers. Our study was designed to clarify the involvement of integrins in WNV infection of cells. A cell culture model, based on wild-type and specific integrin knockout cell lines lacking the integrin subunits αv, β1 or β3, was used to investigate the susceptibility to WNV, and to evaluate binding and replication efficiencies of four distinct strains (New York 1999, Uganda 1937, Sarafend and Dakar). Though all cell lines were permissive, clear differences in replication efficiencies were observed. Rescue of the β3-integrin subunit resulted in enhanced WNV yields of up to 90 %, regardless of the virus strain used. Similar results were obtained for β1-expressing and non-expressing cells. Binding, however, was not affected by the expression of the integrins in question, and integrin blocking antibodies failed to have any effect. We conclude that integrins are involved in WNV infection but not at the level of binding to target cells.


Chronic symmetric symptomatic polyneuropathy in the elderly: a field screening investigation in two Italian regions. I. Prevalence and general characteristics of the sample. Italian General Practitioner Study Group (IGPSG).
The prevalence and general characteristics of chronic symmetric symptomatic polyneuropathy were assessed in two elderly populations living in Varese, northern Italy, and San Giovanni Rotondo, southern Italy. We interviewed 4,191 subjects (3,027 in Varese and 1,164 in San Giovanni Rotondo), 55 years and older, seen in office consultations by 27 general practitioners. A neurologist examined 734 patients who had two or more symptoms of polyneuropathy. A diagnosis of possible polyneuropathy (screening neuropathic symptoms and one of the following findings: bilateral impairment of strength; bilateral impairment of sensation; bilateral impairment of deep tendon reflexes) was made in 213 patients (7.0%) in Varese and 94 (8.1%) in San Giovanni Rotondo. Probable polyneuropathy (screening symptoms and at least two of the physical findings) was present in 111 Varese patients (3.7%) and 40 San Giovanni Rotondo patients (3.4%). The age- and sex-adjusted prevalence rate of probable polyneuropathy was 3.6 per 100 in Varese and 3.3 per 100 in San Giovanni Rotondo. The disease was more prevalent in women in Varese and in men in San Giovanni Rotondo and was significantly correlated with age in Varese. Diabetes was found in association with probable polyneuropathy in 43.7% of patients. Muscle cramps and distal paresthesia were the main symptoms. In general, polyneuropathy was mild to moderate, impairment of deep tendon reflexes and sensation being the most common findings.


Role of hydrogen-bonding in nonelectrolyte diffusion through dense artificial membranes.
The diffusion of two series of alcohols and amides through complex cellulose acetate membranes was studied. The thin dense part of these membranes behaves as a nonporous layer of low water content. In this layer, called the skin, the solute diffusion coefficients, omega, depend upon size, steric configuration, and the partition coefficient, K(8), between membrane and bathing solution. From the experimental values of omega and K(8), the over-all friction, f, experienced by the solutes in the membrane was computed. It was found that f depends upon the chemical nature of the solute and is related to hydrogen-bonding ability. In the coarse, porous layer of the cellulose acetate membrane, diffusion occurs mainly through aqueous channels. In this instance also the hydrogen-bonding ability of the solute seems to exercise a smaller but significant influence.


Infrared multiple photon dissociation action spectroscopy of proton-bound dimers of cytosine and modified cytosines: effects of modifications on gas-phase conformations.
The gas-phase structures of proton-bound dimers of cytosine and modified cytosines and their d6-analogues generated by electrospray ionization are probed via infrared multiple photon dissociation (IRMPD) action spectroscopy and theoretical electronic structure calculations. The modified cytosines examined include the 5-methyl-, 5-fluoro-, and 5-bromo-substituted species. IRMPD action spectra of seven proton-bound dimers exhibit both similar and distinctive spectral features over the range of ∼2600-3700 cm(-1). The IRMPD spectra of all of these proton-bound dimers are relatively simple, but exhibit obvious shifts in the positions of several bands that correlate with the properties of the substituent. The measured IRMPD spectra are compared to linear IR spectra calculated for the stable low-energy tautomeric conformations, determined at the B3LYP/6-31G* level of theory, to identify the conformations accessed in the experiments. Comparison of the measured IRMPD and calculated IR spectra indicates that only a single conformation, the ground-state structure, is accessed for all proton-bound homodimers, whereas the ground-state and a small population of the first-excited tautomeric conformations are accessed for all proton-bound heterodimers. In all cases, three hydrogen-bonding interactions in which the nucleobases are aligned in an antiparallel fashion analogous to that of the DNA i-motif are responsible for stabilizing the base pairing. Thus, base modifications such as 5-methyl- and 5-halo-substitution of cytosine should not alter the structure of the DNA i-motif.


The impact and prevalence of chronic insomnia and other sleep disturbances associated with chronic illness.
Chronic insomnia may coexist with chronic physical and psychiatric conditions, and its prevalence is often higher among patients with these conditions than in the general population. Evidence suggests that insomnia as a feature of chronic disease tends to be more severe and persistent than insomnia that does not occur in the context of chronic illness. Furthermore, comorbid insomnia can have a profound negative impact on patients' quality of life and overall functioning, and may be associated with greater healthcare resource utilization. In some cases, treatment of the underlying disorder may improve sleep, whereas in other cases, treatment of the sleep symptoms may actually improve the underlying disorder. In addition, chronic insomnia may be a precursor to certain psychiatric comorbidities. Further research is needed not only to clarify the efficacy and safety of specific therapeutic approaches but also to further investigate the possibility that successful treatment of sleep disturbances may improve objective and subjective parameters of the disorders themselves. This article reviews the specific associations between chronic insomnia and a wide range of chronic physical and psychiatric disorders.


Factors influencing alcohol consumption during pregnancy and after giving birth.
This study explored the demographic profile of women consuming alcohol during pregnancy and after giving birth, as part of a larger cohort study of smoking during pregnancy. This was a prospective study of a cohort of 665 women registered with a maternity care provider organisation for antenatal care in Wellington. Data were collected from postal questionnaires sent at intervals during gestation and the postnatal period. The questionnaires elicited information about smoking, alcohol consumption and demographic data. At 24 weeks gestation, 74% of women reported not consuming any alcohol in the preceding seven days. Women who were pregnant for the first time, women who experienced nausea, women who were socio-economically deprived and women who smoked were less likely to report having consumed alcohol. At six weeks after giving birth the number of women reporting not consuming any alcohol in the preceding seven days decreased to 46%. Socio-economic deprivation was associated with abstention and tertiary education with alcohol consumption. Approximately a quarter of women continue to drink alcohol during pregnancy. Health education aiming to reduce alcohol consumption in pregnancy needs to take into account the profile of women who drink during pregnancy.


Energy requirements of breast-fed infants.
Current recommendations for energy intake are reviewed in light of emerging data on energy intakes of breast-fed infants and on total daily energy expenditure of infants. For determination of energy requirements, the historical approach based on observed intakes of healthy infants is compared with a newly proposed approach based on energy expenditure and deposition. A data set of exclusively breast-fed infants is used to illustrate the circuity of either approach. Energy intake, expenditure, and stores must be evaluated in an assessment of dietary adequacy. Ultimately, energy requirements of infants should reflect growth rate, body composition, and level of physical activity conducive to optimal health and neurobehavioral development.


Appearance of tuberculoma during treatment of tuberculous meningitis.
Case histories of two young Indian female patients are described who, during the course of regular chemotherapy for tuberculous meningitis, developed tuberculoma as suggested by CT-scan. Such lesions were not seen at the start of treatment. Twelve similar cases are collected from literature. Most of the patients developed new symptoms and/or signs having initially shown good response to drugs. The pathogenetic mechanisms for such an evolution of lesions are not known but possibly include immunological modulations. This development should not lead to excessive anxiety for treating physician. Surgery is not needed and a patient follow up is well rewarded. Pyrazinamide has emerged as a useful drug.


DNA mimic foldamers affect chromatin composition and disturb cell cycle progression.
The use of synthetic chemicals to selectively interfere with chromatin and the chromatin-bound proteome represents a great opportunity for pharmacological intervention. Recently, synthetic foldamers that mimic the charge surface of double-stranded DNA have been shown to interfere with selected protein-DNA interactions. However, to better understand their pharmacological potential and to improve their specificity and selectivity, the effect of these molecules on complex chromatin needs to be investigated. We therefore systematically studied the influence of the DNA mimic foldamers on the chromatin-bound proteome using an in vitro chromatin assembly extract. Our studies show that the foldamer efficiently interferes with the chromatin-association of the origin recognition complex in vitro and in vivo, which leads to a disturbance of cell cycle in cells treated with foldamers. This effect is mediated by a strong direct interaction between the foldamers and the origin recognition complex and results in a failure of the complex to organise chromatin around replication origins. Foldamers that mimic double-stranded nucleic acids thus emerge as a powerful tool with designable features to alter chromatin assembly and selectively interfere with biological mechanisms.


Thromboembolic Events Related to Treatment with Checkpoint Inhibitors: Report of Two Cases.
Despite the significant clinical benefits, checkpoint inhibition is associated with a unique spectrum of immune-related adverse events. It is sometimes difficult to distinguish some rare adverse effects from a cancer progression; thus, such effects should be reported in clinical trials to be diagnosed by physicians. Only a few cases of arterial embolic events have been described in studies related to patients treated by immunotherapy. In this article, we report the cases of 2 patients who presented rare and severe thromboembolic events after using checkpoint inhibitors. The first case describes multiple organ embolism at the same time, associated with other autoimmune symptoms. In the second case, distal digital necrosis emerged after the initiation of immunotherapy. There is insufficient data about the real incidence of thromboembolic and rheumatological events related to checkpoint inhibition. Future trials should be done to establish preventive strategies.


The health of older-adult, long-term cancer survivors.
Research indicates that cancer-related health problems persist for decades among survivors. The combination of late effects of cancer or its treatment and age-related health problems may add to the vulnerability of older survivors. This research reports on the health and functioning of a sample of long-term (5+ years), older-adult (>60 years) survivors of breast, prostate, and colorectal cancer. Data were derived from 321 in-person interviews with a sample randomly selected from a tumor registry at a comprehensive cancer center. Descriptive data analyzed comorbid health conditions and continued cancer symptoms reported by survivors. Correlational analysis examined the association among demographic cancer-related factors and a range of health quality-of-life outcomes, including functioning and illness impact. Nearly 40% of respondents have at least 1 symptom attributed to cancer/treatment. Pain was the most commonly reported symptom, with 21% attributing it to cancer. More than 40% of breast cancer survivors and nearly 20% of prostate cancer survivors reported pain. Being African American or female was significantly associated with more current symptoms and greater functional difficulty. Survivors who had chemotherapy and survivors with more types of treatment reported significantly more symptoms both during treatment and currently. Many older-adult survivors are more vulnerable due to both cancer-related symptoms and comorbid health conditions. Women and African Americans are at special risk. This combined vulnerability is an important factor for clinicians treating long-term survivors.


The income-generating behaviour of injecting drug-users in Oslo.
Drug users' income-generating behaviours, such as prostitution, acquisitive crime and small-scale dealing, have a major influence on the harm caused to the non-using population. Using data on the drug use and income sources of 900 drug-injectors in Oslo, this paper has two aims: to present data on Oslo income-generating behaviours and compare these with those in the Netherlands and Scotland; and to explore conceptual issues in the comparison of self-reported dealing income with other sources. Eighty-three per cent of respondents reported income from social benefit, and 43% had sold drugs in the last month. Half the females reported income from prostitution. The income-generation differences found in the comparisons section do not seem to reflect variations in drug and other social policies, but may relate to differences in the profitability of dealing. Using self-reported dealing income to compare the contributions of different income sources may be misleading, however, since it does not reflect financial profit or the value of dealers' drug consumption. Adjusted figures show that theft accounts for 23% of total drugs expenditure, while the corresponding figures for dealing and prostitution are 42% and 21%, respectively.


Conditions affecting cell seeding onto three-dimensional scaffolds for cellular-based biodegradable implants.
Seeding cells efficiently and uniformly onto three-dimensional scaffolds is a key element for engineering tissues, particularly when only a low-number of cells is available for tissue repair and regeneration. The aim of this study was to evaluate three seeding techniques on two biocompatible scaffolds in vitro using chondrocytes as follows: (1) static; (2) modified centrifugal cell immobilization (CCI); and (3) dynamic oscillating motion. Five milliliters of media containing 5, 10, or 25 million articular, auricular, or costal chondrocytes were used to seed porous PLGA scaffolds and sections of devitalized cartilage. The dynamic oscillating technique resulted in up to 150% higher cellular load at 7 days than CCI seeding. Cell distribution was more homogeneous throughout the scaffold under dynamic conditions versus more sporadic and dispersed cell concentrations on the scaffolds when using either the static or the modified CCI technique. Cell load and distribution, when using a low numbers of chondrocytes at one and two million cells per milliliter, was comparable to that using the much higher number, especially under dynamic seeding conditions. The seeded scaffolds were used as implants to achieve cellular bonding between two devitalized meniscus discs. The constructs were implanted subcutaneously in nude mice for 12 weeks and analyzed histologically. Implants seeded with auricular chondrocytes showed qualitative more integration into native meniscus tissue than articular and costal cell implants. We conclude the dynamic oscillating seeding technique is an efficient technique for seeding low-cell numbers onto scaffolds resulting in consistent and uniform cell distribution throughout porous PLGA scaffolds.


A qualitative study exploring women's personal experiences of their perineum after childbirth: expectations, reality and returning to normality.
to explore the feelings, perceptions and experiences of women in relation to their perineum following childbirth in the early postnatal period. a qualitative study using grounded theory. Data were collected using diaries and interviews and analysed using constant comparative method. hospital and community setting in the South of England. women (n=11) aged 20-42 years who had a vaginal birth. one core category, 'Striving for normality' and five major categories emerged: (1) 'preparing for the unknown', (2) 'experiencing the unexpected', (3) 'adjusting to reality', (4) 'getting back to normal' and (5) 'recovery of self'. 'Striving for normality' was where women wanted to be able to do normal things and feel like their normal selves soon after the birth of their baby. Much of what the women described doing during the early postnatal period was related to achieving this goal. the initial impact of childbirth on the perineum and surrounding area meant that in the first few postnatal days women largely concentrated on managing the effects of this. The impact however, went beyond the immediacy of coping with bodily functions extending into other daily activities in terms of managing and completing them. Examples of daily living activities in this context include bathing, eating, walking as well as completing household chores. Returning to normal following childbirth is significant for women and successfully achieving daily living activities is part of this process. However, women in this study seemed unprepared for the reality of this experience. women may be poorly prepared for the impact that perineal pain and discomfort can have on their lives especially related to successfully completing daily living activities in the early postnatal period. Consideration should be given to finding different ways of communicating the impact to women such as in the early postnatal period, rather than during pregnancy. The underpinning philosophy of care for the postnatal period should encapsulate a holistic approach, where physical symptoms of perineal pain and discomfort experienced by women are not tackled in isolation from any psychosocial impact this may also have.


Stroke in the young in the northern Manhattan stroke study.
Stroke and stroke subtype incidence in young black and Hispanic populations have not been well studied. The purpose of this study was to determine stroke incidence rates in these populations and to compare rates among various race-ethnic, sex, and age groups. A population-based incidence study identified all cases of first stroke in Northern Manhattan from 1993 to 1997. Stroke and stroke subtype incidence rates were calculated for younger (20 to 44 years of age) and older (>/=45 years of age) adults. The relative risk (RR) of stroke in blacks and Hispanics compared with whites was calculated. Stroke subtypes, infarct subtypes, and case fatality rates were compared in the young and old and in different race-ethnic groups and sexes. Over 4 years, 74 cases of first stroke in young patients were discovered (47% women, 12% black, 80% Hispanic, 8% white). The stroke incidence rates (cases per 100 000 persons per year) in the young were 23 overall, 10 for infarct, 7 for intracerebral hemorrhage (ICH), and 6 for subarachnoid hemorrhage. The RR of stroke in the young was greatest for blacks (2.4; 95% CI, 0.8 to 6.7) and Hispanics (2.5; 95% CI, 1.1 to 5.8) compared with whites. ICH was more frequent in men with a RR of 3.7 (95% CI, 1.4 to 10.1). Case fatality rates at 30 days were higher in blacks (38%) and Hispanics (16%) compared with whites (0%). Young blacks and Hispanics have greater stroke incidences than young whites.


A peptide antagonist of Prep1-p160 interaction improves ceramide-induced insulin resistance in skeletal muscle cells.
Prep1 is a homeodomain transcription factor belonging to the TALE protein family. Its overexpression affects glucose metabolism in several tissues. In particular, in skeletal muscle tissue the interaction of Prep1 with its cofactor p160 impairs GLUT4 expression and glucose uptake. In this study, we show that ceramides (C2cer), a class of lipids antagonizing insulin signalling, increase the levels of Prep1 and p160 in a dose and time-dependent fashion in L6 cells and induce their association by 80%. We find that C2cer exposure inhibits insulin receptor, IRS1 and Akt phosphorylation and reduces insulin-stimulated glycogen content and glucose uptake by 1.3- and 2.1-fold, respectively. The synthetic Prep1(54-72) peptide, mimicking the Prep1 region involved in the interaction with p160, reduces in vitro Prep1-p160 binding in a dose-dependent way (IC50 = 0.20μM). In C2cer-treated L6 cells, 10μM Prep1(54-72) restores insulin signalling impaired by ceramide treatment. Prep1 overexpressing L6 cells display similar metabolic alterations observed in ceramide-treated L6 cells and the presence of Prep1(54-72) mitigates these events. All these findings suggest that disruption of the Prep1/p160 molecular interaction enhances insulin sensitivity impaired by ceramides in skeletal muscle cells and indicate this complex as an important target for type 2 diabetes.


Angiotensin peptide regulation of bovine brain microvessel endothelial cell monolayer permeability.
The passage of fluid-phase endocytosis markers--Lucifer yellow and a fluorescein isothiocyanate-conjugated dextran--across confluent primary cultures of bovine brain microvessel endothelial cell (BMEC) monolayers was characterized in the presence of angiotensin II (Ang II) peptides. Exposure to nanomolar concentrations of saralasin, an Ang II agonist, attenuated the passage of the fluorophores across the monolayers by 50-75%. In contrast, exposure to sarathrin, an Ang II antagonist, had no effect on passage of the fluorophores across the BMEC monolayers. Sarathrin, however, did inhibit the saralasin-induced reduction in transendothelial monolayer permeability and suggested specific Ang II binding site mediation. Other experiments performed suggest that saralasin-induced changes in BMEC monolayer permeability can be blocked by pretreatment with inhibitors of prostaglandin synthesis and that substantial saralasin-induced changes in BMEC monolayer permeability occurred only following exposure on the apical side of the endothelial cells. Results were consistent with previous studies demonstrating the existence of specific Ang II binding sites on BMECs and Ang II regulation of fluid-phase endocytosis. In addition, these studies support the role of angiotensin peptides in modulating permeability properties of the blood-brain barrier.


Crystal Violet Staining Alone Is Not Adequate to Assess Synergism or Antagonism in Multi-Species Biofilms of Bacteria Associated With Bacterial Vaginosis.
Bacterial Vaginosis (BV) involves the presence of a multi-species biofilm adhered to vaginal epithelial cells, but its in-depth study has been limited due to the complexity of the bacterial community, which makes the design of in vitro models challenging. Perhaps the most common experimental technique to quantify biofilms is the crystal violet (CV) staining method. Despite its widespread utilization, the CV method is not without flaws. While biofilm CV quantification within the same strain in different conditions is normally accepted, assessing multi-species biofilms formation by CV staining might provide significant bias. For BV research, determining possible synergism or antagonism between species is a fundamental step for assessing the roles of individual species in BV development. Herein, we provide our perspective on how CV fails to properly quantify an in vitro triple-species biofilm composed of Gardnerella vaginalis, Fannyhessea (Atopobium) vaginae, and Prevotella bivia, three common BV-associated bacteria thought to play key roles in incident BV pathogenesis. We compared the CV method with total colony forming units (CFU) and fluorescence microscopy cell count methods. Not surprisingly, when comparing single-species biofilms, the relationship between biofilm biomass, total number of cells, and total cultivable cells was very different between each tested method, and also varied with the time of incubation. Thus, despite its wide utilization for single-species biofilm quantification, the CV method should not be considered for accurate quantification of multi-species biofilms in BV pathogenesis research.


CRISPR-Cas9-Mediated Genetic Screening in Mice with Haploid Embryonic Stem Cells Carrying a Guide RNA Library.
Mouse androgenetic haploid embryonic stem cells (AG-haESCs) can support full-term development of semi-cloned (SC) embryos upon injection into MII oocytes and thus have potential applications in genetic modifications. However, the very low birth rate of SC pups limits practical use of this approach. Here, we show that AG-haESCs carrying deletions in the DMRs (differentially DNA methylated regions) controlling two paternally repressed imprinted genes, H19 and Gtl2, can efficiently support the generation of SC pups. Genetic manipulation of these DKO-AG-haESCs in vitro using CRISPR-Cas9 can produce SC mice carrying multiple modifications with high efficiency. Moreover, transfection of DKO-AG-haESCs with a constitutively expressed sgRNA library and Cas9 allows functional mutagenic screening. DKO-AG-haESCs are therefore an effective tool for the introduction of organism-wide mutations in mice in a single generation.


AiO, combining DNA/protein programs and oligo-management.
AiO (All in One) is a program for Windows, that combines typical DNA/protein features such as plasmid map drawing, finding of ORFs, translate, backtranslate and high quality printing with a number of databases. These databases allow the management of oligonucleotides, oligonucleotide-manufacturers, restriction enzymes, structural DNA and program users in a multi-user/multi-group environment. An AiO specific website, with the possibility to download is at: http://22.214.171.124/aio/ Examples with screen shots- http://22.214.171.124/aio/ : Manual (in PDF format)-http://220.127.116.11/aio/manual.pdf


Devaluation of a conditioned reinforcer requires its reexposure.
A change in motivational state does not guarantee a change in operant behaviour. Only after an organism has had contact with an outcome while in a relevant motivational state does behaviour change, a phenomenon called incentive learning. While ample evidence indicates that this is true for primary reinforcers, it has not been established for conditioned reinforcers. We performed an experiment with rats where lever-presses were reinforced by presentations of an audiovisual stimulus that had previously preceded food delivery; in the critical experimental groups, the audiovisual stimulus was then paired a single time with a strong electric shock. Some animals were reexposed to the audiovisual stimulus. Lever-presses yielding no outcomes were recorded in a subsequent test. Animals that had been reexposed to the audiovisual stimulus after the aversive training responded less than did those that had not received reexposure. Indeed, those animals that were not reexposed did not differ from a control group that received no aversive conditioning of the audiovisual stimulus. Moreover, these results were not mediated by a change in the food's reinforcement value, but instead reflect a change in behaviour with respect to the conditioned reinforcer itself. These are the first data to indicate that the affective value of conditioned stimuli, like that of unconditioned ones, is established when the organism comes into contact with them.


Effect of positive and negative pressure breathing on sodium and water excretion.
Positive and negative pressure breathing purportedly alter renal sodium and water excretion by modifying hemodynamics and/or hormonal regulators of sodium and water homeostasis. To test this hypothesis we monitored hemodynamic and hormonal responses in seven normal men to (1) continuous positive pressure breathing (19 +/- 1 mm Hg for 30 minutes) after water loading (urine volume = 15 +/- 1 ml/min); and (2) continuous negative pressure breathing (11 +/- 1 mm Hg for 30 minutes) after maintenance water ingestion (urine volume = 4 +/- 1 ml/min), in random order. Each study was repeated on a control day without pressure breathing. Results were as follows (mean +/- SE, p less than 0.05): (1) continuous positive pressure breathing decreased urinary sodium from 0.28 +/- 0.07 to 0.17 +/- 0.04 mEq/min, increased atrial natriuretic peptide from 34.2 +/- 4.9 to 48.5 +/- 6.9 pg/ml, and had no effect on osmolar and free water clearances, cardiac output, plasma renin activity, or plasma aldosterone and plasma arginine vasopressin levels; and (2) continuous negative pressure breathing increased free water clearance from 0.6 +/- 0.7 to 4.5 +/- 1.2 ml/min, urine volume from 4.0 +/- 0.8 to 8.9 +/- 1.3 ml/min, and cardiac output from 5.1 +/- 0.4 to 7.0 +/- 0.6 L/min in a proportional manner (r = 0.40, p less than 0.01) and had no effect on osmolar clearance, urinary volumes of sodium and potassium, plasma renin activity, plasma aldosterone, atrial natriuretic peptide, and arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)


Solvation of the N-(1-Phenylethyl)-N'-[3-(triethoxysilyl)propyl]-urea chiral stationary phase in mixed alcohol/water solvents.
A theoretical and experimental study of alcohol/water and alcohol/alcohol solvent mixtures near a surface of N-(1-phenylethyl)-N'-[3-(triethoxysilyl)propyl]-urea (PEPU), a Pirkle-type chiral stationary phase, is presented. Molecular dynamics simulations are performed at room temperature for water/methanol, water/1-propanol, water/2-propanol, and methanol/1-propanol solvent mixtures confined between two PEPU surfaces. The interface was also prepared experimentally by attaching the PEPU molecules to atomic force microscopy tips and oxidized Si(111) substrates. Chemical force spectrometric measurements between such PEPU-terminated tips and samples were taken in the solvent mixtures, and the results are compared to the molecular dynamics study. We find that the extent of hydrogen bonding at the surface is the dominant contributor to the measured forces.


ARID1A-dependent permissive chromatin accessibility licenses estrogen-receptor signaling to regulate circadian rhythms genes in endometrial cancer.
Estrogen receptor α (ER) acts as an oncogenic signal in endometrial endometrioid carcinoma. ER binding activity largely depends on chromatin remodeling and recruitment of transcription factors to estrogen response elements. A deeper understanding of these regulatory mechanisms may uncover therapeutic targets for ER-dependent endometrial cancers. We show that estrogen induces accessible chromatin and ER binding at a subset of enhancers, which form higher-order super enhancers that are vital for ER signaling. ER positively correlates with active enhancers in primary tumors, and tumors were effectively classified into molecular subtypes with chromatin accessibility dynamics and ER-dependent gene signature. ARID1A binds within ER-bound enhancers and regulates ER-dependent transcription. Knockdown of ARID1A or fulvestrant treatment profoundly affects the gene-expression program, and inhibits cell growth phenotype by affecting the chromatin environment. Importantly, we found dysregulated expression of circadian rhythms genes by estrogen in cancer cells and in primary tumors. Knockdown of ARID1A reduces the chromatin accessibility and ER binding at enhancers of the circadian gene ARNTL and BHLHE41, leading to a decreased expression of these genes. Altogether, we uncover a critical role for ARID1A in ER signaling and therapeutic target in ER-positive endometrial cancer.


Chinese hamster ovary cell motility to fibronectin is modulated by the second extracellular loop of CD9. Identification of a putative fibronectin binding site.
CD9, a member of the tetraspanin family of proteins, is characterized by four transmembrane domains and two extracellular loops. Surface expression of CD9 on Chinese hamster ovary (CHO) cells dramatically enhances spreading and motility on fibronectin. To elucidate the mechanistic basis of CD9-fibronectin interaction, binding to fibronectin was investigated using purified and recombinant forms of CD9. The affinity of fibronectin for CD9 in enzyme-linked immunosorbent assay was 81 +/- 25 nm. The binding of fibronectin to immobilized CD9 was enhanced by Ca(2+) ions. Protein binding and peptide competition studies demonstrated that peptide 6 derived from CD9 extracellular loop 2 (amino acids 168-192) contained part of the fibronectin-binding domain. Additionally, enhanced adhesion of CD9-CHO-B2 cells to fibronectin was significantly reduced by peptide 6. CD9-CHO cells had a 5-fold increase in motility to fibronectin as compared with mock-transfected controls, an effect that correlated with CD9 cell surface density. Truncation of CD9 extracellular loop 2 and peptide 6 caused inhibition of CD9-CHO cell motility to fibronectin. Deletion of CD9 extracellular loop 1 had no significant effect on CHO cell motility. These findings demonstrate a critical role for CD9 extracellular loop 2 in cell motility to fibronectin and clarify the mechanism by which CD9-fibronectin interaction modulates cell adhesion and motility.


Delayed Neurosurgical Intervention in Traumatic Brain Injury Patients Referred From Primary Hospitals Is Not Associated With an Unfavorable Outcome.
Background: Secondary transports of patients suffering from traumatic brain injury (TBI) may result in a delayed management and neurosurgical intervention, which is potentially detrimental. The aim of this study was to study the effect of triaging and delayed transfers on outcome, specifically studying time to diagnostics and neurosurgical management. Methods: This was a retrospective observational cohort study of TBI patients in need of neurosurgical care, 15 years and older, in the Stockholm Region, Sweden, from 2008 throughout 2014. Data were collected from pre-hospital and in-hospital charts. Known TBI outcome predictors, including the protein biomarker of brain injury S100B, were used to assess injury severity. Characteristics and outcomes of direct trauma center (TC) and those of secondary transfers were evaluated and compared. Functional outcome, using the Glasgow Outcome Scale, was assessed in survivors at 6-12 months after trauma. Regression models, including propensity score balanced models, were used for endpoint assessment. Results: A total of n = 457 TBI patients were included; n = 320 (70%) patients were direct TC transfers, whereas n = 137 (30%) were secondary referrals. In all, n = 295 required neurosurgery for the first 24 h after trauma (about 75% of each subgroup). Direct TC transfers were more severely injured (median Glasgow Coma Scale 8 vs. 13) and more often suffered a high energy trauma (31 vs. 2.9%) than secondary referrals. Admission S100B was higher in the TC transfer group, though S100B levels 12-36 h after trauma were similar between cohorts. Direct or indirect TC transfer could be predicted using propensity scoring. The secondary referrals had a shorter distance to the primary hospital, but had later radiology and surgery than the TC group (all p < 0.001). In adjusted multivariable analyses with and without propensity matching, direct or secondary transfers were not found to be significantly related to outcome. Time from trauma to surgery did not affect outcome. Conclusions: TBI patients secondary transported to a TC had surgical intervention performed hours later, though this did not affect outcome, presumably demonstrating that accurate pre-hospital triaging was performed. This indicates that for selected patients, a wait-and-see approach with delayed neurosurgical intervention is not necessarily detrimental, but warrants further research.


Treatment of anticonvulsant hypersensitivity syndrome with intravenous immunoglobulins and corticosteroids.
Anticonvulsant hypersensitivity syndrome is a specific severe idiosyncratic reaction to the aromatic antiepileptic drugs. The most frequent presenting symptoms are fever and rash, lymphadenopathy owing to lymphoid hyperplasia, hepatitis, and interstitial nephritis. Severe skin reactions (Stevens-Johnson syndrome or toxic epidermal necrolysis) have also been reported. Early detection is crucial owing to the high mortality rate. Although withdrawal of the offending drug is critical, the optimal treatment approach remains controversial. Previous studies report a severe course and prolonged hospital stay for cutaneous drug-related reactions, including referral to a burn center, skin débridement, and allograft skin coverage. The aim of the present report is to describe four adolescents with antiepileptic drug hypersensitivity syndrome who were treated with intravenous immunoglobulin and systemic corticosteroids. All recovered completely following an uncomplicated and relatively short course and hospitalization. Findings indicate that this regimen might be a promising treatment option in this patient population. Larger, controlled trials are needed to reach a definitive conclusion.


Neurons dissociated from rat myenteric plexus retain differentiated properties when grown in cell culture. III. Synaptic interactions and modulatory effects of neurotransmitter candidates.
We have used intracellular recordings to study synaptic interactions between myenteric neurons grown in dissociated cell culture. Intracellular stimulation of individual myenteric neurons caused several types of synaptic effects in nearby neurons: fast excitatory synaptic potentials mediated by nicotinic acetylcholine receptors; slow, non-cholinergic synaptic potentials; dual transmission having both fast cholinergic and slow non-cholinergic components and inhibition of spontaneously occurring fast nicotinic synaptic potentials. Fast nicotinic synaptic potentials were elicited by about 40% of neurons tested and often occurred spontaneously. The fast synaptic potentials were similar to those that have been studied in other autonomic neurons with respect to their estimated reversal potential and their sensitivity to cholinergic antagonists. The amplitudes of the fast synaptic potentials declined if evoked at frequencies greater than 0.5 Hz. Potentiation of the fast synaptic potentials was observed following high-frequency stimulation of presynaptic neurons. Several transmitter candidates modulated fast cholinergic transmission. Substance P and vasoactive intestinal peptide promoted nicotinic transmission by causing increased amplitudes of evoked and spontaneous fast synaptic potentials and an increased frequency of spontaneous synaptic potentials. gamma-Aminobutyrate and [Met]enkephalin both caused decreased amplitudes and frequency of nicotinic synaptic potentials. Serotonin depressed synaptic potentials in some neurons while enhancing them or having no effect in others. Slow, non-cholinergic, synaptic potentials were elicited by about 10% of neurons tested. These synaptic effects lasted 15-300s, caused depolarizations of 3-15 mv and were accompanied by increased neuronal input resistance. The transmitter(s) causing these slow synaptic potentials has not yet been identified.(ABSTRACT TRUNCATED AT 250 WORDS)


On the sources of summertime haze in the eastern United States.
The summertime haze transported from the Gulf Coast northward in maritime tropical air masses is partially formed from emissions in the midwestern and northeastern United States. Several cases are documented in which sulfate particulates, formed from emissions in the Midwest and Northeast, traveled to the Gulf of Mexico and, in some cases, returned to their source regions.


Schizencephaly: A case report and review of literature.
Schizencephaly is a congenital condition characterized by cerebrospinal fluid-filled clefts that extend from the pia surface of the cerebral hemisphere to the ependymal surface of the ventricle. Magnetic resonance imaging is the modality of choice for its diagnosis. Very few cases have been described in the literature in this environment. Here, we present an 18-month-old male child who presented in a tertiary hospital in Port Harcourt, Rivers State in Nigeria with 6 months history of recurrent seizures. A cranial MRI done revealed that he had right unilateral opened lip schizencephaly.


New striatal neurons in a mouse model of progressive striatal degeneration are generated in both the subventricular zone and the striatal parenchyma.
Acute striatal lesions increase proliferation in the subventricular zone (SVZ) and induce migration of SVZ neuroblasts to the striatum. However, the potential of these cells to replace acutely degenerated neurons is controversial. The possible contribution of parenchymal progenitors to striatal lesion-induced neurogenesis has been poorly explored. Here, we present a detailed investigation of neurogenesis in the striatum of a mouse model showing slow progressive neurodegeneration of striatal neurons, the Creb1(Camkcre4)Crem⁻/⁻ mutant mice (CBCM). By using BrdU time course analyses, intraventricular injections of a cell tracker and 3D reconstructions we showed that neurodegeneration in CBCM mice stimulates the migration of SVZ neuroblasts to the striatum without altering SVZ proliferation. SVZ-neuroblasts migrate as chains through the callosal striatal border and then enter within the striatal parenchyma as individual cells. In addition, a population of clustered neuroblasts showing high turnover rates were observed in the mutant striatum that had not migrated from the SVZ. Clustered neuroblasts might originate within the striatum itself because they are specifically associated with parenchymal proliferating cells showing features of intermediate neuronal progenitors such as clustering, expression of EGF receptor and multiple glial (SOX2, SOX9, BLBP) and neuronal (Dlx, Sp8, and to some extent DCX) markers. Newborn striatal neurons had a short lifespan and did not replace projection neurons nor expressed sets of transcription factors involved in their specification. The differentiation failure of endogenous neuroblasts likely occurred cell autonomously because transplanted wild type embryonic precursors correctly differentiated into striatal projection neurons. Thus, we propose that under progressive degeneration, neither SVZ derived nor intra-striatal generated neurons have the potential to differentiate into striatal projection neurons.


Cyclic Penta- and Hexaleucine Peptides without N-Methylation Are Orally Absorbed.
Development of peptide-based drugs has been severely limited by lack of oral bioavailability with less than a handful of peptides being truly orally bioavailable, mainly cyclic peptides with N-methyl amino acids and few hydrogen bond donors. Here we report that cyclic penta- and hexa-leucine peptides, with no N-methylation and five or six amide NH protons, exhibit some degree of oral bioavailability (4-17%) approaching that of the heavily N-methylated drug cyclosporine (22%) under the same conditions. These simple cyclic peptides demonstrate that oral bioavailability is achievable for peptides that fall outside of rule-of-five guidelines without the need for N-methylation or modified amino acids.


The influence of rural location on utilization of formal home care: the role of Medicaid.
This research examines the impact of rural-urban residence on formal home-care utilization among older people and determines whether and how Medicaid coverage influences the association between rural-urban location and risk of formal home-care use. We combined data from the 1998 consolidated file of the Medical Expenditure Panel Survey Household Component with data from the Area Resource File to generate the analytical data set. We established two measures of formal home-care utilization: home care reimbursed through any source, and Medicare-reimbursed home health care. Our measures of rural-urban residence included metropolitan counties, nonmetropolitan counties having towns of at least 10,000 people, and nonmetropolitan counties with no towns of 10,000 people. We used logistic regression analyses to examine main effects and interaction effects of Medicaid coverage and residence on the two types of formal home care under controls for person-level characteristics and state fixed effects. The unadjusted logistic analyses demonstrate that older people who reside in the most rural counties (nonmetropolitan counties having no town of 10,000) are significantly more likely than metropolitan residents to use any formal home care and Medicare home health care. The fully adjusted logistic analysis results point to an interplay between residential status and Medicaid coverage with regard to formal home-care use. In comparison with metropolitan residents covered by Medicaid, the adjusted relative risk of any formal home-care use is significantly higher for Medicaid enrollees residing in nonmetropolitan counties having no town of 10,000 people. Use of Medicare home health care is significantly greater for residents of the most rural counties, irrespective of their Medicaid coverage, as well as Medicaid-covered residents of nonmetropolitan counties having a town of at least 10,000 people. In nonmetropolitan areas, Medicaid may be an important mechanism for linking older individuals with formal home care, especially Medicare home health care, and with the services that generate formal home care. Formal home care, including Medicare home health care, may substitute for less available forms of care in the most rural of nonmetropolitan areas. Therefore, policies that limit access to formal home care could lead to increased service-related vulnerabilities among older rural residents.


The genetics and biology of Phytophthora infestans: modern approaches to a historical challenge.
The oomyceteous fungus Phytophthora infestans, which causes the late blight diseases of potato and tomato, has a history that is closely associated with that of mycology and plant pathology. Nevertheless, P. infestans and other oomycetes remain poorly understood relative to fungi in other groups. A resurgence in the worldwide impact of late blight has recently increased interest in the species. Fortunately, over the past decade improved tools for laboratory analysis have been developed which provide an opportunity to advance our understanding of this important pathogen. Since oomycetes do not have a close taxonomic affinity with well-characterized organisms such as ascomycetes and basidiomycetes, it is likely that studies of P. infestans will yield novel biological findings. This review provides an update on the status of research into the fundamental aspects of the biology, genetics, and pathology of P. infestans and describes prospects for future advances.


Fast determination of curcumol, curdione and germacrone in three species of Curcuma rhizomes by microwave-assisted extraction followed by headspace solid-phase microextraction and gas chromatography-mass spectrometry.
Curcumol, germacrone and curdione are the main active ingredients in a common traditional Chinese medicine (TCM) of Rhizoma Curcuma, and commonly used as the TCM quality control markers. In the present work, microwave-assisted extraction (MAE) followed by headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) was developed for the quantitative analysis of curcumol, curdione and germacrone in Rhizoma Curcuma. The MAE and HS-SPME parameters were studied, and the method was validated. The optimal MAE conditions obtained were: microwave power of 700 W and irradiation time of 4 min, and HS-SPME optimal conditions were: fiber coating of 100 microm PDMS, extraction temperature of 80 degrees C, extraction time of 20 min, stirring rate of 1,100 rpm, and salt concentration of 30% NaCl. The proposed method provided good precision (RSD less than 12%) and recoveries between 86% and 93%. The proposed method was applied to the determination of the three marker compounds in three species of Curcuma rhizomes (Curcuma wenyujin, Curcuma phaeocaulis, and Curcuma kwangsiensis). To demonstrate the proposed method reliability, a conventional technique of steam distillation was also used for the analysis of curcumol, germacrone and curdione in the TCMs. The results show that MAE-HS-SPME is a simple, rapid, solvent-free and reliable method for the determination of curdione, curcumol and germacrone in TCM, and also a potential and powerful tool for quality assessment of Rhizoma Curcuma.


Exploring the factors related to adolescent health literacy, health-promoting lifestyle profile, and health status.
Health literacy has been concerned a key factor for determining the use of health information and promoting health. The study aimed to explore adolescent health literacy, health-promoting lifestyle profile, and health status and related factors. A cross-sectional study design was used; 918 first year junior college students were recruited in Taiwan. The measurements were the Chinese Health Literacy Survey Questionnaire (HLS-C-Q), the Chinese Health-Promoting Lifestyle Profile (HPLP-S), and the Health Status Questionnaire. The mean score for health literacy was 36.15 (±6.21), with 30.17% of the participants having insufficient or problematic health literacy. Further, 19.9% of participants were obese and 11.2% experienced emotional instability. Health literacy and health-promoting lifestyle profile showed significant positive and negative correlations with perceived health status and depression, respectively (p < 0.05). An exercise frequency of ≥3 times/week was a predictor of health literacy, health-promoting lifestyle profile, and emotional stability. Adolescent health literacy, health-promoting lifestyle profile, and health status require careful consideration. In adolescents, developing regular exercise may increase health literacy, thereby developing healthy lifestyle profiles and ameliorating obesity and depression-related issues.


A mechanism for the indirect transfer of photosynthetically reduced nicotinamide adenine dinucleotide phosphate from chloroplasts to the cytoplasm.
A triose phosphate/3-phosphoglycerate shuttle for the indirect transfer of photosynthetically reduced NADP from chloroplasts to the cytoplasm has been demonstrated in vitro. Triose phosphate, formed from 3-phosphoglycerate in the chloroplast, was oxidized back to 3-phosphoglycerate outside the chloroplast by the nonreversible d-glyceraldehyde 3-phosphate dehydrogenase reaction which is specific for NADP. The 3-phosphoglycerate could presumably return to the chloroplast to complete the shuttle. The properties of nonreversible d-glyceraldehyde 3-phosphate dehydrogenase are considered particularly suitable for effective operation of this shuttle system.


[Cultivation of aerobic granular sludge in SBR by seeding anaerobic granular sludge].
Anaerobic granular sludge was inoculated to an aerobic SBR, where CH3COONa was used as the carbon source. Observations on the change of granules' shape and structure revealed that the granules experienced a shape-keeping and component-replacing process. The sludge concentration increased at first 4 weeks and then decreased to reach a constant of 5g/L at 35d with its SVI of 30 - 40mL/g. Granular sludge dominated in the reactor and suspended sludge concentration was less than 0.5g/L during the end of the process. Anaerobic granular sludge, in which spheral bacteria was the main microorganism, was successfully developed to aerobic granular sludge in which filamentous and bacillius bacteria were the dominant microorganism.


Oxalic Acid Production in Clarireedia jacksonii Is Dictated by pH, Host Tissue, and Xylan.
Dollar spot is caused by the fungus Clarireedia jacksonii and is the most common disease of golf course turfgrass in temperate climates. Oxalic acid (OA) is an important pathogenicity factor in other fungal plant pathogens, such as the dicot pathogen Sclerotinia sclerotiorum, but its role in C. jacksonii pathogenicity on monocot hosts remains unclear. Herein, we assess fungal growth, OA concentration, and pH change in potato dextrose broth (PDB) following incubation of C. jacksonii. In addition, OA production by C. jacksonii and S. sclerotiorum was compared in PDB amended with creeping bentgrass or common plant cell wall components (cellulose, lignin, pectin, or xylan). Our results show that OA production is highly dependent on the environmental pH, with twice as much OA produced at pH 7 than pH 4 and a corresponding decrease in PDB pH from 7 to 5 following 96 h of C. jacksonii incubation. In contrast, no OA was produced or changes in pH observed when C. jacksonii was incubated in PDB at a pH of 4. Interestingly, C. jacksonii increased OA production in response to PDB amended with creeping bentgrass tissue and the cell wall component xylan, a major component of grass cell walls. S. sclerotiorum produced large amounts of OA relative to C. jacksonii regardless of treatment, and no treatment increased OA production by this fungus, though pectin suppressed S. sclerotiorum's OA production. These results suggest that OA production by C. jacksonii is reliant on host specific components within the infection court, as well as the ambient pH of the foliar environment during its pathogenic development.


Social Pre-treatment Modulates Attention Allocation to Transient and Stable Object Properties.
Increasing evidence suggests that ostensive-communicative signals in social learning situations enable observers to focus their attention on the intrinsic features of an object (e.g., color) at the expense of ignoring transient object properties (e.g., location). Here we investigated whether off-line social cues, presented as social primes, have the same power to modulate attention allocation to stable and transient object properties as on-line ostensive-communicative cues. The first part of the experiment consisted of a pre-treatment phase, where adult male participants either received intensive social stimulation or were asked to perform non-social actions. Then, they participated in a change detection test, where they watched pairs of pictures depicting an array of five objects. On the second picture, a change occurred compared to the first picture. One object changed either its location (moving forward or backward) or was replaced by another object, and participants were required to indicate where the change had happened. We found that participants detected the change more successfully if it had happened in the location of the object; however, this difference was reduced following a socially intense pre-treatment phase. The results are discussed in relation to the claims of the natural pedagogy theory.


Robotic microsurgical spermatic cord denervation for chronic orchialgia: a case series.
Chronic orchialgia is a frustrating urologic condition that is commonly refractory to conservative modes of therapy. Microscopic spermatic cord denervation is a proven solution for patients who do not achieve relief from nonsurgical treatments. However, current widely used techniques require additional training in microsurgery. To describe an adaptation and improvement of spermatic cord microdenervation technique that leveraged the robotic surgical training common for new urologists and is also accessible for urologists not specifically trained in microsurgery. Robotic-assisted microdenervation of the spermatic cord was performed in three patients using a fluorescence vascular imaging tool to improve visualization of vascular structures (Firefly™; Innovative Surgical, Sunnyvale, CA, USA), along with a tissue matrix allograft to allow for better healing (AminoFix™; MiMedx®, Marietta, GA, USA). All three patients (100%) experienced postoperative resolution of their chronic orchialgia, and none reported any new pain. Utilization of robotic-assisted surgery offers more urologists the ability to use familiar techniques to treat chronic orchialgia when conservative measures are unsuccessful.


Progesterone-dependent decidualization of the human endometrium is mediated by cAMP.
Progesterone is a key factor in regulating endometrial cell decidualization, but the signal transduction pathways involved in mediating the effects of progesterone are not known. A role of the cAMP pathway in decidualization has been suggested by in vitro studies demonstrating that cAMP agonists can stimulate decidualization, in the absence of sex steroids. In this article, we have used an in vitro culture model of progesterone-dependent decidualization of human endometrial stromal cells to examine whether progesterone-induced decidualization is associated with activation of the cAMP signal transduction pathway in which the prolactin gene expression is a marker of decidualization. Following a lag period of approx 3 d, progesterone induced prolactin secretion and elevated intracellular cAMP levels. By d 15, cAMP and prolactin levels were approx 10- and 60-fold greater, respectively, than those on d 3. Changes in cAMP levels showed a positive correlation with prolactin secretion. Prostaglandin E2 (PGE2), which enhances progesterone-dependent decidualization, also increased both prolactin secretion and cAMP levels approx two- to fourfold on d 15 compared with d 3, whereas PGE2 alone, which does not induce decidualization, did not stimulate prolactin secretion or intracellular cAMP accumulation. Conversely, all-trans retinoic acid, which attenuates progesterone-dependent decidualization, significantly (p < 0.05) decreased both prolactin secretion and cAMP levels. Furthermore, the protein kinase A (PKA) inhibitor, 8-bromoadenosine-3',5'-cyclic monophosphorothioate, significantly (p < 0.05) suppressed progesterone-dependent prolactin expression. Since activation of the PGE2 receptor subtype EP2 stimulates adenylate cyclase, reverse transcription-polymerase chain reaction (RT-PCR) analysis of endometrial cells was undertaken. Expression of EP2 mRNA was induced in cells treated with progesterone and estradiol alone or with PGE2, compared with untreated controls. The data suggest that the cAMP signal transduction cascade is activated during progesterone-dependent decidualization.


Polyinosinic:polycytidylic acid aggravates calcipotriol-induced atopic dermatitis-like skin lesions in mice by increasing the expression of thymic stromal lymphopoietin.
Polyinosinic:polycytidylic acid [poly (I:C)] is a synthetic viral double-stranded RNA analog that can activate Toll-like receptor 3 (TLR3) and induce the release of thymic stromal lymphopoietin (TSLP). TSLP has been shown to contribute to atopic dermatitis (AD). This study explored the effects of poly (I:C) in a calcipotriol-induced model of murine AD. Calcipotriol (MC903) was used to establish AD-like mice model. Mice in the MC903 + poly (I:C) group were then treated with poly (I:C) in a concentration of 5 µg/g bodyweight. The impact of poly (I:C) treatment on these animals was assessed based upon changes in lesions, bodyweight, ear thickness, and histopathological findings. In addition, serum interleukin 4 (IL-4), interferon-γ (IFN-γ), immunoglobulin E (IgE), IL-13, and TSLP levels were measured using enzyme-linked immunosorbent assay (ELISA), while tissue IL-13 and TSLP levels were assessed using ELISA, Western blotting, and immunohistochemical staining, and mast cell infiltration was assessed through toluidine blue (TBO) staining. Relative to vehicle control treatment, poly (I:C) administration was associated with a significant exacerbation of calcipotriol-induced AD-like murine skin lesions. In animals treated with poly (I:C), the levels of serum IL-4, IL-13 and TSLP increased significantly, while the level of IFN-γ did not change. It also increased IL-13 and TSLP levels in skin lesions relative to the control-group mice and increased dermal mast cell infiltration and IgE production. These data indicate that poly (I:C) treatment and exogenous activation of TLR3 exacerbate murine calcipotriol-induced AD-like skin lesions in part by increasing the production of TSLP and other T-helper 2 (Th2)-related cytokines. Atopic dermatitis (AD); polyinosinic:polycytidylic acid [poly (I:C)]; thymic stromal lymphopoietin (TSLP); Toll-like receptor 3 (TLR3).


[Volume controlled fixation of the lung by formalin vapor (author's transl)].
A new method of lung fixation by formalin vapor is presented. A simple Engstrøm type respirator modified for postmortem formalin insufflation of the lung was developed. Rapid fixation requires use of hot formalin vapor which would destroy available equipment. The main advantage compared to other described methods beside the constant volume is sufficient stirring of formalin and formalin vapor. In order to prevent condensation of water within the lung parenchyma any cooling of the vapor should be avoided. If the lungs are fixed by this method the tissue will stiffen in a position between in- and exspiration. Slices of 1 cm are cut. Radiographs in soft tissue technique guarantee unusual high resolution. Positive findings are identified easily and furthermore studied by microscopy: the direct correlation between X-ray finding and microscopy becomes possible.


[Clinical considerations on a case of Caroli disease].
A case of Caroli's disease is presented. Stress is laid on the importance of transcutaneous cholangiography in the diagnosis of this morbid form, and the usefulness of both echotomography and computed tomography. The latter permits visualisation of the intra- and extrahepatic bile ducts and indicates the extent of the disease. At the same time, it permits evaluation of any alterations of other organs. Attention is also drawn to the importance of careful diagnostic employment of these means of investigation. Emphasis is equally placed on the way complications can be prevented through medical and surgical management.


[A household approach to the analysis of elderly migration: a comparison between Italy and the United States].
"Who moves among the elderly? With whom do the elderly move? With whom will they stay once they have migrated? These are the main questions discussed in this paper. On the basis of a sample of individual data obtained from the censuses of Italy and the United States, data which were analysed by taking the household--and not, as is traditionally done, the individual--as the observation unit, the author concludes that there are some significant differences between the two countries as far as migration behavior of the elderly is concerned, even if there are also many similarities." (SUMMARY IN ENG AND SPA)


The effect of ONCE Renal on minerals and electrolytes in predialysis patients with chronic kidney disease.
Malnutrition is one common adverse consequence in patients with advanced chronic kidney disease (CKD), and most patients have a lower-than-normal dietary energy intake. The present study was undertaken to examine whether orally administered ONCE Renal formula (ORF) supplement would improve energy intake without minerals and electrolytes disturbances in predialysis patients with CKD. All eligible nondiabetic patients with CKD received ORF supplement for 1 week. Nutrition markers, renal function, and minerals and electrolytes were evaluated before and after supplementing. All patients kept a 3-day food record and were interviewed by a registered dietitian. A total of 29 patients with mean age 64.9±13.3 years were included. Mean estimated glomerular filtration rate was 37.7±12.1 mL/min/1.73 m(2). A significant increase was observed in amount of energy, fat, fiber, calcium, and magnesium intake after 1 week of ORF supplement. Moreover, in comparison with baseline values, the patients displayed decreased dietary protein intake and blood urea nitrogen and increased serum magnesium. However, no significant change was found in renal function, nutritional markers (body weight, prealbumin, albumin, and protein equivalence of total nitrogen appearance), serum calcium, phosphorus, sodium, potassium, and bicarbonate. In patients with CKD, ingestion of ORF was well tolerated and had a positive effect with an increase in dietary energy, fat, and fiber intake, as well as a decreased dietary protein intake. No mineral or electrolyte abnormalities were observed during the study.


A single amino acid substitution in the group 1 Trypanosoma brucei gambiense haptoglobin-hemoglobin receptor abolishes TLF-1 binding.
Critical to human innate immunity against African trypanosomes is a minor subclass of human high-density lipoproteins, termed Trypanosome Lytic Factor-1 (TLF-1). This primate-specific molecule binds to a haptoglobin-hemoglobin receptor (HpHbR) on the surface of susceptible trypanosomes, initiating a lytic pathway. Group 1 Trypanosoma brucei gambiense causes human African Trypanosomiasis (HAT), escaping TLF-1 killing due to reduced uptake. Previously, we found that group 1 T. b. gambiense HpHbR (TbgHpHbR) mRNA levels were greatly reduced and the gene contained substitutions within the open reading frame. Here we show that a single, highly conserved amino acid in the TbgHpHbR ablates high affinity TLF-1 binding and subsequent endocytosis, thus evading TLF-1 killing. In addition, we show that over-expression of TbgHpHbR failed to rescue TLF-1 susceptibility. These findings suggest that the single substitution present in the TbgHpHbR directly contributes to the reduced uptake and resistance to TLF-1 seen in these important human pathogens.


Epidemiology of diseases of unknown etiology, specified as "intractable diseases".
In Japan, epidemiological studies on intractable diseases have been undertaken and greatly promoted for more than 20 years by the Research Committee on Epidemiology of Intractable Diseases, with the financial supports from the Ministry of Health and Welfare of Japan. In this paper, chronological history of development of the Research Committee and some scientific accomplishments by the recent Research Committee (1993-1995) were summarized, mainly focusing on descriptive, analytical and other epidemiological studies. Hoped is that the readers are to be acquainted with the recent research activities by the Research Committee and seek for possible international collaborations in epidemiological studies on intractable diseases.


Identification and cloning of a glycoprotein hormone receptor from sea lamprey, Petromyzon marinus.
A full-length transcript encoding a functional lamprey glycoprotein hormone receptor I (lGpH-R I, GenBank AY750688) was cloned from the testes of the sea lamprey, Petromyzon marinus, using the GpH-R protein fingerprint GLYCHORMONER from the PRINTS database. The present study is the first to identify a GpH-R transcript in an agnathan, which is one of the only two representatives of the oldest lineage of vertebrates. The 719-amino acid full-length cDNA encoding lGpH-R I is highly similar and is likely a homolog of the vertebrate GpH-Rs (including LH, FSH, and TSH receptors). The key motifs, sequence comparisons, and characteristics of the identified GpH-R reveal a mosaic of features common to all other classes of GpH-Rs in vertebrates. The lGpH-R I was shown to activate the cAMP signaling system using human chorionic gonadotropin in transiently transfected COS-7 cells. The highest expression of the receptor transcript was demonstrated in the testes using reverse transcriptase-PCR. Lower levels of the receptor transcript were also detected in brain, heart, intestine, kidney, liver, muscle, and thyroid. The high expression of lGpH-R I in the testis and the high similarity with gnathostome gonadotropin hormone receptors suggest that lGpH-R I functions as a receptor for lamprey gonadotropin hormones. We hypothesize from these data that there is lower specificity of gonadotropin and its receptor in agnathans and that during co-evolution of the ligand and its receptor in gnathostomes, there were increased specificities of interactions between each GpH (TSH, LH, and FSH) and its receptor.


Short-Term Responses of Soil Respiration and C-Cycle Enzyme Activities to Additions of Biochar and Urea in a Calcareous Soil.
Biochar (BC) addition to soil is a proposed strategy to enhance soil fertility and crop productivity. However, there is limited knowledge regarding responses of soil respiration and C-cycle enzyme activities to BC and nitrogen (N) additions in a calcareous soil. A 56-day incubation experiment was conducted to investigate the combined effects of BC addition rates (0, 0.5, 1.0, 2.5 and 5.0% by mass) and urea (U) application on soil nutrients, soil respiration and C-cycle enzyme activities in a calcareous soil in the North China Plain. Our results showed soil pH values in both U-only and U plus BC treatments significantly decreased within the first 14 days and then stabilized, and CO2emission rate in all U plus BC soils decreased exponentially, while there was no significant difference in the contents of soil total organic carbon (TOC), dissolved organic carbon (DOC), total nitrogen (TN), and C/N ratio in each treatment over time. At each incubation time, soil pH, electrical conductivity (EC), TOC, TN, C/N ratio, DOC and cumulative CO2 emission significantly increased with increasing BC addition rate, while soil potential activities of the four hydrolytic enzymes increased first and then decreased with increasing BC addition rate, with the largest values in the U + 1.0%BC treatment. However, phenol oxidase activity in all U plus BC soils showed a decreasing trend with the increase of BC addition rate. Our results suggest that U plus BC application at a rate of 1% promotes increases in hydrolytic enzymes, does not highly increase C/N and C mineralization, and can improve in soil fertility.


Humoral immunity prevents clinical malaria during Plasmodium relapses without eliminating gametocytes.
Plasmodium relapses are attributed to the activation of dormant liver-stage parasites and are responsible for a significant number of recurring malaria blood-stage infections. While characteristic of human infections caused by P. vivax and P. ovale, their relative contribution to malaria disease burden and transmission remains poorly understood. This is largely because it is difficult to identify 'bona fide' relapse infections due to ongoing transmission in most endemic areas. Here, we use the P. cynomolgi-rhesus macaque model of relapsing malaria to demonstrate that clinical immunity can form after a single sporozoite-initiated blood-stage infection and prevent illness during relapses and homologous reinfections. By integrating data from whole blood RNA-sequencing, flow cytometry, P. cynomolgi-specific ELISAs, and opsonic phagocytosis assays, we demonstrate that this immunity is associated with a rapid recall response by memory B cells that expand and produce anti-parasite IgG1 that can mediate parasite clearance of relapsing parasites. The reduction in parasitemia during relapses was mirrored by a reduction in the total number of circulating gametocytes, but importantly, the cumulative proportion of gametocytes increased during relapses. Overall, this study reveals that P. cynomolgi relapse infections can be clinically silent in macaques due to rapid memory B cell responses that help to clear asexual-stage parasites but still carry gametocytes.


Expression profiling of transcription factors in B- or T-acute lymphoblastic leukemia/lymphoma and burkitt lymphoma: usefulness of PAX5 immunostaining as pan-Pre-B-cell marker.
The optimal use of transcription factors to determine B-lineage specificity in B-acute lymphoblastic leukemia/lymphoma (B-ALL) has not been fully investigated. We undertook an extensive immunohistochemical study of a panel of B-cell transcription factors in B- and T-ALL and Burkitt lymphoma to evaluate those with the best specificity and sensitivity. Tissue microarrays were constructed from 34 B-ALL, 19 T-ALL, and 30 Burkitt lymphoma samples. All 34 (100%) cases of B-ALL expressed PAX5; 32 (94%), BOB.1; 33 (97%), PU.1; 29 (85%), CD79a; 27 (79%), CD22; 2 (6%), CD20; 9 (26%), OCT-2; and 3 (9%), MUM1. Burkitt lymphoma cases were positive for PAX5 (30/30 [100%]), BOB.1 (27/30 [90%]), PU.1 (23/30 [77%]), CD79a (29/30 [97%]), CD22 (14/30 [47%]), CD20 (30/30 [100%]), OCT-2 (23/30 [77%]), and MUM1 (5/30 [17%]). T-ALLs were only positive for PU.1 (15/19 [79%]) and BOB.1 (12/19 [63%]). PAX5 demonstrated better specificity for B-lineage determination than BOB.1 and PU.1 and better sensitivity than CD79a, CD22, and CD20. These findings suggest that PAX5 has the greatest diagnostic usefulness and lineage determination in B-ALL, especially in cases with an inadequate specimen for flow cytometric analysis.


[Neurogenic inflammation and arthritis].
Over the past decade, numerous studies have supported the involvement of the sensory and sympathetic nervous system in the regulation of inflammation. This article reviews the neurogenic mechanisms and mediators of the sensory nervous system involved in the generation of inflammatory responses. The implications of neuropeptide-induced immunoregulation are discussed in the context of inflammation in rheumatoid arthritis.


An Ancient Science to Improve Today's Clinical Practice: Oral Surgery Meets Human Anatomy.
Human body dissection was a ubiquitous practice in the past, to better understand anatomy and to develop medicine. Today, its role could still be important to answer everyday clinical queries and help surgeons. The example of the possible lack of anesthesia during symphysis surgeries can emphasize the usefulness of dissection. The mandibular symphysis usually receives innervation from inferior alveolar nerve terminations, but, in some rare cases, a particular anastomosis involves the lingual nerve and the nerve to the mylohyoid. The anatomical knowledge resulting from body dissections could help oral surgeons to understand the reason why the patient could feel pain during the surgery, and ensure performance of the right lingual nerve block to obtain complete anesthesia. This clinical situation shows the educational role of an ancient, yet still valid, practice, human dissection, and the importance of anatomical studies to improve surgical skills, to provide better treatment for the patient.


Tractor risk abatement and control as a coherent strategy.
The agricultural tractor was the principal source of fatal injury on American farms for the latter part of the 20th century, and they maintain that distinction today. Much has been learned about the toll of these fatalities and how to prevent them over the last ten years, yet public policy has generally been unsuccessful in reducing this toll. A policy conference entitled Tractor Risk Abatement and Control convened in 1997 to develop recommendations to reduce this death toll. Several stakeholders at the conference agreed on 25 action items, which if implemented would reduce the number of tractor-related deaths by more than 2,000 by the year 2015. These recommendations relate to tractor overturns, runovers, and traffic collisions as well as youth operators. This article addresses the completeness of a strategy for preventing tractor-related injuries for each of these four areas based upon an evaluation model derived from the Theory of Planned Behavior and an antecedent model. The ultimate result of this model is to influence an individual's intention to act to prevent injury. The set of recommendations was found to provide a coherent strategy. In addition, implementing the strategy at an organizational level is discussed.


Mechanisms of enhanced vascular smooth muscle contraction induced by sickle erythrocyte constituents.
The mechanisms of the increased vascular tone associated with vaso-occlusive crisis of sickle cell disease have not been clearly defined. The goal of the present study was to examine the role of vascular smooth muscle membrane Na+-K+-ATPase enzyme activity as well as nitric oxide synthase inhibition on the contractile responses induced by sickle erythrocyte constituents. 2 mm ring segments of rabbit carotid arterial ring preparations were placed in 20 ml organ baths containing physiological salt solution (PSS) bubbled with 95% O2, 5% CO2, at 37oC and pH 7.4 and isometric contractions recorded, under an initial load of 2g. Arterial rings were exposed to 50 µl of each erythrocyte constituent at an adjusted haematocrit of 0.6. The magnitude of K+-induced relaxation of 10-7 M phenylephrine (PE)-precontracted rings exposed for 30 minutes to K+-free PSS (which inhibits Na+-K+ pump) was estimated in the absence (control) or presence of RBC constituents (ghosts, erythrocytes or haemoglobin solution) from Hb SS subjects. Secondly, the influence of 20-minute exposure of the rings to SS GHOSTS on acetylcholine-induced, endothelium-dependent relaxation of 10-7 M PE phenylephrine-precontraction (in the absence or presence of L-NAME) was evaluated. Our results show that K+-induced relaxation was significantly and differentially attenuated by erythrocyte constituents (p<0.05) in the order: SS GHOST > SS HBS > SS RBC. NO synthase inhibition with L-NAME further potentiated the enhanced PE contractions induced by SS GHOSTS and caused a greater attenuation of Ach-induced relaxation (compared with SS GHOSTS alone). The results suggest that SS erythrocyte GHOSTS induce enhancement of vascular smooth muscle tone via impairment of vascular Na+-K+ ATPase enzyme activity as well as attenuate endothelium-dependent relaxation. These functional changes in vascular smooth muscle and endothelial function may contribute to the pathophysiology of vaso-occlusive crisis of sickle cell disease.


Localized microcystic lymphatic malformations--ultrasound diagnosis.
Microcystic lymphatic malformations present with a wide variety of clinical manifestations that may make diagnosis difficult. We present four patients with microcystic lymphatic malformations that have been confirmed by both histology and ultrasound appearance. Five further cases of microcystic lymphatic malformations with unusual presentations, in which ultrasound was used to support the diagnoses, are then presented. The use of ultrasound as a tool to aid in the diagnosis of microcystic lymphatic malformations is then discussed and compared with other investigative techniques.


Outcome of mother to infant acquired GBV-C/HGV infection.
Twelve children born to hepatitis C virus antibody GBV-C/HGV RNA positive mothers who acquired GBV-C/HGV infection by the vertical or perinatal route were studied. Most (91%) were persistently GBV-C/HGV RNA positive up to 12 months of age. Four out of six cases who acquired GBV-C/HGV alone had normal alanine amino transferase activities. Long lasting evidence of hepatocellular injury was detected only in children with GBV-C/HGV and hepatitis C virus and HIV coinfection.


Efficiently cleaved HIV-1 envelopes: can they be important for vaccine immunogen development?
The enormous diversity of HIV-1 is a significant impediment in selecting envelopes (Envs) that can be suitable for designing vaccine immunogens. While tremendous progress has been made in developing soluble, trimeric, native-like Env proteins, those that have elicited neutralizing antibodies (Abs) in animal models are relatively few. A strategy of selecting naturally occurring Envs suitable for immunogen design by studying the correlation between efficient cleavage on the cell surface and their selective binding to broadly neutralizing Abs (bNAbs) and not to non-neutralizing Abs (non-NAbs), properties essential in immunogens, may be useful. Here we discuss some of the challenges of developing an efficacious HIV-1 vaccine and the work done in generating soluble immunogens. We also discuss the study of naturally occurring, membrane-bound, efficiently cleaved (naturally more sensitive to furin) Envs and how they may positively add to the repertoire of HIV-1 Envs that can be used for vaccine immunogen design. However, even with such Envs, the challenges of developing well-folded, native-like trimers as soluble proteins or using other immunogen strategies such as virus-like particles with desirable antigenic properties remain, and are formidable. In spite of the progress that has been made in the HIV-1 vaccine field, an immunogen that elicits neutralizing Abs with significant breadth and potency in vaccines has still not been developed. Efficiently cleaved Envs may increase the number of available Envs suitable for immunogen design and should be studied further.