Immune Modulation to Improve Survival of Viral Pneumonia in Mice.
Viral pneumonias remain global health threats, as exemplified in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, requiring novel treatment strategies both early and late in the disease process. We have reported that mice treated before or soon after infection with a combination of inhaled Toll-like receptor (TLR) 2/6 and 9 agonists (Pam2-ODN) are broadly protected against microbial pathogens including respiratory viruses, but the mechanisms remain incompletely understood. The objective of this study was to validate strategies for immune modulation in a preclinical model of viral pneumonia and determine their mechanisms. Mice were challenged with the Sendai paramyxovirus in the presence or absence of Pam2-ODN treatment. Virus burden and host immune responses were assessed to elucidate Pam2-ODN mechanisms of action and to identify additional opportunities for therapeutic intervention. Enhanced survival of Sendai virus pneumonia with Pam2-ODN treatment was associated with reductions in lung virus burden and with virus inactivation before internalization. We noted that mortality in sham-treated mice corresponded with CD8+ T-cell lung inflammation on days 11-12 after virus challenge, after the viral burden had declined. Pam2-ODN blocked this injurious inflammation by minimizing virus burden. As an alternative intervention, depleting CD8+ T cells 8 days after viral challenge also decreased mortality. Stimulation of local innate immunity within the lungs by TLR agonists early in disease or suppression of adaptive immunity by systemic CD8+ T-cell depletion late in disease improves outcomes of viral pneumonia in mice. These data reveal opportunities for targeted immunomodulation to protect susceptible human subjects.


Added value of radiologist consultation to family practitioners in the outpatient setting.
To measure the added value of a radiologist's consultation to the interpretation of radiographs previously read by a family practitioner. The authors reviewed 1,674 chest and extremity radiographs previously read by a family practitioner and consulting radiologist. The 196 radiographs in which there was a discrepancy between the family practitioner's and radiologist's report were evaluated by a radiologist and family physician not involved in and blinded to the original interpretations. The overall accuracy of the participants was determined and differences statistically quantified. The overall sensitivity of the radiologists was greater than that of the family practitioners (92% vs 86%); specificity was not significantly different. For extremity examinations, there were no significant differences in accuracy of the radiologists and family practitioners; the sensitivity of radiologists for chest studies was considerably greater (89% vs 80%). Radiologic consultation was of particular value in the detection of pneumonia and masses. At a family practice center, the radiologist's role for extremity radiographs might be limited to individual consultation, with review of all chest radiographs.


Reconsidering the tectorial membrane: A morphological study.
Published descriptions of the tectorial membrane have been inconsistent. Descriptions vary from a simple ligamentous band extending between the axis and occiput to a more complex layered structure composed of bands of fibers. The purpose of this study was to examine and document the macrostructure of the tectorial membrane. The tectorial membrane was examined by fine dissection in 11 formalin-fixed human adult cadavers. Detailed descriptions of the macrostructure and attachments were recorded. Each tectorial membrane examined consisted of two distinct layers. The superficial layer was composed variably of three or four bands. Its fibers extend caudally over multiple spinal levels, becoming continuous with the posterior longitudinal ligament. The deeper layer routinely consisted of three bands, each being firmly adherent to the posterior aspect of the body of the second cervical vertebra. Attachments of fibers from both layers extended beyond the foramen magnum to create a semicircular attachment onto the base of the skull. The tectorial membrane has a more complex structure than has been described to date in standard anatomical texts. The existence of a layered and banded composition may have implications for understanding its function and for the clinical assessment of this structure.


A giant rheumatoid nodule of the cubital fossa: A mimicker of malignancy.
Rheumatoid nodules (RNs) are the most common extraarticular manifestation in patients with rheumatoid arthritis, appearing in up to 30%. They are typically localized subcutaneously in pressure points or joints, such as the extensor surface of the elbow. But when they have atypical localizations, they provide a confusing differential diagnosis including the possibility of a malignancy. Herein, we report a 53-year-old female patient with known rheumatoid arthritis who presented with a painless mass in the right cubital fossa. The uncommon site and the presence of cortical disruption made us proceed to computed tomography-guided biopsy to exclude the presence of a malignancy. Biopsy established the RN diagnosis.


Waist circumference measurement in clinical practice.
The obesity epidemic is a major public health problem worldwide. Adult obesity is associated with increased morbidity and mortality. Measurement of abdominal obesity is strongly associated with increased cardiometabolic risk, cardiovascular events, and mortality. Although waist circumference is a crude measurement, it correlates with obesity and visceral fat amount, and is a surrogate marker for insulin resistance. A normal waist circumference differs for specific ethnic groups due to different cardiometabolic risk. For example, Asians have increased cardiometabolic risk at lower body mass indexes and with lower waist circumferences than other populations. One criterion for the diagnosis of the metabolic syndrome, according to different study groups, includes measurement of abdominal obesity (waist circumference or waist-to-hip ratio) because visceral adipose tissue is a key component of the syndrome. The waist circumference measurement is a simple tool that should be widely implemented in clinical practice to improve cardiometabolic risk stratification.


[Results of 2 multicenter therapy studies in inoperable non-small cell bronchial cancer].
A total of 166 patients with non-small cell lung cancer (NSCLC) were included in two multicenter trials testing different treatment regimens. In study I, 116 patients received 4 cycles of aggressive polychemotherapy consisting of cis-platinum 100 mg/m2 (day 1), etoposide 100 mg/m2 (days 4-6), and vindesine 3 mg/m2 (day 1) (CEV); patients without distant metastases subsequently received chest irradiation with 50 Gy. In study II, 50 patients were treated with monochemotherapy consisting of etoposide 250 mg/m2 (days 1-3), and ifosfamide 5 g/m2 as 24-h infusion (day 29). While this program was repeated in responders with extensive disease (ED), patients with limited disease (LD) subsequently received chest irradiation with 50 Gy using 20 mg/m2 cis-platinum weekly as a radiosensitizer. Response rates (CR + PR) to chemotherapy were higher in study I than in study II, and were 26% (CR 3%) vs. 8% (CR 0%) for all patients, 18% (CR 0%) vs. 4% (CR 0%) for ED, and 45% (CR 11%) vs. 13% (CR 0%) for LD. The increase in response rates by radiotherapy was marginal in study I (CR + PR 47%, CR 18%), but remarkable in study II (CR + PR 42%, CR 29%). While median survival was slightly longer in study I than in study II for ED (7.7 vs. 6.6 months) and LD (14.4 vs. 12.0 months), the 2-year survival rate was in favor of study II (10% vs. 25%). Toxicity was clearly more pronounced in study I, including 3 lethal complications and 16 discontinuations of therapy due to side effects or refusal. Thus, while in ED the efficacy of both treatment regimens was very restricted, in LD radiotherapy with cis-platinum as a radiosensitizer achieved a relatively high 2-year survival rate which justifies further testing of this treatment strategy.


Diagnostic significance of surfactant proteins A and D in sera from patients with radiation pneumonitis.
Radiation pneumonitis (RP) is the most common complication of radiotherapy for thoracic tumours. The aim of this study was to evaluate the significance of pulmonary surfactant proteins (SP)-A and SP-D as new serum markers for RP. Twenty-five patients with lung tumour, who had received radiotherapy, were studied. At the completion of radiotherapy, the presence of RP was judged by chest plain radiography and chest high resolution computed tomography (HRCT). RP findings detected on chest plain radiography were seen in only three of 12 patients in whom RP was detected by HRCT. Nevertheless, both SP-A and SP-D concentrations in sera from the patients with RP were significantly higher than those from the 13 patients without RP (p = 0.0065, p = 0.0011, respectively). As with SP-A, ratios of SP-D at the completion, compared to at the initiation (1 week post/pre ratio), were also significantly higher in patients with RP than in patients without RP. When a post/pre ratio > 1.6 was considered positive, the SP-A and SP-D assays showed an 83% and 85% specificity, respectively. In conclusion, serum assays of surfactant proteins A and D may be of diagnostic value for detection of radiation pneumonitis, even when the radiographic change is faint.


Post-sclerotherapy bacterial peritonitis.
Endoscopic variceal sclerotherapy has been associated with a number of complications. Peritonitis after sclerotherapy has rarely been reported. In this retrospective review of 213 consecutive sclerotherapy procedures among 65 patients over a 3-yr period, we found that six cases of peritonitis occurred, for an incidence of approximately 3%. All patients developing post-sclerotherapy peritonitis had low ascitic fluid protein. However, this did not differ from patients who did not develop peritonitis. No patient on antibiotics at the time of sclerotherapy developed peritonitis. Peritonitis should be considered in the diagnosis of post-sclerotherapy fever. The role of prophylactic antibiotics to prevent this complication is uncertain.


Branch duct IPMTs: value of cross-sectional imaging in the assessment of biological behavior and follow-up.
Branch duct intraductal papillary mucinous tumors (IPMTs) are increasingly being described and represent a challenge for the physician. Recent imaging modalities, especially computed tomography and magnetic resonance, allow for a correct diagnosis, but IPMTs can manifest with different degrees of cellular atypia so it is very important to be able to establish the biological behavior of the lesion. Sixty-five patients were included in this study: 29 of them underwent surgery, and the other 36 were followed with cross-sectional imaging. Among patients who underwent surgery, 11 had benign lesions and 18 had malignant lesions. Overall sensitivity, specificity, and accuracy in the diagnosis of malignancy for all the cross-sectional imaging techniques were 61%, 81%, and 69%, respectively. Among patients who were followed and had a magnetic resonance cholangiopancreatographic diagnosis of branch duct IPMT with imaging features indicative of benignity, only two showed modifications over the follow-up period. Even considering some important biases (small number of patients and relatively short follow-up), interesting conclusions can be drawn: the imaging diagnosis of malignancy can be trusted, whereas that of benignity cannot be relied upon, but if the signs of malignancy are absent, the slow growth of the lesions justifies watchful follow-up in the correct clinical setting.


Infectious waste surveys in a Saudi Arabian hospital: an important quality improvement tool.
To analyze the composition by weight of the infectious waste stream, better segregate waste, reduce disposal costs, reduce the load on the hospital incinerator, identify inappropriate items having significant cost or safety implications, and provide a safer work environment for housekeepers. Four infectious waste surveys were conducted between 1991 and 1999 that involved opening a total of 7364 bags of infectious waste. The contents of each infectious waste bag were separated into 20 different components and weighed. Inappropriately discarded items were removed and tagged with the date and hospital unit of origin. Dhahran Health Center, a 410-bed hospital operated by the Saudi Arabian Oil Company (Saudi Aramco) in Dhahran, Saudi Arabia. The surveys show a continuing trend in a higher percentage of plastics and a decrease in paper due to increased use of disposables. Much of the infectious waste consisted of plastic intravenous bottles, intravenous lines, and paper wrappers for sterile instrument sets that were not infectious. Dhahran Health Center was producing a total of 1163 kg of infectious waste per day before the first survey. This was reduced to 407 kg per day after implementation of a waste segregation program in 1991 (a reduction of 65%). Incineration operation was reduced from daily to 3 days per week, with a corresponding reduction in incinerator emissions. Infectious waste from inpatient, surgical, and obstetric areas was reduced by a total of 70% between 1991 and 1999, from 2.8 kg (6.1 lb) to 0.85 kg (1.9 lb) per patient per day. This is in the range of 2 to 4 lb per patient per day that is generally reported. Numerous inappropriately discarded items were discovered during the surveys with cost or safety implications. Each survey, including the latest one of November-December 1999, has shown that further improvements are possible in the hospital's waste management program. Specific educational efforts and changes in procedures are described. We believe this is the first report of such an extensive analysis of a hospital's infectious waste. Many hospitals do not have the resources to conduct such detailed surveys of their waste streams. However, regardless of the method of treatment and disposal, such surveys are valuable quality improvement tools because all health care facilities want to reduce disposal costs, identify high-value items mistakenly discarded, and improve safety.


Effect of hydraulic retention time on suppression of methanogens during a continuous biohydrogen production process using molasses wastewater.
This study was undertaken to investigate the reduction of the hydraulic retention time (HRT) to decrease methane generation and recover hydrogen production during the long-term operation of biohydrogen production in a continuous stirred tank reactor (CSTR) using molasses wastewater. Reduction of HRT can be a simple and economic method to immediately control unfavorable methane generated during continuous operation of a hydrogen production system. The steady-state performance of the CSTR showed a hydrogen content of 41.3 ± 3.30% and a hydrogen production rate (HPR) of 63.7 ± 10.01 mmol-H2L-1d-1 under an organic loading rate (OLR) of 29.7 g CODL-1 at an HRT of 24 h. Increase in the methane level above 40% during long-term operation caused decrease in the hydrogen content and HPR to 5.9 ± 1.6% and 2.1 ± 1.1 mmoL-H2L-1d-1, respectively. When methane increased to a high level over 40%, the CSTR at the HRT of 24 h was operated at the HRT of 12 h. Reduction of the HRT from 24 to 12 h led to decrease in the methane content of 12.1 ± 4.44% and recovery of the HPR value to 48.9 ± 15.37 mmol-H2L-1d-1 over a duration of 13-22 d. When methane is generated in a continuously operated reactor, reduction of the HRT can be an easy way to suppress methanogens and recover hydrogen production without any additives or extra treatments.


Medical and surgical aspects of parathyroidectomy.
A more logical approach to the management of the chronic dialysis patient with parathyroid hyperplasia has become possible thanks to recent progress in cellular and molecular analysis of surgically removed parathyroid glands and accumulation of clinical experience. When one or more parathyroid glands progress to the stage of nodular hyperplasia, it is usually difficult to control PTH secretion even by calcitriol pulse therapy. For such patients, we have developed two new therapeutic approaches, i.e., selective percutaneous ethanol injection therapy (PEIT) and direct calcitriol injection therapy, in combination with medical therapy. For optimal selection of therapeutic modalities it is indispensable to evaluate the degree and stage of parathyroid hyperplasia. For successful management, prevention of nodular hyperplasia is the most important strategy.


Interleukin-8 primes human neutrophils for enhanced superoxide anion production.
Interleukin-8 (IL-8), a novel chemotactic cytokine, has been shown to play an important role in inflammation. In this study, we investigated the effect of recombinant human (rh) IL-8 on superoxide (O2-) production by neutrophils. We found that rhIL-8 (1-10 ng/ml) did not stimulate neutrophil O2- production on its own, but primed neutrophils for an enhanced response to other stimuli, such as N-formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol 12-myristate 13-acetate (PMA) and platelet-activating factor (PAF). The priming effect of rhIL-8 was dose dependent, rapid and long lasting. Recombinant human IL-8 increased both the maximal rate and the total O2- production, but did not prolong the response to FMLP. Stimulation of neutrophils with rhIL-8 increased intracellular-free calcium concentration ([Ca2+]i) by mobilizing calcium from internal stores and by increasing calcium influx. The increase in [Ca2+]i was dose dependent and occurred in the same range of rhIL-8 concentrations that primed neutrophils for O2- production. In addition, rhIL-8 enhanced the FMLP-stimulated increase in [Ca2+]i. These observations suggest that calcium may play an important role in priming phenomenon.


Synthesis of early heat shock proteins in young leaves of barley and sorghum.
The in vivo synthesis of early heat-shock proteins in young leaves of barley (Hordeum vulgare L.) and sorghum (Sorghum bicolor L.) was studied by one- and two-dimensional electrophoresis. Analysis of whole leaf protein patterns demonstrated clearly the enhanced resolution of heat-shock proteins, especially those of low molecular weight, when separated by two-dimensional electrophoresis. Comparison between the two cereals showed that a greater number and diversity of heat-shock proteins were induced in the subtropical C(4) (sorghum) species compared to the temperate C(3) (barley) species. Fractionation of whole leaf proteins into soluble and membrane fractions showed the majority of heat-shock proteins to be associated with the soluble fraction in both sorghum and barley. However, several low molecular mass (17-24 kilodalton) heat-shock proteins were clearly identified in the membrane fractions, indicating a likely association with thylakoid membranes in vivo during the early stages of a heat-shock response in both species.


Enhancement of adenosine triphosphatase activity of purified chloroplast coupling factor 1 in aqueous organic solvent.
The ATPase activity of purified coupling factor 1 (CF1) of spinach chloroplasts [EC 220.127.116.11] was reversibly enhanced in some aqueous organic solvents, notably methanol, ethanol, and acetone. Pretreatment of CF1 with 20% (v/v) methanol did not affect the subsequent activity. The activity depended entirely on the final concentration of methanol in the reaction mixture. In the presence of 20% methanol, the Km of Ca2+-ATPase from ATP was lowered from 0.4 mM to 0.2 mM. Not only Ca2+, but also Cd2+, Mg2+, Mn2+, and Zn2+ supported the ATPase activity at rates of higher than 7 mumol.mg protein-1 . min-1. Co2+, Ni2+, and Pb2+ supported the activity at rates of 0.5-1.0 mumol.mg protein-1 . min-1. The activities supported by the following cations, if any, were less than 0.2 mumol.mg protein-1 . min-1; Ba2+, Cu2+, Fe2+, Hg2+, Sn2+, and Sr2+. The optimum concentration of methanol for Ca2+-ATPase and Mg2+-ATPase activities was about 30% (v/v). The optimum pH values for Ca2+-ATPase and Mg2+-ATPase activities were about 8.0 and 8.8, respectively. The enhancing effect of organic solvents appears to be associated with their relative lipophilic character as defined by the octanol-water partition coefficient. The Ca2+-ATPase activities of th trypsin-activated and the heat-activated CF1 were inhibited and their Mg2+-ATPase activities were enhanced by the presence of methanol in the reaction mixture.


Comparison of selection methods to deduce natural background levels for groundwater units.
Establishment of natural background levels (NBL) for groundwater is commonly performed to serve as reference when assessing the contamination status of groundwater units. We compare various selection methods to establish NBLs using groundwater quality data for four hydrogeologically different areas in the highly populated and developed subcatchment Western River Rhine, The Netherlands: selection of old groundwater (before 1945), of tritium-free groundwater (i.e., infiltrated before 1950), and of groundwater having no agricultural contamination by NO3 and SO4. Differences as well as similarities in percentile values for Cl, NH4, and SO4 concentrations are observed among the selection methods as well as the spatial units, pointing out that selection of the data setis a crucial step in deducing NBLs. The following general points of attention are deduced: (1) reference to composition of recharge water (rain or river infiltrate) is necessary to confirm the statistical outcomes, (2) old analyses are affected by conservation errors after sampling for redox-sensitive solutes and may be obtained by selective sampling, (3) old analyses are the only direct reference for NBLs for groundwater units having only anthropogenically influenced, young groundwater at present, and (4) establishment of a priori percentile values as maximum NBL is not right and confirmation by additional process-based insight in the controls on water composition is necessary.


Inline high frequency ultrasonic particle sizer.
This paper reports the development of a new method of particle sizing in a liquid. This method uses high frequency focused ultrasounds to detect particles crossing the focal zone of an ultrasonic sensor and to determine their size distribution by processing the reflected echoes. The major advantage of this technique compared to optical sizing methods is its ability to measure the size of particles suspended in an opaque liquid without any dedicated sample preparation. Validations of ultrasonic measurements were achieved on suspensions of polymethyl methacrylate beads in a size range extending from a few micrometer to several hundred micrometer with a temporal resolution of 1 s. The inline detection of aggregate formation was also demonstrated.


Odor emission rate estimation of indoor industrial sources using a modified inverse modeling method.
Odor emission rates are commonly measured in the laboratory or occasionally estimated with inverse modeling techniques. A modified inverse modeling approach is used to estimate source emission rates inside of a postdigestion centrifuge building of a water reclamation plant. Conventionally, inverse modeling methods divide an indoor environment in zones on the basis of structural design and estimate source emission rates using models that assume homogeneous distribution of agent concentrations within a zone and experimentally determined link functions to simulate airflows among zones. The modified approach segregates zones as a function of agent distribution rather than building design and identifies near and far fields. Near-field agent concentrations do not satisfy the assumption of homogeneous odor concentrations; far-field concentrations satisfy this assumption and are the only ones used to estimate emission rates. The predictive ability of the modified inverse modeling approach was validated with measured emission rate values; the difference between corresponding estimated and measured odor emission rates is not statistically significant. Similarly, the difference between measured and estimated hydrogen sulfide emission rates is also not statistically significant. The modified inverse modeling approach is easy to perform because it uses odor and odorant field measurements instead of complex chamber emission rate measurements.


Glutamate activation of a single NMDA receptor-channel produces a cluster of channel openings.
Activations of the N-methyl-D-aspartate (NMDA) receptor by glutamate were studied in outside-out patches from CA1 cells in rat hippocampal slices. Very low glutamate concentrations (20-100 nM) were used so that individual receptor activations would be well separated. The shut-time distribution contained at least five components, only the longest component being obviously concentration dependent. The three briefest shut-time components had time constants of 56 microseconds, 0.68 ms and 10.1 ms; all of these were independent of glutamate concentration. An individual activation of the receptor therefore produces a long cluster of channel openings that contains longer gaps than have been reported for receptor activations by other fast neurotransmitters. In addition, (i) some activations may contain still longer (mean 78 ms) shut periods generating 'super clusters', and (ii) a significant amount of NMDA current may be carried by prolonged ('high P(open)') periods during which the channel is open for most of the time. Such periods occur intermittently even at these very low glutamate concentrations. It is suggested that the slow time course of the NMDA receptor-mediated synaptic currents may be determined mainly by the channel activation kinetics.


Characterization of Glass-Ceramic Sealant for Solid Oxide Fuel Cells at Operating Conditions by Electrochemical Impedance Spectroscopy.
A commercially available glass-ceramic composition is applied on a ferritic stainless steel (FSS) substrate reproducing a type of interface present in solid oxide fuel cells (SOFCs) stacks. Electrochemical impedance spectroscopy (EIS) is used to study the electrical response of the assembly in the temperature range of 380-780 °C and during aging for 250 h at 780 °C. Post-experiment analyses, performed by means of X-ray diffraction (XRD), and along cross-sections by scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) analysis, highlight the microstructural changes promoted by aging conditions over time. In particular, progressive crystallization of the glass-ceramic, high temperature corrosion of the substrate and diffusion of Fe and Cr ions from the FSS substrate into the sealant influence the electrical response of the system under investigation. The electrical measurements show an increase in conductivity to 5 × 10-6 S∙cm-1, more than one order of magnitude below the maximum recommended value.


Medicare episodes of illnesses: a study of hospital, skilled nursing facility, and home health agency care.
This paper analyzes charges incurred under the Medicare program for inpatient hospital, skilled nursing facility (SNF), and home health agency (HHA) care for 1976. This research was made possible through the construction of a new data set which links a beneficiary's use of these three services. Summary highlights reveal that an overwhelming majority of the 7.5 million Medicare episodes of illness do not involve post-hospital SNF or HHA care. Those episodes of illness that use only hospital care are substantially (53%) cheaper than all other episodes. A large percentage of these charge differences reflect the greater number of hospital days of care associated with post-hospital care services. However, an analysis of the beneficiaries' demographic characteristics suggests that persons who use post-hospital care generally differ from those who receive only hospital care. We found that persons who use post-hospital SNF or HHA, or both types of care are likely to be female, to have cancer, diabetes, fractured bones or a central nervous or vascular system disease, and to be older than persons who do not use these types of care. The data also show that a beneficiary's area of residence greatly influences the amount and types of care received. Persons who reside in the New England, Middle Atlantic and Pacific Divisions are more likely to receive post-hospital care services than person who live elsewhere in the United States. These persons also incur among the highest per capita institutional charges in the United States. Part of this variation in institutional charges per capita is explained by the high input price index found in these areas, and in some cases by the high quantity of services index.


Effects of cues to event segmentation on subsequent memory.
To remember everyday activity it is important to encode it effectively, and one important component of everyday activity is that it consists of events. People who segment activity into events more adaptively have better subsequent memory for that activity, and event boundaries are remembered better than event middles. The current study asked whether intervening to improve segmentation by cuing effective event boundaries would enhance subsequent memory for events. We selected a set of movies that had previously been segmented by a large sample of observers and edited them to provide visual and auditory cues to encourage segmentation. For each movie, cues were placed either at event boundaries or event middles, or the movie was left unedited. To further support the encoding of our everyday event movies, we also included post-viewing summaries of the movies. We hypothesized that cuing at event boundaries would improve memory, and that this might reduce age differences in memory. For both younger and older adults, we found that cuing event boundaries improved memory-particularly for the boundaries that were cued. Cuing event middles also improved memory, though to a lesser degree; this suggests that imposing a segmental structure on activity may facilitate memory encoding, even when segmentation is not optimal. These results provide evidence that structural cuing can improve memory for everyday events in younger and older adults.


Pharmacokinetics of pyrazoloacridine in the rhesus monkey.
Pyrazoloacridine is a rationally synthesized acridine derivative with in vitro activity against solid tumor cell lines, noncycling and hypoxic cells, and tumor cell lines that exhibit the multidrug resistance phenotype. The pharmacokinetic behavior of pyrazoloacridine after a 1- or 24-h i.v. infusion was studied in 5 rhesus monkeys that received a total of 10 courses of pyrazoloacridine at 300 or 600 mg/m2. Pyrazoloacridine levels in plasma and cerebrospinal fluid were measured by high-pressure liquid chromatography. For 1-h infusions, the plasma disappearance was biexponential with a t 1/2 alpha of 31 min and t 1/2 beta of 11 h. The mean volume of distribution at steady state was 1380 liters/m2. The clearance was 1660 ml/min/m2. For the 300 mg/m2 dose, the mean area under the concentration-time curve was 759 microM.min, and the mean peak concentration was 1.3 microM. For the 600 mg/m2 dose, the area under the concentration-time curve was 1330 microM.min, and the peak concentration was 2.5 microM. The steady-state plasma concentrations during the 24-h continuous infusions were 0.27 microM for the 300 mg/m2 dose and 0.45 microM for the 600 mg/m2 dose. The mean clearance calculated from these steady-state concentrations was 2420 ml/min/m2. Cerebrospinal fluid levels were less than 0.1 microM for all doses and schedules. There was no evidence of toxicity at any dose or schedule. These results contrast strikingly with those obtained in mice and dogs in which, despite a more rapid clearance of pyrazoloacridine, significant toxicities were observed at doses that were nontoxic in the monkey. These interspecies differences in the pharmacokinetic and pharmacodynamic behavior of pyrazoloacridine have important implications for the design of Phase I trials in humans.


Hsa-miR-181a-5p expression and effects on cell proliferation in gastric cancer.
MicroRNAs (miRNAs) are small endogenous, non-coding, single-stranded RNAs (approximately 22 nt). Accumulating evidence has shown that aberrant miRNA expression is pronounced and correlated with gastric cancer genesis and progression. Expression levels of miR-181a-5p in GC tissues and cell lines were assessed by qRT-PCR and tested for correlation with clinical features. In addition, effects of miR-181a-5p on GC cell growth were investigated. Our findings indicate that miR-181a-5p is upregulated in GC, in correlation with lymph node invasion, nerve invasion and vascular invasion (P<0.05). Enforced expression of miR-181a -5p promoted cell proliferation ability. This study suggested that increased miR-181a-5p is related to GC progression. MiR-181a-5p may represent a potential therapeutic target for GC.


Mosaicism in von Hippel-Lindau disease: lessons from kindreds with germline mutations identified in offspring with mosaic parents.
von Hippel-Lindau disease (VHL [MIM 193300]) is a heritable autosomal dominant multiple-neoplastic disorder with high penetrance. It is characterized by brain and spinal-cord hemangioblastomas, retinal angiomas, clear-cell renal carcinoma, neuroendocrine tumors and cysts of the pancreas, pheochromocytomas, endolymphatic-sac tumors, and papillary cystadenomas of the epididymis and broad ligament. Although most index cases have a positive family history of VHL, some do not and may represent de novo cases. Cases without a family history of VHL may or may not have a germline mutation in their VHL tumor-suppressor gene. We present two cases of VHL mosaicism. In each of two families, standard testing methods (Southern blot analysis and direct sequencing) identified the germline mutation in the VHL gene of the offspring, but not in their clinically affected parent. Additional methods of analysis of the affected parents' blood detected the VHL-gene mutation in a portion of their peripheral blood lymphocytes. In one case, detection of the deleted allele was by FISH, and, in the second case, the 3-bp deletion was detected by conformational sensitive gel electrophoresis and DNA sequencing of cloned genomic DNA. Mosaicism in VHL is important to search for and recognize when an individual without a family history of VHL has VHL. Patients diagnosed without family histories of the disease have been reported in as many as 23% of kindreds with VHL. Identification of individuals potentially mosaic for VHL will affect counseling of families, and these individuals should themselves be included in clinical screening programs for occult disease.


Identifying lung cancer patients who may be eligible for epidermal growth factor receptor (EGFR) mutation testing.
To characterise patients with non-squamous, non-small cell lung cancer (NSCLC) diagnosed at Counties Manukau District Health Board (CMDHB; South Auckland, New Zealand) to estimate the number who may be eligible for EGFR mutation testing. Retrospective review of clinical records of 206 patients diagnosed at CMDHB with primary lung cancer between 01/07/2011 and 30/06/2012 RESULTS: Of the 206 patients, 141 (68.4%) had non-squamous, non-small cell lung cancer (NSCLC). Of these 141 cases: 87 (62%) were adenocarcinomas; 73 (51.8%) were male; 78 (55.3%) were European, 16 (18.4%) were Pacific Islanders, 22 (15.4%) were Maori and 15 (10.7%) were Asian, with nine being from South East Asia; 28 (19.9%) had never smoked; 103 (73.0%) had advanced cancer (stage IIIA or more advanced); and 112 (79.4%) cases had an ECOG performance score of two or less. There were four patients with advanced adenocarcinoma who were South East Asian females and had never smoked, all of whom had an ECOG performance score of less than two. In a 1-year cohort of primary lung cancer patients, 68% had non-squamous, NSCLC and were potentially eligible for EGFR mutation testing. Patients with advanced stage, non-squamous NSCLC comprised half of all lung cancer patients.


Factors affecting the activation state and the level of total activity of ribulose bisphosphate carboxylase in tobacco protoplasts.
The relationship between the activation state and the level of total activatable activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) was examined in tobacco protoplasts. When darkened protoplasts were illuminated, both activation and total activity increased, but at different rates; the t((1/2)) were 2.3 and 6.7 minutes, respectively. The light response of rubisco activation state and total activity, measured after 15 minutes of illumination, were similar but their responses to light transitions and photosynthetic inhibitors were different. When irradiance was reduced from saturating to subsaturating, deactivation of rubisco in protoplasts was immediate, whereas there was little change in total activity during the first 20 minutes following the transition. The light-induced increases in activation state and total activity were inhibited by nigericin, but activation was more sensitive exhibiting a response similar to that of photosynthesis. Treatment of tobacco protoplasts and leaves with methyl viologen at limiting irradiance increased rubisco activation, but inhibited the light-induced increase in total activity. These results indicate that light activation of rubisco is mechanistically distinct from the light-dependent changes in total activity in tobacco, a species containing carboxyarabinitol 1-phosphate, an endogenous inhibitor of total rubisco activity.


Factors Influencing beta-Glucan Synthesis by Particulate Enzymes from Suspension-Cultured Lolium multiflorum Endosperm Cells.
Particulate enzymes from suspension-cultured ryegrass (Lolium multiflorum Lam.) endosperm cells incorporated glucosyl residues from UDP-glucose and GDP-glucose into beta-glucans. Three types of beta-glucans were produced from UDP-glucose: 1,3-beta-glucan; 1,4-beta-glucan; and mixed-linkage 1,3;1,4-beta-glucan. As in other systems, relatively more 1,4-beta-glucan was produced from a low (10 micromolar) UDP-glucose concentration, and relatively more 1,3-beta-glucan was produced from a high (1 millimolar) UDP-glucose concentration. However, in ryegrass, 1,3;1,4-beta-glucan represented a major proportion of the products at both low and high UDP-glucose concentrations. The arrangement of linkages in the 1,3;1,4-beta-glucan was different at the two concentrations; at the low UDP-glucose concentration, more sequences of three consecutive 1,4-linkages were produced.The effects of pH, temperature, and metal ion concentrations on incorporation were dependent on the UDP-glucose concentration. At the low UDP-glucose concentration, incorporation into all three types of beta-glucan increased with increasing pH. At the high UDP-glucose concentration, 1,3-beta-glucan was the major product at pH 7 and below; 1,4-beta-glucan synthesis was optimal at pH 8; and synthesis of 1,3;1,4-beta-glucan was greatest above pH 8.With 10 micromolar GDP-glucose as substrate, 1,4-beta-glucan, but no 1,3;1,4-beta-glucan, was produced. Incorporation from either UDP-glucose or GDP-glucose was not influenced by the presence of the other.


Dietary predictors of visceral adiposity in overweight young adults.
The purpose of the present study was to determine the dietary predictors of visceral adipose tissue (VAT) area in overweight young adults. A total of 109 young adults (fifty males and fifty-nine females) ate ad libitum in a university cafeteria for 14 d. All food and beverages consumed in the cafeteria were measured using observer-recorded weighed plate waste. Food consumption outside the cafeteria (i.e. snacks) was assessed by multiple-pass 24 h recall procedures. VAT was determined using computed tomography. Stepwise regression demonstrated that the best predictor of visceral adiposity in women was total dietary fat (P <or= 0.05). In men, the model for predicting visceral adiposity included Ca and total dietary fat. We concluded that total dietary fat is the best predictor of VAT area in both men and women. While this relationship was independent in women, in men there was a synergistic relationship between dietary fat consumption and Ca consumption in predicting VAT.


Lumbar mechanical traction: a biomechanical assessment of change at the lumbar spine.
Lumbar traction is a traditional treatment modality for chronic low back pain (CLBP) in many countries. However, its effectiveness has not been demonstrated in clinical practice because of the following: (1) the lack of in vivo biomechanical confirmation of the mechanism of lumbar traction that occurs at the lumbar spine; (2) the lack of a precise delivery system for traction force and, subsequently, the lack of reproducibility; and (3) few randomized controlled trials proving its effectiveness and utility. This study was planned as a preparatory experiment for a randomized clinical trial, and it aimed (1) to examine the biomechanical change at the lumbar area under lumbar traction and confirm its reproducibility and accuracy as a mechanical intervention, and (2) to reconfirm our clinical impression of the immediate effect of lumbar traction. One hundred thirty-three patients with non-specific CLBP were recruited from 28 orthopaedic clinics to undergo a biomechanical experiment and to assess and determine traction conditions for the next clinical trial. We used two types of traction devices, which are commercially available, and incorporated other measuring tools, such as an infrared range-finder and large extension strain gauge. The finite element method was used to analyze the real data of pelvic girdle movement at the lumbar spine level. Self-report assessments with representative two conditions were analyzed according to the qualitative coding method. Thirty-eight participants provided available biomechanical data. We could not measure directly what happened in the body, but we confirmed that the distraction force lineally correlated with the movement of traction unit at the pelvic girdle. After applying vibration force to preloading, the strain gauge showed proportional vibration of the shifting distance without a phase lag qualitatively. FEM simulation provided at least 3.0-mm shifting distance at the lumbar spine under 100 mm of body traction. Ninety-five participants provided a treatment diary and were classified as no pain, improved, unchanged, and worsened. Approximately 83.2% of participants reported a positive response. Lumbar traction can provide a distractive force at the lumbar spine, and patients who experience the application of such force show an immediate response after traction. University Hospital Medical Information Network - Clinical Trial Registration: UMIN-CTR000024329 (October 13, 2016).


Beneficial Effects of Citrus Flavonoids on Cardiovascular and Metabolic Health.
The prevalence of cardiovascular disease (CVD) is increasing over time. CVD is a comorbidity in diabetes and contributes to premature death. Citrus flavonoids possess several biological activities and have emerged as efficient therapeutics for the treatment of CVD. Citrus flavonoids scavenge free radicals, improve glucose tolerance and insulin sensitivity, modulate lipid metabolism and adipocyte differentiation, suppress inflammation and apoptosis, and improve endothelial dysfunction. The intake of citrus flavonoids has been associated with improved cardiovascular outcomes. Although citrus flavonoids exerted multiple beneficial effects, their mechanisms of action are not completely established. In this review, we summarized recent findings and advances in understanding the mechanisms underlying the protective effects of citrus flavonoids against oxidative stress, inflammation, diabetes, dyslipidemia, endothelial dysfunction, and atherosclerosis. Further studies and clinical trials to assess the efficacy and to explore the underlying mechanism(s) of action of citrus flavonoids are recommended.


MAN3 gene regulates cadmium tolerance through the glutathione-dependent pathway in Arabidopsis thaliana.
Pollution of soil by the heavy metal cadmium (Cd) is a global environmental problem. The glutathione (GSH)-dependent phytochelatin (PC) synthesis pathway is one of the most important mechanisms contributing to Cd accumulation and tolerance. However, the regulation of this pathway is poorly understood. Here, we identified an Arabidopsis thaliana cadmium-tolerant dominant mutant xcd1-D (XVE system-induced cadmium-tolerance 1) and cloned XCD1 gene (previously called MAN3), which encodes an endo-β-mannanase. Overexpression of MAN3 led to enhanced Cd accumulation and tolerance, whereas loss-of-function of MAN3 resulted in decreased Cd accumulation and tolerance. In the presence of estradiol, enhanced Cd accumulation and tolerance in xcd1-D was associated with GSH-dependent, Cd-activated synthesis of PCs, which was correlated with coordinated activation of gene expression. Cd stress-induced expression of MAN3 and the consequently increased mannanase activity, led to increased mannose content in cell walls. Moreover, mannose treatment not only rescued the Cd-sensitive phenotype of the xcd1-2 mutant, but also improved the Cd tolerance of wild-type plants. Significantly, this mannose-mediated Cd accumulation and tolerance is dependent on GSH-dependent PC concentrations via coordinated control of expression of genes involved in PC synthesis. Our results suggest that MAN3 regulates the GSH-dependent PC synthesis pathway that contributes to Cd accumulation and tolerance in A. thaliana by coordinated control of gene expression.


Asian pheretimoid earthworms in North America north of Mexico: An illustrated key to the genera Amynthas, Metaphire, Pithemera, and Polypheretima (Clitellata: Megascolecidae).
The invasion of the pheretimoid earthworms in North America, especially the genera Amynthas and Metaphire, has raised increasing concerns among ecologists and land managers, in turn increasing the need for proper identification. However, the commonly used keys to this group are more than 30 years old with outdated taxonomic information and are based primarily on internal morphology. The requirement of significant amount of taxonomic expertise and dissection, even from the first entry of the key, has prevented broader use of these keys. As a result, many publications in the United States have used Amynthas spp. to represent the group without identifying the species. We present here a new key and diagnoses for the 16 pheretimoid earthworm species recorded in North America north of Mexico, including four genera: Amynthas (10), Metaphire (4), Pithemera (1), and Polypheretima (1). The descriptions were based on published records with modifications following inspection of specimens archived at the National Museum of Natural History, Smithsonian Institution, Washington, D.C. Photos of external and internal characters, including male pores, spermathecal pores, genital markings, spermathecae, prostate glands, and intestinal caeca, are presented to help identification. A summary of current knowledge about the ecology and historical context is provided for each species. We also highlight the previously overlooked and potentially common and widespread co-occurrence of three species-A. agrestis, A. tokioensis, and M. hilgendorfi-and point out that many recent claims of invasion of A. agrestis need to be re-evaluated for potential misidentification.


Landscape determinants of pelagic and benthic primary production in northern lakes.
Global change affects gross primary production (GPP) in benthic and pelagic habitats of northern lakes by influencing catchment characteristics and lake water biogeochemistry. However, how changes in key environmental drivers manifest and impact total (i.e., benthic + pelagic) GPP and the partitioning of total GPP between habitats represented by the benthic share (autotrophic structuring) is unclear. Using a dataset from 26 shallow lakes located across Arctic, subarctic, and boreal northern Sweden, we investigate how catchment properties (air temperature, land cover, hydrology) affect lake physico-chemistry and patterns of total GPP and autotrophic structuring. We find that total GPP was mostly light limited, due to high dissolved organic carbon (DOC) concentrations originating from catchment soils with coniferous vegetation and wetlands, which is further promoted by high catchment runoff. In contrast, autotrophic structuring related mostly to the relative size of the benthic habitat, and was potentially modified by CO2 fertilization in the subarctic, resulting in significantly higher total GPP relative to the other biomes. Across Arctic and subarctic sites, DIC and CO2 were unrelated to DOC, indicating that external inputs of inorganic carbon can influence lake productivity patterns independent of terrestrial DOC supply. By comparison, DOC and CO2 were correlated across boreal lakes, suggesting that DOC mineralization acts as an important CO2 source for these sites. Our results underline that GPP as a resource is regulated by landscape properties, and is sensitive to large-scale global changes (warming, hydrological intensification, recovery of acidification) that promote changes in catchment characteristics and aquatic physico-chemistry. Our findings aid in predicting global change impacts on autotrophic structuring, and thus community structure and resource use of aquatic consumers in general. Given the similarities of global changes across the Northern hemisphere, our findings are likely relevant for northern lakes globally.


Estimating the potential health gain and cost consequences of introducing a pre-school DTPa pertussis booster into the UK child vaccination schedule.
This work estimates the health and cost impacts of a pre-school booster vaccination for Bordetella pertussis, when added to existing UK primary vaccination. A transition state simulation model of pertussis infection in a closed population was constructed comprising of susceptible, infected and immune population sub-groups, across eight age bands. Epidemiological, service use and cost data were sourced from routine statistics, published literature and clinician estimates. The introduction of a pre-school booster is predicted to reduce the number of hospitalisations by approximately 1400 and pertussis cases suffered by up to 28,000 at a net investment of under 13 million pounds over a 5-year period.


Establishment of an iodine model for prevention of iodine-excess-induced thyroid dysfunction in pregnant women.
This study aims to explore the relationship between the iodine status and thyroid dysfunction (TD) in pregnant women and establish a model to guide them to prevent excessive iodine intake. A total of 515 pregnant women were enrolled in the study. Urinary iodine concentration (UIC), thyroid hormones, and thyroid autoantibodies were measured, and then a logistic regression model was established. The median UIC of pregnant women was 174 ± 120 μg/L. Multivariate logistic regression analysis indicated that multivitamin supplements containing iodine and frequent seafood consumption were risk factors for excessive iodine (UIC ≥500 μg/L). Besides, excessive iodine was a risk factor for TD. Iodine excess was associated with a high prevalence of TD in pregnant women, especially TPOAb-positive women (P < 0.05). A logistic regression model based on potential risk factors was established to predict the risk of excessive iodine intake among pregnant women and provide guidance to minimize the risk of excessive iodine intake, thus reducing the risk of TD.


Planning and implementing a community-based public health advocacy campaign: a transport case study from Australia.
Facilitating community action is a key goal of health promotion. This paper describes a public health advocacy framework. It then presents a case study of its application for planning community action by a community alliance concerned about increased heavy traffic on roads through a small regional city in the South West region of Western Australia. The case study illustrates defining the public health problem, the solution and the target for action; and the implementation of a comprehensive range of strategies including a media advocacy strategy to attract public attention, to reframe media messages, and to provide a policy alternative to government and industry. The campaign was evaluated in terms of process and outcomes, and was successful in putting pressure on key stakeholders and achieving the alliance's two main goals. The case study demonstrates the value of a well-planned campaign and including public health advocacy in public health practice, as an important strategy to facilitate the creation of healthy environments through healthy public policy.


The wild-type nucleotide sequence of the rpoBC-attenuator region of Escherichia coli DNA and its implications for the nature of the rifd18 mutation.
To investigate the possibility that the unusual dominant rifampicin-resistance characteristic of the rifd18 allele of E. coli rpoB is due to a secondary, regulatory mutation, we have determined the nucleotide sequence of a 1.1 Kbp wild-type DNA fragment, including the transcriptional attenuator and translational start-site of rpoB. We have also re-investigated the previously published sequences of this region in lambda rifd18 and lambda rifd47 DNA. Our results indicate that all three sequences are identical, and reveal some errors in the published data. We discuss the basis of dominance of rifd18.


PPI-MASS: An Interactive Web Server to Identify Protein-Protein Interactions From Mass Spectrometry-Based Proteomics Data.
Mass spectrometry-based proteomics methods are widely used to identify and quantify protein complexes involved in diverse biological processes. Specifically, tandem mass spectrometry methods represent an accurate and sensitive strategy for identifying protein-protein interactions. However, most of these approaches provide only lists of peptide fragments associated with a target protein, without performing further analyses to discriminate physical or functional protein-protein interactions. Here, we present the PPI-MASS web server, which provides an interactive analytics platform to identify protein-protein interactions with pharmacological potential by filtering a large protein set according to different biological features. Starting from a list of proteins detected by MS-based methods, PPI-MASS integrates an automatized pipeline to obtain information of each protein from freely accessible databases. The collected data include protein sequence, functional and structural properties, associated pathologies and drugs, as well as location and expression in human tissues. Based on this information, users can manipulate different filters in the web platform to identify candidate proteins to establish physical contacts with a target protein. Thus, our server offers a simple but powerful tool to detect novel protein-protein interactions, avoiding tedious and time-consuming data postprocessing. To test the web server, we employed the interactome of the TRPM4 and TMPRSS11a proteins as a use case. From these data, protein-protein interactions were identified, which have been validated through biochemical and bioinformatic studies. Accordingly, our web platform provides a comprehensive and complementary tool for identifying protein-protein complexes assisting the future design of associated therapies.


CT lung densitometry: dependence of CT number histograms on sample volume and consequences for scan protocol comparability.
Our goals were to determine the dependence of CT number histograms of the lung on section thickness and reconstruction filter and to evaluate the consequences for scan protocol conformity required for universally comparable densitometry of the lungs. The effects of section thickness and reconstruction filter were parameterized with the CT's sample volume [V approximately (section thickness x in-plane resolution2)]. In a study of 31 patients, we determined as a function of V the following CT number histogram parameters: percentiles P(10) and P(90), pixel indexes PI(-905) and PI(-950), and standard deviation. Patient histogram parameters depended strongly on sample volume. Large differences were found between protocols using 1 and 10 mm sections. For small variations in somewhat larger sample volumes (> 8 mm3), discrepancies were much smaller. To obtain comparable histogram parameters, nearly identical sample volumes (> or = 8 mm3) should be used. When this condition is satisfied, available data suggest that universally comparable densitometry is feasible.


The study of women, infant feeding and type 2 diabetes after GDM pregnancy and growth of their offspring (SWIFT Offspring study): prospective design, methodology and baseline characteristics.
Breastfeeding is associated with reduced risk of becoming overweight or obese later in life. Breastfed babies grow more slowly during infancy than formula-fed babies. Among offspring exposed in utero to maternal glucose intolerance, prospective data on growth during infancy have been unavailable. Thus, scientific evidence is insufficient to conclude that breastfeeding reduces the risk of obesity among the offspring of diabetic mothers (ODM). To address this gap, we devised the Study of Women, Infant Feeding and Type 2 Diabetes after GDM Pregnancy and Growth of their Offspring, also known as the SWIFT Offspring Study. This prospective, longitudinal study recruited mother-infant pairs from the SWIFT Study, a prospective study of women with recent gestational diabetes mellitus (GDM). The goal of the SWIFT Offspring Study is to determine whether breastfeeding intensity and duration, compared with formula feeding, are related to slower growth of GDM offspring during the first year life. This article details the study design, participant eligibility, data collection, and methodologies. We also describe the baseline characteristics of the GDM mother-infant pairs. The study enrolled 466 mother-infant pairs among GDM deliveries in northern California from 2009-2011. Participants attended three in-person study exams at 6-9 weeks, 6 months and 12 months after delivery for infant anthropometry (head circumference, body weight, length, abdominal circumference and skinfold thicknesses), as well as maternal anthropometry (body weight, waist circumference and percent body fat). Mothers also completed questionnaires on health and lifestyle behaviors, including infant diet, sleep and temperament. Breastfeeding intensity and duration were assessed via several sources (diaries, telephone interviews, monthly mailings and in-person exams) from birth through the first year of life. Pregnancy course, clinical perinatal and newborn outcomes were obtained from health plan electronic medical records. Infant saliva samples were collected and stored for genetics studies. This large, racially and ethnically diverse cohort of GDM offspring will enable evaluation of the relationship of infant feeding to growth during infancy independent of perinatal characteristics, sociodemographics and other risk factors. The longitudinal design provides the first quantitative measures of breastfeeding intensity and duration among GDM offspring during early life.


Mast cells migrate from blood to brain.
It is well established that mast cells (MCs) occur within the CNS of many species. Furthermore, their numbers can increase rapidly in adults in response to altered physiological conditions. In this study we found that early postpartum rats had significantly more mast cells in the thalamus than virgin controls. Evidence from semithin sections from these females suggested that mast cells were transiting across the medium-sized blood vessels. We hypothesized that the increases in mast cell number were caused by their migration into the neural parenchyma. To this end, we purified rat peritoneal mast cells, labeled them with the vital dyes PKH26 or CellTracker Green, and injected them into host animals. One hour after injection, dye-filled cells, containing either histamine or serotonin (mediators stored in mast cells), were located close to thalamic blood vessels. Injected cells represented approximately 2-20% of the total mast cell population in this brain region. Scanning confocal microscopy confirmed that the biogenic amine and the vital dye occurred in the same cell. To determine whether the donor mast cells were within the blood-brain barrier, we studied the localization of dye-marked donor cells and either Factor VIII, a component of endothelial basal laminae, or glial fibrillary acidic protein, the intermediate filament found in astrocytes. Serial section reconstructions of confocal images demonstrated that the mast cells were deep to the basal lamina, in nests of glial processes. This is the first demonstration that mast cells can rapidly penetrate brain blood vessels, and this may account for the rapid increases in mast cell populations after physiological manipulations.


Forebrain ischemia in the gerbil increases lambda opiate binding in hippocampal mossy fibers.
Transient forebrain ischemia was produced in gerbils by short-term occlusion of the common carotid arteries under halothane anesthesia. Histological analysis of brains 7 days post-ischemia demonstrated characteristic destruction of CA1 pyramidal cells. lambda Opiate binding (measured with [3H]naloxone in the presence of 300 nM diprenorphine) at 7 days post-ischemia was significantly increased in the stratum lucidum of the hippocampus (the mossy fiber layer), but not in any other region measured, including other hippocampal regions, cortex, amygdala, caudate putamen, thalamus, and hypothalamus. The increase in mossy fiber lambda binding was slow to develop (no increase detected up to 48 h post-ischemia), and long-lasting (binding remained elevated at 32 days post-ischemia). While MK-801 significantly inhibited CA1 pyramidal cell destruction when administered 20 min prior to ischemia, the increase in mossy fiber lambda binding was still evident. None of seven different opioid agonists and antagonists examined had an effect on either the pyramidal cell damage or increased mossy fiber lambda binding seen 7 days after ischemia.


Impact of experimental blockade of peripheral growth hormone (GH) receptors on the kinetics of endogenous and exogenous GH removal in healthy women and men.
Organs that respond to and metabolize GH are enriched in cognate high-affinity receptors. However, whether isologous receptors mediate the de facto access of ligand to cellular degradative pathways is not known. To address this query, we assessed the distribution and whole-body elimination kinetics of (endogenous and exogenous) GH before and after administration of a novel, potent, and selective recombinant human (rh) GH receptor antagonist peptide, pegvisomant. Sixteen healthy young adults (nine men and seven women) participated in a double-blind, prospectively randomized, within-subject cross-over study. The intervention comprised a single sc injection of placebo vs. a high dose of pegvisomant (1 mg/kg sc) timed 62 and 74 h before the overnight sampling and daytime infusion sessions, respectively. The half-life, metabolic clearance rate (MCR), and distribution volume of GH were quantitated by way of: 1) deconvolution analysis of serum GH concentration time series collected every 10 min for 10 h; 2) exponential regression analysis of the decay of GH concentrations after a 6-min iv pulse of rhGH (1 and 10 micro g/kg); 3) calculation of the MCR during constant iv infusion of rhGH (0.5 and 5.0 micro g/kg every 2 h); and 4) exponential fitting of the elimination time-course of GH concentrations following cessation of each constant infusion. Concentrations of GH and pegvisomant were measured in separate, noncross-reactive, two-site monoclonal, immunofluorometric assays. Pegvisomant concentrations averaged 4860 +/- 480 micro g/liter (+/-SEM) across the infusion interval, thus exceeding low steady state GH concentrations by 3000-fold. Inhibitory efficacy of the GH receptor antagonist peptide was affirmed by way of a 34% reduction in the serum total IGF-I concentration, i.e., from 257 +/- 37 (placebo) to 170 +/- 24 (drug) micro g/liter (P < 0.001); and a reciprocal 77% elevation of the (10-h) mean GH concentration, i.e., from 1.3 +/- 0.23 (placebo) to 2.3 +/- 0.42 (drug) micro g/liter (P = 0.003). ANOVA disclosed that prior administration of pegvisomant (compared with placebo) did not alter: 1) the calculated half-life (minutes) of secreted GH, which averaged 15 +/- 1.3 (placebo) and 14 +/- 0.69 (drug); 2) the half-time of disappearance (minutes) of an iv pulse of rhGH, 15 +/- 1.0 (placebo) and 13 +/- 0.5 (drug) (for the 10 micro g/kg dose); 3) the distribution volume (milliliters per kilogram) of rhGH, 59 +/- 6.2 (placebo) and 58 +/- 3.5 (drug); 4) the steady state GH concentration (micrograms per liter) attained during constant iv infusion of rhGH (at a rate of 5 micro g/kg every 2 h), 18.2 +/- 2.4 (placebo) and 18.3 +/- 2.3 (drug); 5) the half-life (minutes) of elimination of GH from equilibrium, 16 +/- 0.98 (placebo) and 16 +/- 1.8 (drug); and 6) the steady state MCR (liters per kilogram per day) of rhGH, 3.8 +/- 0.32 (placebo) and 3.5 +/- 0.31 (drug). In ensemble, the present data refute the a priori postulate that vascular-accessible GH receptors determine the in vivo pseudoequilibrium kinetics of GH disappearance in the human.


Thalamic Pain Misdiagnosed as Cervical Disc Herniation.
Thalamic pain is a primary cause of central post-stroke pain (CPSP). Clinical symptoms vary depending on the location of the infarction and frequently accompany several pain symptoms. Therefore, correct diagnosis and proper examination are not easy. We report a case of CPSP due to a left acute thalamic infarction with central disc protrusion at C5-6. A 45-year-old-male patient experiencing a tingling sensation in his right arm was referred to our pain clinic under the diagnosis of cervical disc herniation. This patient also complained of right cramp-like abdominal pain. After further evaluations, he was diagnosed with an acute thalamic infarction. Therefore detailed history taking should be performed and examiners should always be aware of other symptoms that could suggest a more dangerous disease.


Induction of gamma-glutamyl transpeptidase in primary cultures of normal rat hepatocytes by liver tumor promoters and structurally related compounds.
Rat hepatocytes maintained for up to 6 days in primary culture were used to test a variety of xenobiotics and steroids for effects on the activity of gamma-glutamyltranspeptidase (GGT) in normal cells. In control cultures GGT activity was low and increased slowly with time. When added to cultures for 5 days, a variety of xenobiotics and steroids increased GGT activity to levels 2- to 6-times those of control cultures. Induction of GGT was potentiated for most test compounds by 20-30 nM dexamethasone and diminished by nicotinamide or adenosine-3',5'-monophosphate. Effective non-genotoxic inducers included phenobarbital and some structurally related compounds, p,p'-dichlorodiphenyltrichloroethane,alpha- and gamma-hexachlorocyclohexanes, Aroclor 1254, butyl hydroxytoluene, nafenopin, various estrogens, progesterone, pregnenolone-16 alpha-carbonitrile and cyproterone acetate. A number of compounds including barbituric acid, butyl hydroxyanisole, acetaminophen, saccharin, caffeine, clofibrate and some bile acids failed to induce GGT. Except for 2-acetylaminofluorene and diethylnitrosamine, genotoxic compounds tested did not increase GGT. The results establish that a structurally diverse group of xenobiotics and steroids, many of which are considered to be liver tumour promoters, may directly enhance GGT gene expression in normal hepatocytes. Thus, a variety of compounds used in experimental studies of liver cancer induction as promoters may elevate GGT by mechanism(s) not necessarily related to carcinogenesis.


Locking compression plate fixation of Vancouver type-B1 periprosthetic femoral fractures.
Fractures occurring at or near the distal tip of a hip prosthesis with a stable femoral stem (Vancouver type-B fractures) are associated with many complications because of the inherently unstable fracture pattern. Locking compression plates use screws that lock into the plate allowing multiple points of unicortical fixation. Such unicortical fixation may lower the risk of damage to the cement mantle or a stable femoral stem during the treatment of a periprosthetic femoral fracture. The purpose of this study was to analyze clinically and radiographically a group of patients with a Vancouver type-B1 periprosthetic femoral fracture treated with open reduction and internal fixation with use of a locking compression plate. Fourteen consecutive patients (fourteen hips) with a Vancouver type-B1 periprosthetic femoral fracture were treated with a locking compression plate. There were five men and nine women with an average age of sixty-eight years at the time of fracture. All of the fractures occurred after a total hip arthroplasty performed with cement, and eleven of the arthroplasties were revisions. In addition to the plate, cortical strut allografts were used to stabilize five fractures. The patients were assessed clinically and radiographically. The average duration of follow-up was twenty months. Eight fractures healed uneventfully at an average of 5.4 months. Three treatment constructs failed with fracture of the plate within twelve months after surgery. An additional three constructs also failed because of plate pullout. All failures except one occurred in constructs in which a cortical strut allograft had not been utilized. On the basis of the high failure rate in this series of patients, locking compression plates do not appear to offer advantages over other types of plates in the treatment of type-B1 periprosthetic femoral fractures. Despite the potential to preserve the cement mantle, the locked screws did not appear to offer good pullout resistance in this fracture type. We believe that supplementation with strut allografts should be used routinely if this type of locking compression plate is selected to treat these fractures.


Adolescent preferences for human immunodeficiency virus testing methods and impact of rapid tests on receipt of results.
Rapid human immunodeficiency virus (HIV) tests may be more acceptable to adolescents and may improve receipt of test results. We conducted a study to determine (a) adolescent preferences for different HIV testing methods (rapid oral fluid vs. rapid fingerstick vs. traditional venipuncture), (b) factors associated with choice of a rapid vs. traditional test, and (c) whether those who chose a rapid method were more likely to receive test results. Participants (N=99, 13-22 years old, both genders) were recruited from an urban hospital-based adolescent primary care clinic, agreed to HIV testing with their choice of method, and completed a questionnaire assessing demographic characteristics and attitudes about HIV testing. Logistic regression modeling was used to determine factors associated with choice of a rapid versus traditional test. Half (50.5%) of participants chose rapid oral fluid testing, 30.3% traditional venipuncture testing, and 19.2% rapid fingerstick testing (p < .01). Factors independently associated with choice of a rapid versus traditional method included preference for an oral fluid versus blood test and perceived approval of HIV testing by one's healthcare provider. Participants who chose a rapid test were more likely to receive their test results within the follow-up period than participants who chose a traditional test (91.3% vs. 46.7%, p < .001). In this study, 70% of adolescents preferred rapid to traditional HIV testing, and rapid testers were more likely to receive their results within the follow-up period. Offering rapid testing may lead to improved receipt of results among adolescents in urban primary care settings.


Engaging African American Pastors in COVID-19 Research During a Pandemic: Lessons Learned.
African American pastors are recognized as trusted information sources for their communities. The pastors willing to address health-related concerns such as preventing the spread of the coronavirus are invaluable for leading their congregation through relevant health programs. Underlining the importance of religion, spirituality, and faith-based leaders in addressing and furthering health promotion research, the article discusses lessons learned during the study implementation and the recommendations for engaging minority pastors in research during a global health pandemic.


Survival benefits of lung cancer patients undergoing laser and brachytherapy.
We aimed to compare the duration of survival among subjects receiving brachytherapy (BT) in combination with Nd:YAG laser therapy (LT), and those receiving LT or BT alone. The medical records of subjects who received endobronchial treatment for unresectable tracheobronchial malignancies between January 1997 and December 1999 in a single center were reviewed retrospectively. A total of 80 patients were evaluated. The overall symptomatic response rate after treatment was 86.5%. Median survival durations for the LT, BT, and combined therapy (CT) group were 111, 115, and 264 days, respectively. The survival duration was significantly longer in the CT group than in the BT group (p=0.0078), but the difference was not statistically significant between the CT and the LT group. The bronchoscopic finding of endobronchial polypoid lesion was associated with a longer survival time than extraluminal with compression type (p=0.0023) by univariate analysis. Other factors associated with the better prognosis included hemoglobin > or = 12.5 g/dL, serum albumin level > or = 37 g/L, and BT dose > or = 15 Gy at 1 cm distance. Of these factors, specific bronchoscopic findings, serum albumin level, CT modality, and dose of BT retained statistical significance in multivariate analysis. In conclusion, combined LT and BT is associated with increased patient survival compared with BT alone. Combined therapy may improve survival time in selected patients with endobronchial malignancies.


Microsatellite markers derived from Calophyllum inophyllum (Clusiaceae) expressed sequence tags.
Robust markers are required (inter alia) for assessing origins of Calophyllum inophyllum populations on the Bonin Islands, Japan. Therefore, informative expressed sequence tag (EST)-based microsatellite or simple sequence repeat (SSRs) markers in the species were sought. Using 135378 ESTs derived from de novo pyrosequencing, primers for 475 EST-SSRs were developed, 48 of which were tested for PCR amplification. Thirty-six of the 48 primers showed clear amplification, with 23 displaying polymorphism in sampled populations. Expected heterozygosity in the samples from the Bonin Islands and Ryukyu Islands populations ranged from 0.041 to 0.697 and from 0.041 to 0.773, respectively. As EST-SSRs are potentially tightly linked with functional genes, and reportedly more transferable to related species than anonymous genomic SSRs, the developed primers have utility for future studies of the origins, genetic structure, and conservation of C. inophyllum and related species.


Local adaptation at the range peripheries of Sitka spruce.
High-dispersal rates in heterogeneous environments and historical rapid range expansion can hamper local adaptation; however, we often see clinal variation in high-dispersal tree species. To understand the mechanisms of the species' distribution, we investigated local adaptation and adaptive plasticity in a range-wide context in Sitka spruce, a wind-pollinated tree species that has recently expanded its range after glaciations. Phenotypic traits were observed using growth chamber experiments that mimicked temperature and photoperiodic regimes from the limits of the species realized niche. Bud phenology exhibited parallel reaction norms among populations; however, putatively adaptive plasticity and strong divergent selection were seen in bud burst and bud set timing respectively. Natural selection appears to have favoured genotypes that maximize growth rate during available frost-free periods in each environment. We conclude that Sitka spruce has developed local adaptation and adaptive plasticity throughout its range in response to current climatic conditions despite generally high pollen flow and recent range expansion.


[Relationship between household safe drinking water, hygienic toilet and prevalence of stunting for Chinese children aged 0 to 5 years old in 2013].
To investigate the relationship between household drinking water, toilet status and the prevalence of stunting for Chinese children aged 0 to 5 years old in 2013. Data was extracted from the Chinese National Nutrition and Health Surveillance in 2013. A total of 32 861 children aged 0 to 5 years old were selected from 165 townships(streets) of 55 counties(cities/districts) in 30 provinces. Caregivers were face to face interviewed to collect data, including demographic characteristics of children, mothers and household, main source of household drinking water and main type of household toilet. Height/Length of children was measured using a standard procedure. Height(Length) for age Z score(HAZ(LAZ)) was calculated using WHO Anthro Survey Analyser software(online version), and stunting was defined as HAZ(LAZ)<-2. SAS 9. 4 was used to analyze. SURVEYFREQ procedure was used to calculate the coverage rate of safe drinking water, hygienic toilet, and the prevalence of stunting. SURVEYLOGISTIC procedure was used to analyze the relationship between household safe drinking water, hygienic toilet and prevalence of stunting for Chinese children aged 0 to 5 years old in 2013. A total of 32 861 children completed the study. The coverage rate of safe drinking water was 86. 9%. The proportion of water piped into household, a public tab and water from a protected spring or well was 49. 4%, 15. 9% and 15. 6%, respectively. The coverage rate of hygienic toilet was 56. 8%. The proportion of pour-flush toilet and pit latrine were 52. 1% and 4. 7%. The prevalence of stunting for 0 to 5 years old children was 8. 1% in China. The prevalence of stunting were 8. 1% for children aged 0-5 years old with safe household drinking water and 7. 8% for those without safe household drinking water. The difference was not significant(P=0. 882). The prevalence of stunting was 6. 6% for children aged 0-5 years old with hygienic household toilet and 10. 0% for those without hygienic household toilet. The difference was not significant(P=0. 069). There was no significant relationship between household sanitary condition and stunting for children aged 0 to 5 years old. Household sanitary conditions, including main source of household drinking water and the main type of household toilet may not be associated with the prevalence of stunting for children aged 0 to 5 years old in this settings.


Seroprevalence of Toxoplasma gondii in Pinnipeds under Human Care and in Wild Pinnipeds.
Toxoplasma gondii infection has been reported in numerous species of marine mammals, some of them with fatal consequences. A serosurvey for T. gondii infection was conducted in pinnipeds from an oceanographic park in Portugal (n = 60); stranded pinnipeds on the Portuguese coast (n = 10); and pinnipeds captured in Lorenzensplate, Germany (n = 99). Sera from 169 pinnipeds were tested for the presence of antibodies to T. gondii by the modified agglutination test with a cut-off titre of 25. An overall seroprevalence of 8.9% (95% confidence interval: 5.1-14.2) was observed. Antibody titres of 25, 50, 100, 1600 and ≥3200 were found in five (33.3%), two (13.3%), five (33.3%), one (6.7%) and two (13.3%) animals, respectively. Pinnipeds under human care had a seroprevalence of 20.0% (12/60), in contrast to 2.8% (3/109) in wild pinnipeds (p < 0.001). General results suggest a low exposure of wild pinnipeds to T. gondii, while the seroprevalence found in pinnipeds under human care highlights the importance of carrying out further studies. This is the first serological survey of T. gondii in pinnipeds in Portugal and the first infection report in South African fur seal (Arctocephalus pusillus pusillus).


Analysis of conditional paralytic mutants in Drosophila sarco-endoplasmic reticulum calcium ATPase reveals novel mechanisms for regulating membrane excitability.
Individual contributions made by different calcium release and sequestration mechanisms to various aspects of excitable cell physiology are incompletely understood. SERCA, a sarco-endoplasmic reticulum calcium ATPase, being the main agent for calcium uptake into the ER, plays a central role in this process. By isolation and extensive characterization of conditional mutations in the Drosophila SERCA gene, we describe novel roles of this key protein in neuromuscular physiology and enable a genetic analysis of SERCA function. At motor nerve terminals, SERCA inhibition retards calcium sequestration and reduces the amplitude of evoked excitatory junctional currents. This suggests a direct contribution of store-derived calcium in determining the quantal content of evoked release. Conditional paralysis of SERCA mutants is also marked by prolonged neural activity-driven muscle contraction, thus reflecting the phylogenetically conserved role of SERCA in terminating contraction. Further analysis of ionic currents from mutants uncovers SERCA-dependent mechanisms regulating voltage-gated calcium channels and calcium-activated potassium channels that together control muscle excitability. Finally, our identification of dominant loss-of-function mutations in SERCA indicates novel intra- and intermolecular interactions for SERCA in vivo, overlooked by current structural models.


Mycetes and urban areas.
Mycetes are ubiquitous organisms that can cause mycoses in human and animals. The role of animals in the epidemiology of human mycoses in urban areas is multiform, but here will be discuss only two features: A) animals as vectors of mycoses and B) animal substrates as growth factor of pathogenic fungi. A) Animals as vectors of mycoses: this role is important as zoofilic dermatophytes are very important agents of zoonosis; the urban dermatophytozoonoses are prevalent caused by Microsporum canis which is prevalent in cats and dogs. Cats are often asymptomatic carriers. The pattern of human dermatomycoses has changed in Italy during the past century: at the beginning of the century anthropophilic fungi were prevalent while at present the zoophilic fungi are the most important causes. B) Animal substrata as growth factor of pathogenic fungi: soil "animalization" (i.e., the addition of such debris as hair, skin scales, dropping and other organic matters) creates an optimal substratum for the growth and the multiplication of geophilic or saprophyitic fungi, such as Microsporum gypseum and Cryptococcus neoformans. The present human lifestyle, which favours a an overpopulation of birds, wild animals, domestic mammals and sinanthropic together with man in crowded areas seems to favour the formation of environments adapted to the abundant growth of some pathogenic fungi with consequent infection for man and animals. Finally, an environment heavily populated by fungi can cause allergic pulmonary reactions as well as reactions in other organs and tissues. The control of human and animal fungi, and the efficient use of a monitoring system require ample knowledge of mycological problems both in human and veterinary medicine and of efficient laboratories capable of resolving the needs of both disciplines. Close collaboration between veterinarians, doctors and mycologists is necessary in order to resolve health problems linked to mycosis.


The role of perioperative warming in surgery: a systematic review.
The objective of this review was to systematically analyze the trials on the effectiveness of perioperative warming in surgical patients. A systematic review of the literature was undertaken. Clinical trials on perioperative warming were selected according to specific criteria and analyzed to generate summative data expressed as standardized mean difference (SMD). Twenty-five studies encompassing 3,599 patients in various surgical disciplines were retrieved from the electronic databases. Nineteen randomized trials on 1785 patients qualified for this review. The no-warming group developed statistically significant hypothermia. In the fixed effect model, the warming group had significantly less pain and lower incidence of wound infection, compared with the no-warming group. In the random effect model, the warming group was also associated with lower risk of post-anesthetic shivering. Both in the random and the fixed effect models, the warming group was associated with significantly less blood loss. However, there was significant heterogeneity among the trials. Perioperative warming of surgical patients is effective in reducing postoperative wound pain, wound infection and shivering. Systemic warming of the surgical patient is also associated with less perioperative blood loss through preventing hypothermia-induced coagulopathy. Perioperative warming may be given routinely to all patients of various surgical disciplines in order to counteract the consequences of hypothermia.


Neoadjuvant FEC 100 for operable breast cancer: eight-year experience at Centre Jean Perrin.
This study investigated the efficacy and tolerability of FEC 100 (epirubicin 100 mg/m2 with 5-fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2) every 21 days as neoadjuvant chemotherapy in women with stage I-III primary operable breast cancer. Forty patients were treated with 6 cycles of FEC 100, followed by surgery and radiation therapy. In addition, most patients also received an adjuvant treatment for residual disease (11 chemotherapies and 31 tamoxifen). After 6 cycles of FEC 100, the overall clinical response rate of 75% (CI 95%, 61.6-88.4) was achieved, 22.5% of which were complete responses. Breast conservation was achieved in 70% of patients. A pathologic complete response was confirmed in 6 patients (15%; CI 95%, 3.9-26.1) using Chevallier's classification and in 10 patients (25%; CI 95%, 11.6-38.4) using Sataloff's classification. After a median follow-up of 29.5 months, 3 metastatic relapses were observed. The principal toxicity of FEC 100 was myelosuppression; 51.3% of patients developed grade 3/4 neutropenia. Neoadjuvant FEC 100 was both effective and well tolerated in patients with early-stage operable breast cancer.


An innovative technology based on aerobic granular biomass for treating municipal and/or industrial wastewater with low environmental impact.
The paper reports the results of an investigation carried out at lab scale to assess the effectiveness of an innovative technology (SUPERBIO) for treating municipal and/or industrial wastewater. When this technology was applied for treating municipal wastewater, the results showed that even at maximum organic load (i.e. 7 kg COD m(-3) d(-1)), the COD in the treated effluent was lower than 50 mg L(-1). In addition, both ammonia and TKN removal efficiencies resulted in higher than 87% up to an organic load of 5.7 kg COD m(-3) d(-1) corresponding to a nitrogen load of 0.8 kg TKN m(-3) d(-1). Very satisfactory process performances also resulted during tannery wastewater treatment, when a chemical oxidation step (i.e. ozonation) was inserted in the treatment cycle of SUPERBIO. In such an instance, at organic and nitrogen loadings of 3 kgCOD m(-3) d(-1) and 0.20 kg N m(-3) d(-1), COD, NH4+ -N and TSS average removals were 96, 99 and 98%, respectively. Finally, during the whole experimentation, SUPERBIO was always characterised by a very low sludge production. Such a result was ascribed mainly to the characteristics of biomass that grew in the form of very dense granules (i.e. 130 gVSS L(Biomass)(-1) allowing a biomass concentration as high as 50-60 gTSS l(bed)(-1) to be achieved.


Different relationships between central dopamine system and sub-processes of inhibition: Spontaneous eye blink rate relates with N2 but not P3 in a Go/Nogo task.
Clinical studies show that dysfunction of the dopamine (DA) system could differently modulate N2 and P3 components in a Go/Nogo task, a classical inhibition task. However, results of previous clinical studies cannot be arbitrarily generalized to healthy adults. Thus, the present exploratory study aimed to investigate whether there are significant and variable relationships between individual differences of the DA system in normal healthy persons and N2- and P3-related sub-processes of inhibition in a Go/Nogo task. DA function was measured by spontaneous eye blink rate (EBR), which is an effective clinical and non-invasive measure and strongly related to the activity of the central dopaminergic system. A total of 28 young adults participated in this experiment. Results showed that Nogo-N2 and Nogo-P3 of all participants were larger than Go-N2 and Go-P3, while Nogo-N2 and Nogo-P3 were significantly related with Nogo-accuracy. Moreover, it was shown that higher EBRs were significantly correlated with larger and more negative N2 amplitudes under Go- and Nogo-conditions; however, there were no significant correlations between participants' EBRs and N2 latencies, and between EBRs and average amplitudes of P3 under the two conditions. Based on these results, we concluded that the central DA system was associated with the N2-related conflict monitoring rather than P3-related sub-process of inhibition.


Oral vitamin A in acne vulgaris. Preliminary report.
Oral vitamin A (retinol) is generally not considered useful in the treatment of acne vulgaris. We conducted a study which showed that retinol was indeed ineffective at the usual doses of 50,000 to 100,000 IU daily. Retinol was highly efficacious in doses of 300,000 units for women and 400,000 to 500,000 units for men, toxicity was slight and limited mainly to skin (xerosis) and mucous membranes (cheilitis). The danger of hypervitaminosis A in this dosage range has been exaggerated. Retinol is a valuable drug for treating stubborn, severely inflammatory acne vulgaris. It is administered until the disease is brought under control, usually within three to four months. Then the dosage is progressively reduced relying on conventional drugs to keep the disease in abeyance.


Use of the JKR model for calculating adhesion between rough surfaces.
A simple method for using the JKR model to determine interfacial adhesion between two ideal rough surfaces is demonstrated for individual asperity-asperity and asperity-flat contacts both in air and in water. The model takes into account the effect of a modified contact area at separation due to viscoelastic effects. The equilibrium version of the model significantly underestimates the measured adhesion, whereas the viscoelastic version of the model is much closer to the measured data. The asperity-flat geometry used with the viscoelastic version of the model seems to fit the experimental results best. This was thought to be due to the unlikely occurrence of direct asperity-asperity contacts. Instead, it would seem that the asperities have a far higher chance of fitting between each other on opposing surfaces, leading to correspondingly higher pull-off forces measured on separation. Many possible extensions to the roughness model described here may be made, allowing a much-improved understanding of the contact mechanics between two rough surfaces.


Expressional Modulation of Aquaporin 1 and 9 in the Rat Epididymis by an Anabolic-Androgenic Steroid, Nandrolone Decanoate.
The spermatozoa become mature in the epididymis which is divided into initial segment and caput, corpus, and cauda epididymis. The water movement across the epididymal epithelium is important for creating luminal microenvironment for sperm maturation. Aquaporins (Aqps) are water channel proteins, and expression of Aqps is regulated by androgens. The current research was focused to examine expressional regulation of Aqp1 and Aqp9 by an androgenic-anabolic steroid, nandrolone decanoate (ND). The ND at the low dose (2 mg/ kg body weight/week) or high dose (10 mg) was subcutaneously administrated into male rats for 2 or 12 weeks. Transcript levels of Aqp1 and Aqp9 were determined by quantitative real-time polymerase chain reaction (PCR) analyses. In the initial segment, level of Aqp1 was decreased with 12 week-treatment, while Aqp9 level was decreased by the high dose treatment for 12 weeks. In the caput epididymis, Aqp9 expression was decreased by the low dose treatment. The 2 week-treatment resulted in an increase of Aqp1 level but a decrease of Aqp9 expression in the corpus epididymis. In the corpus epididymis, the 12 week-treatment at the low dose caused the reduction of Aqp1 and Aqp9 levels, but the high dose treatment resulted in an increase of Aqp1 expression and a decrease of Aqp9 level. In the cauda epididymis, Aqp1 expression was decreased by 2 and 12 week-treatments, while increases of Aqp9 levels was detected with the high dose treatment for 2 weeks and with 12 week-treatment. These findings indicate differential regulation of Aqp1 and Aqp9 expression among epididymal segments by ND.


Isolated sarcoid myopathy.
A 75-year-old housewife presented with a 5-year history of slowly progressive, painless limb weakness with wasting particularly of the pretibial muscles and without sensory involvement. She was otherwise healthy, but had a history of mild pulmonary sarcoidosis 20 years earlier. Abnormal laboratory findings included serum calcium (3.2 mmol/L; normal 2.15-2.6 mmol/L) and serum angiotensin-converting enzyme (ACE; 38.2 U/L; normal <22.5 U/L). All other laboratory investigations, including antibody studies and diagnostic work-up for systemic sarcoidosis, were negative. Muscle biopsy revealed noncaseating epitheloid granulomas, multinuclear giant cells, and lymphoplasmacellular infiltration. The patient was started on methylprednisolone and recovered to some extent. These findings represent a rare case of isolated sarcoid myopathy without concurrent systemic sarcoidosis.


Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices.
Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age-related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age-related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age-related sensory loss. Together, our results suggest that the age-related alteration of glial cells in sensory cortical areas can be accelerated by activity-driven central mechanisms that result from an age-related loss of peripheral sensitivity. In light of our observations, these age-related changes in sensory function should be considered when investigating cellular, cortical, and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models.


Ion pair charge-transfer complexes between anionic and cationic metal-dithiolenes [M(II) = Pd, Pt].
New [M(R(2)pipdt)(2)](BF(4))(2) salts [R(2)pipdt = N,N'-dialkyl-piperazine-2,3-dithione; M = Pd(II), R = Me and M = Pt(II), R = Me, Et, Pr(i)] bearing redox-active cationic dithiolene complexes have been prepared and characterized. These cations react with the redox-active [M(mnt)(2)](2-) [M = Pd(II), Pt(II); mnt = maleonitrile-2,3-dithiolate] anionic dithiolenes to form salts describable as ion pair charge-transfer complexes. X-ray crystallographic studies have shown that [M(Me(2)pipdt)(2)][M(mnt)(2)] complexes, with M = Pd(II) and Pt(II), are isomorphous. Crystal data of the Pt salt (3a): triclinic, Ponemacr; (No. 2); Z = 1; T = 293(2) K; a = 6.784(7) A, b = 8.460(6) A, c = 13.510(5) A, alpha = 100.63(2) degrees, beta = 104.04(2) degrees, gamma = 96.90(2) degrees; R1 = 0.0691 [wR2 = 0.2187 (all data)]. Structural data show that approximately square-planar [Pt(Me(2)pipdt)(2)] dications and regular square-planar [Pt(mnt)(2)] dianions form an infinite anion-cation one-dimensional stack along axis a with a Pt...Pt a/2 distance of 3.392 A and a Pt...Pt...Pt angle of 180 degrees. Anions and cations arrange themselves face-to-face so as to take on a staggered arrangement. These salts exhibit strong absorptions in the visible-near-infrared region assigned to ion pair charge-transfer transitions. A relation between the optical and thermal electron transfer in the solid state is obtained using a "Marcus-Hush model", and a solid-state electrical conductivity in agreement with expectations is observed. Vibrational spectroscopy is in agreement with the existence of charge-transfer interactions between the cationic and anionic components of the salts.