A cell-based protein-protein interaction method using a permuted luciferase reporter.
We have developed a novel cell-based protein-protein interaction assay method. The method relies on conversion of an inactive permuted luciferase containing a Tobacco Etch Virus protease (TEV) cleavage sequence fused onto protein (A) to an active luciferase upon interaction and cleavage by another protein (B) fused with the TEV protease. We demonstrate assay applicability for ligand-induced protein-protein interactions including G-protein coupled receptors, receptor tyrosine kinases and nuclear hormone receptors.


A case report of bilateral mirror clubfeet and bilateral hand polydactyly.
We report a rare case of a patient with bilateral mirror clubfeet and bilateral hand polydactyly. The patient presented to our orthopaedic clinic with bilateral mirror clubfeet, each with eight toes, and bilateral hands with six fingers and a hypoplastic thumb. The pattern does not fit any described syndrome such as Martin or Laurin-Sandrow syndrome. Treatments by an orthopaedic pediatric surgeon and an orthopaedic pediatric hand surgeon are described. The patient achieved excellent functional and cosmetic outcomes at four year follow-up.


A histological and immunohistochemical analysis of lymphoid tissues of the Tasmanian devil.
Tasmanian devil lymphoid tissues (thymus, spleen, and lymph node) from seven animals, including pouch young, juvenile, and adult devils, were investigated using histological and immunohistochemical techniques. Antibodies against the conserved intracytoplasmic portion of CD3 and CD79b (T- and B-cell markers, respectively) and MHC II were used to label immune cells. The thymus from the juvenile devils and the pouch young had CD3+ cells that were primarily located in the medulla of the organ. The spleen consisted of red and white pulp areas with characteristic lymphoid follicles with CD79b+ and MHC II+ cells and nonfollicular T-cell-dominated periarteriolar lymphoid sheaths. Peripheral lymph nodes presented three distinct regions, outer cortex and medulla (both with primarily CD79b+ and MHC II+ cells) and paracortex (mainly CD3+ cells). Tissue architecture and distribution of the immune cells were similar to that seen in eutherian mammals and other marsupials, indicating that the Tasmanian devil has all the structural elements necessary for effective adaptive immunity.


Religious coping, health, and health service use among bereaved adults.
This report examined associations between religious coping, health, and health service use among a sample of 265 recently bereaved adults. Participants were interviewed an average of 6.3 (SD = 7.4) months after their loss and again 4 months later. Multivariate regression models and repeated measures ANOVA analyses estimated the influence of religious coping on health and health service use at baseline and follow-up, controlling for significant confounding influences, such as health promoting behaviors. At baseline, those high on religious coping had significantly more functional disabilities than did those low on religious coping. Controlling for health status, participants with higher religious coping scores were significantly less likely to visit their doctor during the 60 days prior to the baseline interview. Despite worse health and less health service use at baseline, those high on religious coping had equivalent health status to those low on religious coping at follow-up. Greater use of religious coping is associated with more functional disabilities and fewer outpatient physical health care visits at baseline, but a lack of decline in health at 4-month follow-up among the bereaved, a sub-group at risk for numerous health impairments. Possible reasons for this association and its implications are discussed.


Methods Used to Investigate the Plasmodium falciparum Digestive Vacuole.
Plasmodium falciparum malaria remains a global health problem as parasites continue to develop resistance to all antimalarials in use. Infection causes clinical symptoms during the intra-erythrocytic stage of the lifecycle where the parasite infects and replicates within red blood cells (RBC). During this stage, P. falciparum digests the main constituent of the RBC, hemoglobin, in a specialized acidic compartment termed the digestive vacuole (DV), a process essential for survival. Many therapeutics in use target one or multiple aspects of the DV, with chloroquine and its derivatives, as well as artemisinin, having mechanisms of action within this organelle. In order to better understand how current therapeutics and those under development target DV processes, techniques used to investigate the DV are paramount. This review outlines the involvement of the DV in therapeutics currently in use and focuses on the range of techniques that are currently utilized to study this organelle including microscopy, biochemical analysis, genetic approaches and metabolomic studies. Importantly, continued development and application of these techniques will aid in our understanding of the DV and in the development of new therapeutics or therapeutic partners for the future.


Vacuolar Processing Enzymes Modulating Susceptibility Response to Fusarium oxysporum f. sp. cubense Tropical Race 4 Infections in Banana.
Fusarium oxysporum f. sp. cubense tropical race 4 (FocTR4) is a destructive necrotrophic fungal pathogen afflicting global banana production. Infection process involves the activation of programmed cell death (PCD). In this study, seven Musa acuminata vacuolar processing enzyme (MaVPE1-MaVPE7) genes associated with PCD were successfully identified. Phylogenetic analysis and tissue-specific expression categorized these MaVPEs into the seed and vegetative types. FocTR4 infection induced the majority of MaVPE expressions in the susceptible cultivar "Berangan" as compared to the resistant cultivar "Jari Buaya." Consistently, upon FocTR4 infection, high caspase-1 activity was detected in the susceptible cultivar, while low level of caspase-1 activity was recorded in the resistant cultivar. Furthermore, inhibition of MaVPE activities via caspase-1 inhibitor in the susceptible cultivar reduced tonoplast rupture, decreased lesion formation, and enhanced stress tolerance against FocTR4 infection. Additionally, the Arabidopsis VPE-null mutant exhibited higher tolerance to FocTR4 infection, indicated by reduced sporulation rate, low levels of H2O2 content, and high levels of cell viability. Comparative proteomic profiling analysis revealed increase in the abundance of cysteine proteinase in the inoculated susceptible cultivar, as opposed to cysteine proteinase inhibitors in the resistant cultivar. In conclusion, the increase in vacuolar processing enzyme (VPE)-mediated PCD played a crucial role in modulating susceptibility response during compatible interaction, which facilitated FocTR4 colonization in the host.


High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma.
Recent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC. Between 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0-7.0 cm), and the median dose was 51 Gy (range, 33-60 Gy). LC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45-54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT. This study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.


Faculty perceptions of university students with psychiatric disabilities.
Information sources such as professional training, the media, personal relationships, and one's own experience may impact perceptions about people with psychiatric disabilities (PDs). The purpose of this study was to assess the relationship between information sources and university faculty members' perceptions of working with university students who have PDs. Specific types of personal experience were then analyzed: having a family member, friend, and student with a PD, and having a PD oneself. Faculty who had a friend or a student with a PD had more positive perceptions of university students with PDs than faculty who had neither of these experiences.


A Systematic Review and Meta-Analysis: Safety and Efficacy of Mesenchymal Stem Cells Therapy for Heart Failure.
Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating Heart Failure (HF). However, the effects of stem cell therapy in patients with heart failure is an ongoing debate and the safety and efficacy of MSCs therapy are not well-known. We conducted a systematic review of clinical trials that evaluated the safety and efficacy of MSCs for HF. This study aimed to assess the safety and efficacy of MSCs therapy compared to the placebo in heart failure patients. We searched PubMed, Embase, Cochrane library systematically, with no language restrictions. Randomized Controlled Trials (RCTs) assessing the influence of MSCs treatment function controlled with placebo in heart failure were included in this analysis. We included RCTs with data on safety and efficacy in patients with heart failure after mesenchymal stem cell transplantation. Two investigators independently searched the articles, extracted data, and assessed the quality of the included studies. Pooled data was performed using the fixed-effect model or random-effect model by the use of Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The primary outcome was safely assessed by death and rehospitalization and the secondary outcome was efficacy, which was assessed by six-minute walk distance and Left Ventricular Ejection Fraction (LVEF), Left Ventricular End-systolic Volume (LVESV), Left Ventricular End-diastolic Volume (LVEDV) and Brain Natriuretic Peptide (BNP). A total of twelve studies were included, involving 823 patients who underwent MSCs or placebo treatment. The overall rate of death showed a trend of reduction of 27% (RR [CI]=0.73 [0.49, 1.09], p=0.12) in the MSCs treatment group. The incidence of rehospitalization was reduced by 47% (RR [CI]=0.53[0.38, 0.75], p=0.0004). The patients in the MSCs treatment group realised an average of 117.01m (MD [95% CI]=117.01m [94.87, 139.14], p<0.00001) improvement in 6MWT. MSCs transplantation significantly improved Left Ventricular Ejection Fraction (LVEF) by 5.66 % (MD [95% CI]=5.66 [4.39, 6.92], p<0.00001), decreased Left Ventricular End-Systolic Volume (LVESV) by 14.75 ml (MD [95% CI]=-14.75 [-16.18, - 12.83], p<0.00001) and Left Ventricular End-Diastolic Volume (LVEDV) by 5.78 ml (MD [95% CI]=- 5.78[-12.00, 0.43], p=0.07), in the MSCs group, BNP was decreased by 133.51 pg/ml MD [95% CI]= - 133.51 [-228.17,-38.85], p=0.54, I2= 0.0%) than did in the placebo group. Our results suggested that mesenchymal stem cells as a regenerative therapeutic approach for heart failure are safe and effective by virtue of their self-renewal potential, vast differentiation capacity and immune modulating properties. Allogenic MSCs have superior therapeutic effects and intracoronary injection is the optimum delivery approach. In the tissue origin, patients who received treatment with umbilical cord MSCs seem more effective than bone marrow MSCs. As to dosage injected, (1-10)*10^8 cells were of better effect.


Determining sample size and power in clinical trials: the forgotten essential.
Estimation of the sample size is a fundamental but usually ignored requirement of the randomized controlled trial (RCT). Indeed, the publication of small trials without consideration of sample size is worrisome from both medical and ethical viewpoints. Type II errors are common, and readers and investigators may reject worthwhile treatments and interventions. Before embarking on an RCT, the investigator must choose an alpha, a beta, and the rates of outcomes anticipated in both treatment groups. This should reflect the characteristics of the condition and its treatment. If limited sample size or available resources pose a problem, the use of continuous outcome measures, paired before-after measurements, and more common outcome measures can minimize sample size requirements. If these approaches are not satisfactory, then a multicenter trial may be in order.


Development of particle induced gamma-ray emission methods for nondestructive determination of isotopic composition of boron and its total concentration in natural and enriched samples.
We report simple particle induced gamma-ray emission (PIGE) methods using a 4 MeV proton beam for simultaneous and nondestructive determination of the isotopic composition of boron ((10)B/(11)B atom ratio) and total boron concentrations in various solid samples with natural isotopic composition and enriched with (10)B. It involves measurement of prompt gamma-rays at 429, 718, and 2125 keV from (10)B(p,αγ)(7)Be, (10)B(p, p'γ)(10)B, and (11)B(p, p'γ)(11)B reactions, respectively. The isotopic composition of boron in natural and enriched samples was determined by comparing peak area ratios corresponding to (10)B and (11)B of samples to natural boric acid standard. An in situ current normalized PIGE method, using F or Al, was standardized for total B concentration determination. The methods were validated by analyzing stoichiometric boron compounds and applied to samples such as boron carbide, boric acid, carborane, and borosilicate glass. Isotopic compositions of boron in the range of 0.247-2.0 corresponding to (10)B in the range of 19.8-67.0 atom % and total B concentrations in the range of 5-78 wt % were determined. It has been demonstrated that PIGE offers a simple and alternate method for total boron as well as isotopic composition determination in boron based solid samples, including neutron absorbers that are important in nuclear technology.


Inhibition of cytochromes P450 by nitric oxide and a nitric oxide-releasing agent.
The effect of nitric oxide (NO) on cytochrome P450-mediated benzyloxyresorufin and ethoxyresorufin O-dealkylase activity of rat hepatic postmitochondrial (S-9) or microsomal subfractions, or purified rat liver CYP2B1, was examined. Two distinct inhibitory phases were observed regardless of whether the NO was added prior to initiation of the reactions with NADPH or during the course of substrate turnover. The first was a reversible inhibition characterized by complete cessation of catalytic activity, the duration of which was NO concentration-dependent with an IC50 in the range of 8-60 microM. This phase was followed by a second, irreversible, inhibitory phase characterized by a varying extent of recovery of activity, with inhibition ranging from < 1 to approximately 100%. The extent of this diminution in substrate conversion rate was also NO concentration-dependent, with an IC50 in the range of 13-72 microM, and could be partially abrogated by the inclusion of bovine serum albumin in the reaction mixture. Lower IC50 values for both inhibitory phases were obtained in the case of benzyloxyresorufin O-dealkylase activity than in the case of ethoxyresorufin O-dealkylase activity, suggesting a differential susceptibility to inhibition by NO for the two O-dealkylase activities. A nitric oxide-releasing compound ([Et2NN(O)NO]Na,DEA/NO) caused qualitatively similar inhibitory effects on benzyloxyresorufin O-dealkylase activity when added prior to the initiation of the reactions with NADPH, or during the course of substrate turnover. Based upon these results, it is possible that NO may play a role in the regulation of P450 activity in vivo.


Analysis of Seasonal Risk for Importation of the Mediterranean Fruit Fly, Ceratitis capitata (Diptera: Tephritidae), via Air Passenger Traffic Arriving in Florida and California.
The Mediterranean fruit fly, Ceratitis capitata (Wiedemann), is one of the most economically damaging pests in the world and has repeatedly invaded two major agricultural states in the United States, Florida and California, each time requiring costly eradication. The Mediterranean fruit fly gains entry primarily in infested fruit carried by airline passengers and, since Florida and California each receive about 13 million international passengers annually, the risk of Mediterranean fruit fly entering the United States is potentially very high. The risk of passengers bringing the pest into Florida or California from Mediterranean fruit fly-infested countries was determined with two novel models, one estimated seasonal variation in airline passenger number and the other defined the seasonal and spatial variability in Mediterranean fruit fly abundance. These models elucidated relationships among the risk factors for Mediterranean fruit fly introduction, such as amount of passenger traffic, routes traveled, season of travel, abundance of Mediterranean fruit fly in countries where flights departed, and risk of the pest arriving at destination airports. The risk of Mediterranean fruit fly being introduced into Florida was greatest from Colombia, Brazil, Panama, Venezuela, Argentina, and Ecuador during January-August, whereas primarily the risk to California was from Brazil, Panama, Colombia, and Italy in May-August. About three times more Mediterranean fruit flies were intercepted in passenger baggage at airports in Florida than California, although the data were compromised by a lack of systematic sampling and other limitations. Nevertheless, this study achieved the goal of analyzing available data on seasonal passenger flow and Mediterranean fruit fly population levels to determine when surveillance should be intensified at key airports in Florida and California.


Does body height reduction influence interpretation of lung function in COPD patients?
Vertebral deformities are prevalent in chronic obstructive pulmonary disease (COPD) patients and may cause excessive loss of height. As height is used for calculating reference values for pulmonary function tests, larger than normal height reduction could cause overestimation of lung function. In this cross-sectional study of 465 COPD patients and 462 controls, we explored how often lung function is misinterpreted due to height reduction in COPD patients, and whether the number or severity of vertebral deformities correlate with height reduction. Measured height was compared to recalled tallest height (RTH) and height calculated from arm span (ASH) to assess height reduction. Vertebral deformities were assessed from radiographs and pulmonary function was assessed using standard formulae. Height reduction was frequent in both the study and control groups, and increased with the number and severity of vertebral deformities. When using current measured height, lung function was overestimated in a significant proportion of COPD patients at relatively modest height reductions. The effects were smallest for forced expiratory volume in 1 s and forced vital capacity, and most pronounced for total lung capacity and residual volume. Therefore, we propose that in COPD patients with excessive height reduction, one might use RTH or ASH in calculating predicted values. Furthermore, such patients should be evaluated for co-existing vertebral deformities and osteoporosis.


Prenatal cocaine exposure affects the acoustic startle response in adult rat.
This study investigated whether prenatal exposure to cocaine alters reflux excitability in adulthood. Pregnant rats received 30 or 60 mg/kg/day cocaine HCl i.g. during gestational days 8-22. Vehicle-treated control rats were pair-fed/watered to rats receiving 60 mg/kg cocaine. A non-treated control group was also maintained. At parturition, litters from all four groups were surrogate fostered and then weaned at 21 days of age. In adulthood, rats were tested in an acoustic startle response (ASR) apparatus for 120 trials using a 116 dB signal on 2 consecutive days. On Day 2, subjects received a single injection of d-amphetamine sulfate s.c. (1.0 mg/kg) just prior to testing. ASR amplitude and latency were recorded. For average amplitude, significant effects for prenatal treatment were observed. Cocaine-exposed female rats demonstrated decreased ASR amplitude compared to offspring of pair-fed controls during both the initial test Session and following amphetamine administration as well. Overall, amphetamine increased startle. For latency, there were no significant treatment effects or effects of amphetamine administration. However, preplanned comparisons indicated that prenatal cocaine exposure interacted with trial block. Therefore, these data indicate that prenatal cocaine decreased startle amplitude in adults, primarily in females, and that startle-elicited amphetamine responses were dampened as well. The effects on latency indicate that amphetamine does not alter reaction times in prenatal cocaine exposed rats while it does in controls.


[A case of trigeminal neurinoma with marked extracranial extension].
A case of trigeminal neurinoma with marked extracranial extension is reported with a review of the literature. A 60-year-old female noticed numbness over the left side of the face during the proceeding 15 years. Two years prior to admission, she began to complain of itching and lancinating pain at the left lateral aspect of the nose. Neurologic examination on admission revealed diminished corneal reflex on the left side and hypesthesia in the distribution of the left trigeminal nerve. There was no weakness or atrophy of the ipsilateral masticatory muscles. The remaining cranial nerves and cerebellar functions were normal. Craniograms showed destruction of the left petrous apex, enlargement of the left superior orbital fissure and an extensive bone defect in the floor of the left middle cranial fossa. CT disclosed a huge heterogeneously enhancing mass lesion in the left middle cranial fossa, which extended posteriorly into the left cerebellopontine angle and inferiorly into the pterygoid and infratemporal fossae. Cerebral angiograms revealed medial displacement of the left internal cerebral artery in the ganglionic, cavernous and supraclinoid portions, and elevation of the left middle cerebral artery in the sphenoidal portion. Although the left meningohypophyseal trunk was dilated, no tumor stain was observed. A transantral biopsy specimen provided the diagnosis of neurinoma with Antoni type A tissue. The patient was followed up at the outpatient clinic as radical operations were not agreed upon. Eight cases of trigeminal neurinoma with extracranial extension are reviewed including the presented case. There were two males and six females, and the age varied from 16 to 65 years.(ABSTRACT TRUNCATED AT 250 WORDS)


[Magnetic resonance findings in chronic osteomyelitis fistula].
Osteomyelitis is a common inflammatory process caused by an infection which is usually from gram-positive germs. Acute, subacute and chronic forms can be distinguished both clinically and radiographically, each of them presenting different patterns but which are not always easy to recognize. Besides clinical-laboratory data, imaging methods are also useful to make the diagnosis; in chronic forms, MRI has higher sensitivity in recognizing the active foci and the presence of sinus tracts than the other techniques. We examined nine patients with suspected chronic osteomyelitis with a sinus tract, all of them submitted to radiographic and MR examinations. MRI was performed with a .5 T magnet using a surface coil for joint studies; T1-weighted SE (TR 300-500, TE 20), T2-weighted GE (TR 500-700, TE 20, FA 35 degrees) and FIR sequences with fat suppression (TR 3000, TE 20, TI 100) were performed on the axial, sagittal and coronal planes. Three patients underwent CT too. Radiography showed the osteostructural changes as osteolytic and osteosclerotic areas. CT depicted not only the changes seen radiographically, but also increased bone marrow density. MRI demonstrated active foci of bone marrow appearing as low-intensity areas in T1, with increased intensity in T2 GE and fat-suppressed FIR images; it also depicted the sinus tracts as areas of decreased signal on T1 and of increased signal on FIR images. Based on our experience and in agreement with the literature data, we believe that MRI is more useful to diagnose the active foci of bone marrow and the sinus tracts in chronic osteomyelitis, especially with T1-weighted SE and fat-suppressed FIR sequences.


Early prognosis in traumatic tetraplegia.
This is a retrospective study of 18 acute traumatic tetraplegic patients admitted to the Cardiff Royal Infirmary within 12 hours of injury. The nursing charts of pulse rate, blood pressure and respiratory rate were scrutinized and the mean values over a 24-hour period were plotted against outcome with regard to mortality and respiratory complications. A systolic blood pressure below 115 mmHg was found to be associated with a high morbidity and mortality. A hypothesis is advanced that this finding is related to autonomic imbalance.


Astronomical infrared telescopes.
Consideration is given to the requirements on the image quality and potential gain in observing efficiency with large infrared telescopes. It is concluded that such large instruments cannot be light buckets with poor image quality. Specific engineering designs of large instruments should be undertaken to determine designs and costs associated with producing large instruments with image quality less than 2 see of arc. It is important that such instruments be built so that the field of infrared astronomy can be extended to the detection of fainter infrared sources. The question of optimum size of telescopes from the point of view of information gained per dollar is considered. If such a most economical size exists, it is certainly much larger than presently existing 1.5-m (60-in.) infrared telescopes.


USE OF OPTICAL COHERENCE TOMOGRAPHY IN DETECTION OF CYSTOID MACULAR EDEMA AFTER TREATMENT WITH NONSTEROIDAL ANTI-INFLAMMATORY DRUGS.
The aim of the study was to determine the correlation between implanted IOL material type to detect CME after NSAID use in cataract surgery. Study involved 94 eyes of 72 patients. Eyes were equally divided into two groups (n-47 in each). Post-operatively treatment regimen for participants from Group I included antibiotic and NSAID eye drops, while participants from group II were treated only with antibiotic eye drops. Acrylic hydrophobic intraocular lens (IOL) was implanted in all patients comprising both groups. No patient developed cystoid macular edema from either group (CME). In both groups (with or without NSAID eye drops cover) mean central retinal thickness (CRT) was 230±0.005 microns before the surgery. No statistically significant changes of CRT was noted in both groups (5± 0.09 microns ) (p<0.5). Study analysis has shown, that cystoid macular edema has not developed in patients, who underwent uncomplicated cataract surgery with hydrophobic IOL implantation, with or without NSAID eye drop cover. There was no statistically and clinically significant difference between the groups in terms of CRT. Implantation of acrylic hydrophobic intraocular lens(IOL) has shown to provide high uveal biocompatibility. Major risk factors of CME in cataract surgery are intraoperative surgical complications. Certain systemic and local ophthalmic diseases, as well as topical use of prostaglandin analogs are also strongly linked to postoperative CME development. In conclusion, usage of NSAID eye drops in combination with antibiotic regimen in eyes undergoing cataract surgery, showed to have a beneficial effect on prevention of postoperative CME.


Influence of pitch, timbre and timing cues on melodic contour identification with a competing masker (L).
Pitch, timbre, and/or timing cues may be used to stream and segregate competing musical melodies and instruments. In this study, melodic contour identification was measured in cochlear implant (CI) and normal-hearing (NH) listeners, with and without a competing masker; timing, pitch, and timbre cues were varied between the masker and target contour. NH performance was near-perfect across different conditions. CI performance was significantly poorer than that of NH listeners. While some CI subjects were able to use or combine timing, pitch and/or timbre cues, most were not, reflecting poor segregation due to poor spectral resolution.


Growth patterns in the first three years of life in children with classical congenital adrenal hyperplasia diagnosed by newborn screening and treated with low doses of hydrocortisone.
Linear growth is the best clinical parameter for monitoring metabolic control in classical congenital adrenal hyperplasia (CAH). to analyze growth patterns in children with CAH diagnosed by newborn screening and treated with relatively low doses of hydrocortisone during the first year of life. 51 patients (27 females) were diagnosed with classical CAH by newborn screening. All patients were treated with relatively low doses of hydrocortisone (9-15 mg/m(2) body surface area). 47 patients were additionally treated with fludrocortisone. at birth, height SDS (H-SDS) was 1.1 ± 1 in girls and 0.9 ± 1.5 in boys. After 3 months, H-SDS decreased to 0.4 ± 0.9 in girls and to 0.1 ± 1.3 in boys. Over the 3-year period, H-SDS further decreased to -0.4 ± 1.8 in girls and to -0.8 ± 1 in boys and approached the genetic height potential (target H-SDS of girls -0.5 ± 0.3 and target H-SDS of boys -0.9 ± 0.7). During the first 9 months of age, growth velocity was slightly decreased in girls (18.2 ± 1.9 cm) and boys (17.3 ± 1.6 cm) when compared to a healthy reference population (girls 19.0 ± 3.9 cm and boys 18.7 ± 4.7 cm). At the age of 3 years, bone age was appropriate for chronological age in both girls (2.7 ± 0.5 years) and boys (2.9 ± 0.5 years). birth length is above average in children with classical CAH, which might be the result of untreated hyperandrogenism in utero. With relatively low doses of hydrocortisone treatment, growth velocity decreases slightly during the first 9 months and H-SDS then approaches the genetic height potential.


Premalignant quiescent melanocytic nevi do not express the MHC class I chain-related protein A.
The MHC class I chain-related protein A (MICA) is an inducible molecule almost not expressed by normal cells but strongly up-regulated in tumor cells. MICA-expressing cells are recognized by natural killer (NK) cells, CD8+ abTCR and gdTCR T lymphocytes through the NKG2D receptor. Engagement of NKG2D by MICA triggers IFN-g secretion and cytotoxicity against malignant cells. Although most solid tumors express MICA and this molecule is a target during immune surveillance against tumors, it has been observed that high grade tumors from different histotypes express low amounts of cell surface MICA due to a metalloprotease-induced shedding. Also, melanomas develop after a complex process of neotransformation of normal melanocytes. However, the expression of MICA in premalignant stages (primary human quiescent melanocytic nevi) remains unknown. Here, we assessed expression of MICA by flow cytometry using cell suspensions from 15 primary nevi isolated from 11 patients. When collected material was abundant, cell lysates were prepared and MICA expression was also analyzed by Western blot. We observed that MICA was undetectable in the 15 primary nevi (intradermic, junction, mixed, lentigo and congenital samples) as well as in normal skin, benign lesions (seborrheic keratosis), premalignant lesions (actinic keratosis) and benign basocellular cancer. Conversely, a primary recently diagnosed melanoma showed intense cell surface MICA. We conclude that the onset of MICA expression is a tightly regulated process that occurs after melanocytes trespass the stage of malignant transformation. Thus, analysis of MICA expression in tissue sections of skin samples may constitute a useful marker to differentiate between benign and malignant nevi.


β-hCG-induced mutant BRCA1 ignites drug resistance in susceptible breast tissue.
β-hCG expression in breast cancer is highly controversial with reports supporting both protective and tumorigenic effects. It has also been reported that risk of breast cancer at an early age is increased with full-term pregnancies if a woman is a BRCA1 mutation carrier. We have already demonstrated that BRCA1-defective cells express high levels of β-hCG and that when BRCA1 is restored, β-hCG level is reduced. Also, BRCA1 can bind to the promoter and reduce the levels of β-hCG. β-hCG induces tumorigenicity in BRCA1-defective cells by directly binding to TGFBRII and induces TGFBRII-mediated cell proliferation. In this study, we analyzed the mechanism of action of β-hCG on BRCA1 expression and its influence on drug sensitivity in breast cancer cells. We demonstrate that β-hCG induces mutant BRCA1 protein expression in BRCA1 mutant cells; however, in BRCA1 wild-type cells, β-hCG reduced wild-type BRCA1 protein expression. Transcriptionally, β-hCG could induce Slug/LSD1-mediated repression of wild-type and mutant BRCA1 messenger RNA levels. However, β-hCG induces HSP90-mediated stabilization of mutant BRCA1 and hence the overexpression of mutant BRCA1 protein, resulting in partial restoration of homologous recombination repair of damaged DNA. This contributes to drug resistance to HSP90 inhibitor 17AAG in BRCA1-defective cancer cells. A combination of HSP90 inhibitor and TGFBRII inhibitor has shown to sensitize β-hCG expressing BRCA1-defective breast cancers to cell death. Targeting the β-hCG-HSP90-TGFBRII axis could prove an effective treatment strategy for BRCA1-mutated breast tumors.


Cardioprotective effect of saffron extract and safranal in isoproterenol-induced myocardial infarction in wistar rats.
This study was designed to evaluate the cardioprotective effect of Crocus sativus L. (saffron) aqueous extract and safranal, the major constituent of the essential oil of saffron, on lipid peroxidation, biochemical parameters and histopathological findings in isoproterenol (ISO)-induced myocardial infarction in Wistar rats. The saffron extract (20, 40, 80 and 160 mg/kg/day IP) or control were administered for 9 days along with ISO (85 mg/kg, SC, at 24 hr interval) on 8th and 9th day in rats. Activities of creatine kinase-muscle, brain (CK-MB) and lactate dehydrogenase (LDH) were measured using standard commercial kits. The level of malondialdehyde in heart tissue was estimated with thiobarbituric acid reactive species test. For histopathological examination, hematoxylin and eosin (H&E) staining was used. ISO administration induced a statistically significant increase (P< 0.001) in serum LDH and CK-MB and a significant increase (P< 0.001) in the levels of thiobarbituric acid reactive substances (TBARs) in the heart as compared to vehicle control rats. Saffron pretreatment (20, 40, 80 and 160 mg/kg IP) or safranal pretreatment (0.025, 0.050, 0.075 ml/kg IP) for 8 days, significantly decreased (P< 0.001) the serum LDH and CK-MB and myocardial lipid peroxidation as compared to ISO- induced rats. Histological findings of the heart sections confirmed myocardial injury with ISO administration and preserved nearly normal tissue architecture with saffron or safranal pretreatment. Saffron and safranal may have cardioprotective effect in ISO-induced myocardial infarction through modulation of oxidative stress in such a way that they maintain the redox status of the cell.


Incidence of Daytime Sleepiness and Associated Factors in Two First Nations Communities in Saskatchewan, Canada.
Excessive daytime sleepiness (EDS) is the tendency to sleep at inappropriate times during the day. It can interfere with day-to-day activities and lead to several health issues. The objective of this study was to investigate the association between income, housing conditions, and incidence of EDS in adults living in two Cree First Nations communities. The data for this study involved 317 individuals aged 18 years and older who participated in baseline and follow-up evaluations (after four years) of the First Nations Lung Health Project, which was conducted in Saskatchewan in 2012-2013 and 2016. Both at baseline and follow-up survey after four years, an Epworth Sleepiness Scale (ESS) score >10 was considered to be abnormal. Logistic regression models were used to assess relationships between abnormal ESS and covariates at baseline. In 2016, 7.6% (24/317) of the participants reported an ESS >10 with the mean being 12.8 ± 2.0. For the same group, the mean ESS at baseline was 6.9 ± 2.2. The incidence of subjective EDS based on the ESS >10 was estimated at 7.6% over four years. This study showed an association between incidence of subjective EDS and less money left over at end of the month, having a house in need of repairs, having water or dampness in the past 12 months, and damage caused by dampness.


A possible role for CCL27/CTACK-CCR10 interaction in recruiting CD4 T cells to skin in human graft-versus-host disease.
Graft-versus-host disease (GvHD) is a serious complication of allogeneic stem cell transplantation (SCT) affecting the skin, gut and liver. The involvement of distinct organs suggests a role for tissue-specific chemokines and their receptors in directing activated donor T cells to these sites. In this study the potential involvement of the skin-specific CCL27/CTACK-CCR10 interaction was investigated in 15 paediatric SCT patients with skin GvHD. During the course of skin GvHD, peripheral blood T cells from these patients contained a high proportion of CD4+ CCR10+ T cells that disappeared after the GvHD was resolved. These cells were CD45RO+, expressed additional skin homing markers (cutaneous lymphocyte-associated antigen and CCR4), and produced the T-cell helper type 1-cytokines tumour necrosis factor-alpha and interleukin-2. The increase in CD4+ CCR10+ T cells was absent in SCT patients without GvHD. Immunohistochemical investigations showed CD4+ CCR10+ T cells in the GvHD skin biopsies of the same patients, but not in the gut biopsies of patients also suffering from gut GvHD. The infiltration of CD4+ CCR10+ T cells in the GvHD-affected skin correlated with an enhanced epidermal expression of CCL27/CTACK, the ligand for CCR10. These findings support the involvement of CCL27/CTACK-CCR10 interaction in recruiting CD4+ T cells to the skin, thus contributing to the pathogenesis of acute GvHD.


ICEA of Mycoplasma agalactiae: a new family of self-transmissible integrative elements that confers conjugative properties to the recipient strain.
Horizontal gene transfer (HGT) is a major force of microbial evolution but was long thought to be marginal in mycoplasmas. In silico detection of exchanged regions and of loci encoding putative Integrative Conjugative Elements (ICE) in several mycoplasma genomes challenged this view, raising the prospect of these simple bacteria being able to conjugate. Using the model pathogen Mycoplasma agalactiae, we demonstrated for the first time that one of these elements, ICEA, is indeed self-transmissible. As a hallmark of conjugative processes, ICEA transfers were DNase resistant and required viable cells. ICEA acquisition conferred ICE-negative strains with the new ability to conjugate, allowing the spread of ICEA. Analysis of transfer-deficient mutants indicated that this process requires an ICEA-encoded lipoprotein of unknown function, CDS14. Formation of a circular extrachromosomal intermediate and the subsequent chromosomal integration of ICEA involved CDS22, an ICEA-encoded product distantly related to the ISLre2 transposase family. Remarkably, ICEA has no specific or no preferential integration site, often resulting in gene disruptions. Occurrence of functional mycoplasma ICE offers these bacteria with a means for HGT, a phenomenon with far-reaching implications given their minute-size genome and the number of species that are pathogenic for a broad host-range.


Different cytokines induce surface lymphotoxin-alphabeta on IL-7 receptor-alpha cells that differentially engender lymph nodes and Peyer's patches.
The formation of lymph nodes (LN) and Peyer's patches (PP) can be distinguished by the requirement of RANK for LN but not IL-7R(alpha), which is essential for PP development. However, lymphotoxin-alphabeta (LT(alpha)beta) signaling is required for both organs. The cellular basis underlying this dichotomy was revealed by the finding that the fetal IL-7R(alpha)(+) population responded equally well to IL-7 and RANKL to express LT(alpha)beta. IL-7R(alpha)(+) cells harvested from TRAF6(-/-) embryos expressed LTalphabeta in response to IL-7 but not RANKL, demonstrating that the RANK-TRAF6 signaling pathway regulates LT(alpha)beta expression in LN but not in PP. Soluble IL-7 administered to TRAF6(-/-) embryos was sufficient to restore LN genesis indicating the functional similarities of the IL-7R(alpha)(+) inducer cells for LN and PP genesis.


[Analysis of varieties and standards of Composite medicinal plants used in Dai medicine].
The study aims to analyze the varieties and standards of compositae medicinal plants used in Dai medicine. The results showed that there were 78 species (including varieties) compositae plants recorded in literatures, which belongs to 63 medicinal materials varieties. And 47 original plants (60.25%) were recorded in Chinese medicinal material standards. In those standards and literatures of Dai medicine, there are great differences in translated Chinese names, original plants, medicinal parts, and efficacy of medicinal plants. Therefore, the variety systematization and the quality standards of Dai medicine should be strengthened.


Testing three evolutionary models of the demographic transition: Patterns of fertility and age at marriage in urban South India.
Over the last three decades many authors have addressed the demographic transition from the perspective of evolutionary theory. Some authors have emphasized parental investment factors such as the costs of raising children, others have emphasized the effects of mortality and other forms of risk, and others have emphasized the biased transmission of cultural norms from people of high status. Yet the literature says little about the relative strengths of each of these types of motivations or about which ones are more likely to serve as the primary impetus for large-scale demographic change. In this paper, I examine how each of these factors has influenced the demographic transition in urban South India during the course of the 20th century using two measures of fertility transition: number of surviving children and age at marriage. I find that investment-related, risk-related, and cultural transmission predictors all have significant individual effects on the outcome variables, which persist when they are entered in combination. When the three types of predictors are compared, however, investment-related models appear to provide more robust explanations for patterns in both fertility and age of marriage.


Effects of SR 49059, a new orally active and specific vasopressin V1 receptor antagonist, on vasopressin-induced vasoconstriction in humans.
We have evaluated the efficacy of SR 49059, a new orally active and specific vasopressin V1 receptor antagonist (arginine-vasopressin [AVP]), in the blockade of the vascular effects of exogenous AVP in healthy subjects. In preliminary experiments, two procedures to measure the V1 vascular effects of AVP were assessed. First, the AVP-induced changes in skin blood flow were investigated by the injection of increasing doses of AVP intradermally, with or without a previous local vasodilation with calcitonin gene-related peptide (CGRP). In a second protocol, AVP was infused intra-arterially, and the changes in radial artery diameter and blood flow were measured. The intradermal injection of AVP caused significant decreases in skin blood flow, and the use of CGRP increased the sensitivity of the method by a factor of 10(2) to 10(3). AVP infused intra-arterially caused dose-dependent decreases in the radial artery diameter and blood flow. In the main study, the potency and efficacy of SR 49059 to block the AVP-induced changes in skin blood flow were assessed in 12 healthy men with a double-blind, triple crossover study design. The subjects were randomized to receive a placebo orally and 30 mg and 300 mg of the antagonist at a 1-week interval. The subjects were then further randomized to evaluate the efficacy of the same doses of the antagonist to block the vasoconstriction of the radial artery induced by an intra-arterial infusion of AVP. SR 49059 inhibits, dose-dependently and significantly, the AVP-induced changes in skin blood flow, with a peak effect occurring between 2 and 6 hours after injection. In addition, the 300-mg dose of SR 49059 completely blocked the vasoconstriction of the radial artery induced by AVP. In conclusion, skin blood-flow measurement, after intradermal injection of AVP on a skin area vasodilated with CGRP, is an effective method to investigate the V1 vascular effect of AVP in humans. SR 49059 is a potent and specific antagonist of V1 receptors, which blocks the AVP-induced vasoconstriction.


Identification of key candidate genes in neuropathic pain by integrated bioinformatic analysis.
This study aimed to disclose differentially expressed genes (DEGs) in dorsal root ganglia (DRGs) of neuropathic pain (NP) from spared nerve injury (SNI) model, thereby identifying specific and meaningful genetic targets for the diagnosis and treatment of NP. The GSE89224 was downloaded from the GEO database. DEGs were screened using the GEO2R online tool. Functional enrichment analysis of DEGs was then performed using the DAVID and constructed using the R ggplot2 package. Protein-protein interaction (PPI) network was constructed from the STRING database and visualized in Cytoscape software. MicroRNA targeting these DEGs was obtained from the TarBase and miRTarBase database, while transcription factor (TF)-targeting DEGs were predicted from the ENCODE database, both of which utilized the visual analytics platform NetworkAnayst. Finally, a merged microRNA-TF network was constructed based on the above two networks and was then analyzed with Cytoscape. Eighty DEGs were screened, only Vstm2b and Htr3a were downregulated and 78 genes were upregulated. The real-time polymerase chain reaction was applied to validate the gene expression of the top five DEGs (Npy, Atf3, Gpr151, Sprr1a, and Cckbr) in the DRG tissue 5 days after SNI surgery. It was found that Npy, Atf3, and Sprr1a have a significant increase after SNI stimulation, while Gpr151 and Cckbr showed a slight upward trend. Functional analysis was performed on all DEGs, of which 58 biological processes were enriched by gene ontology analysis, and 11 signaling pathways were enriched by KEGG analysis. In the PPI network, Atf3, Jun, Timp, and Npy had a higher degree. Thus, combined with various bioinformatic analyses, Npy and Atf3 may serve as the prognostic and therapeutic targets of NP. Key microRNA (mmu-mir-16-5p) and TF (MEF2A) were predicted to be associated with the pathogenetic process of NP with microRNA-TF regulatory network analysis, which were also identified as key regulators in the progression of NP.


Management of patients with monkeypox virus infection and contacts in the community and in healthcare settings: a French position paper.
Since April 2022, a large number of monkeypox (MPX) cases have emerged across the globe in regions that are known to be totally free of zoonotic reservoir. The High Council for Public Health is a national institute commissioned to provide guidelines to the French Ministry of Health. The objective of these guidelines and recommendations is to inform the public, people at risk of severe MPX infection, infected patients and their families and contacts and healthcare workers in charge of infected patients. A review of the literature from the MEDLINE database was carried out using the single keyword 'monkeypox', including recent and older articles from January 2000 to June 2022. There was no filter for the type of study, except English language. The titles and summaries of all the articles were read by the experts to select articles of interest. The High Council for Public Health brought together specialists with expertise in the field to analyse the scientific literature and international recommendations. Recommendations were classified with clinical practice methodology using four levels (strong recommendation, recommendation, optional recommendation and no recommendation) without grading the level of evidence. To develop and methodologically validate the recommendations, the Appraisal of Guidelines for Research and Evaluation Instrument (AGREE-II)chart was partially used. QUESTIONS ADDRESSED BY THE GUIDELINES AND RECOMMENDATIONS: (a) What are the therapeutic management measures for hospitalized patients with severe forms of MPX infection, and what are the preventive measures to protect healthcare professionals? (b) What are the isolation and prevention measures in the community for patients with mild or moderate severity MPX infection? (c) what are the preventive measures for contacts of an MPX-infected person? (d) Who should be vaccinated? (e) What are the specific prevention measures for children and schools?


Handgrip-induced negative U-wave in electrocardiogram of hypertensive subjects.
To study clinical significance and possible mechanism of negative U-wave observed in hypertensive patients, we applied handgrip test (HG) to 35 patients with hypertension and 20 age-matched normal subjects. HG was sustained for 3 min at 50% of maximum voluntary contraction. ECG recording and measurement of blood pressure were made before, during, and after HG. During HG, systolic blood pressure was 188.7 +/- 3.4 mmHg (mean +/- SE) and diastolic blood pressure was 114.8 +/- 2.1 mmHg in hypertensives, while 145.3 +/- 2.6 mmHg and 93.8 +/- 1.1 mmHg in normals; the difference between hypertensives and normals was statistically significant (p less than 0.001). Incidence of HG-induced negative U-wave was 0% in normals, while 68.6% in hypertensives. In hypertensive subjects, HG-induced negative U-wave appeared in 24 of the 28 patients (85.7%) with minimum to moderate left ventricular hypertrophy shown by ECG and/or UCG findings (QRS-T angle greater than 130 degrees with left high voltage: left ventricular wall thickness greater than 12 mm). Further we recorded UCG during HG in 14 subjects. In 4 patients, negative U waves appeared simultaneously with increase in left ventricular dimension during diastole. In the remaining 10 cases that included both normals and hypertensives, however, neither increase in left ventricular end diastolic dimension nor negative U waves were observed. Thus we conclude that HG-induced negative U waves may be caused by stretch of the ventricular wall resulting from acute left ventricular volume overload.


The benefits of treating hyperlipidemia to prevent coronary heart disease. Estimating changes in life expectancy and morbidity.
To evaluate the lifetime benefits of reducing total serum cholesterol levels to prevent coronary heart disease (CHD). We developed a CHD primary prevention computer model to estimate the benefits associated with lifelong risk factor modification. We validated the model by comparing the computer estimates with the observed results of three primary CHD prevention trials. Men and women age 35 to 65 years who are free of CHD, with total serum cholesterol levels ranging from 5.2 to 7.8 mmol/L (200 to 300 mg/dL), with or without additional CHD risk factors. Serum cholesterol reduction through dietary modification or diet and medications. Changes in life expectancy and the delay of symptomatic CHD. The computer forecasts for CHD end points closely matched the observed results of the Lipid Research Clinics Trial, the Helsinki Heart Study, and MRFIT. We then applied the computer model to low-risk and high-risk men and women with total serum cholesterol levels between 5.2 and 7.8 mmol/L (200 and 300 mg/dL) and estimated that, after reducing serum cholesterol levels 5% to 33%, the average life expectancy would increase by 0.03 to 3.16 years. We also forecast that the average onset of symptomatic CHD would be delayed among these patient groups by 0.06 to 4.98 years. We conclude that this computer model accurately estimates the results of clinical trials and can be used to forecast the changes in life expectancy and morbidity (the development of CHD) associated with specific CHD risk reduction interventions. The wide variation surrounding these estimates underscores the need to better define which groups of individuals will gain the most from cholesterol reduction.


Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody.
T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM-3) blunts anticancer immunity and mediates resistance to programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors. We assessed a novel, first-in-class, TIM-3 mAb, LY3321367, alone or in combination with the anti-PD-L1 antibody, LY300054 in patients with advanced solid tumor. This open-label, multicenter, phase Ia/b study aimed to define the safety/tolerability and recommended phase II dose (RP2D) of LY3321367 with or without LY300054. Secondary objectives included pharmacokinetics/pharmacodynamics, immunogenicity, and efficacy. Biomarkers were assessed in exploratory analysis. No dose-limiting toxicities were observed in the monotherapy (N = 30) or combination (N = 28) dose escalation. LY3321367 treatment-related adverse events (≥2 patients) included pruritus, rash, fatigue, anorexia, and infusion-related reactions. Dose-proportional increase in LY3321367 concentrations was not affected by either LY300054 or antidrug antibodies (observed in 50%-70% of patients). Pharmacokinetic/pharmacodynamic modeling indicated 100% target engagement at doses ≥600 mg. LY3321367 RP2D was 1,200 mg biweekly for four doses followed by 600 mg every 2 weeks thereafter. In the non-small cell lung cancer monotherapy expansion cohort, outcomes varied by prior anti-PD-1 therapy response status: anti-PD-1/L1 refractory patients [N = 23, objective response rate (ORR) 0%, disease control rate (DCR) 35%, progression-free survival (PFS) 1.9 months] versus anti-PD-1/L1 responders (N = 14, ORR 7%, DCR 50%, PFS 7.3 months). In combination expansion cohorts (N = 91), ORR and DCR were 4% and 42%; CD8 infiltration in paired biopsies increased in approximately half these patients. LY3321367 exhibited acceptable safety profile with favorable pharmacokinetics/pharmacodynamics but only modest antitumor activity. The therapeutic relevance of TIM-3 blockade requires further investigation.


Inhibition of the HIV-1 and HIV-2 proteases by a monoclonal antibody.
The monoclonal antibody 1696, directed against the HIV-1 protease, displays strong inhibitory effects toward the catalytic activity of the enzyme of both the HIV-1 and HIV-2 isolates. This antibody cross-reacts with peptides that include the N-terminus of the enzyme, a region that is well conserved in sequence among different viral strains and which, furthermore, is crucial for homodimerization to the active enzymatic form. This observation, as well as antigen-binding studies in the presence of an active site inhibitor, suggest that 1696 inhibits the HIV protease by destabilizing its active homodimeric form. To characterize further how the antibody 1696 inhibits the HIV-1 and HIV-2 proteases, we have solved the crystal structure of its Fab fragment by molecular replacement and refined it at 3.0 A resolution. The antigen binding site has a deep cavity at its center, which is lined mainly by acidic and hydrophobic residues, and is large enough to accommodate several antigen residues. The structure of the Fab 1696 could form a starting basis for the design of alternative HIV protease-inhibiting molecules of broad specificity.


Novel molecular imaging in lung and pleural diseases.
Molecular imaging provides an opportunity to study biological processes in vivo. Specific molecular 'probes' are labelled with radioactive tracers, and imaging is carried out using either PET or gamma-cameras. The imaging is quantitative, and therefore the activity of a specific biological process (e.g. metabolism or proliferation) can be numerically assessed, which may be important for prognosis or therapy monitoring. The use of molecular imaging may lead to the development of a 'molecular profile' of a disease, therefore facilitating individualization of therapy and rational treatment approaches. This review article summarizes the most commonly used molecular imaging agents and their role in lung and pleural diseases. This is a rapidly developing field as new targets and imaging probes are being developed and as their clinical roles are being established.


Adenosquamous carcinoma with different morphologic and histologic components arising from the intrahepatic bile duct: report of a case.
A very rare form of adenosquamous carcinoma arising from the intrahepatic bile duct which had diverse morphologic and histologic components is presented. A 77-year-old female complained of relapsing febrile attack accompanied by upper abdominal pain. From the imaging studies, which revealed an atrophic left lobe with dilated intrahepatic bile duct, cholangiocarcinoma constricting the orifice of B3 was considered the most likely diagnosis. Surgery, which included resection of the left hepatic and caudate lobes with lymph node dissection, revealed an atrophic lateral segment indicating recurrent inflammation. Pathologic examination revealed a combined tumor composed of papillary squamous cell carcinoma arising at the orifice of the lateral inferior segmental bile duct and intramucosal adenocarcinoma spreading distal to the polypoid tumor. Two different components were connected with a thin stalk, but there was no apparent transitional zone. Contrary to ordinary mass-forming adenosquamous carcinoma in the liver, which is reported to pursue a very rapid, fatal course, our patient made an uneventful recovery and has remained in good health without recurrence for 2 years and 3 months since surgery.


A Case of Neuroendocrine Cell Carcinoma with Sigmoidovesical Fistula.
Colonic neuroendocrine cell carcinoma (NEC), which is a rare subtype of colon epithelial neoplasm, has been reported to show extremely aggressive characteristics with a 1-year survival rate of 20%. We report herein a resected case of NEC that manifested bacterial sepsis due to sigmoidovesical fistula. Staged surgery consisted of resecting the sigmoid colon and part of the bladder four weeks after construction of an ileostomy to alleviate septic shock. The resected specimen was histologically diagnosed as NEC invading the wall of the urinary bladder with metastasis to the regional lymph nodes. The patient underwent four cycles of FOLFOX after surgery for additional treatment of residual metastatic lymph nodes around the abdominal aorta diagnosed preoperatively. Although the patient showed stable disease measured by computed tomography scan for the first three months after surgery, he rejected additional chemotherapy thereafter, and died ten months after the initial admission due to progression of residual tumor in the urinary bladder as well as the lymph nodes. This is the first case report describing colonic NEC manifesting perforation into the urinary bladder. Although the optimal chemotherapeutic regimen for colonic NEC has not yet been established, FOLFOX may be one of the choices.


Therapy of bacterial vaginosis using exogenously-applied Lactobacilli acidophili and a low dose of estriol: a placebo-controlled multicentric clinical trial.
The efficacy of vaginal tablets (Gynoflor) containing 50 mg of a lyophilisate of viable, H2O2-producing Lactobacillus acidophilus (at least 10(7) colony forming units/tablet) and 0.03 mg estriol (CAS 50-27-1) for the treatment of bacterial vaginosis (BV) was tested in a multicentric, randomised, placebo-controlled clinical trial with parallel-group design. 32 non-menopausal women with positive diagnoses for BV, including intermediate cases, participated in the trial. Patients were diagnosed using the classical clinical parameters of BV according to Amsel and using microscopic analysis of the Gram-stained vaginal smear. A positive clinical diagnosis of BV required at least 2 of the following 4 clinical criteria to be positive; greyish-white, homogeneous leukorrhea; vaginal pH > 4.5; KOH test for volatile amines; presence of clue cells. Microscopic diagnosis of BV, on the other hand, was obtained if examination of the Gram-stained vaginal smear showed less than 6 lactobacilli per field of view (1000 x magnification). This corresponds to another definition of BV as "lactobacilli deficiency syndrome". The efficacy of the 6-day therapy with 1-2 vaginal tablets daily was evaluated using both clinical and microscopic analysis. Using Amsel's classical clinical parameters of BV, the cure rate (defined as < or = 1 of the 4 clinical criteria positive) two weeks after the start of therapy was 77% in the verum group and 25% in the placebo group. Four weeks after the start of therapy, the cure rate was 88% in the verum group and 22% in the placebo group. At both control examinations, the cure rate for the test group was significantly higher than that for the placebo group (p < 0.05, Fisher's exact test, 2-sided, significance level 0.05). In addition, the trial showed that after 6 days of treatment with the test preparation, the lactobacilli were capable of recolonising the vagina. A significant increase in the number of lactobacilli was observed in the Gram-stained vaginal smear for the patient group treated with the test preparation compared to the placebo patient group (p < 0.05, Fisher's exact test, 2-sided, significance level 0.05), two and four weeks after the start of the 6-day treatment.


Retroperitoneal ancient schwannoma involving the renal hilum.
Schwannomas, a soft-tissue tumor of a Schwann cell, involving the kidney are rare, with few cases available in the literature. Herein, we report a case of a rare variant, an ancient schwannoma of the renal hilum.


Hydrophobic alkyl headgroups strongly promote membrane curvature and violate the headgroup volume correlation due to "headgroup" insertion.
The ability of lipid aggregates to form planar bilayers, rather than highly curved micellar or inverted structures, is dependent on the relative geometries of the headgroup and hydrocarbon regions. The headgroup volume approach to lipid structure provided a quantitative link between a lipid's headgroup size and its ability to promote curved, inverted hexagonal (H(II)) structures in a phosphatidylethanolamine (PtdEtn) matrix [Lee et al. (1993) Biophys. J. 65, 1429-1432]. Phosphatidylalkanols (PtdAlks) are shown here to promote curvature with a potency that far exceeds and a chain length dependence contrary to the expectations of the headgroup volume approach, suggestive of an atypical alkyl "headgroup" conformation. A homologous series of 3-substituted triacylglycerols (TAGs), for which 3-acyl "headgroup" insertion is established, exhibits a chain length dependence similar to the PtdAlks, evidence that the deviation is of common origin. The potency of the TAGs to promote curvature is unprecedented, and the onset of saturation, which parallels the dramatic promotion of curvature, occurs at mole fractions as low as 0.0025. The potency of the PtdAlks or TAGs to promote curvature exceeds that of all mammalian phospholipids examined. Thermodynamic analysis implicates the enthalpic curvature stress imparted upon the membrane matrix as the dominant energetic factor. The imparted stress ranges from -930 J mol(-1) for phosphatidylcholine to +7.5 kJ mol(-1) for 3-palmitoyl TAG. The results affirm the geometric considerations of membrane structure and indicate that alkyl headgroups tend to insert into the bilayer and increase the enthalpic curvature stress within the membrane.


Genetic variants in interleukin genes and susceptibility to IgA nephropathy: a meta-analysis.
Many existing studies have demonstrated that genetic variants in interleukin (IL) genes might have an impact on an individual's susceptibility to IgA nephropathy (IgAN); but individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the relationships between IL genetic variants and IgAN risk. We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and China BioMedicine (CBM) and China National Knowledge Infrastructure (CNKI) databases from inception through August 1, 2013. Meta-analysis was performed using the STATA 12.0 software. Seven case-control studies were included with a total of 1135 IgAN patients and 1603 healthy controls. Our meta-analysis results revealed that genetic variants in IL-1 and IL-1RN genes were associated with an increased risk of IgAN. However, similar associations were not observed in IL-6, IL-10, and IL-22R genes. Subgroup analysis by ethnicity suggested that there were significant associations between IL genetic variants and an increased risk of IgAN among both Asian and Caucasian populations. Meta-regression analyses showed that gene types may be a major source of heterogeneity. No publication bias was detected in this meta-analysis. The present meta-analysis suggests that IL genetic variants may contribute to the risk of IgAN, especially in IL-1 and IL-1RN genes.


Population pharmacokinetics of 3,4-methylenedioxymethamphetamine and main metabolites in rats.
The pharmacokinetics of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) and its mains metabolites have never been modeled together. We therefore designed a model with which to analyze the pharmacokinetics of MDMA, 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-methoxyamphetamine (HMA) and to test the effect of covariates like gender and body weight on the pharmacokinetics. Rats (18 males and 18 females) were given 1 mg/kg MDMA iv, and the concentrations of MDMA, MDA, and HMMA were measured by high-performance liquid chromatography-mass spectrometry. Another 30 rats (15 males) were given 1 mg/kg MDA, and MDA and HMA were measured. A population pharmacokinetic model was developed to describe the changes in MDMA, HMMA, MDA, and HMA concentrations over time and to estimate interanimal variability. The influence of gender was tested using a likelihood ratio test. Estimated exposures of males and females to MDMA and its metabolites were compared using the Wilcoxon nonparametric test. An integrated six-compartment model adequately described the data. MDMA (two compartments) was transformed irreversible to HMMA (one compartment) and MDA (two compartments), which then produced HMA (one compartment). All rate constants were first order. Females given MDMA had significantly smaller MDMA distribution volumes than males, and they converted less MDMA to MDA than did males. Our MDMA, MDA, HMA, and HMMA model is suitable for examining the relationship between drug concentrations and its pharmacological/toxicological effects. Male rats were exposed to significantly more MDA and HMA than were females, which could explain why males are more sensitive to MDMA toxic effects than females.


Light Effects on Behavioural Performance Depend on the Individual State of Vigilance.
Research has shown that exposure to bright white light or blue-enriched light enhances alertness, but this effect is not consistently observed in tasks demanding high-level cognition (e.g., Sustained Attention to Response Task-SART, which measures inhibitory control). Individual differences in sensitivity to light effects might be mediated by variations in the basal level of arousal. We tested this hypothesis by measuring the participants' behavioural state of vigilance before light exposure, through the Psychomotor Vigilance Task. Then we compared the effects of a blue-enriched vs. dim light at nighttime on the performance of the auditory SART, by controlling for individual differences in basal arousal. The results replicated the alerting effects of blue-enriched light, as indexed by lower values of both proximal temperature and distal-proximal gradient. The main finding was that lighting effects on SART performance were highly variable across individuals and depended on their prior state of vigilance. Specifically, participants with higher levels of basal vigilance before light exposure benefited most from blue-enriched lighting, responding faster in the SART. These results highlight the importance of considering basal vigilance to define the boundary conditions of light effects on cognitive performance. Our study adds to current research delineating the complex and reciprocal interactions between lighting effects, arousal, cognitive task demands and behavioural performance.


Mortality attributed to misuse of psychoactive drugs, 1979-88.
To assess mortality attributed to misuse of psychoactive drugs in the United States from 1979 through 1988, the authors obtained from death certificates the annual number of, and age-, sex-, and race-specific data for, deaths in which psychoactive drugs were coded as the underlying or contributing cause. Deaths with psychoactive drugs specified as underlying cause (drug-induced) increased from 6,500 (2.9 per 100,000) in 1979 to more than 10,000 (3.8 per 100,000) in 1988. Deaths with psychoactive drugs specified as either underlying or contributing cause (drug-related) increased from 7,200 (3.2 per 100,000) in 1979 to more than 14,400 (5.5 per 100,000) in 1988. The drugs that primarily accounted for this increase were illicit, in particular, the opiates (heroin) and cocaine, with most of the remainder accounted for by misuse of various legal drugs. The largest increases between 1979 and 1988 occurred among black men ages 35-44 whose drug-induced death rates rose from 8 to 36 per 100,000 and whose drug-related death rates from 10 to 82 per 100,000. These data identify a high-risk group for targeting efforts to prevent deaths due to misuse of psychoactive drugs.


Prevalence of anemia and its associated factors among married women in 19 sub-Saharan African countries.
Sub-Saharan Africa (SSA) remains the region with the highest burden of anemia globally. Since anemia has both health and non-health-related consequences, its reduction is one of the Sustainable Development Goals. Therefore, this study aimed to examine the prevalence of anemia and its associated factors among married women in SSA. Using Stata version-14 software, the analysis was done on 89,029 married women from the Demographic and Health Surveys of 19 countries in SSA. Pearson Chi-Square test and Binary logistic regression analyses were used to examine the factors associated with anemia. The results were presented using adjusted Odds Ratio (aOR) at a 95% Confidence Interval (CI). A p-value less than or equal to 0.05 (p ≤ 0.05) was considered statistically significant. The pooled analysis showed that 49.7% of married women were anemic. Of these, 1.04% and 15.05% were severely and moderately anemic respectively, and the rest 33.61% were mildly anemic. Husband education (primary school-aOR = 0.84, 95% CI; 0.71-0.99), wealth index (middle-aOR = 0.81, 95% CI; 0.68-0.96, richer-aOR = 0.69, 95% CI; 0.57-0.84, richest-aOR = 0.68, 95% CI; 0.51-0.91), modern contraceptive use (yes-aOR = 0.68, 95% CI; 0.56-0.81) and religion (Muslim-aOR = 1.27, 95% CI; 1.11-1.46, others-aOR = 0.73, 95% CI; 0.59-0.90) were factors associated with anemia among married women. The findings show that nearly half of the married women are affected by anemia. Enhancing partners' educational levels, and economic empowerment of women, strengthening family planning services, and working with religious leaders to reduce the perception and religious beliefs related to food restrictions can be the main focus to reduce the burden of anemia among married women in SSA.


[Analysis of left ventricular function using 2-dimensional and pulsed Doppler echocardiography in type I diabetics].
In 44 patients with type I diabetes mellitus divided into a group of 29 patients (mean age 25 years, duration of diabetes 6 years on the average) without microangdiopathic complications and into a second group of 15 patients (mean age 31 years, duration of diabetes 16 years on the average) with retinopathy and/or nephropathy, parameters of cardiac function were studied by means of two-dimensional (2D) and pulsed Doppler (PD) echocardiography. The obtained results were compared with findings recorded in a third group of 20 healthy subjects (mean age 29 years). 2D measurements of parameters such as ejection fraction, diastolic diameter of left ventricle (LV), thickness of septum and posterior wall did not reveal any significant differences between the groups studied. On analysing diastolic function expressed by maximal velocity of rapid LV filling (E), atrial systole (A), E/A ratio, and atrial systole ejection time (AET), compared to the control group, the second group presented with significantly decreased E, increased A, and reduced E/A (p less than 0.001). In the first group only a shortened AET (p less than 0.01) was recorded. AET was changed also in the second group and was found to be inversely correlated with the duration of the disease, r = -0.43, p less than 0.05).


PTRF/Cavin-1 Deficiency Causes Cardiac Dysfunction Accompanied by Cardiomyocyte Hypertrophy and Cardiac Fibrosis.
Mutations in the PTRF/Cavin-1 gene cause congenital generalized lipodystrophy type 4 (CGL4) associated with myopathy. Additionally, long-QT syndrome and fatal cardiac arrhythmia are observed in patients with CGL4 who have homozygous PTRF/Cavin-1 mutations. PTRF/Cavin-1 deficiency shows reductions of caveolae and caveolin-3 (Cav3) protein expression in skeletal muscle, and Cav3 deficiency in the heart causes cardiac hypertrophy with loss of caveolae. However, it remains unknown how loss of PTRF/Cavin-1 affects cardiac morphology and function. Here, we present a characterization of the hearts of PTRF/Cavin-1-null (PTRF-/-) mice. Electron microscopy revealed the reduction of caveolae in cardiomyocytes of PTRF-/- mice. PTRF-/- mice at 16 weeks of age developed a progressive cardiomyopathic phenotype with wall thickening of left ventricles and reduced fractional shortening evaluated by echocardiography. Electrocardiography revealed that PTRF-/- mice at 24 weeks of age had low voltages and wide QRS complexes in limb leads. Histological analysis showed cardiomyocyte hypertrophy accompanied by progressive interstitial/perivascular fibrosis. Hypertrophy-related fetal gene expression was also induced in PTRF-/- hearts. Western blotting analysis and quantitative RT-PCR revealed that Cav3 expression was suppressed in PTRF-/- hearts compared with that in wild-type (WT) ones. ERK1/2 was activated in PTRF-/- hearts compared with that in WT ones. These results suggest that loss of PTRF/Cavin-1 protein expression is sufficient to induce a molecular program leading to cardiomyocyte hypertrophy and cardiomyopathy, which is partly attributable to Cav3 reduction in the heart.


Combined percutaneous and surgical approach to a postnephrectomy arteriovenous fistula.
The case of a patient with long-standing severe heart failure that was ultimately found to be secondary to a large communication between the right renal artery stump and the inferior vena cava is reported. The occurrence of an arteriovenous fistula should be suspected in patients who underwent previous nephrectomy since early diagnosis would avoid relevant cardiac complications and the demise of a patient suffering from a disease that may be corrected surgically or percutaneously. We describe a combined approach that allowed the percutaneous decompression of the inferior vena cava and relief of the volume overload to the heart prior to the surgical ligation of the arteriovenous fistula. This approach should be considered a valuable option for treating long-standing high output postnephrectomy arteriovenous fistulas.


Coulomb excitation paths of high-K isomer bands in 178Hf.
Three distinctly different mechanisms are shown to populate the K(pi)=6(+) (t(1/2)=77 ns), 16(+) (31 yr), and 8(-) (4 s) isomer bands of 178Hf by Coulomb excitation. High spin states of the three isomer bands were populated by Coulomb excitation of a hafnium target with a 650 MeV 136Xe beam. Although direct population of high-K bands is highly K-forbidden, isomer bands in 178Hf were populated up to spins 13(+)(K=6), 20(+)(K=16), and 14(-)(K=8) with in-band gamma yields of approximately 10(-4) of the ground state band. The data are consistent with a rapid increase in K mixing with increasing spin in the isomer bands.


Dose Administration Aid Service in Community Pharmacies: Characterization and Impact Assessment.
Adherence to therapies is a primary determinant of treatment success. Lack of medication adherence is often associated with medical and psychosocial issues due to complications from underlying conditions and is an enormous waste of medical resources. Dose Administration Aid Service (DAAS) can be seen as part of the solution, allowing individual medicine doses to be organized according to the dosing schedule determined by the patient's prescriber. The most recent systematic reviews admit the possibility of a positive impact of this service. In line with this background, the study reported in this paper aimed to characterize DAAS implementation in Portugal and understand the perceptions of pharmacists and owners of community pharmacies regarding the impact of DAAS, preferred methodology types, and State contribution. The study was guided by qualitative description methodology and reported using the consolidated criteria for reporting qualitative research (COREQ) checklist. Data were collected through semi-structured interviews with 18 pharmacists and/or owners of community pharmacies. Using qualitative content analysis, we identified categories that revealed that automated weekly methodology is the preferred methodology, because of its easiness of use and lower cost of preparation. However, the investment cost was felt to be too high by the participants considering the number of potential users for implementation in practice. Participants were also unanimous in recognizing that DAAS has a very positive impact in terms of safety and medication adherence, and the majority agreed that it also helped reduce medication waste. Implications of these findings for medication adherence are discussed.


Participation in physical activity decreased more in people with rheumatoid arthritis than the general population during the COVID-19 lockdown: a cross-sectional study.
The COVID-19 pandemic and social distancing restrictions have significantly reduced population-wide physical activity (PA) levels. However, the impact of the pandemic and relevant restrictions on PA participation, and any potential barriers to it, in people with rheumatoid arthritis (RA) are not clear. Furthermore, we are unsure if any such PA changes have affected their body weight, mental wellbeing, and/or quality of life (QoL). Thus, the aim of this study was to examine the impact of the lockdown on PA participation in people with RA, versus people without RA. Participants (n = 128; RA = 27, non-RA = 101) completed a self-administered online survey, which included questions on PA, body weight, mental wellbeing and QoL. PA participation during lockdown was significantly lower among RA versus non-RA participants (p < 0.001). Additionally, a similar profile of results was found where more RA participants vs non-RA participants reported reduced habitual PA (59% vs 33%) and increased body weight (59% vs 35%). Mental wellbeing scores were similarly low in both groups during lockdown (RA: 20.8 ± 4.2; non-RA: 22.2 ± 3.4, p = 0.080). Matched group comparisons identified similar trends to full sample analyses. In the first months of the lockdown, more people with RA reported decreased PA participation and increased body weight than their non-RA counterparts. Access to exercise equipment and facilities appears to be the main cause for these results. Looking beyond COVID-19, specific PA promotion for people with RA will be required to prevent a pandemic of inactivity.


High-Resolution Computational Fluid Dynamic Simulation of Haemodialysis Cannulation in a Patient-Specific Arteriovenous Fistula.
Arteriovenous fistulae (AVF) are the preferred choice of vascular access in hemodialysis patients; however, complications such as stenosis can lead to access failure or recirculation, which reduces dialysis efficiency. This study utilized computational fluid dynamics on a patient-specific radiocephalic fistula under hemodialysis treatment to determine the dynamics of access recirculation and identify the presence of disturbed flow. Metrics of transverse wall shear stress (transWSS) and oscillatory shear index (OSI) were used to characterize the disturbed flow acting on the blood vessel wall, while a power spectral density (PSD) analysis was used to calculate the any turbulence within the access. Results showed that turbulence is generated at the anastomosis and continues through the swing segment. The arterial needle dampens the flow as blood is extracted to the dialyzer, while the venous needle reintroduces turbulence due to the presence of jet flows. Adverse shear stresses are present throughout the vascular access and coincide with these complex flow fields. The position of the needles had no effect in minimizing these forces. However, improved blood extraction may occur when the arterial needle is placed further from the anastomosis, minimizing the effects of residual turbulent structures generated at the anastomosis. Furthermore, the arterial and venous needle may be placed in close proximity to each other without increasing the risk of access recirculation, in a healthy mature fistula, due to the relatively stable blood flow in this region. This may negate the need for a long cannulation segment and aid clinicians in optimizing needle placement for hemodialysis.


Seizures in patients simultaneously receiving theophylline and imipenem or ciprofloxacin or metronidazole.
Five patients had apparently drug-induced seizures while simultaneously receiving theophylline and either imipenem (three patients), ciprofloxacin (one patient), or ciprofloxacin and metronidazole (one patient). Seizures ceased upon reduction in dosage or discontinuation of the suspected offending agents. Imaging studies failed to reveal new structural lesions in the central nervous system in any patient, and only one had a history of neurologic disease. Although the exact mechanism for seizure induction cannot be determined from these cases, potential drug interactions exist, because theophylline, imipenem, and ciprofloxacin are all believed to increase excitation of the central nervous system by inhibition of gamma-aminobutyric acid binding to receptors. In addition, ciprofloxacin decreases the clearance of theophylline from the body, predisposing the patient to elevated theophylline levels. Physicians prescribing theophylline with imipenem, ciprofloxacin, or metronidazole should carefully monitor patients for indications for drug therapy, drug dosage, organ impairment affecting drug metabolism, and signs of toxicity. Seizures may accompany oral theophylline therapy, even at "therapeutic" serum theophylline concentrations.


Herzberg-Teller Effect on the Vibrationally Resolved Absorption Spectra of Single-Crystalline Pentacene at Finite Temperatures.
The line shape of an electronic spectrum conveys the coupling between electronic and vibrational degrees of freedom. In the present study, the light absorption spectra of single-crystalline pentacene were measured by polarized UV-vis microscopy at 77, 185, and 293 K. The vibronic coupling encoded in each spectrum was resolved by the Herzberg-Teller theory that considers the contributions from the Franck-Condon (FC) factor, Franck-Condo/Herzberg-Teller (FC/HT) interference, and Herzberg-Teller (HT) coupling. Specifically, excitation energies, electronic transition dipole moments, and their nuclear gradients were evaluated by the GW method to ensure numerical accuracy, while the computationally efficient density function theory was employed to determine the optimized structures and vibrational normal modes. For every pair of electronic transition and normal mode that gives rise to a strong vibronic transition intensity, we examined their spatial characteristics by projecting them onto the three crystal axes. It was found that all normal modes strongly coupled to the lowest-lying a-polarized electronic transitions oscillate along axis a, whereas none of their counterparts for the lowest-lying b-polarized electronic transitions is predominantly along axis b. This notable difference on the alignment between the electronic transition and molecular vibration could help the directional control of charge dissociation and/or spin separation. Moreover, a significant variance of the destructive FC/HT interference was discovered with increasing temperatures that can well explain the a-polarized fading tableland near 650 nm. Finally, the importance of HT coupling was corroborated by comparing its intensity with those of FC factor and FC/HT interference. Taken all together, the vibrational dependence of the electronic wave function is critical to resolve the light absorption spectra of single-crystalline pentacene and its temperature effects, facilitating the systematic design of functional optical materials based on pentacene and its derivatives.


Occult bacteremia in the 3-month-old to 3-year-old age group.
Occult bacteremia precedes many serious infections in children. The vast majority of patients with occult bacteremia have an elevated temperature (> or = 39 degrees C), but fever is an extraordinarily common presenting complaint in the 3- to 36-month-old age group, which is at highest risk for S pneumoniae, H influenzae type b, and N meningitidis bacteremia. On examination, most patients with bacteremia will have no findings that distinguish them from nonbacteremic children. A white blood cell count of > 15,000/microL in a child with fever will identify about two thirds of children with occult bacteremia. Blood culture remains the most definitive test. It is important to establish a rational strategy to identify and treat these children before significant sequelae occur.


Environmental scanning electron microscope imaging of vesicle systems.
The structural characteristics of liposomes have been widely investigated and there is certainly a strong understanding of their morphological characteristics. Imaging of these systems, using techniques such as freeze-fracturing methods, transmission electron microscopy, and cryo-electron imaging, has allowed us to appreciate their bilayer structures and factors that influence this. However, there are a few methods that study these systems in their natural hydrated state; commonly, the liposomes are visualized after drying, staining and/or fixation of the vesicles. Environmental scanning electron microscopy (ESEM) offers the ability to image a liposome in its hydrated state without the need for prior sample preparation. We were the first to use ESEM to study the liposomes and niosomes, and have been able to dynamically follow the hydration of lipid films and changes in liposome suspensions as water condenses onto, or evaporates from, the sample in real-time. This provides an insight into the resistance of liposomes to coalescence during dehydration, thereby providing an alternative assay for liposome formulation and stability.


[Reimbursement strategies for botulinum toxin type A in Austria].
In the last two decades, botulinum toxin A (BtxA) has become the treatment of choice for spasmodic torticollis, blepharospasm and hemifacial spasm. Since 1999 Dysport and Botox are approved in Austria for the treatment of these indications. BtxA is applied in the hospital (out- and in-patient clinics) and by specialists (especially neurologists) in private practices. Complete reimbursement of the costs by the health insurance is provided only if the treatment has taken place in the specialist's private practice. The costs of BtxA application in the hospital are partially covered by the so called "LKF points" (Austrian system for reimbursement of costs in the hospital) or by the flat rate fee for out-patients. Approval for other indications for BtxA is expected in the next years, therefore appropriate cost reimbursement for BtxA is of immense importance. Different reimbursement systems are discussed in the following article. It seems useful to adopt approved procedures in special situations, such as reimbursement for the ambulatory application of chemotherapy and Betainterferon in Austria. The appropriate reimbursement system has to consider the indication and documentation of Btx-treatments as well as the qualification of the Btx-user.


The life (and death) of CD4+ CD28(null) T cells in inflammatory diseases.
Inflammation contributes to the development and perpetuation of several disorders and T lymphocytes orchestrate the inflammatory immune response. Although the role of T cells in inflammation is widely recognized, specific therapies that tackle inflammatory networks in disease are yet to be developed. CD4(+) CD28(null) T cells are a unique subset of helper T lymphocytes that recently shot back into the limelight as potential catalysts of inflammation in several inflammatory disorders such as autoimmunity, atherosclerosis and chronic viral infections. In contrast to conventional helper T cells, CD4(+) CD28(null) T cells have an inbuilt ability to release inflammatory cytokines and cytotoxic molecules that can damage tissues and amplify inflammatory pathways. It comes as no surprise that patients who have high numbers of these cells have more severe disease and poor prognosis. In this review, I provide an overview on the latest advances in the biology of CD4(+) CD28(null) T cells. Understanding the complex functions and dynamics of CD4(+) CD28(null) T cells may open new avenues for therapeutic intervention to prevent progression of inflammatory diseases.


Effects of moderate salt restriction alone and in combination with cilazapril on office and ambulatory blood pressure.
The purpose of the present study was to examine the effects of salt-restriction alone and in combination with an angiotensin-converting enzyme (ACE) inhibitor (cilazapril) on both office and ambulatory blood pressure (BP) levels in free living subjects with elevated BP. The study was carried out in an out-patient setting with subjects recruited from occupational health care system mainly. After exclusions, 39 subjects (24 men, 15 women, aged 28-65 years) with mildly to moderately elevated BP completed the study. After 3 months run-in period with placebo (first month on normal-salt and the next 2 months on sodium-restricted diet) the subjects were randomised into either salt-restriction placebo or salt-restriction cilazapril (2.5 mg daily) groups for 3 months. In the whole group, 24-h urinary sodium excretion decreased (mean +/- s.d.) from 198 +/- 60 to 112 +/- 59 mmol (4 weeks vs 24 weeks, P < 0.001). Systolic and diastolic office BP decreased during the placebo-sodium-restriction phase (-7.1 [95% Cl -11.2; -3.0] and -4.2 [95% Cl -6.6; -1.8] mm Hg for systolic and diastolic BP), and similarly the daytime ambulatory BP (ABP) was reduced during this period (-2.8 [95% Cl -5.2; -0.5] and -2.8 [95% Cl -4.5; -1.2] mm Hg, systolic (SBP) and diastolic blood pressure (DBP) respectively). No changes were observed in the night time ABP. Addition of cilazapril to sodium-restriction enhanced significantly the office BP (-13.2, [95% Cl -20.2; -6.2], and -9.1 [95% Cl -13.5; -4.7]) and daytime ABP (-5.9, [95% Cl -10.1; -1.8] and -5.3, [95% Cl -8.8; -1.9]) reduction. Blood glucose, plasma insulin or serum lipids did not change during the study. Moderate sodium restriction seems to lower the office and daytime ABP levels in subjects with mild-to-moderate hypertension. The antihypertensive effect of cilazapril could be enhanced by sodium restriction.


TurfPQ, a pesticide runoff model for turf.
Environmental assessments of golf courses and other turf systems must often rely on mathematical modeling. However, in the case of pesticide runoff, successful modeling applications are rare. Available models were developed for agricultural applications and have seen very limited testing for turf. TurfPQ is a pesticide runoff model developed exclusively for turf. The model is based on a curve number calculation for runoff volume and linear partitioning of pesticide into adsorbed and dissolved components during a precipitation or irrigation event. Calibration is optional, so the model can be applied, using default parameter values, to situations where runoff and chemical loss data are unavailable. TurfPQ was tested with default parameter values for 52 pesticide runoff events involving six pesticides measured in plot studies in four states. The model typically produced conservative overpredictions of pesticide runoff, particularly with strongly adsorbed pesticides. Mean predicted pesticide runoff was 2.9% [corrected] of application, compared with an observed mean of 2.1%. TurfPQ captured the dynamics of the pesticide runoff events well with R2 = 0.65 [corrected]. Sensitivity analyses indicated that prediction errors could be reduced by better estimates of adsorption parameters and runoff curve numbers. However, even with default parameters, TurfPQ predictions are at least as accurate as those produced by more complex models.


Ring Chromosome 4 in a Child with Multiple Congenital Abnormalities: A Case Report and Review of the Literature.
A female child born preterm with intrauterine growth retardation and presenting with facial dysmorphism with clefts, microcephaly, limb deformities, and congenital abnormalities involving cardiovascular and urinary systems is described. Chromosomal analysis showed a de novo 46,XX,r(4)(p15.3q35) karyotype. The clinical features of the patient were compared with the phenotypic characteristics of 17 previously reported cases with ring chromosome 4 and those with Wolf-Hirschhorn syndrome (4p-). Clinical features observed in this case are consistent with the consensus phenotype in ring chromosome 4. Patent ductus arteriosus and bilateral talipes equinovarus observed in this baby widen the phenotypic spectrum associated with ring chromosome 4.


Update on the Diagnosis and Management of Spinal Infections.
Pyogenic spinal infections are uncommon, but their incidence has increased. Diagnosis is based on clinical, laboratory, and imaging findings. Delayed diagnosis occurs frequently and can lead to poor outcomes. Early radiographic findings are nonspecific; MRI is the best imaging study for diagnosis. The goal of treatment is to eradicate infection, prevent recurrence, preserve spinal stability, avoid deformity, relieve pain, and prevent or reverse neurologic deficit. Current guidelines recommend antibiotics be administered for 6 weeks if there is resolution of symptoms and normalization of inflammatory parameters. Surgery is required in patients with neurologic deficit, uncontrolled sepsis, spinal instability, deformity, and failure of medical treatment and to manage epidural abscess. Classic treatment of epidural abscess is surgical, but recent studies have challenged this approach. Surgical techniques used to manage these infections are varied; they include anterior, posterior, and combined approaches, and minimally invasive surgery. Current management has decreased mortality; however, the prognosis is affected by treatment failure, recurrent infection, or potential of persistent disability secondary to deformity, chronic pain, or permanent neurologic impairment.


Psychiatric illness and facebook: a case report.
There is relatively little content available addressing the use of social media, such as Facebook in psychiatric populations. There has been significant growth of various social media websites in the last 10 years, such as Facebook, and yet little is written about their overall impact on this population. There are articles in the scientific literature about the use of social media in adolescents and young adults and also about its use among physicians and medical students. This article reviews the literature addressing social media and describes a therapeutic interaction with a patient with significant psychiatric comorbities and his use of social media. Furthermore, this is a unique example in current literature of an overall positive interaction and social improvement of this patient in large degree due to his use of Facebook. Physicians themselves must be very cautious in their interaction with patients online and especially via social media, while acknowledging that social media can serve as a spring board for more reclusive patients into greater societal integration.