Acceptability of rapid oral fluid HIV testing among male injection drug users in Taiwan, 1997 and 2007.
Rapid oral fluid HIV testing (rapid oral testing) is in the process of being adapted in Taiwan and elsewhere given its advantages over prior HIV testing methods. To guide this process, we examined the acceptability of rapid oral testing at two time points (i.e., 1997 and 2007) among one of the highest risk populations, male injection drug users (IDUs). For this purpose, an anonymous self-administered survey was completed by HIV-negative IDUs involved in the criminal justice system in 1997 (N (1)=137 parolees) and 2007 (N (2)=106 prisoners). A social marketing model helped guide the design of our questionnaire to assess the acceptability of rapid oral testing. This included assessing a new product, across four marketing dimensions: product, price, promotion, and place. Results revealed that in both 1997 and 2007, over 90% indicated that rapid oral testing would be highly acceptable, particularly if the cost was under US$6, and that a pharmacy would be the most appropriate and accessible venue for selling the rapid oral testing kits. The vast majority of survey respondents believed that the cost of rapid oral testing should be federally subsidized and that television and newspaper advertisements would be the most effective media to advertise for rapid oral testing. Both the 1997 and 2007 surveys suggested that rapid oral HIV testing would be particularly accepted in Taiwan by IDUs after release from the criminal justice system.


Life Course Socioeconomic Disadvantage and the Aging Immune System: Findings From the Health and Retirement Study.
Previous research has documented a consistent association between current socioeconomic status (SES) and cytomegalovirus (CMV). Early life is likely a critical period for CMV exposure and immune development, but less is known about early-life socioeconomic factors and CMV, particularly in older age populations. Using data from the Health and Retirement Study, we investigated the association between life course socioeconomic disadvantage and immune response to CMV among older adults. Using ordered logit models, we estimated associations between several measures of socioeconomic disadvantage and the odds of being in a higher CMV Immunoglobulin G (IgG) response category in a sample of 8,168 respondents aged older than 50 years. We found a significant association between educational attainment and CMV IgG response. Those with less than a high school education had 2.00 (95% confidence interval [CI]: 1.67-2.40) times the odds of being in a higher CMV category compared to those with a college degree or greater. In addition, we also observed a significant association with parental education and CMV response. Individuals with parents having 8 years or less of schooling had 2.32 (95% CI: 2.00-2.70) times the odds of higher CMV response compared to those whose parents had greater than high school education. CMV IgG levels in older adults are associated with both early-life and adult SES. Life course socioeconomic disadvantage may contribute to disparities in immunological aging.


Long-term oral beta-carotene supplementation in patients with cystic fibrosis - effects on antioxidative status and pulmonary function.
To investigate the efficacy of long-term oral beta-carotene supplementation for optimizing the antioxidant status and pulmonary function in patients with cystic fibrosis (CF), 24 patients (aged 12. 8 +/- 6.3 years) were randomized to a CF supplementation or to a CF placebo group. As controls 14 healthy age-matched subjects (aged 14. 7 +/- 6.2 years) were studied. Patients of the CF supplementation group received 1 mg beta-carotene/kg body weight (BW)/day (maximally 50 mg beta-carotene/day) for the first 12 weeks; during the following 12 weeks, dosage was reduced to 10 mg beta-carotene/day. At study entry, plasma beta-carotene concentrations were significantly lower in CF patients than in controls (p < 0.001). In the CF supplementation group, plasma beta-carotene concentrations were significantly increased (baseline: 0.08 +/- 0.04 micromol/l) at the end of high-dose treatment (12th week; 0.6 +/- 0.4 micromol/l; p < 0.001), but decreased again during supplementation with 10 mg beta-carotene/day to 0.3 +/- 0.2 micromol/l at the end of the study (p < 0.001). beta-Carotene supplementation did not affect plasma concentrations of other carotenoids and retinol, but an increase in plasma alpha- and gamma-tocopherol concentrations was noticed. During high-dose treatment, a significant decrease in TBA-MDA complexes and a correction of total antioxidative capacity was observed. During the treatment, pulmonary exacerbation could be corrected significantly (p < 0.05). We conclude that CF patients can be efficiently supplemented with 1 mg beta-carotene/kg BW/day (maximally 50 mg beta-carotene/day) to achieve plasma concentrations of healthy control subjects and to minimize oxidative stress, improving the quality of life of CF patients.


Attention modulates spinal cord responses to pain.
Reduced pain perception while being distracted from pain is an everyday example of how cognitive processes can interfere with pain perception. Previous neuroimaging studies showed distraction-related modulations of pain-driven activations in various cortical and subcortical brain regions, but the precise neuronal mechanism underlying this phenomenon is unclear. Using high-resolution functional magnetic resonance imaging of the human cervical spinal cord in combination with thermal pain stimulation and a well-established working memory task, we demonstrate that this phenomenon relies on an inhibition of incoming pain signals in the spinal cord. Neuronal responses to painful stimulation in the dorsal horn of the corresponding spinal segment were significantly reduced under high working memory load compared to low working memory load. At the individual level, reductions of neuronal responses in the spinal cord predicted behavioral pain reductions. In a subsequent behavioral experiment, using the opioid antagonist naloxone in a double-blind crossover design with the same paradigm, we demonstrate a substantial contribution of endogenous opioids to this mechanism. Taken together, our results show that the reduced pain experience during mental distraction is related to a spinal process and involves opioid neurotransmission.


Surface sensitivity of Rayleigh anomalies in metallic nanogratings.
Sensing schemes based on Rayleigh anomalies (RAs) in metal nanogratings exhibit an impressive bulk refractive-index sensitivity determined solely by the grating period. However, the surface sensitivity (which is a key figure of merit for label-free chemical and biological sensing) needs to be carefully investigated to assess the actual applicability of this technological platform. In this paper, we explore the sensitivity of RAs in metal nanogratings when local refractive-index changes are considered. Our studies reveal that the surface sensitivity deteriorates up to two orders of magnitude by comparison with the corresponding bulk value; interestingly, this residual sensitivity is not attributable to the wavelength shift of the RAs, which are completely insensitive to local refractive-index changes, but rather to a strictly connected plasmonic effect. Our analysis for increasing overlay thickness reveals an ultimate surface sensitivity that approaches the RA bulk value, which turns out to be the upper-limit of grating-assisted surface-plasmon-polariton sensitivities.


Image-guided optical spectroscopy in diagnosis of osteoarthritis: a clinical study.
This goal of this study was to clinically evaluate the potential of a novel hybrid imaging techniques, called x-ray guided multispectral diffuse optical tomography, for identifying physiological parameters of joint tissues that can be used to distinguish between osteoarthritic and healthy joints in the hand. Between 2006 and 2009, the distal interphalangeal (DIP) finger joints from 40 subjects including 22 osteoarthritis patients and 18 healthy controls were examined clinically and scanned by the hybrid imaging platform that integrated a C-arm based x-ray tomosynthetic system with a mutlispectral diffuse optical imaging system. Based on the reconstructed results from the 40 subjects, it was observed that oxygen saturation and water content were two statistically most significant physiological discriminators for differentiation of the healthy joints from the osteoarthritic ones.


Cannabinoids in clinical practice.
Cannabis has a potential for clinical use often obscured by unreliable and purely anecdotal reports. The most important natural cannabinoid is the psychoactive tetrahydrocannabinol (delta9-THC); others include cannabidiol (CBD) and cannabigerol (CBG). Not all the observed effects can be ascribed to THC, and the other constituents may also modulate its action; for example CBD reduces anxiety induced by THC. A standardised extract of the herb may be therefore be more beneficial in practice and clinical trial protocols have been drawn up to assess this. The mechanism of action is still not fully understood, although cannabinoid receptors have been cloned and natural ligands identified. Cannabis is frequently used by patients with multiple sclerosis (MS) for muscle spasm and pain, and in an experimental model of MS low doses of cannabinoids alleviated tremor. Most of the controlled studies have been carried out with THC rather than cannabis herb and so do not mimic the usual clincal situation. Small clinical studies have confirmed the usefulness of THC as an analgesic; CBD and CBG also have analgesic and antiinflammatory effects, indicating that there is scope for developing drugs which do not have the psychoactive properties of THC. Patients taking the synthetic derivative nabilone for neurogenic pain actually preferred cannabis herb and reported that it relieved not only pain but the associated depression and anxiety. Cannabinoids are effective in chemotherapy-induced emesis and nabilone has been licensed for this use for several years. Currently, the synthetic cannabinoid HU211 is undergoing trials as a protective agent after brain trauma. Anecdotal reports of cannabis use include case studies in migraine and Tourette's syndrome, and as a treatment for asthma and glaucoma. Apart from the smoking aspect, the safety profile of cannabis is fairly good. However, adverse reactions include panic or anxiety attacks, which are worse in the elderly and in women, and less likely in children. Although psychosis has been cited as a consequence of cannabis use, an examination of psychiatric hospital admissions found no evidence of this, however, it may exacerbate existing symptoms. The relatively slow elimination from the body of the cannabinoids has safety implications for cognitive tasks, especially driving and operating machinery; although driving impairment with cannabis is only moderate, there is a significant interaction with alcohol. Natural materials are highly variable and multiple components need to be standardised to ensure reproducible effects. Pure natural and synthetic compounds do not have these disadvantages but may not have the overall therapeutic effect of the herb.


Efficacy of Atlantoaxial Joint Glucocorticoid Injection in Patients with Rheumatoid Arthritis: A Randomized Trial.
The atlantoaxial joint (AAJ) plays a pivotal role in the cervical spine motion. Unfortunately, it is the most common cervical spine joint that is affected in patients with rheumatoid arthritis. Inflammation of the AAJ results in neck disability, nerve root compression, and finally spinal cord compression. We aim to evaluate the efficacy of intraarticular triamcinolone injection of the AAJ on neck pain and disability. A prospective randomized, controlled clinical trial. An interventional pain unit in a tertiary center at a university hospital in Egypt. Sixty patients with rheumatoid arthritis complaining of AAJ arthritis were randomized into 2 groups. Group AAJI (n = 30) received AAJ injection with 1.0 mL of a mixture of 0.5 mL of bupivacaine 0.5% and 0.5 mL of 20 mg of triamcinolone, in addition to oral placebo tablets (2 tablets every 8 hours for one week). Group SS (n = 30) received systemic steroids, oral prednisolone tablets (5 mg, 2 tablets every 8 hours for one week), in addition to AAJ injection with 1.0 mL of a mixture of 0.5 mL of bupivacaine 0.5% and 0.5 mL of normal saline solution. The percentage of patients who showed >/= 50% reduction of their visual analog scale (VAS) pain score (measured at 1, 2, and 3 months postoperatively), VAS pain score and neck disability index (NDI) (measured at 2, 4, 6, 8, and 12 weeks postoperatively), and the magnetic resonance imaging (MRI) changes of AAJ (assessed 4 weeks postoperatively) were all evaluated. There was significant reduction in the percentage of patients who showed ≥50% reduction of their VAS pain score postoperatively in group AAJI compared with group SS at one month (75% vs. 46.45%; P = 0.033), 2 months (60.7% vs. 25%; P = 0.009), and 3 months (53.6% vs. 17.9%; P = 0.007). There was significant reduction in overall VAS and overall NDI in group AAJI compared with group SS (mean ± standard error) (41.5 ± 2.6 vs. 52.1 ± 2.6; P = 0.005) and (43.7 ± 3.1 vs. 52.4 ± 3.1; P = 0.040), respectively. Analysis of postoperative MRI findings revealed significant improvement of bone marrow edema in group AAJI (AAJI vs. SS) (71.4% vs. 42.9%; P = 0.033), also the synovial enhancement disappeared significantly in group AAJI compared with group SS, (16/22 [72.7%] vs. 10/23 [43.5%]; P = 0.026), moreover, there was a significant reduction in pannus size in group AAJI compared with group SS, (6/10 [60%] vs. 1/9 [11%]; P = 0.041). The study follow-up period was limited to only 3 months. For acutely inflamed AAJ due to rheumatoid arthritis, AAJ steroid injection is a potential therapeutic option; it decreased cervical neck pain, improved neck mobility, and hastened recovery of the joint from an acute inflammatory stage. Rheumatoid arthritis, atlantoaxial joint injection.


Active Tumoral/Tumor Environmental Dual-Targeting by Non-Covalently Arming with Trispecific Antibodies or Dual-Bispecific Antibodies on Docetaxel-Loaded mPEGylated Nanocarriers to Enhance Chemotherapeutic Efficacy and Minimize Systemic Toxicity.
This study was aimed at developing the trispecific antibodies (anti-EGFR/anti-FAP/anti-mPEG, TsAb) or dual bispecific antibodies (anti-EGFR/anti-mPEG and anti-FAP/anti-mPEG) docetaxel (DTX)-loaded mPEGylated lecithin-stabilized micelles (mPEG-lsbPMs) for improving the targeting efficiency and therapeutic efficacy. mPEG-lsbPMs were simply prepared via thin film method. The trispecific antibodies or bispecific antibodies bound the mPEG-lsbPMs by anti-mPEG Fab fragment. The formulations were characterized by DLS and TEM; in vitro and in vivo studies were also conducted to evaluate the cellular uptake, cell cytotoxicity and therapeutic efficacy. The particle sizes of mPEG-lsbPMs with or without the antibodies were around 100 nm; the formulations showed high encapsulation efficiencies of 97.12%. The TsAb and dual bispecific antibodies were fabricated and demonstrated their targeting ability. Two EGFR-overexpressed cell lines (HT-29 and MIA PaCa-2) were co-cultured with FAP-overexpressed WS1 cells (HT-29/WS1; MIA PaCa-2/WS1) to mimic a tumor coexisting in the tumor microenvironment. Cellular binding study revealed that the binding of anti-FAP micelles to three co-culture ratios (4:1, 1:1, and 1:4) of HT-29/EGFR to WS1/FAP was significantly higher than that for TsAb micelles and dual (1:1) micelles, and the binding of those targeting antibodies to WS1/FAP and MIA PaCa-2/EGFR was equally efficacious resulting in a similar binding amount of the TsAb and dual BsAbs (1:1) with the co-culture of MIA PaCa-2/EGFR and WS1/FAP at a 1:1 ratio. Antitumor efficacy study showed that treatment with DTX-loaded mPEG-lsbPMs modified with or without BsAbs, dual BsAbs (1:1), and TsAbs was enhanced in inhibiting tumor growth compared with that for Tynen® while showing fewer signs of adverse effects. Active targeting of both tumors and TAF-specific antigens was able to increase the affinity of DTX-loaded mPEG-lsbPMs toward tumor cells and TAFs leading to successive uptake by tumor cells or TAFs which enhanced their chemotherapeutic efficacy against antigen-positive cancer cells.


Structure and function of the molecular chaperone Hsp104 from yeast.
The molecular chaperone Hsp104 plays a central role in the clearance of aggregates after heat shock and the propagation of yeast prions. Hsp104's disaggregation activity and prion propagation have been linked to its ability to resolubilize or remodel protein aggregates. However, Hsp104 has also the capacity to catalyze protein aggregation of some substrates at specific conditions. Hence, it is a molecular chaperone with two opposing activities with respect to protein aggregation. In yeast models of Huntington's disease, Hsp104 is required for the aggregation and toxicity of polyglutamine (polyQ), but the expression of Hsp104 in cellular and animal models of Huntington's and Parkinson's disease protects against polyQ and alpha-synuclein toxicity. Therefore, elucidating the molecular determinants and mechanisms underlying the ability of Hsp104 to switch between these two activities is of critical importance for understanding its function and could provide insight into novel strategies aimed at preventing or reversing the formation of toxic protein aggregation in systemic and neurodegenerative protein misfolding diseases. Here, we present an overview of the current molecular models and hypotheses that have been proposed to explain the role of Hsp104 in modulating protein aggregation and prion propagation. The experimental approaches and the evidences presented so far in relation to these models are examined. Our primary objective is to offer a critical review that will inspire the use of novel techniques and the design of new experiments to proceed towards a qualitative and quantitative understanding of the molecular mechanisms underlying the multifunctional properties of Hsp104 in vivo.


Extension of prior idiopathic scoliosis fusions to the sacrum: a matched cohort analysis of sixty patients with minimum two-year follow-up.
Comparative study. To compare the radiographic and clinical outcomes of patients undergoing extension of a previous idiopathic scoliosis fusion to the sacrum using either autogenous bone graft or recombinant human bone morphogenetic protein-2 (rhBMP-2). Extension of an existing idiopathic scoliosis fusion to the sacrum for distal degeneration or sagittal imbalance has been associated with a high rate of pseudarthrosis. We hypothesized that rhBMP-2 could be successfully used as a substitute for distant autograft in this challenging population. Consecutive patients were identified from a single institution prospective database. The control group (autogenous harvesting without rhBMP-2, 1998-2002) included 24 of 25 patients with minimum 2-year follow-up while the study group (rhBMP-2 without distant autograft, 2002-2006) included 36 of 39 patients with minimum 2-year follow-up. Radiographs were measured using standard adult deformity criteria. Fusions were evaluated by independent observers using a published 4-point scale. Clinical outcomes were evaluated using Scoliosis Research Society and Oswestry Disability Index Questionnaires. Groups were well matched with respect to demographic, radiographic, and surgical data with the following exceptions: the control group (autogenous graft, no BMP) was younger (43.5 vs. 49.8 years; P = 0.04), had more anterior levels fused (3.3 vs. 1.7; P = 0.01), more thoracoabdominal approaches (25% vs. 2.7%; P = 0.01), and greater estimated blood loss (1938 vs. 1221 mL; P = 0.01). There was 1 wound complication (deep infection) in each group. Rates of radiographic pseudarthrosis (11.1% vs. 20.8%) and revision for pseudarthrosis (5.6% vs. 12.5%) were lower in the rhBMP-2 group, although this did not reach statistical significance. Preoperative, postoperative, and improvements in Scoliosis Research Society and Oswestry Disability Index scores were similar between groups. We did not observe any increase in adverse events with the use of rhBMP-2. BMP-2 is a safe and effective alternative to iliac or rib harvesting when extending an existing idiopathic scoliosis fusion to the sacrum.


Risk factors and consequences of delayed graft function.
The impact of delayed graft function (DGF) on the outcome of renal transplantation remains controversial. We analyzed the risk factors for DGF and its impact on graft and patient survival. A total of 354 renal transplants performed between June 1986 and April 2000 were analyzed. Variables analyzed included donor and recipient age, method and duration of renal replacement therapy, HLA mismatch, cold and warm ischemia times, biopsy-confirmed acute rejection, length of stay in the hospital, serum creatinine at the end of first hospitalization as well as graft and patient survival at one, three, five and ten years. The study patients were divided into two groups: patients with DGF (G1) and those without DGF (G2). DGF occurred in 50 patients (14.1%), and it was seen more frequently in patients transplanted from deceased donors (60% vs. 40%, P <0.0001). The cause of DGF was acute tubular necrosis, seen in 98% of the cases. Univariate analysis showed a statistically significant difference between the two groups G1 and G2 in the following parameters: average duration on dialysis (52.3 vs. 36.4 months, P = 0.006), HLA mismatch (44.9% vs. 32.11% P = 0.015), donor age (35.9 vs. 40.2 years, P = 0.026), cold ischemia time (23 vs. 18.2 h, P = 0.0016), warm ischemia time (41.9 vs. 38.6 mn, P = 0.046), length of stay in the hospital during first hospitalization (54.7 vs. 33.2 days, P <0.0001), serum creatinine at the end of first hospitalization (140 vs. 112 μmol/L, P <0.0001) and at three months following transplantation (159 vs. 119 μmol/L, P = 0.0002). Multivariate analysis revealed the following independent risk factors for DGF: deceased donor (RR = 13.2, P <0.0001) and cold ischemia time (RR = 1.17, P = 0.008). The graft survival at one, three, five and ten years was 100%, 93%, 88.3% and 78.3% in G1 versus 100%, 95.9% 92.8% and 82.3% in G2; there was no statistically significant difference. The patient survival at one, three, five and ten years was 100%, 91.3%, 83.6% and 74.4% in G1 versus 100%, 95.9%, 94% and 82.6% in G2 with a statistically significant difference (P = 0.04). Prolonged cold ischemia time and transplantation of kidneys from deceased donors were the main risk factors for DGF in our study. Also, DGF significantly affected patient survival but had no influence on graft survival.


Effect of mitomycin-C applied through different approaches following tracheal surgery on development of granulation tissue and level of nephrotoxicity in rats.
This study aims to evaluate the effect of mitomycin-C applied through different drug administration approaches on the development of granulation tissue in the field of surgery and renal functions in rats which underwent tracheal surgery. Fifty male adult Sprague Dawley rats (weighing mean 200 g to 300 g) were divided into five groups. An incision was performed between the fifth and sixth cartilage ring of the trachea in all groups under anesthesia and the incision was primarily repaired with a 6/0 monofilament absorbable suture. A single dose of mitomycin-C 0.5 mg was applied in the experimental animals appropriate with their assigned groups as topical, intraperitoneal injection, injection to the wound edges, and through inhalation. No mitomycin-C was administered in one group which was accepted as the control group. Rats were sacrificed four weeks after surgery and their tracheas were excised subsequently. Tracheal tissue samples were histopathologically evaluated in terms of epithelization, fibrosis, amount of fibroblasts, angiogenesis, and inflammatory response. Diameter and wall thickness of the tracheas were measured. Blood urea and creatinine levels were evaluated for nephrotoxicity, and the rats were immunohistochemically examined for glomerular pathology. Epithelization was statistically significantly decelerated (p<0.01), diameter of the trachea was statistically significantly larger (p<0.05), and wall thickness of the trachea was significantly thicker in the group with topical mitomycin-C application compared to the control group (p<0.01). Topically applied mitomycin-C following tracheal surgery slows down epithelization and, thus, decreases the development of granulation tissue and maintains a wider diameter of the trachea.


Design of a wearable four-channel near-infrared spectroscopy system for the measurement of brain hemodynamic responses.
Objectives This work describes the design and development of a four-channel near-infrared spectroscopy system to detect the oxygenated and deoxygenated hemoglobin concentration changes in the brain during various motor tasks. Methods The system uses light-emitting diodes corresponding to two wavelengths of 760 nm and 850 nm sensitive to deoxygenated and oxygenated hemoglobin concentration changes, respectively. The response is detected using a photodetector with an integrated transimpedance amplifier. The system is designed with four channels for functional near-infrared spectroscopy (fNIRS) signals acquisition. Two experiments were conducted to demonstrate the ability of the system to detect the changes in hemodynamic responses of different tasks. In the first experiment, the hemodynamic changes during motor execution and imagery of right- and left-fist clenching tasks were acquired by the developed system and validated against a standard multichannel NIRS system. In another experiment, the fNIRS signals during rest and motor execution of right-fist clenching task were acquired using the system and classified. Results The results demonstrate the ability of the designed system to detect the brain hemodynamic changes during various tasks. Also, the activation patterns obtained by the developed system with a minimum number of channels are on par with those obtained by the commercial system. Conclusions The developed four-channel NIRS system is user-friendly and has been designed with inexpensive components, unlike the commercially available NIRS instruments that are cumbersome and expensive.


Silent ischemic lesion recurrence on magnetic resonance imaging predicts subsequent clinical vascular events.
Previous studies identified a high frequency of silent ischemic lesion recurrence on magnetic resonance imaging (MRI) after an index stroke. To investigate whether ischemic lesion recurrence on MRI predicts subsequent clinical events. Retrospective cohort study. General community hospital. Patients We recruited 120 patients who experienced an acute ischemic stroke (IS) and who underwent initial MRI within 24 hours of onset and subsequent MRI on day 5. Of those patients, 68 underwent follow-up MRI up to 90 days after onset. Early silent lesion recurrence was defined as new asymptomatic ischemic lesions on 5-day MRI, and late silent lesion recurrence was defined as those on 30- or 90-day MRI. Patients were followed up for recurrent vascular events by interviews. Among the 104 patients (86.7%) who had available clinical outcome data, 35 (33.7%) had early silent lesion recurrence; 15 (22.1%) of 68 patients had late silent lesion recurrence. Of the patients, 8 experienced a recurrent IS, 3 experienced a transient ischemic attack, and 3 had vascular deaths during a mean +/- SD follow-up of 19.3 +/- 9.0 months. For recurrent IS as a clinical end point, late silent lesion recurrence independently predicted recurrent IS (odds ratio, 6.55; 95% confidence interval, 1.09-39.55) by the Cox proportional hazards model. For combined clinical end points, early (odds ratio, 3.19; 95% confidence interval, 1.02-10.00) and late (odds ratio, 8.09; 95% confidence interval, 1.29-50.91) silent lesion recurrences independently predicted clinical recurrent IS, transient ischemic attack, or vascular deaths. These data suggest that silent ischemic lesion recurrence on MRI may be a potential surrogate marker of clinical recurrence.


New Developments on the Hirao Reactions, Especially from "Green" Point of View.
The Hirao reaction discovered ca. 35 years ago is an important P-C coupling protocol between dialkyl phosphites and aryl halides in the presence of Pd(PPh3)4 as the catalyst and a base to provide aryl phosphonates. Then, the reaction was extended to other Preagents, such as secondary phosphine oxides and H-phosphinates and to other aryl and hetaryl derivatives to afford also phosphinic esters and tertiary phosphine oxides. Instead of the Pd(PPh3)4 catalyst, Pd(OAc)2 and Ni-salts were also applied as catalyst precursors together with a number of mono- and bidentate P-ligands. In our review, we undertook to summarize the target reaction with a special stress on the developments attained in the last 6 years, hence this paper is an update of our earlier reviews in a similar topic. "Greener" syntheses aimed at utilizing phase transfer catalytic and microwave-assisted approaches, even under "P-ligand-free. or even solvent-free conditions are the up-to date versions of the classical Hirao reaction. The mechanism of the reaction is also in the focus these days.


Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation.
Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes. We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation. The course of investigational pump recipients was compared with that of patients implanted contemporaneously with commercially available devices. The primary outcome, success, was defined as survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days and was evaluated for both noninferiority and superiority. Secondary outcomes included a comparison of survival between groups and functional and quality-of-life outcomes and adverse events in the investigational device group. A total of 140 patients received the investigational pump, and 499 patients received a commercially available pump implanted contemporaneously. Success occurred in 90.7% of investigational pump patients and 90.1% of controls, establishing the noninferiority of the investigational pump (P<0.001; 15% noninferiority margin). At 6 months, median 6-minute walk distance improved by 128.5 m, and both disease-specific and global quality-of-life scores improved significantly. A small, intrapericardially positioned, continuous-flow, centrifugal pump was noninferior to contemporaneously implanted, commercially available ventricular assist devices. Functional capacity and quality of life improved markedly, and the adverse event profile was favorable. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751972.


[Vigilance for veterinary medicinal products: reports of adverse reactions in the year 2011].
167 adverse reactions of Swissmedic-authorized veterinary medicinal products were reported during the year 2011 (2010: 160). Species and drug classes remain comparable with previous years: most of the reactions occurred following the use of antiparasitic products (39 %), antiinfectives (20 %) or non-steroidal antiinflammatory drugs (11 %) in companion animals (85 dogs and 27 cats) followed by cattle/calves (37). We received 15 cases of adverse reactions following reconverted use, 8 of them in treated cats. Additionally the Swiss Toxicological Information Centre in Zürich processed 84 enquiries and transmitted them to Swissmedic. One case of a successful new therapy to treat ivermectin poisoning in a pony is presented. Finally, the vaccinovigilance program received 60 declarations following the application of various vaccines, mainly to dogs or cats.


Attachment of a hydrogen-bonding carboxylate side chain to an [FeFe]-hydrogenase model complex: influence on the catalytic mechanism.
Azapropanedithiolate (adt)-bridged model complexes of [FeFe]-hydrogenase bearing a carboxylic acid functionality have been designed with the aim of decreasing the potential for reduction of protons to hydrogen. Protonation of the bisphosphine complexes 4-6 has been studied by in situ IR and NMR spectroscopy, which revealed that protonation with triflic acid most likely takes place first at the N-bridge for complex 4 but at the Fe-Fe bond for complexes 5 and 6. Using an excess of acid, the diprotonated species could also be observed, but none of the protonated species was sufficiently stable to be isolated in a pure state. Electrochemical studies have provided an insight into the catalytic mechanisms under strongly acidic conditions, and have also shown that complexes 3 and 6 are electro-active in aqueous solution even in the absence of acid, presumably due to hydrogen bonding. Hydrogen evolution, driven by visible light, has been observed for three-component systems consisting of [Ru(bpy)(3)](2+), complex 1, 2, or 3, and ascorbic acid in CH(3)CN/D(2)O solution by on-line mass spectrometry.


The "snacking child" and its social network: some insights from an Italian survey.
The hypothesis underlying this work is that the social network of a child might have an impact on the alimentary behaviors, in particular for what concerns snack consumption patterns. 1215 Italian children 6-10 ys old were interviewed using a CATI facility in January 2010. 608 "snackers" and 607 "no-snackers" were identified. Information regarding family composition, child and relatives BMI, mother perception of child weight, child, father and mother physical activity, TV watching, social network, leisure time habits and dietary habits of peers, were collected. Association of variables with the status of snacker was investigated using a multivariable logistic regression model. Snackers children seem to be part of more numerous social network (1.40 friends vs 1.14, p = 0.042) where the majority of peers are also eating snacks, this percentage being significantly higher (89.5 vs 76.3, p < 0.001) than in the "no-snacker" group. The snacking group is identified by the fact that it tends to practice at least 4 hours per week of physical activity (OR: 1.36, CI: 1.03-1.9). No evidence of an association between snacking consumption and overweight status has been shown by our study. The snacking child has more active peer-to-peer social relationships, mostly related with sport activities. However, spending leisure time in sportive activities implies being part of a social environment which is definitely a positive one from the point of view of obesity control, and indeed, no increase of overweight/obesity is seen in relation to snack consumption.


Conformational sampling of the intrinsically disordered dsRBD-1 domain from Arabidopsis thaliana DCL1.
DCL1 is the ribonuclease that carries out miRNA biogenesis in plants. Substrate pri-miRNA recognition by DCL1 requires two double stranded RNA binding domains located at the C-terminus of the protein. We have previously shown that the first of these domains, DCL1-A, is intrinsically disordered and folds upon binding pri-miRNA. Integrating NMR and SAXS data, we study here the conformational landscape of free DCL1-A through an ensemble description. Our results reveal that secondary structure elements, corresponding to the folded form of the protein, are transiently populated in the unbound state. The conformation of one of the dsRNA binding regions in the free protein shows that, at a local level, RNA recognition proceeds through a conformational selection mechanism. We further explored the stability of the preformed structural elements via temperature and urea destabilization. The C-terminal helix is halfway on the folding pathway in free DCL1-A, constituting a potential nucleation site for the final folding of the protein. In contrast, the N-terminal helix adopts stable non-native structures that could hinder the correct folding of the protein in the absence of RNA. This description of the unfolded form allows us to understand details of the mechanism of binding-induced folding of the protein.


Anatomical mapping of the biliary tree during laparoscopic cholecystectomy by using indocyanine green dye.
Fluorescent cholangiography using intravenous indocyanine green (ICG) is a noninvasive technique that enables real-time intraoperative imaging of biliary anatomy. The objective of this study was to visualise the biliary anatomy in routine and complicated cases of laparoscopic cholecystectomy (LC). This was a prospective observational study of patients undergoing LC for various indications. After obtaining consent, 5 mg/1 ml of ICG dye was administered intravenously in each patient, 2 h before the incision time. LC was performed by standard critical view of the safety technique. The biliary tree was visualised using near-infrared (NIR) view before clipping any structure. Intra-operative findings, visibility of ducts in the NIR view, conversion, adverse reactions to ICG and post-operative outcomes in all patients were recorded. Out of 43 patients undergoing LC, 24 had cholelithiasis, 10 had acute cholecystitis, 3 had chronic cholecystitis, 1 had mucocele of the gall bladder, 1 had gall bladder polyp and 4 cases had common bile duct (CBD) stone clearance with endoscopic retrograde cholangiopancreatography. Cystic duct (CD) and CBD were visualised in 100% of cases among all groups except for those with acute cholecystitis where CD and CBD were visualised in 90% and 80% of cases, respectively, and in chronic cholecystitis CD and CBD were visualised in 66.6% and 80% of patients, respectively. There was one elective conversion in the chronic cholecystitis group due to dense adhesions and non-progression. Only the CBD was visualised in this case. There were no cases of CBD injury or any allergic reactions to the dye. Fluorescent cholangiography during LC is a safe and non-invasive method, allowing superior anatomical visualisation of the biliary tree in comparison to simple laparoscopy. This method can correct misinterpretation errors and detect aberrant duct anatomy, thus increasing the confidence of the operating surgeon enabling safe dissection. This simple technique has the potential to become standard practice to avoid bile duct injury during LC.


New insights into the interstratification phenomenon in layered double hydroxides (LDHs): a comparison of experimental and computational results for ZnAl-LDH containing bis-tetrazole.
In the present paper, successful preparation of ZnAl layered double hydroxides (LDHs) containing bis-tetrazole anions with both typical and interstratified arrangements is reported. The mechanism of the single-anion interstratified arrangement remains a long-standing and overwhelming challenge in the chemistry of LDHs. To address this issue, the arrangement of layers, the positioning of anions in the interlayer space, and the cationic ratio of layers were studied by the application of a series of laboratory methods including X-ray diffraction (XRD), thermal analyses (TGA, DTG, and DTA), elemental analysis (CHN), and energy dispersive X-ray (EDX) methods, together with computer simulations performed by using Dmol3, Forcite, and Reflex modules. The obtained information demonstrated the dependence of interstratification on the type, size, and charge distribution of the intercalated anions, and the cationic ratio of the LDH layers. At the end, a new comprehensive mechanism is proposed for single-anion interstratification in layered double hydroxides by considering the results of this research study and other related works.


Trinucleotide repeat instability during double-strand break repair: from mechanisms to gene therapy.
Trinucleotide repeats are a particular class of microsatellites whose large expansions are responsible for at least two dozen human neurological and developmental disorders. Slippage of the two complementary DNA strands during replication, homologous recombination or DNA repair is generally accepted as a mechanism leading to repeat length changes, creating expansions and contractions of the repeat tract. The present review focuses on recent developments on double-strand break repair involving trinucleotide repeat tracts. Experimental evidences in model organisms show that gene conversion and break-induced replication may lead to large repeat tract expansions, while frequent contractions occur either by single-strand annealing between repeat ends or by gene conversion, triggering near-complete contraction of the repeat tract. In the second part of this review, different therapeutic approaches using highly specific single- or double-strand endonucleases targeted to trinucleotide repeat loci are compared. Relative efficacies and specificities of these nucleases will be discussed, as well as their potential strengths and weaknesses for possible future gene therapy of these dramatic disorders.


Obstetric complications and schizophrenia: a meta-analysis.
This systematic review of the association between schizophrenia and obstetric complications (OCs) was performed to assess the degree of heterogeneity between studies and to quantify the increased risk of schizophrenia in exposed subjects. Twenty case-control, one prospective cohort and two historical cohort studies were identified using a MEDLINE search supplemented by a manual search and direct communication with other researchers. Individual odds ratios were calculated for each study and a pooled estimate produced. The effect of methodological variation between studies was further assessed by partitioning studies according to study characteristics. Overall, there was no significant heterogeneity of effect between studies, and the pooled odds ratio for the exposure to OCs on subsequent development of schizophrenia was 2.0 (95% CI 1.6-2.4). However, partitioning according to study design revealed significant heterogeneity (z = -2.60, P < 0.01) between the pooled estimate from the case-control studies and that from the historical cohort studies. There was a gap on the funnel plot in the region of small studies finding no effect. Although the result indicates that subjects exposed to OCs are twice as likely to develop schizophrenia, the analysis suggests that the observed association could be inflated by both selection and publication biases.


Artificial Intelligence for PET and SPECT Image Enhancement.
Nuclear medicine imaging modalities such as PET and SPECT are confounded by high noise levels and low spatial resolution, necessitating postreconstruction image enhancement to improve their quality and quantitative accuracy. Artificial intelligence (AI) models such as convolutional neural networks, U-Nets, and generative adversarial networks have shown promising outcomes in enhancing PET and SPECT images. This review article presents a comprehensive survey of state-of-the-art AI methods for PET and SPECT image enhancement and seeks to identify emerging trends in this field. We focus on recent breakthroughs in AI-based PET and SPECT image denoising and deblurring. Supervised deep-learning models have shown great potential in reducing radiotracer dose and scan times without sacrificing image quality and diagnostic accuracy. However, the clinical utility of these methods is often limited by their need for paired clean and corrupt datasets for training. This has motivated research into unsupervised alternatives that can overcome this limitation by relying on only corrupt inputs or unpaired datasets to train models. This review highlights recently published supervised and unsupervised efforts toward AI-based PET and SPECT image enhancement. We discuss cross-scanner and cross-protocol training efforts, which can greatly enhance the clinical translatability of AI-based image enhancement tools. We also aim to address the looming question of whether the improvements in image quality generated by AI models lead to actual clinical benefit. To this end, we discuss works that have focused on task-specific objective clinical evaluation of AI models for image enhancement or incorporated clinical metrics into their loss functions to guide the image generation process. Finally, we discuss emerging research directions, which include the exploration of novel training paradigms, curation of larger task-specific datasets, and objective clinical evaluation that will enable the realization of the full translation potential of these models in the future.


Higher steroid sulfation is linked to successful weight loss in obese children.
Objective Little information is available on the steroid sulfates profile in obese children. Therefore, we examined whether sulfated steroids are linked with weight status and associated comorbidities in obese children. Methods We analyzed 66 obese children (mean age 10.5 ± 2.5 years, 57.6% female, 53.9% prepubertal, mean BMI 27.0 ± 4.6 kg/m2, 50% with BMI-SDS reduction >0.5, 50% without BMI-SDS reduction) who participated in an outpatient 1-year intervention program based on exercise, behavior and nutrition therapy. We measured intact sulfated steroids (cholesterol sulfate (CS), pregnenolone sulfate (PregS), 17αOH pregnenolone sulfate (17OH-PregS), 16αOH dehydroepiandrosterone sulfate (16OH-DHEAS), DHEAS, androstenediol-3-sulfate, androsterone sulfate and epiandrosterone sulfate) by LC-MS/MS, and insulin resistance index HOMA, lipids, blood pressure at baseline and 1 year later. Results All sulfated steroids except 17OH-PregS, 16OH-DHEAS, androsterone sulfate and epiandrosterone sulfate were higher in boys compared to girls. Concentrations of CS before intervention were higher in children who lost weight. After 1 year of treatment, both groups showed increased levels of DHEAS, 16OH-DHEAS and androstenediol-3-sulfate, but PregS was only increased in children with weight loss. None of the steroid sulfates was significantly related to cardiovascular risk factors or HOMA except 17OH-PregS, which was associated with systolic blood pressure both in cross-sectional (β-coefficient: 0.09 ± 0.07, P = 0.020) and longitudinal analyses (β-coefficient: 0.06 ± 0.04, P = 0.013) in multiple linear regression analyses. Conclusions Since higher steroid sulfation capacity was associated with successful weight intervention in children disruption of sulfation may be associated with difficulties to lose weight. Future studies are necessary to prove this hypothesis.


Nanoclay-Reinforced Glass-Ionomer Cements: In Vitro Wear Evaluation and Comparison by Two Wear-Test Methods.
Glass ionomer cement (GIC) represents a major transformation in restorative dentistry. Wear of dental restoratives is a common phenomenon and the determination of the wear resistance of direct-restorative materials is a challenging task. The aim of this paper was to evaluate the wear resistance of novel glass ionomer cement by two wear-test methods and to compare the two wear methods.The wear resistance of a conventional glass ionomer cement (HiFi Advanced Health Care Kent, UK) and cements modified by including various percentages of nanoclays (1, 2 and 4 wt %) was measured by a reciprocating wear test (ball-on-flat) and Oregon Health and Sciences University's (OHSU) wear simulator. The OHSU wear simulation subjected the cement specimens to three wear mechanisms, namely abrasion, three-body abrasion and attrition using a steatite antagonist. The abrasion wear resulted in material loss from GIC specimen as the steatite antagonist forced through the exposed glass particles when it travelled along the sliding path.The hardness of specimens was measured by the Vickers hardness test. The results of reciprocation wear test showed that HiFi-1 resulted in the lowest wear volume 4.90 (0.60) mm³ (p < 0.05), but there was no significant difference (p > 0.05) in the wear volume in comparison to HiFi, HiFi-2 and HiFi-4. Similarly, the results of OHSU wear simulator showed that the total wear volume of HiFi-4 1.49 (0.24) was higher than HiFi-1 and HiFi-2. However, no significant difference (p > 0.05) was found in the OHSU total wear volume in GICs after nanoclay incorporation. The Vickers hardness (HV) of the nanoclay-reinforced cements was measured between 62 and 89 HV. Nanoclay addition at a higher concentration (4%) resulted in higher wear volume and wear depth. The total wear volumes were less dependent upon abrasion volume and attrition volume. The total wear depths were strongly influenced by attrition depth and to some extent by abrasion depth. The addition of nanoclay in higher wt % to HiFi did not result in significant improvement in wear resistance and hardness. Nonetheless, wear is a very complex phenomenon because it is sensitive to a wide number of factors that do not necessarily act in the same way when compared using different parameters.


Inhibition of glutathione efflux in the perfused rat liver and isolated hepatocytes by organic anions and bilirubin. Kinetics, sidedness, and molecular forms.
Using isolated, in situ, single-pass perfused rat livers, incubations of freshly isolated hepatocytes, and sinusoidal membrane-enriched vesicles, we and others have shown the saturability of transport (efflux) of hepatic glutathione (GSH). These observations have implicated a carrier mechanism. Our present studies were designed to provide further evidence in support of a carrier mechanism for hepatic GSH efflux by demonstrating competition by liver-specific ligands which are taken up by hepatocytes. Perfusing livers with different substances, we found that: (a) sulfobromophthalein-GSH (BSP-GSH) had a dose-dependent and fully reversible inhibitory effect on GSH efflux, while GSH alone did not have any effect; (b) taurocholate had no inhibitory effect; (c) all of the organic anions studied, i.e., BSP, rose bengal, indocyanine green, and unconjugated bilirubin (UCB), manifested potent, dose-dependent inhibitory effects, with absence of toxic effects and complete reversibility of inhibition in the case of UCB. The inhibitory effects of UCB could be overcome partially by raising (CoCl2-induced) hepatic GSH concentration. Because of the physiological importance of UCB, we conducted a detailed study of its inhibitory kinetics in the isolated hepatocyte model in the range of circulating concentrations of UCB. Studies with Cl- -free media, to inhibit the uptake of UCB by hepatocytes, showed that the inhibition of GSH efflux by UCB is apparently from inside the cell. This point was confirmed by showing that the inhibition is overcome only when bilirubin-loaded cells are cleared of bilirubin (incubation with 5% bovine serum albumin). Using Gunn rat hepatocytes and purified bilirubin mono- and diglucuronides, we found that both UCB and glucuronide forms of bilirubin inhibit GSH efflux in a dose-dependent manner. We conclude that the organic anions, although taken up by a mechanism independent of GSH, may competitively inhibit the carrier for GSH efflux from inside the hepatocyte.


Trans-10, cis-12-conjugated linoleic acid does not increase body fat loss induced by energy restriction.
Very little evidence exists concerning the effects of conjugated linoleic acid (CLA) on body fat reduction induced by energy restriction. Moreover, although an effect of trans-10, cis-12-CLA on lipolysis has been suggested, it has not been consistently shown. The aims of the present study were to determine whether trans-10, cis-12-CLA increases the reduction of body fat induced by energy restriction, and to analyse its effect on lipolysis and adipose tissue lipase expression (hormone-sensitive lipase (HSL) and adipose tissue TAG lipase (ATGL)). Male Syrian Golden hamsters were fed a high-fat diet during 7 weeks in order to make them fatter. Then they were submitted to a mild energy restriction (25 %) without or with supplementation of 0.5 % trans-10, cis-12-CLA for 3 weeks. Basal glycerol release and lipolysis stimulated by several drugs acting at different levels of the lipolytic cascade were measured in epididymal adipose tissue. The expression of HSL and ATGL was assessed by real-time RT-PCR. No differences were found in adipose tissues size between the experimental groups. Medium adipocyte size and total number of adipocytes were similar in both experimental groups. Animals fed the CLA-enriched diet showed similar lipolytic rates as well as HSL and ATGL expressions to the controls. In conclusion, trans-10, cis-12-CLA does not promote adipose tissue lipid mobilisation nor does it heighten body fat reduction induced by energy restriction. Consequently, this CLA isomer does not seem to be a useful tool to be included in body weight-loss strategies followed in obesity treatment.


Parental age and the risk of autism spectrum disorders: findings from a Swedish population-based cohort.
The objectives of this study were to examine the independent and dependent associations of maternal and paternal age and risk of offspring autism spectrum disorders (ASD), with and without intellectual disability (ID). The sample consisted of 417 303 Swedish children born 1984-2003. ASD case status (N = 4746) was ascertained using national and regional registers. Smoothing splines in generalized additive models were used to estimate associations of parental age with ASD. Whereas advancing parental age increased the risk of child ASD, maternal age effects were non-linear and paternal age effects were linear. Compared with mothers at the median age 29 years, those <29 had similar risk, whereas risk increased after age 30, with an odds ratio (OR) of 1.75 [95% (CI): 1.63-1.89] at ages 40-45. For fathers, compared with the median age of 32 years, the OR for ages 55-59 was 1.39 (1.29-1.50). The risk of ASD was greater for older mothers as compared with older fathers. For example, mothers aged 40-45 (≥97.2th percentile) had an estimated 18.63 (95% CI: 17.25-20.01) ASD cases per 1000 births, whereas fathers aged 55-59 (≥99.7th percentile) had 16.35 (95% CI: 15.11-17.58) ASD cases per 1000 births. In analyses stratified by co-parental age, increased risk due to advancing paternal age was evident only with mothers ≤35 years. In contrast, advancing maternal age increased risk regardless of paternal age. Advancing parental age was more strongly associated with ASD with ID, compared with ASD without ID. We confirm prior findings that advancing parental age increases risk of ASD, particularly for ASD with ID, in a manner dependent on co-parental age. Although recent attention has emphasized the effects of older fathers on ASD risk, an increase of n years in maternal age has greater implications for ASD risk than a similar increase in paternal age.


Myocardial ischemia/reperfusion-induced oxidative renal damage in rats: protection by caffeic acid phenethyl ester (CAPE).
Myocardial ischemia-reperfusion (MI/R) may induce renal damage. A rat model of M/IR injury was established. The left coronary artery was clamped for 30 min, constituting the ischemic period, and was then released for 120 min, thus constituting the reperfusion period. The purpose of this study was to evaluate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant, on renal dysfunction in rats undergoing MI/R. CAPE (50 mumol/kg) was administered by infusion 10 min before ischemia and during occlusion. Hemodynamic changes were recorded during the different periods. At the end of the reperfusion period, rats were sacrificed, and the kidneys were quickly removed for biochemical determination and histopathological analysis. MI/R was accompanied by a significant increase in malondialdehyde (MDA) production and decrease in glutathione (GSH) content in the rat kidney. Administration of CAPE reduced MDA production and prevented depletion of GSH content. These beneficial changes in these biochemical parameters were also associated with parallel changes in histopathological appearance. These findings imply that MI/R plays a causal role in kidney injury through overproduction of oxygen radicals or insufficient antioxidant, and CAPE exerts renal-protective effects probably by its radical scavenging and antioxidant activities.


Managing Spatial Selections With Contextual Snapshots.
Spatial selections are a ubiquitous concept in visualization. By localizing particular features, they can be analysed and compared in different views. However, the semantics of such selections often depend on specific parameter settings and it can be difficult to reconstruct them without additional information. In this paper, we present the concept of contextual snapshots as an effective means for managing spatial selections in visualized data. The selections are automatically associated with the context in which they have been created. Contextual snapshots can also be used as the basis for interactive integrated and linked views, which enable in-place investigation and comparison of multiple visual representations of data. Our approach is implemented as a flexible toolkit with well-defined interfaces for integration into existing systems. We demonstrate the power and generality of our techniques by applying them to several distinct scenarios such as the visualization of simulation data, the analysis of historical documents and the display of anatomical data.


Gap in Capillary Perfusion on Optical Coherence Tomography Angiography Associated With Persistent Macular Edema in Branch Retinal Vein Occlusion.
To evaluate correlations between persistent macular edema associated with branch retinal vein occlusion (BRVO) and the macular perfusion status in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) using optical coherence tomography angiography (OCTA). Retrospective, case-control study. Twenty patients with BRVO followed for 12 months or more were enrolled. Persistent macular edema was defined as central retinal thickness exceeding 300 μm that persisted or recurred less than 3 months after the final treatment. We compared two groups (i.e., seven eyes with persistent macular edema and 13 eyes without macular edema). The macular perfusion status was evaluated using OCTA. We defined a gap vessel as a residual vessel in the SCP that existed simultaneously with capillary loss in the DCP. The gap vessels were determined by subtracting the vessel images of the DCP from the images of the SCP using an image processing technique. In eyes with persistent macular edema, the area with gap vessels was significantly (P = 0.0013) larger than in eyes without macular edema (14.34% vs. 8.02%). Other factors evaluated (i.e., the area of the foveal avascular zone, superficial vessel density, and deep vessel density) did not differ significantly (P = 0.66, P = 0.23, P = 0.34, respectively) between the groups. The difference in capillary loss between the SCP and DCP can facilitate development of persistent macular edema in BRVO.


Condom Use as a Function of Number of Coital Events in New Relationships.
To assess condom use as a function of number of coital events in newly formed sexual relationships. Participants who reported at least one new partner during the 12-week study interval (n = 115; ages 18-29 years; 48% women; 90% African American) completed weekly sexually transmitted infections testing and 3 times daily electronic diary collection assessing individual and partner-specific affect, daily activities, sexual behavior, and condom use. We analyzed event-level condom use percentage and participant-level behavior response effects. generalized additive mixed models were used to estimate condom use probability accounting for within-partner and within-participant correlations via random effects. The average condom use probability at the first coital event in new relationships was 55% for men and 36% for women. Analyses showed that smooth shapes of estimated condom use probabilities were similar for both sexes and were fitted using generalized additive mixed models. Relatively higher condom use percentage was followed by a sharp decline during the first 9 coital events decreasing to 16% for men and 8% for women. More rapid decline in condom use among women was highly associated with higher levels of relationship and sexual satisfaction. The likelihood of condom use declines sharply for both men and women after the early accrual experience with a partner. Relationship and sexual satisfaction also influence declines in condom use, especially among women.


Acute pulmonary hemorrhage during isoflurane anesthesia in two cats exposed to toxic black mold (Stachybotrys chartarum).
Acute pulmonary hemorrhage developed during isoflurane anesthesia in 2 Himalayan cats undergoing routine dental cleaning and prophylaxis. The cats were siblings and lived together. In both cats, results of pre-operative physical examinations and laboratory testing were unremarkable. Blood pressure and oxygen saturation were within reference ranges throughout the dental procedure. Approximately 15 to 20 minutes after administration of isoflurane was begun, frothy blood was noticed within the endotracheal tube. Blood was suctioned from the endotracheal tube, and the cats were allowed to recover from anesthesia. 1 cat initially responded to supportive care but developed a second episode of spontaneous pulmonary hemorrhage approximately 30 hours later and died. The other cat responded to supportive care and was discharged after 4 days, but its condition deteriorated, and the cat died 10 days later. Subsequently, it was discovered that the home was severely contaminated with mold as a result of storm damage that had occurred approximately 7 months previously. Retrospective analysis of banked serum from the cats revealed satratoxin G, a biomarker for Stachybotrys chartarum, commonly referred to as "toxic black mold." Findings highlight the potential risk of acute pulmonary hemorrhage in animals living in an environment contaminated with mold following flood damage.


Cost-effectiveness of a text message programme for the prevention of recurrent cardiovascular events.
To estimate the cost-effectiveness of Tobacco, Exercise and Diet Messages (TEXT ME), a text message-based intervention that provides advice, motivation, information and support to improve health-related behaviours. A lifetime Markov model was used to estimate major vascular events (myocardial infarctions and strokes) avoided, quality-adjusted life years (QALYs) gained, costs to the health system and the incremental cost per QALY gained. The model was informed by data from a randomised controlled trial of TEXT ME, with evidence from systematic reviews and meta-analyses used to estimate the effects of changes in risk factors on the risk of major vascular events. Expected costs and health outcomes were estimated with uncertainty surrounding these characterised using probabilistic sensitivity analysis and a number of scenario analyses. For a target population of 50 000 patients with documented coronary heart disease, the intervention is expected to lead to 563 fewer myocardial infarctions, 361 fewer strokes and 1143 additional QALYs. TEXT ME is expected to lead to an overall saving of $10.56 million for the health system over the patients' lifetimes. The intervention can therefore be considered cost-saving and health-improving. Neither parameter nor structural uncertainty had a significant impact on the conclusion that TEXT ME is cost-effective. The provision of TEXT ME is predicted to lead to better health outcomes and an overall saving in costs for the health system. anzctr.org.au identifier: ACTRN12611000161921.


[Effect of platinum derivatives on microsomal NADPH-oxidoreductase activity].
The influence of platinum derivatives, cisplatin (cis-diamminedichloroplatinum) and imidazolplatin (cis-diimidazoledichloroplatinum) on the activity of rat liver microsomal NADPH-oxidoreductases was investigated in vitro using spectrophotometrical and chemiluminometrical methods. In the range of concentrations from 1 to 12 microM cisplatin inhibited NADPH-cytochrome c-reductase activity and NADPH/lucigenin-dependent chemiluminescence of microsomes. The 3 microM cisplatin decreased the NADPH-dependent reductase activity by 50%. At concentrations less than 2.5 mM sanazole (drug AK-2123) did not prevent the inhibiting influence of cisplatin on microsomal NADPH-dependent reductases. Imidazolplatin insignificantly inhibited NADPH-reductases. It is concluded that negligible inhibiting effect of imidazolplatin on microsomal NADPH-oxidoreductase allows us to consider this platinum derivative as a promising compound for further experimental trials as anticancer drug with low toxic action on the normal tissues of an organism.


First Report of Leaf Spot of Lettuce (Lactuca sativa L.) Caused by Phoma tropica in Italy.
Lettuce (Lactuca sativa L.) is widely grown in Italy, with the production for the preparation of ready-to-eat salads becoming increasingly important. During the spring of 2011, a previously unknown leaf spot was observed on L. sativa plants, cv Rubia, grown in several plastic tunnels in Lumbardy (northern Italy), 20 to 25 days after sowing. Thirty to forty per cent of leaves of the plants growing in the part of the tunnel with the highest relative humidity were affected. Leaves of infected plants showed extensive, irregular, dark brown, necrotic lesions with a chlorotic halo. Lesions initially ranged from 0.5 to 3 mm, then eventually coalesced, reaching 2 to 3 cm, showing a well-defined, dark brown border. Affected leaves senesced and withered. The crown was not affected by the disease. Diseased tissue was excised, immersed in a solution containing 1% sodium hypochlorite for 60 s, rinsed in water, then cultured on potato dextrose agar (PDA), amended with 25 mg/l of streptomycin sulphate. After 5 days, a fungus developed, producing a greenish grey mycelium with a white border when incubated under 12 h/day of fluorescent light at 21 to 23°C. In order to favor the production of conidia, the fungus was transferred on malt extract agar (MA) and maintained under 12 h/day of fluorescent light at 22°C. After 15 days, black pycnidia, 175 to 225 μm, developed, with hyaline, elliptical, unicellular conidia, measuring 3.21 to 6.7 × 1.08 to 3.2 (average 5.5 × 1.9) μm. On the basis of these morphological characteristics, the fungal causal agent of the disease could be related to the genus Phoma (2). The internal transcribed spacer (ITS) region of rDNA of the isolate PHT30 was amplified using the primers ITS1/ITS4 and sequenced. BLAST analysis (1) of the 466-bp segment showed a 99% similarity with the sequence of Phoma tropica (GenBank Accession No. JF923820.1). The nucleotide sequence has been assigned the GenBank Accession No. JQ954396. Pathogenicity tests were performed by spraying healthy 20-day-old lettuce plants, cv Rubia, with a spore suspension (1 × 105 conidia/ml) prepared from 14-day-old colonies of the strain PHT30 grown on MA cultures. Plants inoculated with water alone served as controls. Ten plants per isolate were used. Plants were covered with plastic bags for 5 days after inoculation and maintained in a growth chamber at 20°C and 80% relative humidity. The first foliar lesions, similar to those occurring on the naturally infected plants, developed on leaves 12 days after inoculation. Control plants remained healthy. The pathogen was consistently reisolated from leaf lesions. The pathogenicity test was completed twice. To our knowledge, this is the first report of the presence of P. tropica on lettuce in Italy as well as worldwide. In the United States, the presence of P. exigua was reported in 2006 (3). The economic importance of the disease at present is limited, probably also because symptoms can be confused with those caused by Botrytis cinerea. However, P. tropica could become a more significant problem because of the importance of the crop. References: (1) S. F. Altschul et al. Nucleic Acids Res. 25:3389, 1997. (2) G. H. Boerema. Trans. Br. Mycol. Soc. 67:289, 1976. (3) S. Y. Koike. Plant Dis. 90:1268, 2006.


Comparative, collaborative, and on-site validation of a TaqMan PCR method as a tool for certified production of fresh, campylobacter-free chickens.
Certified Campylobacter-free poultry products have been produced in Denmark since 2002, the first example of fresh (unprocessed and nonfrozen) chickens labeled "Campylobacter free." This success occurred partly through use of a 4-hour gel-based PCR testing scheme on fecal swabs. In this study, a faster, real-time PCR approach was validated in comparative and collaborative trials, based on recommendations from the Nordic system for validation of alternative microbiological methods (NordVal). The comparative real-time PCR trial was performed in comparison to two reference culture protocols on naturally contaminated samples (99 shoe covers, 101 cloacal swabs, 102 neck skins from abattoirs, and 100 retail neck skins). Culturing included enrichment in both Bolton and Preston broths followed by isolation on Preston agar and mCCDA. In one or both culture protocols, 169 samples were identified as positive. The comparative trial resulted in relative accuracy, sensitivity, and specificity of 98%, 95%, and 97%, respectively. The collaborative trial included nine laboratories testing neck skin, cloacal swab, and shoe cover samples, spiked with low, medium, and high concentrations of Campylobacter jejuni. Valid results were obtained from six of the participating laboratories. Accuracy for high levels was 100% for neck skin and cloacal swab samples. For low levels, accuracy was 100% and 92% for neck skin and cloacal swab samples, respectively; however, detection in shoe cover samples failed. A second collaborative trial, with an optimized DNA extraction procedure, gave 100% accuracy results for all three spiking levels. Finally, on-site validation at the abattoir on a flock basis was performed on 400 samples. Real-time PCR correctly identified 10 of 20 flocks as positive; thus, the method fulfilled the NordVal validation criteria and has since been implemented at a major abattoir.


Generation of Novel Plasmodium falciparum NF135 and NF54 Lines Expressing Fluorescent Reporter Proteins Under the Control of Strong and Constitutive Promoters.
Transgenic reporter lines of malaria parasites that express fluorescent or luminescent proteins are valuable tools for drug and vaccine screening assays as well as to interrogate parasite gene function. Different Plasmodium falciparum (Pf ) reporter lines exist, however nearly all have been created in the African NF54/3D7 laboratory strain. Here we describe the generation of novel reporter lines, using CRISPR/Cas9 gene modification, both in the standard Pf NF54 background and in a recently described Cambodian P. falciparum NF135.C10 line. Sporozoites of this line show more effective hepatocyte invasion and enhanced liver merozoite development compared to Pf NF54. We first generated Pf NF54 reporter parasites to analyze two novel promoters for constitutive and high expression of mCherry-luciferase and GFP in blood and mosquito stages. The promoter sequences were selected based on available transcriptome data and are derived from two housekeeping genes, i.e., translation initiation factor SUI1, putative (sui1, PF3D7_1243600) and 40S ribosomal protein S30 (40s, PF3D7_0219200). We then generated and characterized reporter lines in the Pf NF135.C10 line which express GFP driven by the sui1 and 40s promoters as well as by the previously used ef1α promoter (GFP@ef1α, GFP@sui1, GFP@40s). The GFP@40s reporter line showed strongest GFP expression in liver stages as compared to the other two lines. The strength of reporter expression by the 40s promoter throughout the complete life cycle, including liver stages, makes transgenic lines expressing reporters by the 40s promoter valuable novel tools for analyses of P. falciparum.


Outcomes after auto-SCT in African Americans with multiple myeloma.
To study the impact of auto-SCT on the outcomes in African Americans (AA) with multiple myeloma (MM), we evaluated 101 consecutive AA patients who underwent auto-SCT. The median PFS and OS were 15.6 and 50.8 months, respectively. The median OS from diagnosis was 60 months. Traditional pre and post transplant prognostic variables earlier examined in Caucasian Americans (CA), including beta-2 microglobulin (B2M), chromosome 13 deletion, CR status after auto-SCT, gender, stage, Ig subtype, time to transplant, number of prior regimens and presence of lytic lesions, were not predictive of improved PFS or OS on univariate analysis. Age, lower CD34 cell dose infused, history of palliative radiation therapy (XRT) prior to auto-SCT and refractory disease at the time of auto-SCT were predictive of inferior PFS. History of palliative XRT was the only predictive factor of inferior PFS and OS after auto-SCT on multivariate analysis. In conclusion, MM in AA tends to relapse early after auto-SCT. It is unclear whether early relapses impact OS. Common prognostic peritransplant variables known in CA with MM may not be applicable to AA with MM.


Sea Change for Marine Omega-3s: Randomized Trials Show Fish Oil Reduces Cardiovascular Events.
Recently, 3 large randomized controlled trials (RCTs) have assessed the effects of supplementation with marine omega-3 fatty acids on the occurrence of cardiovascular disease (CVD) events. We reviewed this evidence and considered it in the context of the large and growing body of data on the CV health effects of marine omega-3s. One RCT examining 8179 patients, most with coronary heart disease (CHD), reported that 4 grams/day of a highly purified omega-3 product containing eicosapentaenoic acid (EPA) reduced the risk for major adverse CV events by 25% (P<.001). Two other recent RCTs in primary prevention populations showed that approximately 1 gram/day of purified fish oil containing 840 mg/day of EPA and docosahexaenoic acid (DHA) significantly reduced risks of CHD and CV death, especially in individuals who did not consume fish and seafood frequently. The American Heart Association (AHA) continues to emphasize the importance of marine omega-3s as a nutrient for potentially reducing risks of congestive heart failure, CHD, ischemic stroke, and sudden cardiac death. Marine omega-3s should be used in high doses for patients with CHD on statins who have elevated triglycerides and at about 1 gram/day for primary prevention for individuals who do not consume at least 1.5 fish or seafood meals per week.


A Model for Osteonecrosis of the Jaw with Zoledronate Treatment following Repeated Major Trauma.
This study aims to develop a reproducible rat model for post-traumatic bisphosphonate-related osteonecrosis of the jaw (BRONJ). In our previous studies using dental extraction as an inducing factor, only 30%-60% of zoledronate-treated animals fulfilled the definition of clinical BRONJ. We modified the zoledronate regimen and introduced repeated surgical extraction to illicit quantifiable BRONJ in all animals. Eighty retired-breeder female Sprague-Dawley rats were divided between the treatment (i.v. zoledronate; 80 μg/kg/week for 13 weeks) and control (saline) groups. On week 13, the left mandibular first molar was surgically extracted, followed by the second molar a week later. Animals were euthanized at 1-week, 2-weeks, and 8-weeks following extraction. The occurrence and severity of BRONJ were scored in each animal based on gross and MicroCT analysis. Parameters of bone formation and osteoclast functions at the extraction site were compared between groups. All zoledronate-treated animals developed a severe case of BRONJ that fulfilled the clinical definition of the condition in humans. Osteoclast attachment continued to be defective eight weeks after stopping the treatment. There were no signs of kidney or liver toxicity. Our data confirmed that repeated surgical extraction (major trauma) by itself consistently precipitated massive bone necrosis in ZA-treated animals, eliminating the need to induce pre-existing infection or comorbidity. These results will be the basis for further studies examining the in-vivo pathogenesis and prevention of BRONJ.


Ethical challenges in conducting clinical research in lung cancer.
The article examines ethical challenges that arise with clinical lung cancer research focusing on design, recruitment, conduct and dissemination. problems related to equipoise can arise in lung cancer studies. Equipoise is an ethics precondition for RCTs and exists where there is insufficient evidence to decide which of two or more treatments is best. Difficulties arise in deciding what level of uncertainty constitutes equipoise and who should be in equipoise, for example, patients might not be even where clinicians are. Patient and public involvement (PPI) can reduce but not remove the problems. Recruitment: (I) lung cancer studies can be complex, making it difficult to obtain good quality consent. Some techniques can help, such as continuous consent. But researchers should not expect consent to be the sole protection for participants' welfare. This protection is primarily done elsewhere in the research process, for example, in ethics review; (II) the problem of desperate volunteers: some patients only consent to a trial because it gives them a 50/50 option of the treatment they want and can be disappointed or upset if randomised to the other arm. This is not necessarily unfair, given clinical equipoise. However, it should be avoided where possible, for example, by using alternative trial designs; (III) the so-called problem of therapeutic misconception: this is the idea that patients are mistaken if they enter trials believing this to be in their clinical best interest. We argue the problem is misconceived and relates only to certain health systems. Conduct: lung cancer trials face standard ethical challenges with regard to trial conduct. PPI could be used in decisions about criteria for stopping rules. as in other trial areas, it is important that all results, including negative ones, are reported. We argue also that the role of PPI with regard to dissemination is currently under-developed.


Counseling the patient who has genital herpes or genital human papillomavirus infection.
Educational counseling has an important role in managing patients who have viral STIs, such as genital herpes and genital HPV infections. Given the lack of a curative therapy for both, patients may require long-term management and may need to be attentive to recurring symptoms. In addition, both diagnoses may raise issues of persisting infectiousness along with a need for patient counseling about the potential risk to partners and risk reduction strategies. Lastly, dozens of published papers over the years describe potential psychosocial sequelae for patients who have genital herpes, and there is a growing psychosocial literature on genital HPV as well. Clinicians can make a significant difference in patient adjustment to the diagnosis of an STI, and addressing these challenging issues will benefit patients greatly.


Testing one or multiple: How beliefs about sparsity affect causal experimentation.
What is the best way of discovering the underlying structure of a causal system composed of multiple variables? One prominent idea is that learners should manipulate each candidate variable in isolation to avoid confounds (sometimes known as the control of variables [CV] strategy). We demonstrate that CV is not always the most efficient method for learning. Using an optimal actor model, which aims to minimize the average number of tests, we show that when a causal system is sparse (i.e., when the outcome of interest has few or even just one actual cause among the candidate variables), it is more efficient to test multiple variables at once. Across a series of behavioral experiments, we then show that people are sensitive to causal sparsity and adapt their strategies accordingly. When interacting with a dense causal system (high proportion of actual causes among candidate variables), they use a CV strategy, changing one variable at a time. When interacting with a sparse causal system, they are more likely to test multiple variables at once. However, we also find that people sometimes use a CV strategy even when a system is sparse. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


New evidence on the Affordable Care Act: coverage impacts of early medicaid expansions.
The Affordable Care Act expands Medicaid in 2014 to millions of low-income adults in states that choose to participate in the expansion. Since 2010 California, Connecticut, Minnesota, and Washington, D.C., have taken advantage of the law's option to expand coverage earlier to a portion of low-income childless adults. We present new data on these expansions. Using administrative records, we documented that the ramp-up of enrollment was gradual and linear over time in California, Connecticut, and D.C. Enrollment continued to increase steadily for nearly three years in the two states with the earliest expansions. Using survey data on the two earliest expansions, we found strong evidence of increased Medicaid coverage in Connecticut (4.9 percentage points; $$p ) and positive but weaker evidence of increased coverage in D.C. (3.7 percentage points; $$p=\mathbf{\boldsymbol{0.08}}$$). Medicaid enrollment rates were highest among people with health-related limitations. We found evidence of some crowd-out of private coverage in Connecticut (30-40 percent of the increase in Medicaid coverage), particularly for healthier and younger adults, and a positive spillover effect on Medicaid enrollment among previously eligible parents.


Automated microfluidic droplet sampling with integrated, mix-and-read immunoassays to resolve endocrine tissue secretion dynamics.
A fully automated droplet generation and analysis device based on pressure driven push-up valves for precise pumping of fluid and volumetric metering has been developed for high resolution hormone secretion sampling and measurement. The device consists of a 3D-printer templated reservoir for single cells or single tissue culturing, a Y-shaped channel for reagents and sample mixing, a T-junction channel for droplet formation, a reference channel to overcome drifts in fluorescence signal, and a long droplet storage channel allowing incubation for homogeneous immunoassays. The droplets were made by alternating peristaltic pumping of aqueous and oil phases. Device operation was automated, giving precise control over several droplet parameters such as size, oil spacing, and ratio of sample and reference droplets. By integrating an antibody-oligonucleotide based homogeneous immunoassay on-chip, high resolution temporal sampling into droplets was combined with separation-free quantification of insulin secretion from single islets of Langerhans using direct optical readout from the droplets. Quantitative assays of glucose-stimulated insulin secretion were demonstrated at 15 second temporal resolution while detecting as low as 10 amol per droplet, revealing fast insulin oscillations that mirror well-known intracellular calcium signals. This droplet sampling and direct optical analysis approach effectively digitizes the secretory time record from cells into droplets, and the system should be generalizable to a variety of cells and tissue types.


Opportunities for glyconanomaterials in personalized medicine.
In this feature article we discuss the particular relevance of glycans as components or targets of functionalized nanoparticles (NPs) for potential applications in personalized medicine but we will not enter into descriptions for their preparation. For a more general view covering the preparation and applications of glyconanomaterials the reader is referred to a number of recent reviews. The combination of glyco- and nanotechnology is already providing promising new tools for more personalized solutions to diagnostics and therapy. Current applications relevant to personalized medicine include drug targeting, localized radiation therapy, imaging of glycan expression of cancer cells, point of care diagnostics, cancer vaccines, photodynamic therapy, biosensors, and glycoproteomics.


Explaining adherence success in sub-Saharan Africa: an ethnographic study.
Individuals living with HIV/AIDS in sub-Saharan Africa generally take more than 90% of prescribed doses of antiretroviral therapy (ART). This number exceeds the levels of adherence observed in North America and dispels early scale-up concerns that adherence would be inadequate in settings of extreme poverty. This paper offers an explanation and theoretical model of ART adherence success based on the results of an ethnographic study in three sub-Saharan African countries. Determinants of ART adherence for HIV-infected persons in sub-Saharan Africa were examined with ethnographic research methods. 414 in-person interviews were carried out with 252 persons taking ART, their treatment partners, and health care professionals at HIV treatment sites in Jos, Nigeria; Dar es Salaam, Tanzania; and Mbarara, Uganda. 136 field observations of clinic activities were also conducted. Data were examined using category construction and interpretive approaches to analysis. Findings indicate that individuals taking ART routinely overcome economic obstacles to ART adherence through a number of deliberate strategies aimed at prioritizing adherence: borrowing and "begging" transport funds, making "impossible choices" to allocate resources in favor of treatment, and "doing without." Prioritization of adherence is accomplished through resources and help made available by treatment partners, other family members and friends, and health care providers. Helpers expect adherence and make their expectations known, creating a responsibility on the part of patients to adhere. Patients adhere to promote good will on the part of helpers, thereby ensuring help will be available when future needs arise. Adherence success in sub-Saharan Africa can be explained as a means of fulfilling social responsibilities and thus preserving social capital in essential relationships.


A randomized controlled trial of mindfulness-based cognitive therapy for bipolar disorder.
To compare the efficacy of mindfulness-based cognitive therapy (MBCT) plus treatment as usual (TAU) to TAU alone for patients with bipolar disorder over a 12-month follow-up period. Participants with a DSM-IV diagnosis of bipolar disorder were randomly allocated to either MBCT plus TAU or TAU alone. Primary outcome measures were time to recurrence of a DSM-IV major depressive, hypomanic or manic episode; the Montgomery-Åsberg Depression Rating Scale (MADRS); and Young Mania Rating Scale (YMRS). Secondary outcome measures were number of recurrences, the Depression Anxiety Stress Scales (DASS), and the State Trait Anxiety Inventory (STAI). Ninety-five participants with bipolar disorder were recruited to the study (MBCT = 48; TAU = 47). Intention-to-treat (ITT) analysis found no significant differences between the groups on either time to first recurrence of a mood episode or total number of recurrences over the 12-month period. Furthermore, there were no significant between-group differences on the MADRS or YMRS scales. A significant between-group difference was found in STAI - state anxiety scores. There was a significant treatment by time interaction for the DAS - achievement subscale. While MBCT did not lead to significant reductions in time to depressive or hypo/manic relapse, total number of episodes, or mood symptom severity at 12-month follow-up, there was some evidence for an effect on anxiety symptoms. This finding suggests a potential role of MBCT in reducing anxiety comorbid with bipolar disorder.


Tumors of the infratemporal fossa.
Neoplastic processes involving the infratemporal fossa may originate from the tissues in the region, but more often are the result of extension from neighboring structures. Metastatic lesions located in the region are rarely encountered. Because of its concealed localization, tumors may remain unnoticed for some time. Clinical signs and symptoms often arise late, are insidious, and may be mistakenly attributed to other structures. The close proximity of the area to the intracranial structures, the orbit, the paranasal sinuses, the nasopharynx, and the facial area demands careful planning of surgical excision and combined procedures may be called for. Modern imaging techniques have made three-dimensional visualization of the extent of the pathology possible. Treatment depends on the histopathology and staging of the tumor. Several surgical approaches have been developed over the years. Radical tumor excision with preservation of the quality of life remain the ultimate goal for those tumors where surgery is indicated. Experience over a decade with various pathologies is presented.


Essential oils and low-intensity electromagnetic pulses in the treatment of androgen-dependent alopecia.
This double-blind randomized study vs placebo in healthy male and female volunteers demonstrates the positive biologic effect on hair loss and hair regrowth of a pulsed electromagnetic field in combination with essential oils administered according to a regular treatment schedule of 26 weeks. Mean hair count comparisons within the groups significantly favor the treatment group, which exhibited a decrease in hair loss in 83% of the volunteers and a more than 20% hair count increase over baseline in 53% of patients. The process exhibited no side effects or untoward reactions. The histologic examination correlated with the clinical study. A parallel immunohistochemical examination showed an increase in the proliferation index, and when the expression of Ki67 (a cell proliferation marker) is increased, the mitoses are barely visible in the histologic examination. The rationale of this phenomenon is considered to be due to an electrophysiologic effect on the quiescent hair follicle.


Evaluation of three neonicotinoid insecticides against the common pistachio psylla, Agonoscena pistaciae, and its natural enemies.
The common pistachio psylla, Agonoscena pistaciae Burckhardt and Lauterer (Hemiptera: Psyllidae), is a key pest in pistachio orchards in Iran. Chemical control is a common method to manage this pest. Compatibility between natural enemies and pesticides is a primary concern in programs of integrated pest management of the psyllid pest. In this research, susceptibility of fifth instar nymphs of Ag. pistaciae and fourth instar larvae of the two most common predators of this pest, Adalia bipunctata L. (Coleoptera: Coccinellidae) and Coccinella undecimpunctata aegyptiaca Reiche, to acetamiprid, thiamethoxam, and imidacloprid was investigated. Probit analysis of concentration-mortality data was conducted to estimate the LC50 value. The results showed that thiamethoxam with an LC50 value of 56.35 mg a.i./L was more toxic to fifth instar nymphs of Ag. pistaciae in comparison to acetamiprid (60.75 mg a.i/L) and imidacloprid (138.21 mg a.i/L) . Imidacloprid with an LC50 value of 218.89 mg a.i/L compared to acetamiprid (222.65 mg a.i/L) and thiamethoxam (232.37 mg a.i/L) had more lethal effects on fourth instar larvae of Ad. bipunctata. However, on the fourth instar larvae of C. undecimpunctata aegyptica, acetamiprid with an LC50 value of 263.44 mg a.i/L was more toxic than thiamethoxam (296.62 mg a.i/L) and imidacloprid (447.82 mg a.i/L). The laboratory findings showed that the three tested insecticides were more toxic to the common pistachio psylla than to its natural predators. Thiamethoxam was the most toxic against Ag. pistaciae. However, its toxicity to the predators was lower than imidacloprid and acetamiprid. This result suggests that thiamethoxam is the best insecticide for control of Ag. pistaciae in combination with predatory lady beetles.


The digestibility and accumulation of dietary phytosterols in Atlantic salmon (Salmo salar L.) smolt fed diets with replacement plant oils.
Phytosterols occur in high concentration in canola (Brassica napus L.) and other vegetable oils such as from the borage plant Echium (Echium plantagineum L.). We investigated if Atlantic salmon (Salmo salar) digest and accumulate dietary phytosterols in significant amounts in muscle and liver. Phytosterols are lipid soluble, lower cholesterol and reduce the risk of coronary heart disease in humans. We aimed to determine if fatty fish, such as salmon, can be used as a delivery source of this functional food component. Three diets containing canola oil (CO), Echium oil (EO) and fish oil (FO) were fed to Atlantic salmon smolt over 9 weeks. The digestibility of natural abundances of phytosterols by Atlantic salmon was poor compared to cholesterol. However, phytosterols accumulated in liver and muscle of fish. Significantly increased concentrations of 24-methylenecholesterol, campesterol, beta-sitosterol and total phytosterol occurred in livers of EO fed fish compared to FO fed fish. Campesterol concentrations increased in CO fed fish compared to the FO fed fish. We demonstrated that natural abundances of dietary phytosterols are digested by and accumulated in liver and white muscle of Atlantic salmon smolt. However, phytosterol levels in salmon muscle will not be a major source of phytosterols in human diets and would not be expected to significantly effect human cardiovascular health.


A Topographic Atlas of the Human Brainstem in the Ponto-Mesencephalic Junction Plane.
The human brainstem harbors neuronal aggregates that ensure the maintenance of several vital functions. It also acts as a major relay structure for the neuronal information that travels between the cerebral cortex, the cerebellum and the spinal cord. As such, this relatively small portion of the human brain houses a multitude of ascending and descending fibers that course among numerous nuclei whose exact boundaries are still uncertain. Such a large number of nuclei and fiber tracts confined to a relatively small and compact brain region imposes upon the brainstem a highly complex cytoarchitectonic organization that still needs to be deciphered. The present work provides a topographic atlas of the human brainstem composed of 45 anatomical plates, each containing a pair of adjacent sections stained with Cresyl Violet and Luxol Fast Blue to help delineating brainstem nuclei and fiber tracts, respectively. The plates, which cover the entire midbrain, pons and medulla oblongata, are composed of equally-spaced sections referenced and aligned parallel to the ponto-mesencephalic junction rather than the fastigium or the obex. This topographic landmark is particularly suitable for neurosurgical interventions aiming at specific nuclei of the mesencephalic tegmentum. In complement, we provide 8 anatomical plates containing adjacent sections stained for choline acetyltransferase and Luxol Fast Blue, taken through the midbrain and the pons. This open access atlas of the human brainstem is intended to assist neuroanatomists, neurosurgeons and neuropathologists in their work.


Identification and functional assay of the interaction motifs in the partner protein OsNAR2.1 of the two-component system for high-affinity nitrate transport.
A partner protein, NAR2, is essential for high-affinity nitrate transport of the NRT2 protein in plants. However, the NAR2 motifs that interact with NRT2s for their plasma membrane (PM) localization and nitrate transporter activity have not been functionally characterized. In this study, OsNAR2.1 mutations with different carbon (C)-terminal deletions and nine different point mutations in the conserved regions of NAR2 homologs in plants were generated to explore the essential motifs involved in the interaction with OsNRT2.3a. Screening using the membrane yeast two-hybrid system and Xenopus oocytes for nitrogen-15 ((15)N) uptake demonstrated that either R100G or D109N point mutations impaired the OsNAR2.1 interaction with OsNRT2.3a. Western blotting and visualization using green fluorescent protein fused to either the N- or C-terminus of OsNAR2.1 indicated that OsNAR2.1 is expressed in both the PM and cytoplasm. The split-yellow fluorescent protein (YFP)/BiFC analyses indicated that OsNRT2.3a was targeted to the PM in the presence of OsNAR2.1, while either R100G or D109N mutation resulted in the loss of OsNRT2.3a-YFP signal in the PM. Based on these results, arginine 100 and aspartic acid 109 of the OsNAR2.1 protein are key amino acids in the interaction with OsNRT2.3a, and their interaction occurs in the PM but not cytoplasm.


Everolimus for the treatment of refractory seizures associated with tuberous sclerosis complex (TSC): current perspectives.
Up to 90% of patients with tuberous sclerosis complex (TSC) have epilepsy, and in over half of patients seizure control cannot be achieved by regular antiepileptic drugs. The underlying problem is mTOR hyperactivation due to loss of function of the TSC proteins. Treatment with everolimus, an mTOR inhibitor, has been shown to be of great benefit to TSC patients, both in reducing tumor growth and as a treatment for intractable epilepsy. Up to 40% of TSC patients with intractable epilepsy show a clinically relevant seizure response to everolimus. It has not yet fully lived up to its promise as a disease-modifying drug, however, as half of TSC patients with intractable epilepsy do not show a clinically relevant seizure frequency reduction. There is no evidence yet of a positive effect on the cognitive and neuropsychiatric deficits in TSC patients. In preclinical studies, mTOR inhibition can rescue abnormal neuronal migration and synapse formation that is caused by mTOR hyperactivation. These studies show a critical time window that suggests that mTOR inhibition may be most beneficial in young children. The trials done so far have not studied treatment in children under 2 years of age, although case series suggest that the safety profile is similar to that in older children. Further studies into the optimal time window, dosing schedules and possibly combination with other drugs may further improve the benefit of everolimus for TSC patients.