Efficacy of lettuce seed syrup on insomnia in patients with breast cancer: a pilot double blind randomized placebo controlled clinical trial.
Insomnia and sleep disorders are common and can be severe amongst patients with cancer, especially during chemotherapy. The aim of this study was to evaluate the efficacy of lettuce seed syrup in breast cancer patients who suffer from insomnia or disordered sleep. This pilot study was a double-blinded randomized controlled clinical trial conducted in Shoha-e-Tajrish Hospital (Tehran, Iran) from September 2018 to June 2019. 50 adult patients with breast cancer with insomnia or sleep disorders were enrolled. Participants were randomly allocated to lettuce seed syrup (5 mL twice daily), or placebo syrup at the same dose for four weeks. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality before and after the intervention. Compared to placebo, the mean of the total PSQI score decreased significantly in participants who received lettuce seed syrup (p=0.014). In addition, there were statistically significant reductions in the mean scores of subject quality sleep (p=0.002), sleep duration (p=0.038), habitual sleep efficacy (p=0.029) and sleep disturbance (p=0.032) in patients who received lettuce seed syrup. Lettuce seed syrup may improve self-reported sleep quality in participants with breast cancer. Larger trials are indicated in diverse samples of participants with caner to learn if these finds are generalizable.


Endoscopic endonasal anatomy of the ophthalmic artery in the optic canal.
The endoscopic endonasal opening of the optic canal has been recently proposed for tumors with medial invasion of this canal, such as tuberculum sellae meningiomas. Injury of the ophthalmic artery represents a dramatic risk during this maneuver. Therefore, the aim of this study was to analyze the endoscopic endonasal anatomy of the precanalicular and canalicular portion of this vessel, discussing its clinical implication. The course of the ophthalmic artery was analyzed through five endoscopic endonasal dissections, and 40 nonpathological consecutive MRAs were reviewed. The ophthalmic artery arises from the intradural portion of the supraclinoid internal carotid artery, in 93 % of cases about 1.9 mm (range: 1-3) posterior to the falciform ligament. At the entrance into the optic canal, the ophthalmic artery is located infero-medially to the optic nerve in 13 % of cases. In 50 % of these cases the artery moves infero-laterally along its course, remaining in a medial position in the others. In cases with an non medial entrance of the ophthalmic artery, it runs infero-lateral to the optic nerve for its entire canalicular portion, with just one exception. The endoscopic endonasal approach gives a direct, extensive and panoramic view of the course of the precanalicular and canalicular portion of the ophthalmic artery. Dedicated high-field neuroimaging studies are of paramount importance in preoperative planning to evaluate the anatomy of the ophthalmic artery, reducing the risk of jeopardizing the vessel, particularly for those uncommon cases with an infero-medial course of the artery.


Carbonyl emissions from vehicular exhausts sources in Hong Kong.
Vehicular emission (VE) is one of the important anthropogenic sources for airborne carbonyls in urban area. Six types of VE-dominated samples were collected at representative locations in Hong Kong where polluted by a particular fueled type of vehicles, including (i) a gas refilling taxis station (liquefied petroleum gas [LPG] emission); (ii) a light-duty passenger car park (gasoline emission); (iii) a minibus station (diesel emission); (iv) a single-deck-bus depot (diesel emission); (v) a double-deck-bus depot (diesel emission); and (vi) a whole-food market entrance for light- and heavy-duty vehicles (diesel emission). A total of 15 carbonyls in the samples were quantified. Formaldehyde was the most abundant carbonyl among the VE-dominated samples, and its contribution to the total quantified amount on a molar basis ranged from 54.8% to 60.8%. Acetaldehyde and acetone were the next two abundant carbonyls. The carbonyls were quantified at three roadside locations in Hong Kong. The highest concentrations of formaldehyde and acetaldehyde, 22.7 +/- 8.4 and 6.0 +/- 2.8 microg/m3, respectively, were determined in the samples collected at a main transportation gate for goods between Hong Kong and Mainland China. The total quantified carbonyl concentration, 37.9 +/- 9.3 microg/m3, was the highest at an entrance of a cross-harbor tunnel in downtown area. The theoretical carbonyls compositions of the three roadside locations were estimated according to the VE-dominated sample profiles and the statistics on vehicle numbers and types during the sampling period. The measured compositions of formaldehyde were much higher than the theoretical compositions in summer, demonstrating that photochemical reactions significantly contributed to the formaldehyde production in the roadsides.


Combined Effects of Mirror Therapy and Exercises on the Upper Extremities in Children with Unilateral Cerebral Palsy: A Randomized Controlled Trial.
Purpose: This study investigated the combined effects of mirror therapy involving power and strength exercises of the upper extremities in children with Unilateral Spastic Cerebral Palsy (USCP).Methods: Thirty children were included in either an experimental group or a control group. All participants were evaluated with the Quality of Upper Extremity Skill Test (QUEST), Canadian Occupational Performance Measure (COPM), and a handheld dynamometer to measure isometric muscle strength.Results: Compared to the control group, greater improvement was found in dissociated movements (p < .001, d = 1.82), grasp (p < .001, d = 1.38), weight bearing (p = .006, d = 0.91), and total scores (p = .001, d = 1.16) of QUEST; performance (p < .001, d = 2.9), satisfaction (p < .001, d = 1.91), and total scores (p < .001, d = 2.87) of COPM; and isometric muscle strength of the biceps brachii (p < .001, d = 1.27) and triceps brachii (p = .002, d = 2.22) of the affected upper limbs in the experimental group.Conclusions: Mirror therapy combined with power and strength exercises is a promising intervention approach to improve activity performance and upper-limb function in children with USCP.


Comparison of two cadaveric acellular dermal matrices for immediate breast reconstruction: A prospective randomized trial.
AlloDerm RTU® and AlloMaxTM are two acellular dermal matrices (ADMs) used in implant-based breast reconstruction. In this study, we examined whether different processing methods for the ADMs lead to a disparity in histologic, clinical, and financial outcomes after breast reconstruction. Thirty patients undergoing implant-based breast reconstruction were randomized into AlloMax or AlloDerm arms (n = 15, each). ADM was placed at the time of immediate reconstruction. Patients were evaluated for complications on postoperative days 7, 14, and 30. During implant exchange, ADM biopsies were taken and compared histologically for vascular and cellular infiltration. Patient satisfaction was evaluated using the BRECON-31 questionnaire 1 year after implant exchange. A cost analysis was performed comparing the two ADMs. Patient demographics and complication rates were similar between the two groups (p > 0.05). Histologically, vessel density and fibroblast/inflammatory cell infiltrate were greater on the dermal side than on the implant side (p < 0.01) in both ADMs, suggesting greater vascular and cellular in-growth from the dermal side. Vessel density in the middle portion of the Allomax biopsies was significantly higher than the same site in the Alloderm biopsies (p < 0.05). The extent of fibroblast/inflammatory cell infiltration was similar in both arms (p > 0.05). The BRECON-31 satisfaction questionnaire yielded similar responses across all metrics between the two study arms. The negotiated price was slightly different when comparing the two ADMs, with no significant difference in ADM reimbursement. In this study, AlloDerm RTU and AlloMax were successfully used for implant-based breast reconstruction with comparable outcomes.


[Pyo-necrotic injuries in case of the neuro-ischemic form of diabetic foot syndrome].
It was analyzed the results of examination and treatment of 217 patients with neuro-ischemic form of the diabetic foot syndrome. Diabetic macroangiopathy with critical limb ischemia (TASC II) was diagnosed in all patients. Tissue foot damage of grade 3 (Wagner) was observed in 100 (46.1%) patients, grade 4 - in 117 (53.9%) patients. The developed strategy of surgical treatment includes the revascularization of an affected limb, surgical management of a pyo-necrotic focus and the plastic reconstruction of the foot after rapid relief of ischemia symptoms. An application of such treatment strategy led to preserve a foot or a stump of the foot in 205 (94.5%) patients.


Cadmium exposure and MEG3 methylation differences between Whites and African Americans in the NEST Cohort.
Cadmium (Cd) is a ubiquitous environmental pollutant associated with a wide range of health outcomes including cancer. However, obscure exposure sources often hinder prevention efforts. Further, although epigenetic mechanisms are suspected to link these associations, gene sequence regions targeted by Cd are unclear. Aberrant methylation of a differentially methylated region (DMR) on the MEG3 gene that regulates the expression of a cluster of genes including MEG3, DLK1, MEG8, MEG9 and DIO3 has been associated with multiple cancers. In 287 infant-mother pairs, we used a combination of linear regression and the Getis-Ord Gi* statistic to determine if maternal blood Cd concentrations were associated with offspring CpG methylation of the sequence region regulating a cluster of imprinted genes including MEG3. Correlations were used to examine potential sources and routes. We observed a significant geographic co-clustering of elevated prenatal Cd levels and MEG3 DMR hypermethylation in cord blood (P = 0.01), and these findings were substantiated in our statistical models (β = 1.70, se = 0.80, P = 0.03). These associations were strongest in those born to African American women (β = 3.52, se = 1.32, P = 0.01) compared with those born to White women (β = 1.24, se = 2.11, P = 0.56) or Hispanic women (β = 1.18, se = 1.24, P = 0.34). Consistent with Cd bioaccumulation during the life course, blood Cd levels increased with age (β = 0.015 µg/dl/year, P = 0.003), and Cd concentrations were significantly correlated between blood and urine (ρ > 0.47, P < 0.01), but not hand wipe, soil or house dust concentrations (P > 0.05). Together, these data support that prenatal Cd exposure is associated with aberrant methylation of the imprint regulatory element for the MEG3 gene cluster at birth. However, neither house-dust nor water are likely exposure sources, and ingestion via contaminated hands is also unlikely to be a significant exposure route in this population. Larger studies are required to identify routes and sources of exposure.


Skateboarding injuries.
Skateboarding has experienced intermittent periods of popularity since the 1960s. Along with this popularity, there have been concomitant increases in numerous types of injuries. Most documented cases occur in boys aged from 10 to 14 years, with injuries ranging from minor cuts and abrasions to multiple fractures and, in some cases, even death. Although head injuries account for approximately 3.5 to 9% of all skateboarding injuries, fractures of both upper and lower extremities account for 50% of all musculoskeletal trauma. Not surprising is the fact that 33% of those injured on skateboards are injured within the first week of skateboarding. Most individuals experience some form of trauma during the initial attempt at skateboarding. Because of the nature of skateboarding, encompassing both high speed and extreme manoeuvres, injuries often occur when the skateboarder collides with an immovable object, falls from the skateboard or is involved in vehicular traffic. Most injuries occur when the skateboard strikes an irregularity in the riding surface, projecting the skateboarder in the direction of travel. Despite traffic legislation, 65% of injured adolescent skateboarders sustain injuries on public roads, on footpaths, and in parking lots. Several organisations have recommended safety guidelines and restrictions based on age and common sense. Use of a helmet, knee and elbow pads, and wrist guards should be required of all skateboarders, as well as some type of formal education. The American Academy of Pediatrics recommends that children under 5 years of age should not be allowed to ride skateboards. At an early age, injuries occur due to several reasons. These include high centre of mass, immature skeletal development, an undeveloped neuromuscular system, and simply poor judgement. Skateboarding injuries are expected to rise with the increasing number of participants, high-tech equipment development and renewed advertising. Although limited preventative measures exist which will totally eradicate skateboarding trauma, some thought to actual restrictions may decrease the incidence and severity of injuries.


The effect of a catechin-rich extract of Cocos nucifera on lymphocytes proliferation.
Catechins are polyphenols with antioxidant activity. The fruit Cocos nucifera (Palmae) has a fi ber husk rich in catechins and the local population of northeast Brazil uses it as a medicine against various diseases. An anti-bacterial and anti-viral activity has been already observed using this substance. Plant extracts, from other sources, rich in catechins are inhibitory to tumour cells, suppressing their proliferation. The aim of the present work was to verify if catechins isolated from Cocos nucifera were capable of inhibiting cell proliferation. An extract obtained from Cocos nucifera was purified through adsorption chromatography using the resin XAD-2. The purified material was used in cultures of an erythroleukaemia cell line (K562) and on normal human peripheral blood lymphocytes. Cell viability was assessed using MTT. Cellular proliferation was measured by [(3)H]-thymidine incorporation and cell cycle analysis in a fl ow cytometer. A dose-dependent inhibitory effect was observed on tumour cells and on lymphocytes activated by phytohemaglutinin (PHA) or phorbol ester. For PHA this effect was irreversible being already established on the fi rst four hours of culture.


Familial Adult-onset Alexander Disease: Clinical and Neuroradiological Findings of Three Cases.
The adult-onset Alexander disease (AOAD) dramatically differs from the early onset AD with respect to clinical and neuroradiological findings. Herein we report the detailed clinical and neuroradiological findings of a Turkish family with AOAD. In all three cases, magnetic resonance imaging revealed marked atrophy of the mesencephalon, bulbus, and cervical spinal cord accompanied with signal abnormalities in the same regions along with supratentorial white matter. Basal ganglia were affected in two cases. Molecular genetic analysis revealed heterozygous mutation in the 8th exon of the glial fibrillary acidic protein gene M451I (c.1245G>A), leading to the diagnosis of AOAD in all cases.


Psychiatric Treatment of Medical Colleagues and Their Families: Potential Risks.
Clinicians treating "very important persons" face potential problems that can negatively impact the quality of care they provide. Mental health professionals face similar pressures, particularly when asked to treat a particular kind of patient who is a very important person: medical colleagues or their family members. The authors present 3 cases that exemplify possible risks associated with the psychiatric treatment of these individuals, including negative effects on the physician-patient relationship, lapses in patient confidentiality, and violations of medical ethics. Preventive and mitigative steps to avoid these pitfalls are discussed. Awareness of these issues when treating fellow physicians or their family members is an important consideration for any mental health clinician.


Impact of a Scalable, Multi-Campus "Foodprint" Seminar on College Students' Dietary Intake and Dietary Carbon Footprint.
Dietary patterns affect both human health and environmental sustainability. Prior research found a ten-unit course on food systems and environmental sustainability shifted dietary intake and reduced dietary carbon footprint among college students. This research evaluated the impact of a similar, more scalable one-unit Foodprint seminar taught at multiple universities. We used a quasi-experimental pre-post nonequivalent comparison group design (n = 176). As part of the Menus of Change University Research Collaborative, research was conducted at three university campuses in California over four academic terms. All campuses used the same curriculum, which incorporates academic readings, group discussions, and skills-based exercises to evaluate the environmental footprint of different foods. The comparison group comprised students taking unrelated one-unit courses at the same universities. A questionnaire was administered at the beginning and end of each term. Students who took the Foodprint seminar significantly improved their reported vegetable intake by 4.7 weekly servings relative to the comparison group. They also reported significantly decreasing intake of ruminant meat and sugar-sweetened beverages. As a result of dietary shifts, Foodprint seminar students were estimated to have significantly decreased their dietary carbon footprint by 14%. A scalable, one-unit Foodprint seminar may simultaneously promote environmental sustainability and human health.


Frequency map for the human cochlear spiral ganglion: implications for cochlear implants.
The goals of this study were to derive a frequency-position function for the human cochlear spiral ganglion (SG) to correlate represented frequency along the organ of Corti (OC) to location along the SG, to determine the range of individual variability, and to calculate an "average" frequency map (based on the trajectories of the dendrites of the SG cells). For both OC and SG frequency maps, a potentially important limitation is that accurate estimates of cochlear place frequency based upon the Greenwood function require knowledge of the total OC or SG length, which cannot be determined in most temporal bone and imaging studies. Therefore, an additional goal of this study was to evaluate a simple metric, basal coil diameter that might be utilized to estimate OC and SG length. Cadaver cochleae (n = 9) were fixed <24 h postmortem, stained with osmium tetroxide, microdissected, decalcified briefly, embedded in epoxy resin, and examined in surface preparations. In digital images, the OC and SG were measured, and the radial nerve fiber trajectories were traced to define a series of frequency-matched coordinates along the two structures. Images of the cochlear turns were reconstructed and measurements of basal turn diameter were made and correlated with OC and SG measurements. The data obtained provide a mathematical function for relating represented frequency along the OC to that of the SG. Results showed that whereas the distance along the OC that corresponds to a critical bandwidth is assumed to be constant throughout the cochlea, estimated critical band distance in the SG varies significantly along the spiral. Additional findings suggest that measurements of basal coil diameter in preoperative images may allow prediction of OC/SG length and estimation of the insertion depth required to reach specific angles of rotation and frequencies. Results also indicate that OC and SG percentage length expressed as a function of rotation angle from the round window is fairly constant across subjects. The implications of these findings for the design and surgical insertion of cochlear implants are discussed.


[Simultaneous intra- and extrauterine pregnancy].
A report on a case of simultaneous intrauterine and extrauterine pregnancy associated with right-sided tubal pregnancy and rupture in the eighth week of pregnancy and spontaneous parturition in the 42nd week. The incidence rate and aetiological factors, as well as diagnostic possibilities and differential diagnostic considerations are presented.


[Optimal cationic composition of perfusates in relation to temperature during preservation of the liver].
Search for the optimal concentrations of potassium, sodium, magnesium, calcium and H+ under different temperature conditions of preservation was performed in 193 experiments with the 2 h perfusion of the isolated rabbit liver. A nonlinear relation was established between the optimal cationic content of the perfusate and the liver preservation temperature. The sharpest changes to the optimal concentration of cations in the perfusate were found to start when the liver preservation temperature had dropped lower than 10-12 degrees C.


Suprachoroidal triamcinolone versus posterior subtenon triamcinolone either alone or formulated in the management of diabetic macular edema.
This study aims to compare posterior subtenon triamcinolone acetonide injection either formulated or alone versus suprachoroidal triamcinolone in the management of diabetic macular edema. This study is a prospective interventional study that included 75 patients, divided into three groups, each group with 25 patients. Group I received a combination of triamcinolone acetonide (TA) (40 mg) and VISCOAT, which is a combination of sodium chondroitin sulfate (20 mg) and sodium hyaluronate (15 mg). The injection was done in the posterior subtenon space using the NAGATA cannula. Group II received TA (40 mg) in the posterior subtenon space. Group III underwent an injection of 4 mg/100µl of TA in the supra choroidal space. We found a statistically significant difference between the three studied groups regarding BCVA (P = 0.001) and CMT at six months postoperative (P = 0.001) with the highest median BCVA and lowest median CMT observed in the formulated TA group. We concluded that early treatment of DME by formulated TA is better than TA alone, and suprachoroidal TA in the form of increasing the BCVA and decreasing the CMT without any elevation of IOP. Trial registration number NCT05464953. Date of registration 17/7/2022 (retrospectively registered).


High-content imaging-based screening of microenvironment-induced changes to stem cells.
Effective screening methodologies for cells are challenged by the divergent and heterogeneous nature of phenotypes inherent to stem cell cultures, particularly on engineered biomaterial surfaces. In this study, we showcase a high-content, confocal imaging-based methodology to parse single-cell phenotypes by quantifying organizational signatures of specific subcellular reporter proteins and applied this profiling approach to three human stem cell types (embryonic-human embryonic stem cell [hESC], induced pluripotent-induced pluripotent stem cell [iPSC], and mesenchymal-human mesenchymal stem cell [hMSC]). We demonstrate that this method could distinguish self-renewing subpopulations of hESCs and iPSCs from heterogeneous populations. This technique can also provide insights into how incremental changes in biomaterial properties, both physiochemical and mechanical, influence stem cell fates by parsing the organization of stem cell proteins. For example, hMSCs cultured on polymeric films with varying degrees of poly(ethylene glycol) to modulate osteogenic differentiation were parsed using high-content organization of the cytoskeletal protein F-actin. In addition, hMSCs cultured on a self-assembled monolayer platform featuring compositional gradients were screened and descriptors obtained to correlate substrate variations with adipogenic lineage commitment. Taken together, high-content imaging of structurally sensitive proteins can be used as a tool to identify stem cell phenotypes at the single-cell level across a diverse range of culture conditions and microenvironments.


Targeting of promising transmembrane proteins for diagnosis and treatment of pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of cancer due to the relatively late diagnosis and the limited therapeutic options. Current treatment regimens mainly comprise the cytotoxic agents gemcitabine and FOLFIRINOX. These compounds have shown limited efficacy and severe side effects, highlighting the necessity for earlier detection and the development of more effective, and better-tolerated treatments. Although targeted therapies are promising for the treatment of several types of cancer, identification of suitable targets for early diagnosis and targeted therapy of PDAC is challenging. Interestingly, several transmembrane proteins are overexpressed in PDAC cells that show low expression in healthy pancreas and may therefore serve as potential targets for treatment and/or diagnostic purposes. In this review we describe the 11 most promising transmembrane proteins, carefully selected after a thorough literature search. Favorable features and potential applications of each target, as well as the results of the preclinical and clinical studies conducted in the past ten years, are discussed in detail.


Molecular descriptors in chemoinformatics, computational combinatorial chemistry, and virtual screening.
Many contemporary applications in computer-aided drug discovery and chemoinformatics depend on representations of molecules by descriptors that capture their structural characteristics and properties. Such applications include, among others, diversity analysis, library design, and virtual screening. Hundreds of molecular descriptors have been reported in the literature, ranging from simple bulk properties to elaborate three-dimensional formulations and complex molecular fingerprints, which sometimes consist of thousands of bit positions. Knowledge-based selection of descriptors that are suitable for specific applications is an important task in chemoinformatics research. If descriptors are to be selected on rational grounds, rather than guesses or chemical intuition, detailed evaluation of their performance is required. A number of studies have been reported that investigate the performance of molecular descriptors in specific applications and/or introduce novel types of descriptors. Progress made in this area is reviewed here in the context of other computational developments in combinatorial chemistry and compound screening.


[Psychological assistance in organ transplantation].
The aim of this report is introducing with a series of psychological, psychiatric and psychosocial problems, that can arise, at every point, in the procedure of organ transplantations. Different areas of intervention are considered: the assistance to the patients and their families during the pre- and post-operative periods; the evaluation of transplant recipients' quality of life; ethical and psychological problems of living kidney donation; psychosocial support to donors' families; the training of the intensive therapy units to entertain relationships with donors' relatives; the delicate psychological aspects of transplantation during childhood. The sense of awareness about these matters is growing in Italy too, and many initiatives of psychological and psychiatric help are being developed in collaboration with several transplantation centres.


Soybean meal fermented by Aspergillus awamori increases the cytochrome P-450 content of the liver microsomes of mice.
The effect of soybean meal fermented by Aspergillus awamori on the acute lethality of acetaldehyde, pentobarbital sleeping time, and cytochrome P-450 content of the hepatic microsomes was studied in mice. Most of the daidzin and genistin in soybean meal (SBM) were converted into the respective aglycones, daidzein and genistein, by fermentation. In experiment 1, mice were fed isonitrogenic test diets with one of the following five protein sources for 28 d: casein, SBM, fermented and hot-air-dried SBM (FSBM-HD), fermented and freeze-dried SBM (FSBM-FD), or methanol-extracted FSBM-FD (FSMB-FD-R). The acute lethality of acetaldehyde in mice fed the FSBM-FD diet was significantly lower than that in mice fed the SBM, FSBM-HD, or FSBM-FD-R diet. In experiments 2 and 3, mice were fed isonitrogenic test diets with one of the following four protein sources for 28 d: casein, SBM, FSBM-FD, and FSBM-FD-R. The pentobarbital sleeping time was significantly shorter and the cytochrome P-450 content was significantly higher in the mice fed the FSBM-FD diet than the respective value in mice fed the other test diets. In experiment 4, mice were fed one of eight diets which contained different levels of aglycone obtained by varying the proportion of FSBM-FD and FSBM-FD-R, for 28 d. The cytochrome P-450 content in hepatic microsomes increased as the dietary level of isoflavonoid aglycones increased, but there was a saturation phenomenon. These results suggest that soy isoflavonoid aglycones are more potent inducers of cytochrome P-450 than isoflavonoid glycosides.


Holmium:YAG laser ureterolithotripsy.
To report on the experience obtained in the treatment of a series of 150 cases of ureteral stone disease by means of the holmium:yttrium-aluminum-garnet (Ho:YAG) laser. One hundred and fifty consecutive cases treated by means of Ho:YAG laser ureterolithotripsy have been reviewed in order to assess the results. In 81 cases the stones were located in the lower third, in 47 in the medium third, and in 22 cases in the upper third of the ureter. The laser was set at a power of 8-10 W and at a frequency of between 6 and 10 Hz. Thin ureteroscopes were selected, such as the 7-Fr Gautier or the new ultrathin 4.8-Fr Wolf instrument. In some cases other ureteroscopes were chosen. Lasertripsy was effective in every kind of stone, allowing fragmentation into portions measuring at most 4 mm (largest diameter) or disintegration. The clearance rate of the stones was 92.6% during the 30-day follow-up period. Calcium dihydrate stones were of course more easily broken than monohydrate ones. No damage to the ureter was observed following the vaporization which is produced by this kind of laser, since particular attention was paid to avoid any contact between the laser beam and the ureteral mucosa. In some instances ureteroscopic maneuvering provoked some slight lacerations. In a few cases accidental contact of the laser beam with the ureteral mucosa produced extremely small coagulations of no immediate or postoperative relevance. The Ho:YAG laser constitutes an effective instrument for the fragmentation of any kind of ureteral stone; it allows the use of thin or ultrathin instruments and, if manipulated with care, does not damage the ureteral mucosa or the ureteral wall.


Surface-Mediated Aligned Growth of Monolayer MoS2 and In-Plane Heterostructures with Graphene on Sapphire.
Aligned growth of transition metal dichalcogenides and related two-dimensional (2D) materials is essential for the synthesis of high-quality 2D films due to effective stitching of merging grains. Here, we demonstrate the controlled growth of highly aligned molybdenum disulfide (MoS2) on c-plane sapphire with two distinct orientations, which are highly controlled by tuning sulfur concentration. We found that the size of the aligned MoS2 grains is smaller and their photoluminescence is weaker as compared with those of the randomly oriented grains, signifying enhanced MoS2-substrate interaction in the aligned grains. This interaction induces strain in the aligned MoS2, which can be recognized from their high susceptibility to air oxidation. The surface-mediated MoS2 growth on sapphire was further developed to the rational synthesis of an in-plane MoS2-graphene heterostructure connected with the predefined orientation. The in-plane epitaxy was observed by low-energy electron microscopy. Transmission electron microscopy and scanning transmission electron microscopy suggest the alignment of a zigzag edge of MoS2 parallel to a zigzag edge of the neighboring graphene. Moreover, better electrical contact to MoS2 was obtained by the monolayer graphene compared with a conventional metal electrode. Our findings deepen the understanding of the chemical vapor deposition growth of 2D materials and also contribute to the tailored synthesis as well as applications of advanced 2D heterostructures.


Microwave-assisted extraction coupled with single drop microextraction and high-performance column liquid chromatography for the determination of trace estrogen adulterants in soybean isoflavone dietary supplements.
A sensitive and accurate method consisting of microwave-assisted extraction (MAE) coupled with single drop microextraction (SDME) and HPLC was developed for the determination of four trace estrogen adulterants, including estriol (E3), estradiol (E2), ethinyl estradiol (EE), and estrone (E1), in different soybean dietary supplements. The samples were extracted by MAE; the extracts were cleaned up and enriched by SDME, and then analyzed by HPLC. The conditions of MAE were optimized, and the effects of solvent and extraction time in SDME on the enrichment capacity were studied. The enrichment factors of E3, E2, EE, and E1 under the optimized conditions were 247-, 335-, 316-, and 319-fold, respectively. The linear range of the MAE-SDME-HPLC method ranged from 5.0 to 180.0 microg/L, and the detection limit from 1.1 to 1.2 microg/L. The RSD ranged from 7.9 to 9.6%. Three soybean dietary supplements, including oral liquid, capsule, and tablet forms, were analyzed. The spike recovery was more than 70%, with RSD lower than 13.2%. It was shown that the proposed method was accurate, sensitive, and suitable for the determination of trace analytes in complex samples.


Sentinel surveillance of HIV infection in HIV test clinics, Spain 1992-2002.
HIV infection in Spain was monitored in persons undergoing voluntary HIV testing in ten sentinel clinics between 1992 and 2002. Only patients on their first visit were considered for inclusion, and their numbers rose from 4426 in 1992 to 6649 in 2002. Most of them recognised their risk exposure as heterosexual. The proportion of injecting drug users decreased from 19% to 2% of the study population, and the proportion of female sex workers increased from 6% to 26%. The number of patients diagnosed with HIV infection declined from 604 in 1992 to 153 in 2002, and HIV prevalence fell from 13.6% to 2.3% in the same period. In all risk exposure categories, a decrease in HIV prevalence was observed, more pronounced during the first few years and stabilised in the later years. In 2002, the highest HIV prevalence was found in injecting drug users (IDUs) (14.2%), homo/bisexual men (7.5%) and individuals who had an HIV infected heterosexual partner (10.2%).


[Prediction of postoperative pain - beneficial to perioperative pain management?].
Pain treatment of surgical patients is still a deficient area, even if there are evidence-based possibilities of pain management. The aim of this study is to identify patients with a higher risk of severe postoperative pain at an early stage and improve nurses' pain management by identifying pain predictors whilst including them in analgesic treatment. In addition to the identification of predictors by a literature review, a cross-sectional study with 84 surgical patients of a convenience sample was undertaken to find possible predictors. The enquiry was conducted by means of a questionnaire which the patient had to fill in prior surgery. The intensity of pain was surveyed in a personal interview on the first post-operative day. Correlation analysis was applied to verify the statistical significance of patient characteristics as well as surgical variables. Out of the 14 variables preoperative pain was found to increase the risk of postoperative pain. Comparison with other studies showed inconsistent results for pain predictors, and therefore nursing pain management based on pain predictors seems questionable.


[Lectin histochemical studies of retinal pigment epithelium in retinal detachment].
The retinal pigment epithelium (RPE) exhibits a broad spectrum of morphological changes under pathological conditions. Since RPE cells cannot be immunocytochemically characterized with certainty, lectin histochemical investigations were performed to study the lectin binding pattern of different morphological RPE variants in human globes. Normal RPE with attached retinas was compared to reactive changes in RPE following retinal detachment. Lectin binding sites were visualized by a modified PAP technique performed on paraffin-embedded tissue sections. Eight lectins of different sugar affinity (Con A, WGA, PNA, RCA 1, SBA, UEA 1, DBA, LPA) were tested for binding sites on the RPE. Both normal and reactively changed RPE possess receptors for Con A, WGA, PNA, and RCA 1. Modifications in the lectin binding pattern occurred simultaneously with the morphological changes within the RPE cells. RPE cells which form a monolayer on Bruch's membrane mainly have lectin binding sites in their apical portions. Proliferating and migrating RPE cells, especially RPE macrophages, which have withdrawn from the basal cell layer were found to contain lectin binding sites dispersed over the entire cytoplasm. RPE macrophages exhibited additional binding sites for the lectin SBA. These results indicate that RPE cell variants can be designated by means of their specific combination of lectin binding sites for Con A WGA, PNA, and RCA 1 not found on other cell types in the retina.


Specific alkylation of a histidine residue in carnitine acetyltransferase by bromoacetyl-L-carnitine.
Incubation of carnitine acetyltransferase with low concentrations of bromoacetyl-l-carnitine causes a rapid and irreversible loss of enzyme activity; one mol of inhibitor can inactivate one mol of enzyme. Bromoacetyl-d-carnitine, iodoacetate or iodoacetamide are ineffective. l-Carnitine protects the transferase from bromoacetyl-l-carnitine. Investigation shows that the enzyme first reversibly binds bromoacetyl-l-carnitine with an affinity similar to that shown for the normal substrate acetyl-l-carnitine; this binding is followed by an alkylation reaction, forming the carnitine ester of a monocarboxymethyl-protein, which is catalytically inactive. The carnitine is released at an appreciable rate by spontaneous hydrolysis, and the resulting carboxymethyl-enzyme is also inactive. Total acid hydrolysis of enzyme after treatment with 2-[(14)C]bromoacetyl-l-carnitine yields N-3-carboxy[(14)C]methylhistidine as the only labelled amino acid. These findings, taken in conjunction with previous work, suggest that the single active centre of carnitine acetyltransferase contains a histidine residue.


Ribosomal scanning past the primary initiation codon as a mechanism for expression of CTL epitopes encoded in alternative reading frames.
An increasing amount of evidence has shown that epitopes restricted to MHC class I molecules and recognized by CTL need not be encoded in a primary open reading frame (ORF). Such epitopes have been demonstrated after stop codons, in alternative reading frames (RF) and within introns. We have used a series of frameshifts (FS) introduced into the Influenza A/PR/8 /34 nucleoprotein (NP) gene to confirm the previous in vitro observations of cryptic epitope expression, and show that they are sufficiently expressed to prime immune responses in vivo. This presentation is not due to sub-dominant epitopes, transcription from cryptic promoters beyond the point of the FS, or internal initiation of translation. By introducing additional mutations to the construct exhibiting the most potent presentation, we have identified initiation codon readthrough (termed scanthrough here, where the scanning ribosome bypasses the conventional initiation codon, initiating translation further downstream) as the likely mechanism of epitope production. Further mutational analysis demonstrated that, while it should operate during the expression of wild-type (WT) protein, scanthrough does not provide a major source of processing substrate in our system. These findings suggest (i) that the full array of self- and pathogen-derived epitopes available during thymic selection and infection has not been fully appreciated and (ii) that cryptic epitope expression should be considered when the specificity of a CTL response cannot be identified or in therapeutic situations when conventional CTL targets are limited, as may be the case with latent viral infections and transformed cells. Finally, initiation codon readthrough provides a plausible explanation for the presentation of exocytic proteins by MHC class I molecules.


A panel of IgG1 b12 variants with selectively diminished or enhanced affinity for Fcγ receptors to define the role of effector functions in protection against HIV.
Passive transfer of neutralizing antibodies is effective in protecting rhesus macaques against simian/human immunodeficiency virus (SHIV) challenge. In addition to neutralization, effector functions of the crystallizable fragment (Fc) of antibodies are involved in antibody-mediated protection against a number of viruses. We recently showed that interaction between the Fc fragment of the broadly neutralizing antibody IgG1 b12 and cellular Fcγ receptors (FcγRs) plays an important role in protection against SHIV infection in rhesus macaques. The specific nature of this Fc-dependent protection is largely unknown. To investigate, we generated a panel of 11 IgG1 b12 antibody variants with selectively diminished or enhanced affinity for the two main activating FcγRs, FcγRIIa and FcγRIIIa. All 11 antibody variants bind gp120 and neutralize virus as effectively as does wild-type b12. Binding studies using monomeric (enzyme-linked immunosorbent assay [ELISA] and surface plasmon resonance [SPR]) and cellularly expressed Fcγ receptors show decreased (up to 5-fold) and increased (up to 90-fold) binding to FcγRIIa and FcγRIIIa with this newly generated panel of antibodies. In addition, there was generally a good correlation between b12 variant affinity for Fcγ receptor and variant function in antibody-dependent cell-mediated virus inhibition (ADCVI), phagocytosis, NK cell activation assays, and antibody-dependent cellular cytotoxicity (ADCC) assays. In future studies, these b12 variants will enable the investigation of the protective role of individual FcγRs in HIV infection.


Splicing mutations in DMD/BMD detected by RT-PCR/PTT: detection of a 19AA insertion in the cysteine rich domain of dystrophin compatible with BMD.
We have used an RNA based mutation detection method to screen the total coding region of the dystrophin gene of a Duchenne and a Becker muscular dystrophy patient in whom DNA based mutation detection methods have so far failed to detect mutations. By RT-PCR and the protein truncation test (PTT) we could identify point mutations in both cases. DMD patient DL184.3 has a T-->A mutation in intron 59 at position -9, creating a novel splice acceptor site for exon 60. As a result seven intronic bases are spliced into the mRNA, causing a frameshift and premature translation termination 20 codons downstream. Since this patient had died and only fibroblasts were available, we applied MyoD induced myodifferentiation of stored fibroblasts to enhance muscle specific gene expression. With the results of this mutation analysis, prenatal diagnosis could subsequently be performed in this family. BMD patient BL207.1 carries a G-->C mutation at position +5 of intron 64, disrupting the splice donor consensus sequence and activating a cryptic splice donor site 57bp downstream. The inclusion of these 57 intronic bases in the mRNA leaves the reading frame open and results in the insertion of 19 amino acids into the cysteine rich domain of dystrophin. Interestingly, this insertion in a part of the dystrophin considered to interact with the dystrophin binding complex of the sarcolemma is apparently compatible with mild BMD-like clinical features. Both mutations reported are missed by analysis of multiplex PCR products designed for deletion screening of the coding region. Extrapolation from existing point mutation detection efficiencies by DNA and RNA based methods emphasises that RNA based methods are more sensitive and that most of the remaining undetected mutations may affect splice or branch sites or create cryptic splice sites.


On-Ticagrelor Platelet Reactivity and Clinical Outcome in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome.
A strong association between on-thienopyridine platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrelor PR and clinical outcome in this clinical setting. We aimed to investigate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein (VASP) index, and clinical outcome in patients with ACS undergoing PCI. We performed a prospective, multicenter, observational study of patients undergoing PCI for ACS. PR was measured using the VASP index following ticagrelor loading dose. The primary study endpoint was the rate of Bleeding Academic Research Consortium (BARC) type ≥2 at 1 year. The key secondary endpoint was the rate of major adverse cardiovascular events (MACE) defined as the composite of cardiovascular death, myocardial infarction, stroke, and urgent revascularization. We included 570 ACS patients, among whom 33.9% had ST-elevation myocardial infarction. BARC type ≥2 bleeding occurred in 10.9% and MACE in 13.8%. PR was not associated with BARC ≥2 or with MACE (p = 0.12 and p = 0.56, respectively). No relationship between PR and outcomes was observed, neither when PR was analyzed quantitatively nor when it was analyzed qualitatively (low on-treatment PR [LTPR] vs. no LTPR). On-ticagrelor PR measured by the VASP was not associated with bleeding or thrombotic events in ACS patients undergoing PCI. PR measured by the VASP should not be used as a surrogate endpoint in studies on ticagrelor.


Degradation of insulin in vitro by liver and epididymal adipose tissue from obese-hyperglycaemic mice.
The insulin-degrading activity of liver supernatants and epididymal adipose-tissue homogenates from genetically obese-hyperglycaemic mice (ob ob) and their lean litter mates was studied by measurement of radioactive trichloroacetic acid-soluble degradation products of the insulin molecule. Optimum assay conditions for the decomposition of the hormone were devised. The properties of the degrading activity suggested the presence of enzymic insulin destruction in both the liver and epididymal adipose tissue. There was no difference in insulin degradation in liver samples from obese and lean mice when the results were related to the protein content of the supernatants. The epididymal adipose-tissue homogenates from obese mice displayed about eightfold higher degrading activity per unit of protein than did homogenates from lean animals. The physiological significance of this finding is discussed in the light of the increased fat depots, hyperphagia, raised serum insulin concentrations and increased insulin tolerance previously recorded in this strain of mice.


Microfracture in the hip: a matched-control study with average 3-year follow-up.
There is a paucity of literature regarding microfracture surgery in the hip. The purpose of this study was to compare outcomes in patients undergoing hip arthroscopy predominantly for labral tears with focal full thickness chondral damage on the acetabulum or femoral head treated with microfracture and a matched control group that did not have focal full thickness chondral damage. A prospective matched-control study was performed examining four patient-reported outcome (PRO) scores: modified Harris Hip Score (mHHS), non-arthritic hip score, Hip Outcome Score-Activities of Daily Living (HOS-ADL), and Hip Outcome Score-Sports Specific Subscale (HOS-SSS) at minimum 2 years post-operatively between 35 patients undergoing microfracture for chondral defects during hip arthroscopy and 70 patients in a control group that did not have chondral defects. The patients were matched based on gender, age within 7 years, Workman's compensation claim, labral treatment and acetabular crossover percentage less than or greater than 20. There was no significant difference (P > 0.05) in PRO scores preoperatively between the groups. Both groups demonstrated significant improvement (P < 0.05) in all post-operative PRO scores at all time points. There was no statistically significant difference (P > 0.05) in post-operative PRO scores between the microfracture and control groups, except for HOS-ADL and the visual analog scale (VAS) score, both of which were superior in the control group (P < 0.05). Patient satisfaction was 6.9 for the microfracture group and 7.7 for the control group (P > 0.05). Arthroscopic microfracture of the hip during treatment of labral tears results in favorable outcomes that are similar to the results arthroscopic treatment of labral tears in patients without full thickness chondral damage.


New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo Guidelines.
The Tokyo Guidelines for the management of acute cholangitis and cholecystitis were published in 2007 (TG07) and have been widely cited in the world literature. Because of new information that has been published since 2007, we organized the Tokyo Guidelines Revision Committee to conduct a multicenter analysis to develop the updated Tokyo Guidelines (TG13). We retrospectively analyzed 1,432 biliary disease cases where acute cholangitis was suspected. The cases were collected from multiple tertiary care centers in Japan. The 'gold standard' for acute cholangitis in this study was that one of the three following conditions was present: (1) purulent bile was observed; (2) clinical remission following bile duct drainage; or (3) remission was achieved by antibacterial therapy alone, in patients in whom the only site of infection was the biliary tree. Comparisons were made for the validity of each diagnostic criterion among TG13, TG07 and Charcot's triad. The major changes in diagnostic criteria of TG07 were re-arrangement of the diagnostic items and exclusion of abdominal pain from the diagnostic list. The sensitivity improved from 82.8 % (TG07) to 91.8 % (TG13). While the specificity was similar to TG07, the false positive rate in cases of acute cholecystitis was reduced from 15.5 to 5.9 %. The sensitivity of Charcot's triad was only 26.4 % but the specificity was 95.6 %. However, the false positive rate in cases of acute cholecystitis was 11.9 % and not negligible. As for severity grading, Grade II (moderate) acute cholangitis is defined as being associated with any two of the significant prognostic factors which were derived from evidence presented recently in the literature. The factors chosen allow severity assessment to be performed soon after diagnosis of acute cholangitis. TG13 present a new standard for the diagnosis, severity grading, and management of acute cholangitis.


Zinc deficiency in the postnatal rat: implications for lead toxicity.
Zinc (Zn), an essential element in the diet of mammals, appears to have a high affinity for the hippocampus during development, particularly the mossy fiber pathway (MFP). Lead (Pb) competes at several physiological levels with Zn, and is also selectively sequestered in the MFP. It has been suggested that Pb might exert its neurotoxic effects by displacing Zn and disrupting its functioning in the hippocampus. This study was conducted to address this possibility by examining hippocampal structure and function in perinatally Zn-deprived animals, and comparing the results with those previously observed under identical conditions in Pb-exposed rats. From postnatal day 1 (P1) to P25, Long-Evans hooded rat pups and their mothers were placed on a Zn deficient or control diet. On P25, weight-matched pairs of animals were selected for morphometric evaluation of the MFP following Timm's silver sulfide staining; no differences between groups were observed. Animals were tested at maturity in three behavioral tasks considered sensitive to hippocampal dysfunction. Zn deficiency produced no significant alterations in open field activity levels or passive avoidance performance; however, it did induce significantly reduced rates of spontaneous alternation. These results indicate few neurobehavioral similarities between Pb exposed and Zn deficient animals.


The Desirability of Difference: Georges Canguilhem and Body Integrity Identity Disorder.
Opponents of the provision of therapeutic, healthy limb amputation in Body Integrity Identity Disorder cases argue that such surgeries stand in contrast to the goal of medical practice - that of health restoration and maintenance. This paper refutes such a conclusion via an appeal to the nuanced and reflective model of health proposed by Georges Canguilhem. The paper examines the conceptual entanglement of the statistically common with the normatively desirable, arguing that a healthy body can take multiple forms, including that of an amputee, provided that such a form enables the continuing ability to initiate new norms of existence. It concludes that the practice of healthy limb amputation in cases of Body Integrity Identity Disorder is not only compatible with the goal of medicine but is potentially the only method of achieving this goal in the face of a complex and often mischaracterized disorder.


Synergistically Enhanced Electrochemical Performance of Ni3S4-PtX (X = Fe, Ni) Heteronanorods as Heterogeneous Catalysts in Dye-Sensitized Solar Cells.
Platinum (Pt)-based alloys are considerably promising electrocatalysts for the reduction of I-/I3- and Co2+/Co3+ redox couples in dye-sensitized solar cells (DSSCs). However, it is still challenging to minimize the dosage of Pt to achieve comparable or even higher catalytic efficiency. Here, by taking full advantages of the Mott-Schottky (M-S) effect at the metal-semiconductor interface, we successfully strategize a low-Pt-based M-S catalyst with enhanced electrocatalytic performance and stability for the large-scale application of DSSCs. The optimized M-S electrocatalyst of Ni3S4-Pt2X1 (X = Fe, Ni) heteronanorods is constructed by rationally controlling the ratio of Pt to transition metal in the hybrids. It was found that the electrons transferred from Ni3S4 to Pt2X1 at their interface under the Mott-Schottky effect result in the concentration of electrons onto Pt2X1 domains, which subsequently accelerates the regeneration of both I-/I3- and Co2+/Co3+ redox shuttles in DSSCs. As a result, the DSSC with Ni3S4-Pt2Fe1 manifests an impressive power conversion efficiency (PCE) of 8.79% and 5.56% for iodine and cobalt-based electrolyte under AM1.5G illumination, respectively. These PCEs are obviously superior over those with Ni3S4-Pt, PtFe, Ni3S4, and pristine Pt electrodes. The strategy reported here is able to be further expanded to fabricate other low-Pt-alloyed M-S catalysts for wider applications in the fields of photocatalysis, water splitting, and heterojunction solar cells.


Visualizing the functional architecture of the endocytic machinery.
Clathrin-mediated endocytosis is an essential process that forms vesicles from the plasma membrane. Although most of the protein components of the endocytic protein machinery have been thoroughly characterized, their organization at the endocytic site is poorly understood. We developed a fluorescence microscopy method to track the average positions of yeast endocytic proteins in relation to each other with a time precision below 1 s and with a spatial precision of ~10 nm. With these data, integrated with shapes of endocytic membrane intermediates and with superresolution imaging, we could visualize the dynamic architecture of the endocytic machinery. We showed how different coat proteins are distributed within the coat structure and how the assembly dynamics of N-BAR proteins relate to membrane shape changes. Moreover, we found that the region of actin polymerization is located at the base of the endocytic invagination, with the growing ends of filaments pointing toward the plasma membrane.


Cognitive Functioning and Its Relationship with Self-Stigma in Men with HIV Who Have Sex with Men: The Mediating Role of Health-Related Quality of Life.
The human immunodeficiency virus (HIV) stills remains a serious public health problem. HIV acquisition has several negative health consequences, such as a cognitive deterioration or health-related quality of life (HRQoL) impairment. Although these negative consequences could be directly related to a significant increase in self-stigma in this population, few previous studies have analysed the possible associations between these variables. This is especially the case in specific groups of people living with HIV, such as men who have sex with men who could be at a greater risk of stigmatisation. The main aim of the present study was to evaluate the association between cognitive functioning, HRQoL and self-stigma in a group of men with HIV who have sex with men. The present study was conducted in the Infectious Diseases Unit of the General University Hospital of Alicante (Spain). The final sample was composed of 70 participants who passed the inclusion and exclusion criteria. All were men with HIV who had sex with men and the sample's mean age was 45 years. Each participant completed questionnaires on HRQoL and HIV self-stigma. Moreover, they completed an online cognitive assessment through the previously validated platform for cognitive evaluation CogniFit, Inc. The obtained results showed a significant association between memory functioning impairment, lower levels of HRQoL and higher HIV self-stigma scores. Hence, HRQoL, in the mental summary domain, was shown to be a significant mediator in the relationship between low memory performance and higher HIV self-stigma. Neurocognitive impairment could decrease HRQoL in men with HIV who have sex with men, and hence, reinforce the idea widespread in society that having HIV holds serious consequences. This fact, together with the reduced cognitive abilities to fight against their own self-stigma could represent plausible explanations of the obtained results. In this sense, intervention strategies, oriented towards reducing cognitive impairment, such as those based on cognitive training, and other psychological interventions to promote HRQoL could be effective approaches to prevent the negative effects of HIV self-stigma in this population.


Measurement of Skin Surface pH.
The acidic nature of the skin surface was recognised more than a century ago and has been measured since 1928. Several non-invasive methods for measuring skin surface pH have been developed ever since and have contributed to our understanding of healthy and diseased skin. This chapter summarises the endogenous physiological, exogenous and environmental factors that influence skin surface pH and its measurement as well as the different measurement methods for skin surface pH, with specific emphasis on the classic planar glass electrode method. Also, practical guidance for measurement of skin surface pH using the planar glass electrode method is provided. Adherence to practical skin surface pH measurement (method) guidelines with due consideration and practicable control of all factors that may affect skin surface pH will ensure credible pH measurement results in our continuous pursuit of understanding especially diseased skin.


[Current state of diagnostics and treatment of overactive bladder in the Czech Republic - five years ago and today].
Overactive bladder (OAB) presents one of the most frequent medical problems among the current adult population, with a significant impact on the quality of life of the affected patients. A questionnaire survey was carried out in 2006, with the aim to assess the level of knowledge regarding the problem of OAB among gynaecologists and urologists in the Czech republic, as well as to evaluate the currently applied methods of OAB diagnostics and treatment. The aim of this work was to perform a repeated survey after five years, and to evaluate, whether there have been any changes achieved in the monitored parameters. A total of 290 respondents (181 gynaecologists, 109 urologists) were included in the survey in 2006; the study group in 2011 included a total of 285 respondents (180 gynaecologists, 105 urologists). The questionnaire used for the survey in 2011 was identical to the document utilized in the initial survey performed five years ago, with minimal changes. The anonymous questionnaire was designed as "multiple-choice", i.e. with a possible selection from proposed answers; the questions were targeted at the topics of definition, diagnostics and therapy of OAB. The obtained results were processed with the methods of descriptive statistics; the concordance of proportions was evaluated with the Fishers exact test. A total of 114 gynaecologists (63.3%), and 65 urologists (61.9%) were able to determine the correct definition of OAB, which presents a significant increase when compared to 2006 (p<0.0001). The most frequently applied methods of OAB diagnostics were patient history (gynaecologists: 97.8% in 2011 vs. 96.5% in 2006, urologists: 99.0% in 2011 vs. 99.0% in 2006), local examination (gynaecologists: 57.8% vs. 76.4%, urologists: 86.7% vs. 87.2%), bladder diaries (gynaecologists: 62.8% vs. 40.3%, urologists: 79.0% vs. 60.5%), and urine examination (gynaecologists: 71.1% vs. 82.3%, urologists: 96.2% vs. 97.1%). Anticholinergic medication is the first-choice in the OAB treatment in our conditions, which has been confirmed by 146 (81.1%) gynaecologists, and 89 (84.4%) urologists. In cases when the physicians use anticholinergic medication for the treatment of OAB, the first-choice medication is trospium, among both gynaecologists and urologists. In case of failure of the first-choice treatment, twenty-six (14.4%) gynaecologists from the addressed respondents try to continue with a treatment according to their own decision, 154 (85.6%) gynaecologists refer the patient to a specialist. Similarly, a total of 90 (85.7%) urologists try to manage the further course of treatment by their own means, 15 urologists (14.3%) refer the patient to a specialist. The level of understanding and awareness about the problem of OAB among the Czech gynaecologists and urologists has significantly improved during the past five years. The applied diagnostic and treatment methods for OAB are being harmonized with the International Continence Society (ICS) recommendations. Taking into consideration the prevalence of OAB among the population, it is desirable to increase the number of clinical departments who deal with the problem of OAB in a complex manner. The remaining significant task lies in the improvement of foreknowledge about the current possibilities and effectiveness of the OAB treatment among the patient population.


Supplementation freeze-thawed media with selenium protect adipose-derived mesenchymal stem cells from freeze-thawed induced injury.
Successful freezed-thaw of adipose-derived mesenchymal stem cells (ADMSCs) could be a major step in regenerative medicine as well as in the cloning of animal breeds. The aim of this study was to evaluate the efficacy of selenium on the optimizing of freezed-thaw media in the ADMSCs. ADMSCs were extracted from NMRI mice and purified with positive selection Monoclonal CD105 Antibody (PE) and negative selection Monoclonal CD31 and CD45 Antibody using MACS method as well as differentiation to adipose and bone tissue. ADMSCs were divided into four groups. ADMSCs were freezed-thaw under standard condition with or without the addition of 5 ng/ml selenium to both the cryopreservation and thawing solutions. Frozen cells were thawed after four months and viability and cytotoxicity of the cells were analyzed by the Trypan blue test and MTT assay respectively. RNA was extracted and cDNA was synthesized and the expression of apoptotic genes (P53, Fas, Bax, Caspase3, and Bcl2) was examined using Real time-PCR Rotor gene 2009. This study compares slow and rapid methods of cryopreservation. After thawing, viability of the cells treated with selenium was higher than the control group in rapid and slow cryopreserved ADMSCs. Also, the percentage of living cells in the slow cooling method was considerably more than with the rapid cooling method. After analysis of the results using Real time-PCR, the Bcl2 gene was shown to be expressed in both the rapid and slow cooling methods. In the rapid cooling group in addition to the BCL-2 gene, p53 was also expressed. It appears that selenium prevented the apoptotic genes from expression due to its anti-apoptotic effects. The slow cooling method is better and more optimized for ADMSCs protecting them from oxidative damage to a greater extent compared to the rapid cooling method.


Structural and conformational properties of peptides interacting with the glutathione receptor of hydra.
We have made a detailed investigation of structure-activity relationships of the glutathione-induced feeding response in the fresh water coelenterate, Hydra attenuata, to map structural and conformational properties of feeding response agonists. We find that the gamma-glutamyl residue of glutathione contains essential binding sites for receptor interaction, without which antagonistic as well as agonistic properties are lost. Any structural alteration which perturbs either the alpha-amino or the alpha-carboxyl group or their relative spatial orientations within the peptide has yielded an inactive derivative. An absolute requirement for activation of the receptor is a second-residue side chain of the appropriate size; analogues with second-residue side chains too large or too small are inhibitory. On the basis of the activity of conformational analogues of glutathione, torsional angles for the second residue equal to those of a right-handed alpha-helix are compatible with stimulus generation.


Estrogen carcinogenesis in Syrian hamster tissues: role of metabolism.
Evidence for a role of estrogen metabolism in hormonal carcinogenesis was obtained with the Syrian hamster as an in vivo model system. Both natural and synthetic estrogens are capable of inducing a high incidence of renal carcinomas in this species. A high incidence of hepatocellular carcinomas can also be induced in the hamster with synthetic estrogens such as ethinyl estradiol or diethylstilbestrol, provided alpha-naphthoflavone (ANF) is present in the diet. Although steroid receptor-mediated hormonal events appear to be intimately involved in the process of in vivo cell transformation of both tissues, certain observations strongly suggest that nonhormonal events are also important. Despite their potent estrogenic activity at the doses used, ethinyl estradiol and alpha-zearalanol induce relatively low renal tumor incidences after 9.0 and 10.0 months of continuous treatment, respectively. A role for the metabolism of estrogens to reactive intermediates is also suggested by studies showing estrogen-induced renal tumorigenesis can be partially inhibited by concomitant administration of ANF or ascorbic acid. Consistent with this is the general correlation between the amount of catechol estrogen formed by a compound, as mediated by estrogen 2-/4-hydroxylase, and renal carcinogenicity data. Recently, additional supporting evidence has been obtained from studies involving the irreversible binding of reactive metabolites of steroidal or stilbene estrogens to hamster liver microsomal proteins.


Essential fatty acids in the plasma phospholipids of patients with atopic eczema.
We have measured all the essential fatty acids (EFA) in plasma phospholipids in forty-one adults with atopic eczema and fifty normal controls. The major dietary n-6 EFA, linoleic acid, was significantly elevated, but all its metabolites, 18:3n-6, 20:3n-6, 20:4n-6, 22:4n-6, and 22:5n-6 were significantly reduced. The major dietary n-3 EFA, alpha-linolenic acid, was also elevated, though not significantly, while all its metabolites were also significantly reduced. These observations suggest that atopic eczema is associated not with any defect of EFA intake, but with abnormal metabolism, possibly involving the enzyme delta-6-desaturase. Treatment with oral evening primrose oil produced partial correction of the n-6 EFA abnormality, but had no effect on the n-3 EFAs.


A Multi-armed Unfurling Actuator for Airway Lumen Measurement.
Objective measurement of the lumen area demands an intraoperative diagnostic tool to aid on-site decision-making. We present a compliant mechanism-based unfurling actuator assembly integrated with a shaft connected to a motorized encoder to translate torque from the user at the proximal end to the actuator at the distal end. The actuator assembly has flexible arms coiled inside a cylindrical casing that moves radially outward upon actuation. Leveraging 3D printing of flexible materials, the unfurling actuator's four-arm design enables patency measurements in circumferential tracheal stenosis of varying grades. The rotary encoder output is correlated with the radially outward movement of the unfurling arms to estimate the lumen diameter. The measurement stability is analyzed using process control charts; data distribution over ten iterations reveals nearly 100% of process data falls between ±3 sigma (Upper and Lower control limits). Comparing measurements from the tool with direct measurement (vernier caliper) and ImageJ analysis, one-way ANOVA for circular morphology yields no significant differences in diameter p = 0.974 and area measurements p = 0.975.Clinical Relevance- Central airway narrowing reduces the effective lumen area in the tracheal and bronchial segments. Grading the degree of narrowing is often based on a suspicion index. A quick but thorough assessment of the airway caliber is essential in emergent or planned intubation, whether congenital, iatrogenic, or idiopathic tracheal stenosis.


Cerebrovascular ultrasonography for selecting patients for stroke intervention.
Currently employed diagnostic ultrasonography provides clinically relevant information about cerebral hemodynamic changes in patients with cerebrovascular ischemia. The information thus obtained is often helpful to the physician for establishing or confirming the diagnosis and prognosis as well as in taking appropriate therapeutic decisions. It is associated with a high temporal resolution and can be performed bedside for rapid diagnosis as well as prolonged monitoring. Transcranial Doppler (TCD) ultrasonography is a non-invasive diagnostic modality that provides physiological information regarding various intracranial hemodynamic alterations in patients with cerebrovascular ischemia. Extended applications of TCD are useful in understanding various pathophysiological mechanisms responsible for the clinical manifestations of cerebrovascular ischemia. Thus, TCD is aptly called as the 'stethoscope' of a stroke neurologist. Cerebrovascular ultrasonography is considered as an essential component of a comprehensive stroke center. We have reviewed various recent patents pertaining to the applications of cerebrovascular ultrasonography employed in the selection of stroke patients for various therapeutic interventions.


The anger-depression connection: Between-persons and within-person associations from late adolescence to midlife.
Six waves of data from 944 Canadian high school seniors surveyed for 25 years (age 18 to 43) were analyzed to compare three models of the temporal associations between expressed anger and depressive symptoms (anger→depression; depression→anger; anger↔depression) and a between-persons differences only model (↑anger = ↑depression). Perceived availability of social support was examined as a mediator of the anger-depression association. Random intercept cross-lagged panel analyses supported the between-persons differences only model, controlling for sociodemographic variables, within-time covariances between construct residuals, and autoregressive stabilities: Individuals who were higher on expressed anger tended to be higher on depressive symptoms and, within individuals, neither fluctuations in anger nor depression appeared to influence the other across intervals ranging from one year to 18 years. Although social support did not mediate an anger-depression connection, intraindividual increases in expressed anger predicted future intraindividual increases in perceived support (i.e., age 18 anger to age 19 support, and age 20 anger to age 22 support). A similar path from age 19 depressive symptoms to age 20 perceived support was observed. There were also some gender differences in the paths. The results point to stable interindividual differences in negative emotionality in place by age 18 and maintained up to age 43. (PsycINFO Database Record


Anonymous HIV testing using home collection and telemedicine counseling. A multicenter evaluation.
Home human immunodeficiency virus (HIV) testing has been proposed as an alternative to conventional HIV testing. Despite debate over HIV type 1 (HIV-1) home test systems, these concerns have not to our knowledge been previously studied. To evaluate the safety and efficacy of the Home Access Health Corp (Hoffman Estates, Ill) HIV-1 test system compared with traditional HIV-1 testing with venous blood. A total of 1255 subjects were studied prospectively in a blinded, subject-as-control evaluation at 9 outpatient clinics using intent-to-treat analysis. Subjects were provided a home collection kit (Home Access Health Corp) to collect their own finger-stick blood spot samples for laboratory analysis. Subjects received pretest counseling by telephone and their comprehension was subsequently assessed. Subject-collected blood spot samples were compared with professionally drawn blood spot samples for adequacy (sufficient for completing the Food and Drug Administration-endorsed testing) and with venous samples for accuracy. Subjects called 3 days later for anonymous results and posttest counseling. Device safety was evaluated based on adverse events incidence. Subject comprehension of HIV information was measured. Subject-collected blood spot sample results were in complete agreement with venous blood sample results, demonstrating 100% sensitivity and 100% specificity compared with venous controls. Ninety-eight percent of subjects obtained testable blood spot specimens compared with phlebotomists. Following pretest counseling, subjects answered 96% of HIV risk questions correctly. There were no significant adverse events. Anonymous HIV-1 home collection kits with pretest and posttest telephone counseling can provide a safe and effective alternative to conventional venous HIV-1 antibody testing.


Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells.
Human graft endothelial cells (ECs) can act as antigen-presenting cells to initiate allograft rejection by host memory T cells. Rapamycin, an mTOR inhibitor used clinically to suppress T cell responses, also acts on DCs, rendering them tolerogenic. Here, we report the effects of rapamycin on EC alloimmunogenicity. Compared with mock-treated cells, rapamycin-pretreated human ECs (rapa-ECs) stimulated less proliferation and cytokine secretion from allogeneic CD4+ memory cells, an effect mimicked by shRNA knockdown of mTOR or raptor in ECs. The effects of rapamycin persisted for several days and were linked to upregulation of the inhibitory molecules PD-L1 and PD-L2 on rapa-ECs. Additionally, rapa-ECs produced lower levels of the inflammatory cytokine IL-6. CD4+ memory cells activated by allogeneic rapa-ECs became hyporesponsive to restimulation in an alloantigen-specific manner and contained higher percentages of suppressive CD4+CD25(hi)CD127(lo)FoxP3+ cells that did not produce effector cytokines. In a human-mouse chimeric model of allograft rejection, rapamycin pretreatment of human arterial allografts increased graft EC expression of PD-L1 and PD-L2 and reduced subsequent infiltration of allogeneic effector T cells into the artery intima and intimal expansion. Preoperative conditioning of allograft ECs with rapamycin could potentially reduce immune-mediated rejection.


Ruthenium metallopolymer: Dawson polyoxomolybdate α-[Mo18O54(SO4)2]4- adduct films: sensitization for visible photoelectrocatalysis.
Thin films of the adduct formed from the electrostatic association of the metallopolymer, [Ru(bpy)(2)(PVP)(10)](2+), and the Dawson polyoxomolybdate α-[Mo(18)O(54)(SO(4))(2)](4-), POMo, have been formed on ITO electrodes using an alternate immersion approach. The Ru/POMo ratio is 4.5:1, which exceeds the 2:1 ratio expected on the basis of the charges of the Ru(2+) and POMo(4-) building blocks. This behavior arises because of the polymeric character of the cation. In the presence of a substrate that has an abstractable proton such as benzyl alcohol, these ruthenium-sensitized polyoxomolybdate films generate significant photocurrents under visible irradiation. Significantly, increasing the surface coverage of the adduct from 1.4 × 10(-10) to 8.1 × 10(-10) mol cm(-2) does not measurably increase the photocurrent observed. Scan-rate-dependent cyclic voltammetry reveals that the rate of homogeneous charge transport through the film is slow, which most likely results in only a fraction of the film thickness being active for photoelectrocatalysis. The photocurrent increases markedly when the driving force for the oxidation of POMo(5-), created by the photoelectrocatalytic oxidation of benzyl alcohol, is increased. This result is consistent with the dynamics of heterogeneous electron transfer being centrally important to the regeneration of the photoelectrocatalyst. A system in which the surface coverage and applied overpotential are optimized produces a photocurrent density of 190 ± 18 nA cm(-2) under 480 ± 5 nm irradiation.


Light microscopic autoradiographic localization of mu and delta opioid binding sites in the mouse central nervous system.
Much work has been done on opioid systems in the rat CNS. Although the mouse is widely used in pharmacological studies of opioid action, little has been done to characterize opioid systems in this species. In the present study the distribution of mu and delta opioid binding sites in the mouse CNS was examined using a quantitative in vitro autoradiography procedure. Tritiated dihydromorphine was used to visualize mu sites and [3H-d-Ala2-d-Leu5]enkephalin with a low concentration of morphine was used to visualize delta sites. Mu and delta site localizations in the mouse are very similar to those previously described in the rat ( Goodman , R.R., S.H. Snyder, M.J. Kuhar , and W.S. Young, 3d (1980) Proc. Natl. Acad. Sci. U.S.A. 77:6239-6243), with certain exceptions and additions. Mu and delta sites were observed in sensory processing areas, limbic system, extrapyramidal motor system, and cranial parasympathetic system. Differential distributions of mu and delta sites were noted in many areas. Mu sites were prominent in laminae I, IV, and VI of the neocortex, in patches in the striatum, and in the ventral pallidum, nucleus accumbens, medial and midline thalamic nuclei, medial habenular nucleus, interpeduncular nucleus, and laminae I and II of the spinal cord. In contrast, delta sites were prominent in all laminae of the neocortex, olfactory tubercle, diffusely throughout the striatum, and in the basal, lateral, and cortical nuclei of the amygdala. The determination of the differential distributions of opioid binding sites should prove useful in suggesting anatomical substrates for the actions of opiates and opioids.


Double Virus Vector Infection to the Prefrontal Network of the Macaque Brain.
To precisely understand how higher cognitive functions are implemented in the prefrontal network of the brain, optogenetic and pharmacogenetic methods to manipulate the signal transmission of a specific neural pathway are required. The application of these methods, however, has been mostly restricted to animals other than the primate, which is the best animal model to investigate higher cognitive functions. In this study, we used a double viral vector infection method in the prefrontal network of the macaque brain. This enabled us to express specific constructs into specific neurons that constitute a target pathway without use of germline genetic manipulation. The double-infection technique utilizes two different virus vectors in two monosynaptically connected areas. One is a vector which can locally infect cell bodies of projection neurons (local vector) and the other can retrogradely infect from axon terminals of the same projection neurons (retrograde vector). The retrograde vector incorporates the sequence which encodes Cre recombinase and the local vector incorporates the "Cre-On" FLEX double-floxed sequence in which a reporter protein (mCherry) was encoded. mCherry thus came to be expressed only in doubly infected projection neurons with these vectors. We applied this method to two macaque monkeys and targeted two different pathways in the prefrontal network: The pathway from the lateral prefrontal cortex to the caudate nucleus and the pathway from the lateral prefrontal cortex to the frontal eye field. As a result, mCherry-positive cells were observed in the lateral prefrontal cortex in all of the four injected hemispheres, indicating that the double virus vector transfection is workable in the prefrontal network of the macaque brain.


Changes in the structure of synapses associated with learning.
Two experiments were conducted to investigate the effects of training on a region of the chick brain known to be critically involved in imprinting, the intermediate and medial extent of the hyperstriatum ventrale (IMHV). In the first experiment, three groups of chicks were used: (i) dark-reared (n = 9), (ii) trained for 20 min (n = 17), and (iii) trained for 140 min (n = 7). Chicks were trained by exposing them when they were approximately 21 hr old to a flashing red light. Chicks were killed when they were approximately 30 hr old and blocks of tissue were removed from the right and left IMHV. Stereological techniques were used to measure from electron micrographs the numerical density of dendritic spine and shaft synapses and the length of the postsynaptic density of these synaptic junctions. There was a significant effect of training only in the left IMHV and on only one measure, the overall mean length of the postsynaptic density of spine synapses, SPL. This measure was significantly greater by 17.2% in chicks trained for 140 min than in dark-reared controls. There was no significant effect of training for 20 min. In the second experiment one group of chicks (n = 15) was exposed to a rotating red box for a total of 3 hr. Another group of chicks was dark-reared (n = 15). The chicks were killed when they were approximately 46 hr old. Samples from the hyperstriatum accessorium and IMHV of the right and left sides were analyzed. Training was associated with a significant change, an increase, only of SPL in the left IMHV.(ABSTRACT TRUNCATED AT 250 WORDS)


Integrating paleoecology and genetics of bird populations in two sky island archipelagos.
Genetic tests of paleoecological hypotheses have been rare, partly because recent genetic divergence is difficult to detect and time. According to fossil plant data, continuous woodland in the southwestern USA and northern Mexico became fragmented during the last 10,000 years, as warming caused cool-adapted species to retreat to high elevations. Most genetic studies of resulting 'sky islands' have either failed to detect recent divergence or have found discordant evidence for ancient divergence. We test this paleoecological hypothesis for the region with intraspecific mitochondrial DNA and microsatellite data from sky-island populations of a sedentary bird, the Mexican jay (Aphelocoma ultramarina). We predicted that populations on different sky islands would share common, ancestral alleles that existed during the last glaciation, but that populations on each sky island, owing to their isolation, would contain unique variants of postglacial origin. We also predicted that divergence times estimated from corrected genetic distance and a coalescence model would post-date the last glacial maximum. Our results provide multiple independent lines of support for postglacial divergence, with the predicted pattern of shared and unique mitochondrial DNA haplotypes appearing in two independent sky-island archipelagos, and most estimates of divergence time based on corrected genetic distance post-dating the last glacial maximum. Likewise, an isolation model based on multilocus gene coalescence indicated postglacial divergence of five pairs of sky islands. In contrast to their similar recent histories, the two archipelagos had dissimilar historical patterns in that sky islands in Arizona showed evidence for older divergence, suggesting different responses to the last glaciation. This study is one of the first to provide explicit support from genetic data for a postglacial divergence scenario predicted by one of the best paleoecological records in the world. Our results demonstrate that sky islands act as generators of genetic diversity at both recent and historical timescales and underscore the importance of thorough sampling and the use of loci with fast mutation rates to studies that test hypotheses concerning recent genetic divergence.


Unresolved questions of renal magnesium homeostasis.
While the basic tenets of Mg handling by the mammalian kidney have been clearly outlined, Mg homeostasis in the body, the mechanism of extracellular fluid Mg regulation by the kidneys, and the regulation of intracellular Mg concentrations are largely unknown. Only a small fraction of total body Mg is present in the extracellular fluid and handled by the kidney, raising the question whether other organs, intestine, muscle and bone participate in Mg balance as well. In view of the tight regulation of Mg concentration in the plasma and the life-threatening derangements when plasma Mg concentration falls outside the physiological range it is surprising that a hormone responsible for general Mg homeostasis has not yet been identified. A hormone or factor which regulates tubular Mg reabsorption and hence renal Mg excretion is suspected, but it has not been found in any animal. Renal regulation of extracellular Mg involves filtration at the glomerulus and reabsorption in the proximal tubule and the thick ascending limb of the loop of Henle, where respectively, 30 and 60% of the filtered Mg load are reabsorbed. In the nongrowing individual the quantities of Mg excreted match the quantities absorbed from the gut. Mechanisms of tubular Mg transport are largely unknown for lack of understanding of Mg transport across epithelial cell membranes. The unexplored nature of Mg physiology can be attributed to analytical limitations. However, with the advent of a new Mg exchanger suitable for microelectrode work and with the use of Mg-sensitive dyes, Mg research is about to enter the renaissance period.


Physical impairments in Adults with Developmental Dysplasia of the Hip (DDH) undergoing Periacetabular osteotomy (PAO): A Systematic Review and Meta-Analysis.
Developmental dysplasia of the hip (DDH) is a condition associated with hip pain and impairments. Periacetabular osteotomy (PAO) is a common surgical treatment for DDH. Outcomes following PAO have historically been based on radiology or patient reported outcomes, and not physical impairments. To investigate differences in physical impairments in adults with DDH undergoing PAO compared with asymptomatic participants, and to investigate pre- to post-PAO changes in physical impairments. Systematic review with meta-analysis. A literature search was performed in five databases (MEDLINE, CINAHL, EMBASE, Sports Discuss, and PsychINFO), using the PRISMA checklist. Studies were considered eligible if patients were aged 15 years and older, treated with PAO for DDH and if they included a physical impairment outcome measure. Two independent reviewers performed data extraction and assessed methodological quality, using a modified version of the Downs and Black checklist. Of 5,017 studies, 24 studies were included with 2190 patients. The methodological quality scores ranged from 39% to 88%. With low level of evidence, meta-analysis showed 58% of patients had a positive anterior impingement test (95%CI: 39-76%), prior to PAO and one to three years after PAO. Five years after PAO, the proportion fell to 17% (95%CI: 11-24%). Prior to PAO, patients with DDH walked with a lower peak hip extension angle, compared to asymptomatic participants (SMD 0.65 (95%CI 0.21-1.10). Best evidence synthesis of non-pooled data showed limited evidence of increased walking velocity, stride length and improved hip flexion and extension moment 18-months post-PAO compared to pre-op. Cadence, hip abduction and hip flexion strength did not change. Most patients with DDH have a positive hip impingement test, pre-PAO. Compared to asymptomatic participants, patients with DDH demonstrate physical impairments during walking which appear to improve after surgery. Hip abduction and flexion strength did not change pre- to post-PAO. 1b.


Right temporal alpha oscillations as a neural mechanism for inhibiting obvious associations.
Creative cognition requires mental exploration of remotely connected concepts while suppressing dominant ones. Across four experiments using different samples of participants, we provide evidence that right temporal alpha oscillations play a crucial role in inhibiting habitual thinking modes, thereby paving the way for accessing more remote ideas. In the first experiment, participants completed the compound remote associate task (RAT) in three separate sessions: during right temporal alpha (10 Hz) transcranial alternating current brain stimulation (tACS), left temporal alpha tACS, and sham tACS. Participants performed better under right tACS only on RAT items in which two of the three words shared misleading semantic associations. In the second experiment, we measured EEG while the participants solved RAT items with or without shared misleading associations. We observed an increase in right temporal alpha power when participants correctly solved RAT items with misleading semantic associations. The third experiment demonstrated that while solving divergent thinking tasks participants came up with more remote ideas when stimulated by right temporal alpha tACS. In the fourth experiment, we found that participants showed higher right temporal alpha power when generating more remote uses for common objects. These studies altogether indicate that right temporal alpha oscillations may support creativity by acting as a neural mechanism for an active inhibition of obvious semantic associations.


Purification and characterization of colicin D.
Colicin D-CA23, obtained by sonic treatment of mitomycin C-induced cells of Escherichia coli K-12 W1485 (colD), was purified by ammonium sulfate precipitation, gel filtration on Sephadex G200, ion-exchange chromatography on diethylaminoethyl cellulose, and isoelectrofocusing. Polyacrylamide-gel electrophoresis, sedimentation velocity analysis, and antigenic analysis indicated that the preparation was homogeneous. Colicin D is composed entirely of amino acids and hence is a simple protein uncomplexed with lipid or lipopolysaccharide. It contains six residues of cysteine per molecule. The molecular weight of colicin D is approximately 92,000, as determined by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis and gel filtration on Sephadex G200. Its sedimentation coefficient is 4.41S. The behavior of colicin D in solutions of sodium dodecyl sulfate and 2-mercaptoethanol indicates that it does not consist of subunits and exists as a single polypeptide chain. Its high molecular weight and presence of six cysteine residues per molecule distinguish colicin D from all colicins previously described. Although colicins D and E3 have similar modes of action, their gross molecular properties are entirely different.


Satiety testing in diabetic gastroparesis: Effects of insulin pump therapy with continuous glucose monitoring on upper gastrointestinal symptoms and gastric myoelectrical activity.
Symptoms induced by caloric or non-caloric satiety test meals and gastric myoelectrical activity (GMA) have not been studied in patients with diabetic gastroparesis (DGP) before and after intense glucose management. We determined the effects of continuous subcutaneous insulin infusion (CSII) with continuous glucose monitoring (CGM) on GI symptoms, volume consumed, and GMA induced by the caloric meal satiety test (CMST) and water load satiety test (WLST) in DGP. Forty-five patients with DGP underwent CMST and WLST at baseline and 24 weeks after CSII with CGM. Subjects ingested the test meals until they were completely full. Visual analog scales were used to quantify pre- and postmeal symptoms, and GMA was recorded with cutaneous electrodes and analyzed visually and by computer. KEY RESULTS: At baseline and 24-week visits, nausea, bloating, abdominal discomfort, and fullness were immediately increased after CMST and WLST (Ps < 0.01). The meal volumes ingested were significantly less than normal controls at both visits in almost one-third of the subjects. After the CMST, the percentage 3 cycle per minute GMA increased and bradygastria decreased compared with WLST (Ps < 0.05). After treatment for 24 weeks meal volumes ingested, postmeal symptoms and GMA were no different than baseline. CONCLUSIONS AND INFERENCES: (a) Satiety test meals elicited symptoms of nausea, bloating, and abdominal discomfort; (b) CMST stimulated more symptoms and changes in GMA than WLST; and (c) CSII with CGM for 24 weeks did not improve symptoms, volumes ingested, or GMA elicited by the two satiety test meals in these patients with diabetic GP. Satiety tests in diabetic gastropresis are useful to study acute postprandial symptoms and GMA, but these measures were not improved by intensive insulin therapy.


Trends in healthcare incident reporting and relationship to safety and quality data in acute hospitals: results from the National Reporting and Learning System.
Internationally, there is increasing recognition of the need to collect and analyse data on patient safety incidents, to facilitate learning and develop solutions. The National Patient Safety Agency (NPSA) for England and Wales has been capturing incident data from acute hospitals since November 2003. This study analyses patterns in reporting of patient safety incidents from all acute hospitals in England to the NPSA National Reporting and Learning System, and explores the link between reporting rates, hospital characteristics, and other safety and quality datasets. Reporting rates to the NPSA National Reporting and Learning System were analysed as trends over time, from the point at which each hospital became connected to the system. The relationships between reporting rates and other safety and quality datasets were assessed using correlation and regression analyses. Reporting rates increased steadily over the 18 months analysed. Higher reporting rates correlated with positive data on safety culture and incident reporting from the NHS Staff Survey, and with better risk-management ratings from the NHS Litigation Authority. Hospitals with higher overall reporting rates had a lower proportion of their reports in the "slips, trips and falls" category, suggesting that these hospitals were reporting higher numbers of other types of incident. There was no apparent association between reporting rates and the following data: standardised mortality ratios, data from other safety-related reporting systems, hospital size, average patient age or length of stay. Incident reporting rates from acute hospitals increase with time from connection to the national reporting system, and are positively correlated with independently defined measures of safety culture, higher reporting rates being associated with a more positive safety culture.


[Use of AFLP analysis for the molecular biological fine typing of Campylobacter jejuni strains from turkey flocks].
One of the most promising genotyping methods for microorganisms is the AFLP (amplified fragment length polymorphism)-analysis, originally developed to genotype plants. The AFLP method has a high discriminatory power and an excellent reproducibility. Thus it is suitable for solving taxonomic and epidemiological questions. AFLP analysis was used to reveal the genetic diversity of Campylobacter (C.) jejuni strains from turkeys. The aim was to detect and genotype C. jejuni strains on individual turkeys throughout the complete slaughter process. A broad spectrum of genotypes was detectable on the turkey skin at the beginning of the slaughter line. At the end of the slaughter process-after chilling, only a diminished spectrum of genotypes was detectable by AFLP-analysis, suggesting, that slaughter specific environmental stressors may exert a selective pressure on the strain diversity. Our results proved, that AFLP analysis is an excellent tool for subtyping large numbers of Campylobacter strains.


Representing kidney development using the gene ontology.
Gene Ontology (GO) provides dynamic controlled vocabularies to aid in the description of the functional biological attributes and subcellular locations of gene products from all taxonomic groups (www.geneontology.org). Here we describe collaboration between the renal biomedical research community and the GO Consortium to improve the quality and quantity of GO terms describing renal development. In the associated annotation activity, the new and revised terms were associated with gene products involved in renal development and function. This project resulted in a total of 522 GO terms being added to the ontology and the creation of approximately 9,600 kidney-related GO term associations to 940 UniProt Knowledgebase (UniProtKB) entries, covering 66 taxonomic groups. We demonstrate the impact of these improvements on the interpretation of GO term analyses performed on genes differentially expressed in kidney glomeruli affected by diabetic nephropathy. In summary, we have produced a resource that can be utilized in the interpretation of data from small- and large-scale experiments investigating molecular mechanisms of kidney function and development and thereby help towards alleviating renal disease.