Interruption of Sneddon-Wilkinson Subcorneal Pustulation with Infliximab.
Subcorneal pustular dermatosis (SCPD, Sneddon-Wilkinson disease) is a rare chronic-relapsing skin disorder that typically manifests as flaccid sterile pustules without systemic symptoms. Although the accumulation of neutrophils is acknowledged to be a hallmark of SCPD, its exact pathomechanism is still not known. Several chemotactic factors have been implicated in neutrophil recruitment and invasion, including the proinflammatory cytokine TNF-α. These findings correspond well with clinical reports of successful off-label use of TNF blocking agents in cases that were refractory to first-line therapy, mostly with dapsone. We report the case of a 29-year-old male with atypical and severe manifestation of SCPD that resolved after a single dose of infliximab. Consolidation was observed 1 day after treatment and regression of skin lesions occurred after a few days. Residual scarring and postlesional hyperpigmentation was seen at a 2-month follow-up appointment. The patient was initiated on a daily maintenance therapy with dapsone, which led to a drop in hemoglobin and had to be stopped. Upon development of small, scaly lesions, a maintenance therapy with infliximab was started and the patient has had no recurrence to date. Anti-TNF agents present a promising option for patients affected by severe SCPD. We review the reports of similar cases in the literature to date.


Perforated mucinous cystadenoma of the vermiform appendix: an overview in reasoning clinical decisions.
Recent advances in the management of appendiceal mucinous neoplasms (AMN) such as peritonectomy combined with hyperthermic intraperitoneal chemotherapy have introduced new standards of care. However, many dilemmas are encountered in decision making as in the following patient. A 74-year-old woman was admitted with an appendiceal cystadenoma found in a preadmission CT scan. However, the tumour was not documented by the in hospital investigation due to its perforation and its reduction in size. Consequently, a series of management dilemmas were encountered that were solved by cautious evaluation of the pre and peroperative findings. She was submitted to a right hemicolectomy. A spontaneous perforation was suspected, but the accurate diagnosis was documented postoperatively by histopathology. This paradigm motivated this review which concluded that reasoning clinical decisions in the light of recent advances and appropriate care based on the disease-stage are essential for an optimal outcome in the management of AMN.


Back to basics: the role of health insurance in getting a physical exam.
The social work profession has a long history of advocacy to improve the human condition, especially for groups of people at high risk of discrimination and marginalization. Social workers have been instrumental in identifying, assessing, treating, and preventing illicit drug use as part of this commitment to advocacy. One component of social work's endeavors on behalf of drug users and other populations- at-risk has been advocating for increased access to health care. This article examines the role that having health insurance plays in obtaining the most basic of all health care-getting a physical examination. Featuring a sample of 1,271 chronic and injecting street drug users and comparison group non-users, the analysis demonstrates that having health insurance enhances access and utilization of health care among this at-risk population. Subjects who had health insurance for even one month of the past twelve were twice as likely to participate in basic health care by having a physical exam.


Building capacity for estimating fire emissions from tropical peatlands; a worked example from Indonesia.
Tropical peatlands are globally significant in the terrestrial carbon cycle as they are comprised of a large forest carbon sink and a large peat carbon store-both of which can potentially be exchanged with the atmosphere on decadal time frames. Greenhouse gas emissions from fire-disturbance and development of tropical peatlands over the last few decades, and the potential for ongoing emissions, highlights the need for policy to slow or halt emissions and to activate mechanisms to sequester carbon through restoration of degraded peatlands. The UN REDD + scheme provides a means for developing countries to receive payments for avoided deforestation and forest degradation, but the steps to achieve REDD+ compliance are rigorous and the details required can be a barrier to activating benefits-especially for peatlands where repeated cycles of fire interrupt forest recovery and create a range of recovery classes. Therefore, to improve estimates of peat fire emissions and of carbon balance of tropical peatlands, the biomass and combustion factor parameters need to be developed and applied according to forest recovery stage. In this study we use published activity data from the extensive 1997 fires in the peatlands of Indonesian Borneo to detail a transparent and accountable way to estimate and report emissions from tropical peatland fires. This example for estimating and reporting emissions is provided to assist REDD+ countries to efficiently develop their capacity for improving emissions estimates from fire-impacted tropical peatlands.


In silico and in vitro evaluation of two novel oximes (K378 and K727) in comparison to K-27 and pralidoxime against paraoxon-ethyl intoxication.
Organophosphate (OP) poisoning is a major global health issue; while compounds from this group have been used intensively over the last century, an effective antidote is still lacking. Oxime-type acetylcholinesterase (AChE) reactivators are used to reactivate the OP inhibited AChE. Pralidoxime is the only US Food and Drug Administration approved oxime for therapeutic use but its efficacy has been disappointing. Two novel oximes (K378 and K727) were investigated in silico and in vitro and compared with an experimental oxime (kamiloxime; K-27) and pralidoxime. In silico the molecular interactions between AChE and oximes were examined and binding energies were assessed. LogP (predicted log of the octanol/water partition coefficient) was estimated. In vitro the intrinsic ability of the oximes to inhibit AChE (IC50) and their reactivation potency (R50) when used in paraoxon inhibited human RBC-AChE was determined. Molecular docking revealed that K378 and K727 bind to the peripheral site(s) with high binding energies in contrast to the central binding of K-27 and pralidoxime. LogP values indicating that the novel compounds are significantly less hydrophilic than K-27 or pralidoxime. IC50 of K378 and K727 were comparable (0.9 and 1 µM, respectively) but orders of magnitude lower than comparators. R50 values revealed their inability to reactivate paraoxon inhibited AChE. It is concluded that the novel oximes K378 and K727 are unlikely to be clinically useful. The in silico and in vitro studies described allow avoidance of unnecessary in vivo animal work and contribute to the reduction of laboratory animal use.


Bacterial communities in petroleum oil in stockpiles.
Bacterial communities in crude-oil samples from Japanese oil stockpiles were investigated by 16S rRNA gene cloning, followed by denaturing gradient gel electrophoresis (DGGE) analysis. 16S rRNA genes were successfully amplified by PCR after isooctane treatment from three kinds of crude-oil sample collected at four oil stockpiles in Japan. DGGE profiles showed that bacteria related to Ochrobactrum anthropi, Burkholderia cepacia, Stenotrophomonas maltophilia, Propionibacterium acnes, and Brevundimonas diminuta were frequently detected in most crude-oil samples. The bacterial communities differed in the sampling time and layer. Among the predominant bacteria detected in the crude oil, only three species were found for bacteria isolated on agar plates and were related to Burkholderia, Stenotrophomonas, and Propionibacterium, while Ochrobactrum sp. could not be isolated although this species seemed to be the most abundant bacterium in crude oil from the DGGE profiles. Using an archaea-specific primer set, methanogens were found in crude-oil sludge but not in crude-oil samples, indicating that methanogens might be involved in sludge formation in oil stockpiles.


Mitogen-activated protein kinase activation during IgG-dependent phagocytosis in human neutrophils: inhibition by ceramide.
In FMLP-activated polymorphonuclear leukocytes (PMNs) challenged with IgG-opsonized erythrocytes (EIgG), the termination of phagocytosis correlates with an accumulation of ceramide, a product of sphingolipid metabolism. Furthermore, the exogenous addition of short chain ceramides inhibits EIgG-mediated phagocytosis. In the present study, we identified p42 and p44 mitogen-actived protein (MAP) kinases, referred to as extracellular signal-regulated kinases ERK2 and ERK1, respectively, as intracellular targets of ceramide action during Fc gammaR-mediated phagocytosis. The tyrosine phosphorylation of ERK1 and ERK2 increased within 30 s of addition of EIgG, with maximal phosphorylation by 1 to 5 min. By 30 min, ERK1 and ERK2 were almost completely dephosphorylated. The kinetics of ERK1 and ERK2 tyrosine phosphorylation indicated that MAP kinase activation preceded target ingestion. N-Acetylsphingosine (C2-ceramide) inhibited phagocytosis, reduced ERK1 and ERK2 phosphorylation to basal levels, and reduced ERK1 and ERK2 activity by 85 to 90% and 70 to 80%, respectively. In contrast, N-acetyldihydrosphingosine (dihydro-C2-ceramide) had no effect on either tyrosine phosphorylation or activity of ERK1 and ERK2. In the presence of the MAP kinase kinase (MEK) inhibitor, PD 098059, phagocytosis was reduced by approximately 50%, while ERK1 and ERK2 activity was reduced by 85 to 90%. Thus, engagement of Fc gammaRs led to ERK1 and ERK2 phosphorylation and activation, and the activation of these enzymes was critical for phagocytosis. Furthermore, the inhibition of phagocytosis by C2-ceramide correlated with the inhibition of tyrosine phosphorylation and activation of ERK1 and ERK2. These results suggest that ceramides generated during phagocytosis act on the MAP kinase signaling pathway, ultimately "turning off" the phagocytic response.


Cytotoxic pyrone derivatives from the deep-sea-derived fungus Cladosporium halotolerans FS702.
Two new compounds (R)-6-((8S)-hydroxypropyl)-2-methyl-5,6-dihydro-4H-pyran-4-one (1) and (R)-6-((8R)-hydroxypropyl)-2-methyl-5,6-dihydro-4H-pyran-4-one (2), together with four known compounds were isolated from the marine-derived fungus Cladosporium halotolerans FS702. The structures of these compounds were determined on the basis of extensive spectroscopic analysis including 1D/2D NMR, IR, UV, HRESIMS, ECD calculations as well as the modified Mosher's method. Cytotoxic assay results showed that compound 2 had significant cytotoxic activity against SF-268, MCF-7, HepG-2, and A549 cells lines with IC50 values of 0.16, 0.47, 0.33 and 0.23 µM, respectively.


Production of ethanol by Clostridium thermosaccharolyticum: II. A quantitative model describing product distributions.
The study of the continuous culture of Clostridium thermosaccharolyticum on xylose showed multiple steady states and hysteresis. A quantitative model based on the biochemistry and physiology of xylose fermentation by C. thermosaccharolyticum was developed. The objective in developing this model was to bring together the observations both of this study and of other researchers on the fermentation of xylose. The model equations were written based on the metabolic pathway for xylose utilization by C. thermosaccharolyticum and the requirement that the carbon, ATP, and NADH within the cell be balanced. Given the specific growth rate mu and the specific xylose utilization rate q(s), a set of product distributions (ethanol, acetate, and lactate) satisfying these balances was obtained. This set was plotted on a triangular plot and named the permitted region. The product distributions within this permitted region were shown to be affected by the environmental parameters such as iron concentration and hydrogen partial pressure. The model predicted trends in product distribution which correlate with experimentally observed phenomena. The model was also used to analyze the continuous-culture data from our experimental work.


Effect of the presence or absence of J chain on expression of recombinant anti-Kell immunoglobulin M.
The aim of this study was to determine the effect of expressing a recombinant anti-Kell immunoglobulin (Ig) M from two cell lines, CH0 and NS0, on its ability to function as a diagnostic antibody. As a polymeric immunoglobulin, IgM is able to directly agglutinate red blood cells (RBCs), making it a useful blood grouping reagent. To simplify expression, recombinant human IgM (rIgM) from NS0 (a mouse myeloma line) and CHO (Chinese hamster ovary line) cells was expressed in the absence of human J chain. Whereas NS0 expresses mouse J chain, rIgM expressed from CH0 cells lack J chain. Although the ability to polymerize resides within the tailpiece of IgM heavy chain, J chain can influence the polymeric state. This in turn could affect the ability of rIgM to bind its antigen. The variable region of the heavy chain of an anti-Kell IgG was grafted onto the constant region of human IgM and co-expressed with light chain derived from the same antibody. rIgM was purified from each cell line and the strength of direct agglutination assessed. Both cell lines produced polymeric rIgM that was able to specifically bind the target antigen and to directly agglutinate RBCs to the same degree. The presence or absence of J chain did not affect the ability of the rIgM to bind the Kell antigen or the strength of agglutination. The presence of J chain is not required for the production of a functional rIgM for use as a diagnostic reagent. CHO and NS0 lines are both suitable for production of such a reagent.


Acanthamoeba keratitis presenting as dendritic keratitis in a soft contact lens wearer.
Acanthamoeba keratitis is a rare cause of corneal infection in Taiwan, which can result in devastating visual outcomes. A 37-year-old woman, who wore soft contact lenses, suffered from severe pain in her left eye. Biomicroscopy revealed dendritic keratitis, radial keratoneuritis, and fine keratic precipitates on her cornea. Culture, using non-nutrient agar plate seeded with Escherichia coli, resulted in heavy growth of Acanthamoeba. The inpatient treatment, including topical neomycin-polymyxin B and metronidazole (0.5%) eyedrops, oral ketoconazole, and then oral prednisolone, successfully controlled the corneal infection. The best-corrected visual acuity was 0.9 without any evidence of recurrence of infection after 21 months of follow up. Acanthamoeba keratitis can present as dendritic keratitis, which mimics herpes simplex infection, thus, delays appropriate treatment. Early diagnosis and judicious treatment are essential for restoring the vision and avoiding the subsequent need of penetrating keratoplasty.


Ferritin, cellular iron storage and regulation.
Ferritin is considered the major iron storage protein which maintains a large iron core in its cavity and has ferroxidase activity. There are many types of ferritin particularly in prokaryotes that include the canonical 24-mer FTN molecules, the heme-containing BFR, the smaller 12-mer DPS and the newly recognized EncFtn of encapsulin that forms a very large iron storage compartment. Recent studies show that ferritin function is more dynamic than previous depicted and new mechanisms of ferritin iron recycling are emerging. They participate to the regulation of cellular iron homeostasis as those of ferritin biosynthesis, cooperating also with the iron-dependent mechanism of cellular iron secretion. Some of these basic processes are in common between unicellular and animal cells, and this review aims at discussing the findings on the connections between iron storage, cellular iron regulation and ferritin iron recycling that have been explored in unicellular organisms and in animals. © 2017 IUBMB Life, 69(6):414-422, 2017.


Rhombomere rotation reveals that multiple mechanisms contribute to the segmental pattern of hindbrain neural crest migration.
Hindbrain neural crest cells adjacent to rhombomeres 2 (r2), r4 and r6 migrate in a segmental pattern, toward the first, second and third branchial arches, respectively. Although all rhombomeres generate neural crest cells, those arising from r3 and r5 deviate rostrally and caudally (J. Sechrist, G. Serbedzija, T. Scherson, S. Fraser and M. Bronner-Fraser (1993) Development 118, 691-703). We have altered the rostrocaudal positions of the cranial neural tube, adjacent ectoderm/mesoderm or presumptive otic vesicle to examine tissue influences on this segmental migratory pattern. After neural tube rotation, labeled neural crest cells follow pathways generally appropriate for their new position after grafting. For example, when r3 and r4 were transposed, labeled r3 cells migrated laterally to the second branchial arch whereas labeled r4 cells primarily deviated caudally toward the second arch, with some cells moving rostrally toward the first. In contrast to r4 neural crest cells, transposed r3 cells leave the neural tube surface in a polarized manner, near the r3/4 border. Surprisingly, some labeled neural crest cells moved directionally toward small ectopic otic vesicles that often formed in the ectoderm adjacent to grafted r4. Similarly, they moved toward grafted or displaced otic vesicles. In contrast, surgical manipulation of the mesoderm adjacent to r3 and r4 had no apparent effects. Our results offer evidence that neural crest cells migrate directionally toward the otic vesicle, either by selective attraction or pathway-derived cues.


A Case of Delayed Diagnosis of Idiopathic Infantile Hypercalcemia Due to CYP24A1 Mutation: A 10-Year Journey.
The parathyroid gland is responsible for the synthesis and secretion of parathyroid hormone, which is synthesized and released at an inverse relationship to the level of ionized calcium in the blood. Primary hyperparathyroidism affects women more than men. There are various causes for hyperparathyroidism-induced hypercalcemia and the most common cause is parathyroid adenoma. A less common cause of vitamin D-mediated parathyroid hormone-independent hypercalcemia is the loss of function mutation of the CYP24A1 gene. The CYP24A1 gene encodes the vitamin D 24-hydroxylase enzyme, responsible for hydroxylating the active form of vitamin D into an inactive form, and mutations in the CY24A1 gene can lead to elevated active vitamin D metabolite levels. It can result in hypercalcemia and hypercalciuria-related complications. We present a case of a 72-year-old male patient referred to the endocrine clinic, who had repeated treatments for hypercalcemia and recurrent renal calculi. He underwent ultrasound, computerized tomography, and sestamibi scans, all reported as normal. Following this, the patient underwent a positron emission tomography (PET) scan, which was also normal. He then finally underwent genetic testing and tested positive for the CYP24A1 gene. He was started on fluconazole 50mg once a day and cinacalcet 30mg twice with normalization of calcium level. Three of his family members also tested positive for the condition.


Effect of abdominal drawing-in maneuver with prone hip extension on muscle activation of posterior oblique sling in normal adults.
[Purpose] There have been many studies on ipsilateral erector spinae in regard of prone hip extension (PHE). However, mediating methods have been focusing on the reinforcement of gluteus. Hereupon, this study is intended to identify how an increase of abdominal drawing-in maneuver influences on posterior oblique sling (POS) and suggest a mediating method to effectively reinforce them. [Participants and Methods] This study has been conducted on normal male (10) and female (10), and participants were asked to prove PHE exercise and abdominal drawing-in maneuver prone hip extension exercise (ADIM PHE). Surface electromyography (EMG) was recorded from the contralateral latissimus dorsi, ipsilateral erector spinae, ipsilateral gluteus maximus, and ipsilateral biceps femoris. A pared t-test was used to compare muscle activity POS. [Results] EMG activity of the contralateral latissimus dorsi, ipsilateral gluteus maximus was significantly greater performed ADIM PHE than PHE. As for ipsilateral erector spinae muscle, ipsilateral biceps femoris activation was lower in ADIM PHE than PHE. [Conclusion] According to the results of this study, abdominal drawing-in maneuver seems to be an important factor that influences on muscular activation of POS.


Lu-177-Labeled Hetero-Bivalent Agents Targeting PSMA and Bone Metastases for Radionuclide Therapy.
Prostate-specific membrane antigen (PSMA) is an excellent target for imaging and radionuclide therapy of prostate cancer. Recently, [177Lu]Lu-PSMA-617 (Pluvicto) was approved by the FDA for radionuclide therapy. To develop hetero-bivalent agents targeting both PSMA and bone metastasis, [177Lu]Lu-P17-079 ([177Lu]Lu-1) and [177Lu]Lu-P17-081 ([177Lu]Lu-2) were prepared. In vivo biodistribution studies of [177Lu]Lu-PSMA-617, [177Lu]Lu-1, and [177Lu]Lu-2 in mice bearing PC3-PIP (PSMA positive) tumor showed high uptake in PSMA-positive tumor (14.5, 14.7, and 11.3% ID/g at 1 h, respectively) and distinctively different bone uptakes (0.52, 6.52, and 5.82% ID/g at 1 h, respectively). PET imaging using [68Ga]Ga-P17-079 ([68Ga]Ga-1) in the same mouse model displayed excellent images confirming the expected dual-targeting to PSMA-positive tumor and bone. Results suggest that [177Lu]Lu-P17-079 ([177Lu]Lu-1) is a promising candidate for further development as a hetero-bivalent radionuclide therapy agent targeting both PSMA expression and bone metastases for the treatment of prostate cancer.


Improvement of morning headache in adults with obstructive sleep apnea after positive airway pressure therapy.
The aim of this study was to evaluate the association between obstructive sleep apnea and morning headache and to assess the improvement of morning headache following positive airway pressure therapy. One hundred and sixteen participants were enrolled in this study; all of them received positive airway pressure therapy for at least 3 months. We checked the differences in various sleep apnea-related parameters according to the presence of morning headache and evaluated the improvement of morning headache following positive airway pressure therapy. Among the 116 study participants, 103 were men, with a mean age and body mass index of 50.34 ± 10.23 years and 28.00 ± 4.21 kg/m2, respectively. The severity of morning headache was higher in the severe obstructive sleep apnea group than in the mild to moderate group (2.16 ± 1.70 vs. 1.50 ± 1.57, P = 0.027). However, the various polysomnographic parameters did not significantly differ according to the presence of headache. The Epworth sleepiness scale score was significantly higher in the morning headache presence group than in the absence group (10.90 ± 5.45 vs. 8.13 ± 4.27, P = 0.003). Furthermore, a notable correlation was observed between the reduction in daytime sleepiness and the improvement in morning headache following PAP treatment (r = 0.503, P < 0.001). Morning headache significantly improved following positive airway pressure therapy (prevalence: 53.4-16.4%; severity: 1.92 ± 1.67 vs. 0.86 ± 0.80, all P < 0.001), especially in the patients with morning headache before positive airway pressure therapy. Morning headache is significantly associated with daytime sleepiness and positive airway pressure therapy improves morning headache.


Comparison of Obesity Prevalence and Dietary Intake in School-Aged Children Living in Rural and Urban Area of Croatia.
The aim of this study was to explore the differences in nutritional status and dietary intakes in 12~17 year-old children living in urban (Zagreb) and the rural (Sinj and Drniš) area of Croatia. A validated food frequency questionnaire was used to assess dietary intake. For each participant, body weight and body height were measured and bioelectrical impedance was used to estimate the body fat percentage. There was an overall of 310 children included: 105 (33.9%) from urban area and 205 (66.1%) from rural area; 191 (61.6%) were female with a mean age 14.9 (range 12~17) years. When adjusted for age and gender, there was no statistically significant difference in body mass index for age Z-scores between urban and rural parts (0.23±0.07 vs. 0.30±1.15; P=0.650) or in average daily energy intake (2,479.2±1,111.2 kcal vs. 2,338.2±920.2 kcal; P=0.702). There was a statistically significant difference in nutritional status between genders, with a higher percentage of boys being overweight or obese compared to girls. When combined, 'Fast food' and 'Snacks' were major contributors to the total energy intake for both areas. The mean contribution of 'Fast food' to total energy intake was significantly higher in the urban area. The prevalence of obesity among Croatian children is high and unrelated to the urban/rural setting, which could be partially explained by the high intake of 'Fast food' and 'Snacks'.


Prevalence and Risk Factors of Chronic Constipation Among Women Aged 50 Years and Older in Shanghai, China.
BACKGROUND Chronic constipation (CC) is a major public health problem worldwide, especially in elderly women. This study aimed to investigate the prevalence and risk factors of CC among women aged 50 years and older in Shanghai, China. MATERIAL AND METHODS A cross-sectional survey was conducted on 1950 women aged 50 years and older, randomly sampled in Yangpu District of Shanghai from April to October 2015. Information on demographic characteristics, lifestyle habits, medical history, and defecation situation was collected through in-person interviews. CC was defined according to Rome III criteria. The data were analyzed by chi-square test and multiple logistic regression analysis. RESULTS The response rate to the survey was 80.4%. Of the 1568 participants, 77 were diagnosed with CC, with a prevalence of 4.9%. Moreover, the prevalence increased with advancing age. Multiple logistic analyses showed that body mass index (BMI) ≥25.0 kg/m², non-manual occupation, premenopausal period, no delivery history, poor sleep quality, meat-based diet, and less physical exercise were significant risk factors for CC in the population of women aged 50 years and older. CONCLUSIONS CC was a common health problem among women aged 50 years and older in Shanghai, and the prevalence was positively associated with BMI ≥25.0 kg/m², non-manual occupation, premenopausal period, no delivery history, poor sleep quality, meat-based diet, and less physical exercise. Further studies are needed to identify the risk factors and potential interventions for CC.


Negatively charged lipid membranes promote a disorder-order transition in the Yersinia YscU protein.
The inner membrane of Gram-negative bacteria is negatively charged, rendering positively charged cytoplasmic proteins in close proximity likely candidates for protein-membrane interactions. YscU is a Yersinia pseudotuberculosis type III secretion system protein crucial for bacterial pathogenesis. The protein contains a highly conserved positively charged linker sequence that separates membrane-spanning and cytoplasmic (YscUC) domains. Although disordered in solution, inspection of the primary sequence of the linker reveals that positively charged residues are separated with a typical helical periodicity. Here, we demonstrate that the linker sequence of YscU undergoes a largely electrostatically driven coil-to-helix transition upon binding to negatively charged membrane interfaces. Using membrane-mimicking sodium dodecyl sulfate micelles, an NMR derived structural model reveals the induction of three helical segments in the linker. The overall linker placement in sodium dodecyl sulfate micelles was identified by NMR experiments including paramagnetic relaxation enhancements. Partitioning of individual residues agrees with their hydrophobicity and supports an interfacial positioning of the helices. Replacement of positively charged linker residues with alanine resulted in YscUC variants displaying attenuated membrane-binding affinities, suggesting that the membrane interaction depends on positive charges within the linker. In vivo experiments with bacteria expressing these YscU replacements resulted in phenotypes displaying significantly reduced effector protein secretion levels. Taken together, our data identify a previously unknown membrane-interacting surface of YscUC that, when perturbed by mutations, disrupts the function of the pathogenic machinery in Yersinia.


Stop place coding: an acoustic study of CV, VC#, and C#V sequences.
This study investigated stop + vowel coarticulation as a coding mechanism for differentiation of stop place categories in an F2-defined stimulus space. Locus equations (LEs) were used to index the extent of coarticulation in three contexts: (1) onset stop + vowel utterances [.CV]; (2) within-syllable vowel + coda stop utterances [VC#], and (3) across-syllable/word coda stop + vowel utterances [C#V]. Five speakers of American English and 2 speakers of Persian produced [CV1.CV2] (English and Persian), [tV1C#V2t] (English) and [dV1C#V2t] (Persian) tokens with voiced labial, alveolar/dental, and velar stops surrounded by a variety of vowels. In the across-syllable/word boundary condition [C#V2] the extent of anticipatory coarticulation was much reduced relative to traditionally measured onset [CV2] syllables. LE slopes derived across the syllable/word boundary, however, still differed between stop places in the same order as onset CVs. LE slopes derived from within-syllable [V1C#] sequences, however, did not differ between stop places.


Morphology and molecular phylogeny of Pleuronema orientale spec. nov. and Pleuronema paucisaetosum spec. nov. (Ciliophora, Scuticociliata) from Hangzhou Bay, China.
Two novel species, Pleuronema orientale spec. nov. and Pleuronema paucisaetosum spec. nov., isolated from coastal waters of Hangzhou Bay, China, were investigated with standard methods. Pleuronema orientale is characterized as follows: size in vivo 95-135 × 50-85 μm; usually one spherical macronucleus; 12-15 prolonged caudal cilia; two or three preoral kineties and 42-50 somatic kineties; membranelle 1 (M1) about 20 % of the anterior fragment of membranelle 2 (M2a) in length, consisting of three longitudinal rows of kinetosomes; posterior end of M2a hook-like; membranelle 3 (M3) three-rowed. Pleuronema paucisaetosum is characterized as follows: size in vivo about 55-85 × 25-55 μm; four or five preoral kineties and 21-23 somatic kineties; posterior end of M2a hook-like; M3 three-rowed. The small-subunit rRNA gene was sequenced for both species. Phylogenetic analyses revealed that P. orientale is most closely related to Pleuronema puytoraci and that P. paucisaetosum is sister to Pleuronema grolierei and Pleuronema setigerum (GenBank accession no. JX310015). With the inclusion of the two new sequences, the monophyly of the genus Pleuronema is not supported.


The results of nucleoplasty in patients with lumbar herniated disc: a prospective clinical study of 52 consecutive patients.
Nucleoplasty is a minimally invasive, percutaneous procedure that uses radiofrequency energy to ablate nuclear material and create small channels within the disc. To evaluate the efficacy of nucleoplasty technique in patients with leg pain caused by radicular encroachment. A prospective clinical study of subjects with lumbar disc herniation, and radicular pain resistant to previous medical treatment and physiotherapy for a period of at least 3 months. Fifty-two consecutive patients with leg pain and magnetic resonance imaging evidence of small and medium-sized herniated discs correlating with the patient's symptoms (contained disc herniation<6 mm, with a disc height>/=50% in comparison to normal adjacent discs) were included. Visual analogue scale (VAS) was administered and Oswestry disability questionnaires were filled out at preprocedure and postprocedure 2 weeks, 6 months, and 1 year. Reduction of analgesic treatment and the patients' satisfaction were also recorded. All procedures were performed under local anesthesia and fluoroscopic guidance on an outpatient basis. Patients underwent discography to evaluate annular integrity just before nucleoplasty. Channels were created in the nucleus by advancing the radiofrequency probe (ablating) and withdrawing it (coagulation). In all patients six channels were created. Thirty-four patients had one and 18 had two discs treated; a total of 70 procedures were performed. Mean age of patients was 44.8+/-8.6 years. The mean follow-up period was 12.1+/-1.6 months. Mean VAS reduced from preprocedure 7.5 to 3.1 at postprocedure 6 months and to 2.1 at the latest follow-up. Mean Oswestry index decreased from 42.2 to 24.8 at 6 months and to 20.5 at the latest examination. Analgesic consumption was stopped or reduced in 42 patients (85%) at 6 months and in 46 patients (94%) 1 year after the procedure. Overall patient satisfaction was 81% at 2 weeks, 85% at 6 months, and 88% at the latest follow-up. There were no complications related to the procedures. Our results encourage us to use nucleoplasty in carefully selected patients with leg pain caused by radicular encroachment. We recommend applying this minimally invasive technique only in those patients with small (<6 mm) contained disc herniations, with a disc height of>or=50% and with annular integrity.


Elucidating tuneable ambipolar charge transport and field induced bleaching at the CH3NH3PbI3/electrolyte interface.
Charge transport through lead trihalide based perovskites is more complex than through any other semiconducting materials due to their mixed electronic-ionic conductivity as well as ambipolarity. Here we have investigated charge transport through a perovskite/electrolyte interface using electrochemical impedance spectroscopy (EIS) under illumination and applied bias conditions. Similar trends in EIS were observed with positively biased as well as negatively biased working electrodes, indicating ambipolar charge transport through the perovskite layer. Ionic conductivity upon photo-illumination plays a significant role in modulating charge transport at the interface by creating an additional built-in field which flips its polarity at a moderate applied bias voltage. Therefore, anomalous charge transport resistance is observed under illumination at around 400 to 600 mV applied bias. Electric field induced UV-Vis absorption spectroscopy shows a decrease in absorption when both positive and negative bias voltages are applied to a perovskite coated ITO working electrode, indicating the occurrence of excited state charge transfer at the electrolyte interface. Two distinct electric field induced bleaching bands have been observed at around 480 nm and 750 nm, similar to the two photobleaching bands due to the dual nature of the excited states in lead halide perovskites.


The Fusaric Acid Derivative qy17 Inhibits Staphylococcus haemolyticus by Disrupting Biofilm Formation and the Stress Response via Altered Gene Expression.
Staphylococcus haemolyticus (S. haemolyticus) is the second most commonly isolated coagulase-negative staphylococcus (CoNS) in patients with hospital-acquired infections. It can produce phenol-soluble modulin (PSM) toxins and form biofilms. Compared with the wealth of information on Staphylococcus aureus and Staphylococcus epidermidis, very little is known about S. haemolyticus. There is an urgent need to find an effective preparation to combat the harm caused by S. haemolyticus infection. Chinese herbs have been utilized to cure inflammation and infectious diseases and have a long history of anticancer function in China. Here, we modified fusaric acid characterized from the metabolites of Gibberella intermedia, an endophyte previously isolated from Polygonum capitatum. This study shows that fusaric acid analogs (qy17 and qy20) have strong antibacterial activity against S. haemolyticus. In addition, crystal violet analyses and scanning electron microscopy observations demonstrated that qy17 inhibited biofilm formation and disrupted mature biofilms of S. haemolyticus in a dose-dependent manner. Additionally, it reduced the number of live bacteria inside the biofilm. Furthermore, the antibiofilm function of qy17 was achieved by downregulating transcription factors (sigB), transpeptidase genes (srtA), and bacterial surface proteins (ebp, fbp) and upregulating biofilm-related genes and the density-sensing system (agrB). To further elucidate the bacteriostatic mechanism, transcriptomic analysis was carried out. The following antibacterial mechanisms were uncovered: (i) the inhibition of heat shock (clpB, groES, groL, grpE, dnaK, dnaJ)-, oxidative stress (aphC)- and biotin response (bioB)-related gene expression, which resulted in S. haemolyticus being unable to compensate for various stress conditions, thereby affecting bacterial growth; and (ii) a reduction in the expression of PSM-beta (PSMβ1, PSMβ2, PSMβ3) toxin- and Clp protease (clpP, clpX)-related genes. These findings could have major implications for the treatment of diseases caused by S. haemolyticus infections. Our research reveals for the first time that fusaric acid derivatives inhibit the expression of biofilm formation-related effector and virulence genes of S. haemolyticus. These findings provide new potential drug candidates for hospital-acquired infections caused by S. haemolyticus.


The Cambridge-Perugia Inventory for assessment of Bipolar Disorder.
It is well known that Bipolar Disorder is a condition which is often under diagnosed or misdiagnosed. We propose an inventory of questions which will help assess the longitutinal history of the patient's illness, and to evaluate the presence of mixed affective states, rapid cycling, and comorbidities, all of which have an important bearing on prognosis.


Biomonitoring as a method for assessing exposure to perchlorate.
Biomonitoring provides direct and quantitative information regarding human exposure to environmental toxicants, such as perchlorate (ClO(4)(-)). Because of concerns surrounding widespread exposure to ClO(4)(-), we are using biomonitoring methods to assess exposure to ClO(4)(-) and other physiologically relevant anions that can impact iodide uptake by the thyroid. These methods quantify ClO(4)(-), thiocyanate, nitrate, and iodide in human urine, milk, serum, blood spots, amniotic fluid, and infant formula using ion chromatography coupled with electrospray ionization tandem mass spectrometry. In this paper we summarize recent ClO(4)(-) biomonitoring research and provide three additional examples of the utility of biomonitoring for characterizing ClO(4)(-) exposure. Specifically, we examine variability in ClO(4)(-) excretion, compare the relative importance of different exposure sources in adults, and estimate ClO(4)(-) exposure in formula-fed infants. These applications provide examples of how biomonitoring can improve individual exposure assessment. Individual biomarker data can subsequently be compared with individual thyroid function data to better evaluate potential linkage between ClO(4)(-) exposure and health.


Association of eNOS and Cav-1 gene polymorphisms with susceptibility risk of large artery atherosclerotic stroke.
Endothelial nitric oxide synthase (eNOS) is localized in caveole and has important effects on caveolar coordination through its interaction with caveolin-1 (Cav-1), which supports normal functioning of vascular endothelial cells. However, the relationship between genotypic polymorphisms of e-NOS and Cav-1 genes and ischemic stroke (IS) remains lesser reported. This hospital-based case-control study aimed to determine the genetic polymorphisms of the eNOS (Glu298Asp) and Cav-1 (G14713A and T29107A) genes in association with susceptibility risk in patients who had suffered from a large artery atherosclerotic (LAA) stroke. Genotyping determination for these variant alleles was performed using the TaqMan assay. The distributions of observed allelic and genotypic frequencies for the polymorphisms were in Hardy-Weinberg equilibrium in healthy controls. The risk for an LAA stroke in the Asp298 variant was 1.72 (95% CI = 1.09-2.75) versus Glu298 of the eNOS. In the GA/AA (rs3807987) variant, it was 1.79 (95% CI = 1.16-2.74) versus GG and in TA/AA (rs7804372) was 1.61 (95% CI = 1.06-2.43) versus TT of the Cav-1, respectively. A tendency toward an increased LAA stroke risk was significant in carriers with the eNOS Glu298Asp variant in conjunction with the G14713 A and T29107A polymorphisms of the Cav-1 (aOR = 2.03, P-trend = 0.002). A synergistic effect between eNOS and Cav-1 polymorphisms on IS risk elevation was significantly influenced by alcohol drinking, heavy cigarette smoking (P-trend<0.01), and hypercholesterolemia (P-trend < 0.001). In conclusion, genotypic polymorphisms of the eNOS Glu298Asp and Cav-1 14713A/29107A polymorphisms are associated with the elevated risk of LAA stroke among Han Chinese in Taiwan.


Task-related functional connectivity dynamics in a block-designed visual experiment.
Studying task modulations of brain connectivity using functional magnetic resonance imaging (fMRI) is critical to understand brain functions that support cognitive and affective processes. Existing methods such as psychophysiological interaction (PPI) and dynamic causal modeling (DCM) usually implicitly assume that the connectivity patterns are stable over a block-designed task with identical stimuli. However, this assumption lacks empirical verification on high-temporal resolution fMRI data with reliable data-driven analysis methods. The present study performed a detailed examination of dynamic changes of functional connectivity (FC) in a simple block-designed visual checkerboard experiment with a sub-second sampling rate (TR = 0.645 s) by estimating time-varying correlation coefficient (TVCC) between BOLD responses of different brain regions. We observed reliable task-related FC changes (i.e., FCs were transiently decreased after task onset and went back to the baseline afterward) among several visual regions of the bilateral middle occipital gyrus (MOG) and the bilateral fusiform gyrus (FuG). Importantly, only the FCs between higher visual regions (MOG) and lower visual regions (FuG) exhibited such dynamic patterns. The results suggested that simply assuming a sustained FC during a task block may be insufficient to capture distinct task-related FC changes. The investigation of FC dynamics in tasks could improve our understanding of condition shifts and the coordination between different activated brain regions.


Selection criteria for exercise training in patients with COPD.
The physical performance of patients with chronic obstructive pulmonary disease (COPD) is limited mainly by pathophysiological derangements of the ventilatory system. Thus, the exercise performance can be ameliorated by increasing the level of ventilation that they can sustain, or by reducing the ventilatory requirement for a given level of activity. Almost all studies have yielded negative results in COPD patients, in terms of exercise training having the ability to improve VEmax. The only way to reduce the ventilatory requirement is to reduce CO2 output. Lower levels of lactate result in less non-metabolic CO2 produced by bicarbonate buffering. This is the likely mechanism responsible for a lower ventilatory requirement for work rates above the pre-training anaerobic threshold. We specifically wished to determine, whether a program of intensity, frequency and duration known capable of producing a physiologic training effect in healthy subjects, would do so in COPD patients. Further, we sought to determine, whether exercise training at a work rate associated with lactic acidosis is more effective in inducing a training effect in COPD patients than a work rate not associated with lactic acidosis. Nineteen COPD patients were selected and performed an incremental test as well as two square wave tests at a low and a high work rate. Identical tests were performed after an 8-week program of cycle ergometer training either for 45 min/day at a high work rate or for a proportionally longer time at a low work rate.(ABSTRACT TRUNCATED AT 250 WORDS)


Achieving Congruence among Reference Laboratories for Absolute Abundance Measurement of Analytes for Rare Diseases: Psychosine for Diagnosis and Prognosis of Krabbe Disease.
Measurement of the absolute concentration of the biomarker psychosine in dried blood spots (DBS) is useful for diagnosis and prognosis of Krabbe disease and to support newborn screening of this leukodystrophy. As for assays for more common diseases, it is important to achieve congruence when multiple clinical laboratories provide testing. Four clinical laboratories, one research laboratory, and a commercial vendor collaborated with the goal to achieve congruence in quantitative psychosine measurement in DBS. A set of DBS calibrators was prepared by a single vendor and used in each reference laboratory to make a standard curve of measured psychosine in DBS versus the stated calibrator psychosine level. Congruence between the participating five laboratories was achieved using the psychosine DBS calibrators. This allowed application of disease-specific reference ranges obtained by the reference laboratory with the most extensive data by the other reference laboratories. Congruence between multiple reference laboratories in the measurement of the absolute concentration of biomarkers in DBS (and by extension other samples) is possible by the use of a common set of DBS calibrators.


[Features of the manifestations of bronchopulmonary pathology and hepatitis B in children with hypogammaglobulinemia].
Two cases of hypogammaglobulinemia (Bruton's syndrome) in brothers are described. Their sisters had no this disease. Pronounced changes in the lymph nodes, spleen and thymus typical for this condition were combined in both cases with lung and kidney malformations as well as with chronic pneumonia and inanition. The both boys have viral respiratory infections that followed by marked antibody formation and clear-cut structural alterations characteristic of different stages of these diseases. Besides this the older brother was found to have chronic viral hepatitis B with an unusual giant-cell reaction.


Density functional theory based molecular-dynamics study of aqueous iodide solvation.
We study the solvation of iodide in water using density functional theory based molecular-dynamics simulations. Detailed analysis of the structural and dynamical properties of the first solvation shell is presented, showing a disruptive influence of the ion on the local water structure. Iodide-water hydrogen bonding is weak, compared to water-water hydrogen bonds. This effective repulsive ion-water interaction leads to the formation of a quite unstructured solvation shell. The dynamics of water molecules surrounding the iodide is relatively fast. The intramolecular structural and electronical properties of water molecules around the ion are not affected.


[The effect of human lymphoblastoid interferon (HLBI) on the growth of 2 human malignant melanoma xenografts in nude mice].
The effects of Human Lymphoblastoid Interferon ( HLBI ) on the growth of 2 human malignant melanoma xenografts in nude mice were investigated. At a dose of 6 X 10(5) IU, the growth of SK-14 was significantly inhibited by intratumoral administration, whereas that of AM-1 was only moderately by inhibited. Tumor cell of SK-14 was found to be degenerated and replaced with melanophages by histological observation, while that of AM-1 showed no significant changes. Dose response of the inhibitory effect of HLBI (6 X 10(5)IU, 1 X 10(5)IU) was investigated against tumor cell of SK-14. At a dose of 6 X 10(5)IU, the growth was strongly inhibited, whereas 1 X 10(5)IU showed only a moderate effect. In conclusion, the sensitivity of malignant melanoma xenograft to the inhibitory effect of HLBI varied with the cell line. It was considered that a relative large dose of HLBI was necessary for an appreciable effect on the malignant melanoma xenograft.


Presentation and Delivery of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand via Elongated Plant Viral Nanoparticle Enhances Antitumor Efficacy.
Potato virus X (PVX) is a flexuous plant virus-based nanotechnology with promise in cancer therapy. As a high aspect ratio biologic (13 × 515 nm), PVX has excellent spatial control in structures and functions, offering high-precision nanoengineering for multivalent display of functional moieties. Herein, we demonstrate the preparation of the PVX-based nanocarrier for delivery of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a promising protein drug that induces apoptosis in cancer cells but not healthy cells. TRAIL bound to PVX by coordination bonds between nickel-coordinated nitrilotriacetic acid on PVX and His-tag on the protein could mimic the bioactive "membrane-bound" state in native TRAIL, resulting in an elongated nanoparticle displaying up 490 therapeutic protein molecules. Our data show that PVX-delivered TRAIL activates caspase-mediated apoptosis more efficiently compared to soluble TRAIL; also in vivo the therapeutic nanoparticle outperforms in delaying tumor growth in an athymic nude mouse model bearing human triple-negative breast cancer xenografts. This proof-of-concept work highlights the potential of filamentous plant virus nanotechnologies, particularly for targeting protein drug delivery for cancer therapy.


Mutagenesis of the COOH-terminal region of bacteriophage T4 regA protein.
The bacteriophage T4 regA protein is a translational repressor that regulates the synthesis of > 12 T4 proteins. Earlier studies demonstrated that photocross-linking of the 122-residue regA protein to (dT)16 occurs at two sites, with the major site occurring at Phe-106. Amino acid substitutions were introduced at Phe-106 to evaluate its role in nucleic acid binding. Binding affinities of mutants F106C, F106V, and F106Y for nonspecific and specific RNA ligands indicated little difference between the Kapp of the mutants and wild type regA protein, for either poly(U) or for a specific gene 44 oligoribonucleotide. Thus, Phe-106 does not contribute measurably to the overall free energy of binding. Partial proteolysis of regA protein was carried out to further probe its domain structure. Chymotryptic cleavage produced a fragment of 11,095 Da that has reduced affinity for poly(U) and that contains the first 93 residues of regA protein. Interestingly, proteolysis of regA protein is reduced in the presence of the specific target, gene 44 RNA. Two deletion mutants, 1-->94 and 1-->109, have also been cloned and purified. The binding affinities of these deletion mutants indicated a 100-1000-fold reduction in their affinities for poly(U). These studies indicate the last 13 amino acids in regA protein make a significant contribution to RNA binding.


A family infected with hepatitis B and with concurrently circulating HBsAg and heterotypic anti-HBs.
A family is described, of whom all members were found to be infected with the adw2 subtype hepatitis B virus. The mother and both the children were positive for anti-HBs (anti-y). The usual explanation for the co-occurrence of HBsAg and anti-HBs ("two infections hypothesis") was clinically highly unlikely. HLA typing was performed to investigate the possibility that genetically determined host dependent factors are involved. However, no relationship between the simultaneous presence of HBsAg and anti-HBs and a particular haplotype was observed.


Spinal cord stimulation for non-reconstructable chronic critical leg ischaemia.
Patients suffering from inoperable chronic critical leg ischaemia (NR-CCLI) face amputation of the leg. Spinal cord stimulation (SCS) has been proposed as a helpful treatment in addition to standard conservative treatment. To find evidence for an improvement on limb salvage, pain relief, and the clinical situation using SCS compared to conservative treatment alone. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12). Controlled studies comparing the addition of SCS with any form of conservative treatment to conservative treatment alone in patients with NR-CCLI. Both authors independently assessed the quality of the studies and extracted data. Six studies comprising nearly 450 patients were included. In general the quality of the studies was good. No study was blinded due to the type of intervention.Limb salvage after 12 months was significantly higher in the SCS group (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.56 to 0.90; risk difference (RD) -0.11, 95% CI -0.20 to -0.02). Significant pain relief occurred in both treatment groups, but was more prominent in the SCS group where the patients required significantly less analgesics. In the SCS group, significantly more patients reached Fontaine stage II than in the conservative group (RR 4.9, 95% CI 2.0 to 11.9; RD 0.33, 95% CI 0.19 to 0.47). Overall, no significantly different effect on ulcer healing was observed with the two treatments.Complications of SCS treatment consisted of implantation problems (9%, 95% CI 4 to 15%) and changes in stimulation requiring re-intervention (15%, 95% CI 10 to 20%). Infections of the lead or pulse generator pocket occurred less frequently (3%, 95% CI 0 to 6%). Overall risk of complications with additional SCS treatment was 17% (95% CI 12 to 22%), indicating a number needed to harm of 6 (95% CI 5 to 8).Average overall costs (one study) at two years were EUR 36,500 (SCS group) and EUR 28,600 (conservative group). The difference (EUR 7900) was significant (P < 0.009). There is evidence to favour SCS over standard conservative treatment alone to improve limb salvage and clinical situations in patients with NR-CCLI. The benefits of SCS must be considered against the possible harm of relatively mild complications and the costs.


Ratiometric Fluorescent Nanoprobe for Highly Sensitive Determination of Mercury Ions.
In this study, a novel dual-emission ratiometric fluorescent nanoprobe (RFN) was synthesized and ultilized for highly sensitive determination of mercury ions. In this nanoprobe, fluorescein isothiocyanate (FITC) doped silica (SiO2) served as a reference signal, FITC-SiO2 microspheres were synthesized and modified with amino groups, and then Au Nanoclusters (AuNCs) were combined with the amino groups on the surface of the FITC-SiO2 microspheres to obtain the RFN. The selectivity, stability, and pH of the RFN were then optimized, and the determination of mercury ions was performed under optimal conditions. The probe fluorescence intensity ratio (F520 nm/F680 nm) and Hg2+ concentration (1.0 × 10-10 mol/L to 1.0 × 10-8 mol/L) showed a good linear relationship, with a correlation coefficient of R2 = 0.98802 and a detection limit of 1.0 × 10-10 mol/L, respectively. The probe was used for the determination of trace mercury ion in water samples, and the recovery rate was 98.15~100.45%, suggesting a wide range of applications in monitoring pollutants, such as heavy metal ion and in the area of environmental protection.


Epidemiology of a dominant clonal strain of vancomycin-resistant Enterococcus faecium at separate hospitals in Boston, Massachusetts.
In 1996, the dominant (43%) strain of vancomycin-resistant enterococci (VRE; type A) at Massachusetts General Hospital was identified at Brigham and Women's Hospital (BWH). To characterize the epidemiology of infection with type A isolates of VRE at BWH, we collected demographic and clinical data for all patients from whom VRE were isolated from a clinical specimen through September 1996. The first clinical isolates from all BWH patients from whom VRE were isolated were typed by pulsed-field gel electrophoresis of SmaI digests of chromosomal DNA. Among patients hospitalized after the first patient at BWH infected with a type A isolate of VRE was identified, exposures were compared between patients who acquired type A isolates of VRE and those who acquired other types of VRE. Isolates from 99 patients identified to have acquired VRE were most commonly from blood (n = 27), urine (n = 19), or wounds (n = 19). Three months after the index patient arrived at BWH and at a time when > or =12 types of strains of VRE were present, type A isolates of VRE became dominant; 39 of 75 (52%) of the study cohort had acquired type A isolates of VRE. We found no association between the acquisition of type A isolates of VRE and transfer from another institution or temporal overlap by service, ward, or floor with patients known to have acquired type A isolates of VRE. By multivariate analysis, only residence in the medical intensive care unit (adjusted odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4 to 107) and the receipt of two or more antibiotics per patient-day (adjusted OR, 12.2; 95% CI, 1.2 to 9.0) were associated with the acquisition of strain A. This strain of VRE, dominant at two Boston hospitals, was associated with intensity of antibiotic exposures (i.e., two or more antibiotics per patient-day). We hypothesize that this strain may have unidentified properties providing a mechanism favoring its spread and dominance over other extant isolates, and further studies are needed to define these properties.


Stressed podocytes-mechanical forces, sensors, signaling and response.
Increased glomerular capillary pressure (glomerular hypertension) and increased glomerular filtration rate (glomerular hyperfiltration) have been proven to cause glomerulosclerosis in animal models and are likely to be operative in patients. Since podocytes cover the glomerular basement membrane, they are exposed to tensile stress due to circumferential wall tension and to fluid shear stress arising from filtrate flow through the narrow filtration slits and through Bowman's space. In vitro evidence documents that podocytes respond to tensile stress as well as to fluid shear stress. Several proteins are discussed in this review that are expressed in podocytes and could act as mechanosensors converting mechanical force via a conformational change into a biochemical signal. The cation channels P2X4 and TRPC6 were shown to be involved in mechanosignaling in podocytes. P2X4 is activated by stretch-induced ATP release, while TRPC6 might be inherently mechanosensitive. Membrane, slit diaphragm and cell-matrix contact proteins are connected to the sublemmal actin network in podocytes via various linker proteins. Therefore, actin-associated proteins, like the proven mechanosensor filamin, are ideal candidates to sense forces in the podocyte cytoskeleton. Furthermore, podocytes express talin, p130Cas, and fibronectin that are known to undergo a conformational change in response to mechanical force exposing cryptic binding sites. Downstream of mechanosensors, experimental evidence suggests the involvement of MAP kinases, Ca2+ and COX2 in mechanosignaling and an emerging role of YAP/TAZ. In summary, our understanding of mechanotransduction in podocytes is still sketchy, but future progress holds promise to identify targets to alleviate conditions of increased mechanical load.


[Molecular analysis of the CAG repeat among patients with Type-2 spinocerebellar ataxia in the Mexican population].
Spinocerebellar ataxia type 2 (SCA2) results from the expansion of a CAG triplet located within the coding sequence of the ataxin-2 gene, which ultimately provokes the incorporation of a stretch of polyglutamines in the mutant protein. We determined by PCR and capillary electrophoresis the number of ataxin2 gene CAG repeats in 66 individuals belonging to 3 families, clinically diagnosed with SCA2, and 400 subjects from a sample of the mestizo Mexican population. The CAG repeat expansion was found in 11 symptomatic subjects and four asymptomatic individuals, confirming the SCA2 clinical diagnosis in two out of the three families studied. We noted that patients with longer CAG repeat numbers have an early disease onset, a phenomenon known as anticipation. Wild-type alleles showed a CAG repeat range between 13 and 30, and the allele carrying 22 CAG repeats was the most common among our sample. Mutant alleles also displayed a range between 36 and 54 CAG repeats. The identification of the CAG repeat expansion facilitates an accurate SCA2 diagnosis.


Reading network in dyslexia: Similar, yet different.
Dyslexia is a developmental disorder characterized by reading and phonological difficulties, yet important questions remain regarding its underlying neural correlates. In this study, we used partial least squares (PLS), a multivariate analytic technique, to investigate the neural networks used by dyslexics while performing a word-rhyming task. Although the overall reading network was largely similar in dyslexics and typical readers, it did not correlate with behavior in the same way in the two groups. In particular, there was a positive association between reading performance and both right superior temporal gyrus and bilateral insula activation in dyslexic readers but a negative correlation in typical readers. Together with differences in lateralization unique to dyslexics, this suggests that the combination of poor reading performance with high insula activity and atypical laterality is a consistent marker of dyslexia. These findings emphasize the importance of understanding right-hemisphere activation in dyslexia and provide promising directions for the remediation of reading disorders.


Nucleotide sequence analysis of precursor 5S RNA from Bacillus licheniformis.
The complete nucleotide sequences of the various precursor 5S RNA species occurring in Bacillus licheniformis have been elucidated. The B. licheniformis precursors contain a 5'-precursor-specific segment of 95 nucleotides which is four times as long as the corresponding segment of the p5S RNAs from the closely related strains B. subtilis (Sogin, M.L., Pace, N.R., Rosenberg, M., Weissman, S.M. (1976) J. Biol. Chem. 251, 3480-3488) and Bacillus Q (Stiekema, W.J., Raué, H.A., Planta, R.J. (1980) Nucl. Ac. Res. 8, 2193-2211). However, fourteen of the sixteen nucleotides at the 5'-end are identical in the precursors from all three strains. These conserved nucleotides can form a stem and loop structure which is likely to play an important role in the biosynthesis of 5S RNA. Extension secondary and tertiary structure is present in the 5'-precursor-specific segment as concluded from the results of digestion with RNAase T1 both of the isolated segment and the intact precursors. No sequence homology exists between the 3'-precursor-specific segments of the B. licheniformis precursors and those of the other two strains except for a stretch of U residues at the 3-terminus. This stretch of U residues is not immediately preceded by a hairpin loop, however, as expected for a transcription termination signal (20). The question whether the precursors have already undergone processing at the 3'-end, therefore, remains open. The total number of genetically distinct precursor species in B. licheniformis is at least five and at most ten. Most likely each ribosomal RNA cistron produces a separate p5S RNA as is also the case in Bacillus Q.


A new nonsyndromic X-linked sensorineural hearing impairment linked to Xp21.2.
X-linked deafness is a rare cause of hereditary hearing impairment. We have identified a family with X-linked dominant sensorineural hearing impairment, characterized by incomplete penetrance and variable expressivity in carrier females, that is linked to the Xp21.2, which contains the Duchenne muscular dystrophy (DMD) locus. The auditory impairment in affected males was congenital, bilateral, profound, sensorineural, affecting all frequencies, and without evidence of radiographic abnormality of the temporal bone. Adult carrier females manifested bilateral, mild-to-moderate high-frequency sensorineural hearing impairment of delayed onset during adulthood. Eighteen commercially available, polymorphic markers from the X chromosome, generating a 10-15-cM map, were initially used for identification of a candidate region. DXS997, located within the DMD gene, generated a two-point LOD score of 2.91 at theta = 0, with every carrier mother heterozygous at this locus. Recombination events at DXS992 (located within the DMD locus, 3' to exon 50 of the dystrophin gene) and at DXS1068 (5' to the brain promoter of the dystrophin gene) were observed. No recombination events were noted with the following markers within the DMD locus: 5'DYS II, intron 44, DXS997, and intron 50. There was no clinical evidence of Duchenne or Becker muscular dystrophy in any family member. It is likely that this family represents a new locus on the X chromosome, which when mutated results in nonsyndromic sensorineural hearing loss and is distinct from the heterogeneous group of X-linked hearing losses that have been previously described.


Incidence of cardiovascular risk factors in female patients with systemic lupus erythematosus: a 3-year follow-up cohort.
Objectives To evaluate the incidence and variability of traditional coronary artery disease (CAD) risk factors in a cohort of lupus patients and to investigate if prednisone use predicts an increase in the number of risk factors. Methods A total of 151 women, 37.8 ± 11.1 (mean ± SD) years old at baseline, were reevaluated after a median period of 39 (interquartile range 36.5-42.0) months. The cumulative incidence of traditional risk factors, the incidence rate (with 95% confidence interval) of hypertension, diabetes, dyslipidemia and hypertriglyceridemia, and the frequency of the risk factors' disappearance were calculated. Metabolic syndrome (MetS) and Framingham risk score (FRS) were computed. Logistic regression was used to investigate if maximum or cumulative prednisone dose used during follow-up predicted an increase in the cardiometabolic risk factors' number. Results The cumulative incidence of risk factors varied from 39.1% (abdominal obesity) to zero (smoking), and the incidence rate varied from 133.2 (87.8-178.6) per 1000 person-years (dyslipidemia) to 10.4 (1.3-19.5) per 1000 person-years (diabetes). The cumulative incidence for MetS was 18.8%, and 11.7% of 143 patients with low FRS at baseline (T1) were classified in the high-risk category at the end of the study (T2). Dyslipidemia was the most variable risk factor, with 43.5% disappearance at T2. The maximum prednisone dose used during follow-up was borderline ( p = 0.050) for prediction of an increase in the number of cardiometabolic risk factors in an adjusted model for antimalarial use, modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and age. Conclusion The authors described high incidence and variability of CAD risk factors in female lupus patients, with higher prednisone dose being borderline for an increase in the number of cardiometabolic risk factors.


Detection of hepatitis C core antigen in serum or plasma as a marker of hepatitis C viraemia in the serological window-phase.
A new immunoassay for the detection of hepatitis C core antigen (HCVcoreAg) in peripheral blood during serological window-phase was evaluated among healthy blood donors, commercially available hepatitis C virus (HCV) seroconversion panels and in-house specimens from individuals undergoing seroconversion. Among 1964 low-risk blood donor samples, seven samples were initially reactive but only one was repeat reactive. Reactivity of this specimen was not confirmable by neutralization with specific anti-HCV core antibody, and the sample was negative for HCV RNA by polymerase chain reaction (PCR). The specificity of the HCVcoreAg enzyme-linked immunosorbent assay (ELISA) was 99.95%. In seven commercially available HCV seroconversion panels, HCVcoreAg appeared 23-46 days earlier than anti-HCV antibody by third generation assay. Additional testing with specimens from patients undergoing anti-HCV seroconversion indicated that HCVcoreAg becomes undetectable by the present test format soon after the onset of antibody. This test may be considered as an alternative to nucleic amplification techniques (NAT) for blood donor HCV screening. Additional development of technology for detecting HCVcoreAg may be useful for patient diagnosis and therapy monitoring.


Evaluation of a role functioning computer adaptive test (RF-CAT).
To evaluate the validity and participants' acceptance of an online assessment of role function using computer adaptive test (RF-CAT). The RF-CAT and a set of established quality of life instruments were administered in a cross-sectional study in a panel sample (n = 444) recruited from the general population with over-selection of participants with selected self-report chronic conditions (n = 225). The efficiency, score accuracy, validity, and acceptability of the RF-CAT were evaluated and compared to existing measures. The RF-CAT with a stopping rule of six items with content balancing used 25 of the available bank items and was completed on average in 66 s. RF-CAT and the legacy tools scores were highly correlated (.64-.84) and successfully discriminated across known groups. The RF-CAT produced a more precise assessment over a wider range than the SF-36 Role Physical scale. Patients' evaluations of the RF-CAT system were positive overall, with no differences in ratings observed between the CAT and static assessments. The RF-CAT was feasible, more precise than the static SF-36 RP and equally acceptable to participants as legacy measures. In empirical tests of validity, the better performance of the CAT was not uniformly statistically significant. Further research exploring the relationship between gained precision and discriminant power of the CAT assessment is needed.


Spatially separate cerebral infarction in the posterior cerebral artery territory after combined revascularization of the middle cerebral artery territory in an adult patient with moyamoya disease and fetal-type posterior communicating artery: illustrative case.
Remote cerebral infarction after combined revascularization of the middle cerebral artery (MCA) territory is rare in patients with moyamoya disease (MMD) with a fetal-type posterior communicating artery (PCoA). A 57-year-old woman developed numbness in her right upper limb and transient motor weakness and was diagnosed with MMD. She also had a headache attack and a scintillating scotoma in the right visual field. Preoperative magnetic resonance angiography (MRA) showed stenosis of the left posterior cerebral artery (PCA). Combined revascularization was performed for the left MCA territory. No new neurological deficits were observed for 2 days after the operation, but right hemianopia, alexia, and agraphia appeared on postoperative day (POD) 4. Magnetic resonance imaging showed a new left occipitoparietal lobe infarction, and MRA showed occlusion of the distal left PCA. After that point, the alexia and agraphia gradually improved, but right hemianopia remained at the time of discharge on POD 18. Cerebral ischemia in the PCA territory may occur after combined revascularization of the MCA territory in patients with fetal-type PCoA. For these cases, a double-barrel bypass or indirect revascularization to induce a slow conversion could be considered on its own as a treatment option.


Metabolic adaptations to fasting and chronic caloric restriction in heart, muscle, and liver do not include changes in AMPK activity.
Activation of adenosine monophosphate-activated protein kinase (AMPK) plays a central role in allowing cells to adapt to nutrient deprivation in vitro. This link between AMPK activity and nutritional status has raised the possibility that AMPK plays a role in the metabolic adaptation to acute and chronic nutritional stress. However, the effects of nutritional stress on AMPK activity in vivo have not been systematically evaluated. To address this, we measured the effects of 24 h of fasting and 4 mo of caloric restriction (CR) on AMPK alpha 1 and -alpha 2 activities in heart, skeletal muscle, and liver in mice. Although fasting caused the expected changes in body weight, plasma leptin, and free fatty acids, it did not increase AMPK activity in heart or skeletal muscle and only increased liver AMPK activity by approximately 20% (P = 0.10). Likewise, CR caused the expected changes in body weight, plasma leptin, and free fatty acids but did not alter AMPK activity in any of the three tissues. Although CR did not alter liver AMPK activity, it dramatically decreased the amount of phosphorylated acetyl-CoA carboxylase, and this was found to be due to decreased protein expression. Plasma leptin, a putative activator of AMPK, varied eightfold across the four groups of mice in the absence of changes in AMPK activity in any tissue. We conclude that, although the metabolic adaptations to fasting and CR include changes in plasma leptin concentration and phosphorylated acetyl-CoA carboxylase, these effects occur without changes in AMPK activity.


Does spatial attention modulate the earliest component of the visual evoked potential?
Whether visual spatial attention can modulate feedforward input to human primary visual cortex (V1) is debated. A prominent and long-standing hypothesis is that visual spatial attention can influence processing in V1, but only at delayed latencies suggesting a feedback-mediated mechanism and a lack of modulation during the initial afferent volley. The most promising challenge to this hypothesis comes from an event-related potential (ERP) study that showed an amplitude enhancement of the earliest visual ERP component, called the 'C1', in response to spatially attended relative to spatially unattended stimuli. In the Kelly et al. study, several important experimental design modifications were introduced, including tailoring the stimulus locations and recording electrodes to each individual subject. In the current study, we employed the same methodological procedures and tested for attentional enhancements of the C1 component in each quadrant of the visual field. Using the same analysis strategies as Kelly et al., we found no evidence for an attention-based modulation of the C1 (measured from 50-80 ms). Attention-based amplitude enhancements were clear and robust for the subsequent P1 component (90-140 ms). Thus, despite using methods specifically designed to reveal C1 attention effects, the current study provided no confirmatory evidence for such effects.


A case of late dumping syndrome.
We report a case of late dumping syndrome in a 49-year-old lady who had partial gastrectomy for bleeding peptic ulcer 11 years ago. She presented with unexplained syncopal attacks which did not have any apparent relationship to meal or posture. An unusual reaction to oral glucose tolerance test ordered by her gynaecologist who was seeing her for uterine fibroid led to the diagnosis. Late dumping syndrome was confirmed by a repeat oral glucose tolerance test. At the second hour of the test, she developed hypoglycaemic coma with a blood glucose level of 50 mg/dL and a hypocount of 47 mg/dL. She regained full recovery after dextrose infusion which raised the hypocount to 123 mg/dL. The dizzy spells and syncopal attacks disappeared with dietary adjustment.


Contrast ultrasonography of the digestive tract lumen. Review of the literature and personal experience.
Routine exploration of the digestive tract is performed under "fasting" condition, without further training. The investigation is limited due to hidroaeric and alimentary content and deep location of some digestive parts (gastric fornix, colon flexures). Oral administration contrast agents cause a distension of the digestive lumen which allows a satisfactory viewing of the "hidden" regions and endoluminal detection of small formations. A combination of conventional and contrast ultrasound brings additional information which increase the overall performance of the ultrasound method.


Immunohistochemical localization of the bone morphogenetic protein receptors in the porcine ovary.
The bone morphogenetic protein (BMP) family is emerging as playing a crucial role in regulating normal follicle growth and determining ovulation rate. BMPs exert their effects via BMP receptors (BMPR-IA, -IB and -II). However, there is a paucity of information relating to the expression of the BMPRs within the ovary of large polyovular species such as the pig. Furthermore, there is a lack of information on the expression of BMPRs by fetal ovaries of any species. The purpose of this study was to investigate temporal and spatial expression of the BMPRs in the porcine ovary, at different developmental stages. Immunohistochemistry for BMPR-IA, BMPR-IB and BMPR-II was performed using sections from paraffin wax-embedded ovaries, obtained from fetal (n = 15), prepubertal (n = 3) and cycling postpubertal (n = 4) pigs. Results confirmed the presence of all three receptors in the fetal egg nests and in the granulosa cell layer of follicles ranging from primordial to late antral stages. Immunostaining was also observed in oocytes, theca layer, corpus luteum and ovarian surface epithelium. The expression of BMPRs by fetal ovaries may be related to follicle formation, whereas expression in pre- and post-pubertal animals indicates BMPs are involved in regulating porcine ovarian follicle growth.


The Feasibility of Classifying Breast Masses Using a Computer-Assisted Diagnosis (CAD) System Based on Ultrasound Elastography and BI-RADS Lexicon.
To determine the applicability of a computer-aided diagnostic system strain elastography system for the classification of breast masses diagnosed by ultrasound and scored using the criteria proposed by the breast imaging and reporting data system ultrasound lexicon and to determine the diagnostic accuracy and interobserver variability. This prospective study was conducted between March 1, 2016, and May 30, 2016. A total of 83 breast masses subjected to percutaneous biopsy were included. Ultrasound elastography images before biopsy were interpreted by 3 radiologists with and without the aid of computer-aided diagnostic system for strain elastography. The parameters evaluated by each radiologist results were sensitivity, specificity, and diagnostic accuracy, with and without computer-aided diagnostic system for strain elastography. Interobserver variability was assessed using a weighted κ test and an intraclass correlation coefficient. The areas under the receiver operating characteristic curves were also calculated. The areas under the receiver operating characteristic curve were 0.835, 0.801, and 0.765 for readers 1, 2, and 3, respectively, without computer-aided diagnostic system for strain elastography, and 0.900, 0.926, and 0.868, respectively, with computer-aided diagnostic system for strain elastography. The intraclass correlation coefficient between the 3 readers was 0.6713 without computer-aided diagnostic system for strain elastography and 0.811 with computer-aided diagnostic system for strain elastography. The proposed computer-aided diagnostic system for strain elastography system has the potential to improve the diagnostic performance of radiologists in breast examination using ultrasound associated with elastography.


Expression and Clinical Significance of NOD-Like Receptor Protein 3 (NLRP3) and Caspase-1 in Fetal Membrane and Placental Tissues of Patients with Premature Rupture of Membrane.
BACKGROUND In this study, we aimed to investigate the expression of NOD-like receptor protein 3 (NLRP3) and caspase-1 in fetal membrane and placental tissues of patients with premature rupture of membrane (PROM), and to explore their role in PROM. MATERIAL AND METHODS Ninety women participated in this study: a control group of 30 healthy pregnant women, 30 with PPROM, and 30 with TPROM. Immunohistochemistry streptavidin-peroxidase (SP) assay was used to detect the protein expression of NLRP3 and caspase-1 in the fetal membrane and placental tissues. RT-PCR was used to detect the mRNA expression of NLRP3 and caspase-1 in fetal membrane and placental tissues. RESULTS The results of SP showed that NLRP3 and caspase-1 were mainly expressed in the cytoplasm of epithelial cells, mesenchymal cells, and trophoblast cells in fetal membranes, and the cytoplasm of placental syncytiotrophoblasts and vascular endothelial cells in placental tissues. The expression of NLRP3 and caspase-1 in the TPROM group was significantly higher than that in the PPROM group and control group (p<0.05), and there was a significant difference between the PPROM group and the control group. The results of RT-PCR showed that the mRNA expression level of NLRP3 and caspase-1 in the TPROM group was significantly higher than that in the PPROM group and control group (p<0.05), and the expression of NLRP3 mRNA and caspase-1 mRNA in the PPROM group was significantly different from that in the control group (p>0.05). CONCLUSIONS The increased expression of NLRP3 and caspase-1 in fetal membrane and placental tissues may be associated with the development of PROM.


Coherent interaction between two orthogonal travelling-wave modes in a microdonut resonator for filtering and buffering applications.
We theoretically investigate the coherent interaction between two orthogonal travelling-wave modes in a microdonut resonator symmetrically coupled to two bus waveguides. An analytical model has been developed to describe this structure using transfer matrix method. The simulation reveals that the two-mode microdonut can exhibit either a flat-top response or all-pass transmission, governed by the resonance spacing. Then, we implement analytical simulations to characterize the device and analyze the influence of coupling efficiencies and propagation losses of two resonant modes on behavior. Consequently, finite difference time domain simulations have been performed. The numerical results validate our theoretical analysis, and optical buffering effect is demonstrated in a pulse propagation simulation, when the two resonances are aligned. In addition, we show that the device function can be switched between flat-top filtering and all-pass filtering by tuning the local refractive index in a microdonut. Hence, this structure is promising for on-chip optical filtering and buffering applications.


Reference tissue models in the assessment of 11 C-DTBZ binding to the VMAT2 in rat striatum: A test-retest reproducibility study.
Dopaminergic PET imaging is a useful tool to assess the dopaminergic integrity and to follow-up longitudinal studies. The aim of this study was to evaluate the reliability and reproducibility of different reference tissue-based methods to determine the non-displaceable binding potential (BPND ) as a quantitative measure of 11 C-DTBZ binding to the VMAT2 in rat striatum using cerebellum as reference region. Eight healthy Wistar rats underwent two microPET scans at the age of 12 (test) and 20 weeks (retest). BPND was determined using the simplified reference tissue model, Logan reference tissue model, and multilinear reference tissue models (MRTMo and MRTM2). Additionally, a striatal-to-cerebellar-ratio (SCR) analysis was performed. The reproducibility between the two scans was assessed using the interclass correlation coefficients (ICC) and the variability index. Repeatability indices showed acceptable ICC = 0.66 (SCR) to excellent ICC = 0.98 (MRTM2) reliability for this study and a variability ranging from 12.26% (SCR) to 3.28% (MRTM2). To the best of our knowledge, this is the first report on longitudinal studies for 11 C-DTBZ in rats using reference tissue methods. Excellent intersubject and intrasubject reproducibility was obtained with the multilinear reference MRTM2, suggesting this as the best method to compare longitudinal studies, whereas the SCR method had poor reliability. Logan method, however, is a method simple to compute that shows accurate reproducibility with a reasonable level of inter- and intra-subject variability allowing crossover studies to follow-up the uptake of 11 C-DTBZ in rat striatum.


Kidney Function and the Risk of Stroke and Dementia: The Rotterdam Study.
Longitudinal population-based data on effects of kidney dysfunction in the development of stroke and dementia remains inconclusive. We investigated associations of kidney function with risk of stroke and dementia in 5,993 community-dwelling individuals (mean age: 69.0 years, 57.2% women). We calculated estimated glomerular filtration rates based on creatinine, cystatin-C, and a combination of these two. During a mean follow-up of 11.6 years (69,790 person-years), 1,360 individuals suffered a stroke (n = 601) or developed dementia (n = 759). We found that an impaired kidney function was related to a higher risk of stroke, but not to dementia.


Glutathione deficiency does not elevate susceptibility of bacteria to the mutagenicity of chlorinated humic acids.
1. Rat liver 9,000 g supernatant protected against the mutagenic effect of chlorinated hydrophilic macromolecular humic acids (CHMA) in Salmonella typhimurium strain TA100. 2. Protection against mutagenicity of CHMA was mediated by glutathione and was partially dependent on glutathione S-transferase activity. 3. In contrast to the above findings, CHMA showed lower mutagenicity in Salmonella typhimurium and Escherichia coli strains of bacteria that are deficient in glutathione compared to their mutagenicity in parental (glutathione-rich) bacterial strains. 4. Glutathione-deficient cells do not provide test systems with elevated sensitivity for the detection of mutagenic chlorinated humic substances.


Arrhythmia management in patients with a common arterial trunk and d-transposition of the great arteries.
Arrhythmias in patients with congenital heart disease present a challenge to the care of these patients and can result in significant morbidity and mortality. Transposition of the great arteries and common arterial trunk are no exceptions. It is important to identify risk factors for arrhythmia development in the peri-operative period. The peri-operative arrhythmia burden may relate to the underlying congenital heart disease, haemodynamic perturbations, operative events, and potential residual lesions. In addition, these patients are at risk for developing arrhythmias later in life, and non-invasive and potentially invasive arrhythmia surveillance should be a routine part of the care of these patients. This article highlights important strategies to manage arrhythmia development and prevention in this patient population.


Thermographic characterization of thin liquid film formation and evaporation in microchannels.
The science of transport in microchannels has greatly benefited applications ranging from micro-mixing, chemical synthesis and biological analysis to compact and efficient energy devices. One of the most critical and intricate phenomena in this field of science is the dynamics of thin liquid film formation during the flow of liquid and gas/vapor mixtures. These films can form in microseconds and be less than a micrometer thick, while dominating thermal transport in phase-change processes. Here, we report the captured details of these phenomena using a new measurement technique with unprecedented spatial and temporal resolutions of 20 μm and 100 μs, respectively. Thin films with thicknesses ranging from 1 to 20 μm forming around elongated bubbles over a capillary number range of 0.025 to 0.1 are characterized. The measurements suggest that these films thermally develop and evaporate at timescales in the order of 1-10 ms, two orders of magnitude longer than their formation timescale. The formation, reflow and evaporation of the liquid film constitute a complex dynamic involving variations of the film thickness over the periphery of a rectangular channel, leading to a thicker liquid film feeding (through lateral capillary wicking) a much thinner rapidly evaporating film. As a result, the thinner film dictates the rate of surface heat transfer while the thicker film determines the duration of thin film evaporation. A modified Bretherton model provides the best fit to the experimental results.


Management of osteoporosis.
Osteoporosis is clearly more easily prevented than treated. Prevention should start early for those thought to be most at risk. However, for the majority, menopause is the most convenient time point at which to evaluate the necessity for prevention. While oestrogens are the most effective therapeutic agent for prevention of postmenopausal bone loss, they must be used judiciously with attention to reduction in other nutritional and lifestyle risk factors. When given to women with an intact uterus, oestrogen prescription currently should be accompanied by progestogens, several of which may also reduce bone loss. All individuals should be encouraged to obtain an adequate calcium intake (100-1500 mg day-1) and to continue an active lifestyle. Therapy of the clinically overt disorder follows similar guidelines, with therapeutic options including calcitonin androgens and diphosphonates as well as oestrogens as antiresorptive agents. Methods of stimulating new bone formation are limited, the best documented effects being those of fluoride. However, care must be taken in its use and efficacy has yet to be finally established. Other modalities are as yet experimental. Much can be gained by careful attention to the general health of the patients and their environment, since reduction in risk of falls, and thus fracture, is at least as important as attempts to modify the skeleton.


Repeat HIV testers at a London same-day testing clinic.
To compare the characteristics of repeat HIV testers with first-time testers in a National Health Service HIV testing clinic in London. A self-administered questionnaire was distributed to clinic attenders between September 1995 and January 1996. The sample was stratified by gender and sexual orientation. Repeat and first-time testers were compared with respect to recent sexual risk behaviour, reasons for taking the HIV test, condom use, knowledge of sex partner's HIV status, and sociodemographic and psychosocial variables. Of 965 clinic attenders surveyed, 404 (41.9%) reported at least one previous HIV test outside the window period and were classified as repeat testers: homosexual men, 62.5% (178 out of 285); heterosexual men, 35.1% (126 out of 359); heterosexual women, 31.2% (100 out of 321). Among homosexual men, repeat testers were more likely to report the following: two or more partners in the previous 6 months for both unprotected anal sex (25.8 versus 9.3%; P < 0.01) and unprotected oral sex (53.9 versus 37.4%; P < 0.01); ever having had a sexually transmitted disease (STD) other than HIV (49.4 versus 29.0%; P < 0.01); taking the present test "as part of a regular health check' (48.9 versus 28.0%; P < 0.01); and knowing others who had tested for or been infected with HIV. Repeat testing heterosexual men were more likely to report the following: two or more partners in the previous 6 months for unprotected vaginal sex (42.9 versus 30.9%; P < 0.05) and unprotected oral sex (41.3 versus 25.3%; P < 0.01); ever having had an STD other than HIV (31.7 versus 20.6%; P < 0.05); taking the present test "as part of a regular health check' (36.5 versus 26.2%; P < 0.05); and knowing others who had tested for or been infected with HIV. For heterosexual women, repeat testers were more likely to report ever having had an STD other than HIV (25.0 versus 14.5%; P < 0.05), and knowing others who had tested for or been infected with HIV. Repeat testing was associated with high-risk sexual behaviour, a previous STD, knowledge of others who have tested for or been infected with HIV, and seeking the test as part of a regular health check. Factors contributing to repeat testing are multi-faceted and vary between groups of different sexual orientation. Use of the impact of knowledge of others infected by HIV and the experience of contracting an STD other than HIV may guide the development of HIV counselling interventions aimed at reducing sexual risk behaviour.


MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases.
Magnetic resonance spectroscopy (MRS) is likely in the near future to play a key role in the process of drug discovery and evaluation. As the pharmaceutical industry seeks biochemical markers of drug delivery, efficacy and toxicity, this non-invasive technique offers numerous ways to study adults and children repeatedly and without ionizing radiation. In this article, we survey an array of the information that MRS offers about neurochemistry in general and psychiatric disorders and their treatment in particular. We also present growing evidence of glial abnormalities in neuropsychiatric disorders and discuss what MRS is contributing to that line of investigation. The third major direction of this article is the discussion of where MRS techniques are headed and how those new techniques can contribute to studies of mechanisms of psychiatric disease and drug discovery.


High-Resolution X-ray Diffraction of Muscle Using Undulator Radiation from the Tristan Main Ring at KEK.
High Energy Accelerator Research Organization (KEK), Tsukuba, Japan.High-resolution X-ray diffraction studies on striated muscle fibres were performed using a hard X-ray undulator installed in the Tristan main ring at KEK, Tsukuba, Japan. The performance of the undulator, along with an example experiment which exploited the unique characteristics of undulator radiation, are reported. The vertical divergence angle of the first harmonic of the undulator was approximately 10 micro rad under 8 GeV multi-bunch operating conditions and the peak photon flux density was estimated to be approximately 3 x 10(16) photons s(-1) mrad(-2) (0.1% bandwidth)(-1) (10 mA)(-1). The well collimated X-ray beam from the undulator made it possible to resolve clearly, with high angular resolution ( approximately 700 nm), the closely spaced diffraction peaks on the meridional axis in the X-ray patterns arising from the thick filaments of a striated muscle under static conditions. By fitting the meridional intensity pattern, a model for the molecular arrangement of the constituent proteins in the thick filaments is proposed. These studies of muscle demonstrate the promise of undulator radiation from third-generation sources for high-resolution diffraction studies.


Alternative cone-beam CT method for the analysis of mandibular condylar bone in patients with degenerative joint disease.
The aim of this study was to investigate the use of 3D microstructural bone analysis in patients with degenerative joint disorder (DJD) to enhance the diagnostic capacity of cone beam computed tomography (CBCT) in the evaluation of bone tissue. 147 TMJ CBCT images of 88 participants were assessed with regard to DJD in the mandibular condyle. We divided each condyle into 3 groups (0, 1, 2) according to diagnosis of DJD: 0 indicates normal condyles (control individuals), 1 indicates mild erosive osteoarthritic change (EOC) and 2 indicates severe EOC. 3D fractal dimension (FD) was calculated on CBCT images of mandibular condyle and were compared with the radiographic diagnosis of patients. ANOVA test showed that there was statistically significant difference in FD values among each groups. The average FD value of group 0 was 1.971, group 1 was 1.918 and group 2 was 1.863. Lower FD values and more severe degenerative changes were seen in patient group 2. To evaluate the reliability of fractal analysis (FA) method, receiver operating characteristic (ROC) curve analysis was performed. Area under the curve (AUC) was 0.717 (p < 0.001). This study provides a preliminary conclusion that fractal analysis may be a helpful tool to enhance the diagnostic capacity of CBCT in the evaluation of DJD.


Principles of pharmacotherapy: I. Pharmacodynamics.
This paper and the ensuing series present the principles guiding and affecting the ability of drugs to produce therapeutic benefit or untoward harm. The principles of pharmacodynamics and pharmacokinetics, the physiologic basis of adverse drug reactions and suitable antidotal therapy, and the biologic basis of drug allergy, drug-drug interactions, pharmacogenetics, teratology and hematologic reactions to chemicals are explored. These principles serve to guide those administering and using drugs to attain the maximum benefit and least attendant harm from their use. Such is the goal of rational therapeutics.


Tacrolimus and Single Intraoperative High-dose of Anti-T-lymphocyte Globulins Versus Tacrolimus Monotherapy in Adult Liver Transplantation: One-year Results of an Investigator-driven Randomized Controlled Trial.
The aim of the study is to evaluate whether intra-operative induction with anti-lymphocytic serum (ALS) is superior to no induction in adult liver transplantation (LT). The efficacy of ALS induction remains inconclusive in LT, because of poorly designed trials. A randomized controlled trial was conducted, including 206 adults (>15 years) and comparing tacrolimus monotherapy (TAC, n = 109) and tacrolimus plus a single, intraoperative, high-dose (9 mg/kg), rabbit anti-T-lymphocyte globulins (ATLG; n = 97). All patients had similar follow-up, including Banff-scored biopsies. Rejection was considered clinically relevant and treated if pathologic and biochemical changes were concordant. The primary endpoint was immunosuppression minimization to monotherapy; secondary endpoints were biopsy-proven rejection, clinical rejection, patient (PS) and graft (GS) survival. At 1 year, 79/81 (96.3%) ATLG and 101/102 (99.0%) TAC patients were steroid-free (P = 0.585); 28 (34.6%) ATLG, and 31 (30.4%) TAC patients were on double-drug immunosuppression (P = 0.633). One-year PS and GS of ATLG and TAC patients were 84% and 92% (P = 0.260) and 76% and 90% (P = 0.054).Despite significantly a fewer day-7 moderate-to-severe acute cellular rejections (ACR) in ATLG group (10.0% vs 24.0% in TAC group, P = 0.019), cumulative proportion of patients experiencing steroid-sensitive (11.3% ATLG vs 14.7% TAC, P = 0.539), steroid-resistant (2.1% ATLG vs 3.7% TAC, P = 0.686) and chronic rejection (1.0% ATLG vs 0.9% TAC, P = 1.000) were similar. ATLG administration brought about greater hemodynamic instability and blood products use (P = 0.001). At 1 year from LT, ATLG induction did not significantly affect immunosuppressive load, treated rejection, patient, and graft survival. The observed adverse events justify a modification of dosing and timing of ATLG infusion. Long-term results are required to judge the ATLG possible benefits on immunosuppressive load and tolerance induction.