Degenerate in vitro genetic selection reveals mutations that diminish alfalfa mosaic virus RNA replication without affecting coat protein binding.
The alfalfa mosaic virus (AMV) RNAs are infectious only in the presence of the viral coat protein; however, the mechanisms describing coat protein's role during replication are disputed. We reasoned that mechanistic details might be revealed by identifying RNA mutations in the 3'-terminal coat protein binding domain that increased or decreased RNA replication without affecting coat protein binding. Degenerate (doped) in vitro genetic selection, based on a pool of randomized 39-mers, was used to select 30 variant RNAs that bound coat protein with high affinity. AUGC sequences that are conserved among AMV and ilarvirus RNAs were among the invariant nucleotides in the selected RNAs. Five representative clones were analyzed in functional assays, revealing diminished viral RNA expression resulting from apparent defects in replication and/or translation. These data identify a set of mutations, including G-U wobble pairs and nucleotide mismatches in the 5' hairpin, which affect viral RNA functions without significant impact on coat protein binding. Because the mutations associated with diminished function were scattered over the 3'-terminal nucleotides, we considered the possibility that RNA conformational changes rather than disruption of a precise motif might limit activity. Native polyacrylamide gel electrophoresis experiments showed that the 3' RNA conformation was indeed altered by nucleotide substitutions. One interpretation of the data is that coat protein binding to the AUGC sequences determines the orientation of the 3' hairpins relative to one another, while local structural features within these hairpins are also critical determinants of functional activity.


A nurse-led pulmonary rehabilitation programme for patients with COPD.
A pulmonary rehabilitation programme set out to improve quality of life for patients with COPD by providing education and improving exercise tolerance. Progress was measured and outcomes monitored, the results indicating that such programmes could have a big impact, particularly on patients who are identified in the early stages of the disease.


Optimization of PMA-qPCR for Staphylococcus aureus and determination of viable bacteria in indoor air.
Staphylococcus aureus may cause infections in humans from mild skin disorders to lethal pneumonia. Rapid and accurate monitoring of viable S. aureus is essential to characterize human exposure. This study evaluated quantitative PCR (qPCR) with propidium monoazide (PMA) to quantify S. aureus. The results showed comparable S. aureus counts between exclusively live cells and mixtures of live/dead cells by qPCR with 1.5 or 2.3 μg/mL PMA (P>.05), illustrating the ability of PMA-qPCR to detect DNA exclusively from viable cells. Moreover, qPCR with 1.5 or 2.3 μg/mL PMA performed optimally with linearity over 103 -108 CFU/mL (R2 ≥0.9), whereas qPCR with 10, 23 or 46 μg/mL PMA significantly underestimated viable counts. Staphylococcus aureus and total viable bacteria were further determined with PMA-qPCR (1.5 μg/mL) from 48 samples from a public library and two university dormitories and four from outside. Viable bacteria averaged 1.9×104 cells/m3 , and S. aureus were detected in 22 (42%) samples with a mean of 4.4×103 cells/m3 . The number of S. aureus and viable bacteria were positively correlated (r=.61, P<.005), and percentages of S. aureus relative to viable bacteria averaged 12-44%. The results of field samples suggest that PMA-qPCR can be used to quantify viable S. aureus cells.


Carnitine supplementation improves apolipoprotein B levels in pediatric peritoneal dialysis patients.
There have been conflicting reports concerning the effect of carnitine supplementation on lipid metabolism in patients on peritoneal dialysis (PD). We investigated several parameters of lipid metabolism in pediatric PD patients supplemented with carnitine. The study included 20 patients receiving PD (treatment group) aged 2-18 years and a matched healthy control group. In the treatment group, baseline triglyceride, total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and apolipoprotein B levels were higher than in the control group. High-density lipoprotein cholesterol, free fatty acid, phospholipids, and apolipoprotein A-I levels were not different from those in the control group. The baseline plasma free carnitine level was lower and acyl-carnitine level was higher in the treatment group. No difference was found between the groups with respect to plasma total carnitine levels. Oral l-carnitine supplementation (50 mg/kg per day for 30 days) led to a significant decrease (from a baseline value of 146.6+/-51.8 mg/dl to 63.6+/-22.2 mg/dl, P<0.001) in apolipoprotein B levels, and no significant change in the other lipid parameters of the treatment group. Oral l-carnitine supplementation does not ameliorate the lipid profile in pediatric PD patients, but it causes a significant decrease in apolipoprotein B levels. Hence, carnitine supplementation may be recommended for decreasing apolipoprotein B levels in this patient population.


Review in peeling complications.
Chemical peeling, a procedure wherein a chemical agent is applied to the skin to cause controlled destruction followed by regeneration and remodeling, is a dynamic tool for the treatment of acne, pigmentation issues, and photoaging [Journal of cutaneous and aesthetic surgery vol. 5 (2012) 254-260]. The results and complications are related to the depth of the procedure, with deeper peels producing more marked results and higher rates of complications. Complications are more likely with darker skin types, certain peeling agents, and sun exposure after treatment [Journal of cutaneous and aesthetic surgery vol. 5 (2012) 254-260]. They can range from minor irritations and uneven pigmentation to permanent scarring. In extremely uncommon cases, the complications can be life-threatening. This knowledge is essential to prevent, reduce, and eliminate the occurrence of complications [Cirurgia dermatológica em consultório. São Paulo: Atheneu; 2009]. Swelling, pain, persistent erythema, pruritus, allergic reactions, folliculitis/acne, infection, herpes recurrence, hypopigmentation and hyperpigmentation, demarcation lines, and scarring are some of the complications that will be discussed in this article. The first step in preventing complications is to identify the patients at risk. By doing so, complications can be anticipated, prevented, and, if they still occur, treated as early as possible.


Resistance of Pseudomonas to ciprofloxacin: implications for the treatment of malignant otitis externa.
For fifteen years oral ciprofloxacin has been the standard treatment for malignant otitis externa, a sometimes fatal osteomyelitis of the skull base usually caused by Pseudomonas aeruginosa. Resistance to ciprofloxacin is developing. Over a 16-month period, we saw five cases where malignant otitis externa progressed, with the development of cranial nerve palsies in four cases, despite oral ciprofloxacin. Prolonged intravenous antibiotic therapy became necessary. One case was managed largely as an out-patient, but four patients spent many weeks in hospital. Only two cases had diabetes and this was monitored and controlled. Pseudomonas aeruginosa was isolated in four of the five cases, but antibiotic sensitivity to ciprofloxacin was not determined. In one case a later isolate was tested and found to be ciprofloxacin resistant. Progress was monitored by serial C-reactive protein (CRP) and white cell count. For diagnosis and assessing response to treatment we considered serial magnetic resonance imaging or computed tomography more useful than isotope bone scan. There must be a readiness to use intravenous antibiotics, as a response to ciprofloxacin can no longer be assumed. Bacterial isolates must be tested for sensitivity to antibiotics including ciprofloxacin, and further biopsy and culture are essential if treatment fails.


Integrated multi-trophic aquaculture with sugar kelp and oysters in a shallow coastal salt pond and open estuary site.
Sustainable aquaculture includes the aquaculture of non-fed crops that provide ecosystem services including nutrient extraction and water quality improvement. While shellfish are the most farmed sustainable aquaculture crops in the USA, shellfish farmers in the northeastern US have an interest in diversifying their crops and incorporating seaweeds into their farms. In this study, we worked with oyster farmers to investigate the potential for farming sugar kelp, Saccharina latissima, across different environmental regimes in coastal Rhode Island USA. Kelp seed spools were outplanted at two time points in the fall/winter of 2017 and 2018 at four sites and cultivated until harvest the following spring. Kelp performance (length, width, yield), tissue content, and nutrient extraction were determined for each line in each year; oyster growth was also measured monthly for one year at each site. We found that kelp could successfully grow in both shallow coastal lagoons and estuarine sites, although the timing of planting and placement of sites was important. Lines that were planted earlier (as soon as water temperatures<15°C) grew longer and yielded more biomass at harvest; overall, kelp blade yield ranged from 0.36 ± 0.01 to 11.26 ± 2.18 kg/m long line. We report little variation in the tissue quality (C:N) of kelp among sites, but differences in biomass production led to differences in nutrient extraction, which ranged from 0.28 ± 0.04 to 16.35 ± 4.26 g nitrogen/m long line and 8.93 ± 0.35 to 286.30 ± 74.66 g carbon/m long line. We found extensive variability in kelp growth within and between lines and between years, suggesting that crop consistency is a challenge for kelp farmers in the region. Our results suggest that, as there is a lower barrier in terms of permitting (versus starting a new aquaculture farm), it may be a worthwhile investment to add sugar kelp to existing oyster farms, provided they have suitable conditions. At current market rates of US$0.88-$3.30 per kg, farmers in southern New England have the potential to earn US$2,229 per 60 m longline. While seaweed aquaculture is growing, considerable barriers still exist that prevent wide-scale kelp aquaculture adoption by existing aquafarmers.


[Prospective phase II study of neoadjuvant radiochemotherapy in advanced operable carcinoma of the mouth cavity. 3-year outcome].
The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent as well as in combination drug regimens. In the present outpatient phase II trial, we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable stage III/IV squamous cell carcinoma of the oral cavity and oropharynx. Fifty-three patients were enrolled in this trial during the period from May 1998 to October 2000 and received five cycles weekly of Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3-4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. Fifty-two patients were evaluable for toxicity and response. Complete response was observed in 31 of 52 patients (CR 60%), and partial remission was seen in 21 of 52 patients (PR 40%). In 30 of 52 patients complete pathologic response (pCR 58%) was documented in the resection specimens. The 1-, 2-, and 3-year overall survival rate was calculated as 84%. Our present results demonstrated impressive clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as a preoperative treatment modality in advanced oral and oropharyngeal cancer.


Multimodal Imaging in a Patient with Hemidystonia Responsive to GPi Deep Brain Stimulation.
Dystonia is a syndrome with varied phenomenology but our understanding of its mechanisms is deficient. With neuroimaging techniques, such as fiber tractography (FT) and magnetoencephalography (MEG), pathway connectivity can be studied to that end. We present a hemidystonia patient treated with deep brain stimulation (DBS). After 10 years of left axial hemidystonia, a 45-year-old male underwent unilateral right globus pallidus internus (GPi) DBS. Whole brain MEG before and after anticholinergic medication was performed prior to surgery. 26-direction diffusion tensor imaging (DTI) was obtained in a 3 T MRI machine along with FT. The patient was assessed before and one year after surgery by using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). In the eyes-closed MEG study there was an increase in brain coherence in the gamma band after medication in the middle and inferior frontal region. FT demonstrated over 50% more intense ipsilateral connectivity in the right hemisphere compared to the left. After DBS, BFMDRS motor and disability scores both dropped by 71%. Multimodal neuroimaging techniques can offer insights into the pathophysiology of dystonia and can direct choices for developing therapeutics. Unilateral pallidal DBS can provide significant symptom control in axial hemidystonia poorly responsive to medication.


IDDM incidence in a multiracial population. The Hawaii IDDM Registry, 1980-1990.
The Hawaii IDDM Registry was created to determine the incidence rate of IDDM among children aged < 15 years of Oahu between 1980 and 1990. Because of the multiracial population living in Hawaii, it is an ideal state in which to study the effect of migration on IDDM incidence. Data were collected by a retrospective hospital chart review and physician survey. Registry criteria included 0-14 years of age at IDDM diagnosis and primary residence on Oahu. Children who were military dependents were excluded. Denominator data were compared from two sources. A total of 113 new-onset IDDM cases were identified. Case ascertainment was 97%. The unadjusted annual incidence rate was 7.04-7.61 per 100,000 (95% CI 5.83-9.19), depending on which denominator source was used. Race- and ethnicity-specific rates varied greatly (all rates per 100,000): part Hawaiian, 15.34-16.58; Caucasian, 6.21-6.71; Filipino, 3.66-3.96; and Japanese, 2.85-3.08. Temporally, the incidence fluctuated between a low of 2.96 per 100,000 in 1981 to highs of 11.11 and 11.85 per 100,000 in 1985 and 1989, respectively. Ascertainment-corrected rates for these years (3.70, 11.76, and 13.48 per 100,000, respectively) show that the fourfold incidence increase between 1980 and 1989 was not due to ascertainment differences. IDDM incidence among children < 15 years of age in Hawaii was the lowest documented in the U.S. The incidence among part-Hawaiian children was 2.5 times greater than that of Caucasian children in Hawaii. IDDM incidence rates among Japanese children in Hawaii were comparable with rates in Japan. The temporal variation in IDDM incidence corresponded with a mid-1980s pandemic of IDDM documented elsewhere.


Impact of antiretroviral therapy on glycemia and transaminase levels in patients living with HIV/AIDS in Limbe, Cameroon.
This study aimed to determine the effect of antiretroviral therapy (ART) on glycemia and transaminase levels in HIV-infected patients in Limbe, Cameroon. A total of 200 ART-experienced patients and 30 ART-naive HIV-infected controls were recruited after submitting signed informed consent forms. The blood samples collected were screened for hepatitis B and C, and liver transaminases and random blood sugar (RBS) levels were determined spectrophotometrically. No significant correlation existed between the RBS and transaminase levels with either the duration of ART or the duration since HIV diagnosis. Although both groups of patients appeared to have similar transaminase and RBS levels, after controlling for confounders, patients on ART had significantly higher aspartate aminotransferase levels, significantly lower alanine aminotransferase levels, and slightly (but not significantly) lower glycemia levels (respective mean differences of 14.92 IU/L, P = .00; 11.95 IU/L, P = .00; and 7.60 mg/dL, P = .19). These changes need to be considered in monitoring patients on ART in this setting and other similar settings.


Fine-needle aspiration biopsy of thyroid nodules.
Nodular thyroid disease is a common problem, particularly in women and the elderly population. Furthermore, 5% of thyroid nodules are likely to be malignant. Therefore, assessment for malignant potential is important, and fine-needle aspiration (FNA) biopsy is the most accurate technique. For each nodule, two to four aspirations should be attempted from different areas of the nodule. Although major complications of FNA biopsy are rare, proper cytologic interpretation necessitates special expertise. Cytologic diagnoses are usually categorized as diagnostic or nondiagnostic, and the diagnostic specimens are classified as benign, "suspicious," or malignant. Rebiopsy is indicated for enlarging nodules, recurrent cysts, and nondiagnostic cytologic findings. Because FNA biopsy is a safe, reliable, and rapid means of evaluating thyroid nodules, we recommend its routine use for diagnosis and treatment of thyroid nodular disease.


Environmental persistence, bioaccumulation, and hazards of chemicals in e-cigarette e-liquids: short-listing chemicals for risk assessments.
Increased use and sales of e-cigarettes raises concerns about the potential environmental impacts throughout their life-cycle. However, few available research studies focus on the environmental impacts and ecotoxicity of e-cigarettes. In this study, we short-list e-liquid chemicals from published literature that should be considered in future environmental impact and risk assessments. We used a combination of available laboratory bioassays-based data and predictive methods (eg, Structure-Activity Relationships) to characterise the hazards of the e-liquid chemicals (environmental persistence, bioaccumulation, and aquatic toxicity including hazardous concentration values (concentration affecting specific proportion of species)) for short-listing. Of the 421 unique e-liquid chemicals compiled from literature, 35 are US Environmental Protection Agency's hazardous constituents, 42 are US Food and Drug Administration's harmful or potentially harmful constituents in tobacco products and smoke, and 20 are listed as both. Per hazard characteristics, we short-listed 81 chemicals that should be considered for future environmental impact and risk assessments, including tobacco-specific compounds (eg, nicotine, N'-nitrosonornicotine), polycyclic aromatic hydrocarbons (eg, chrysene), flavours (eg, (-)caryophyllene oxide), metals (eg, lead), phthalates (eg, di(2-ethylhexyl)phthalate) and flame retardants (eg, tris(4-methylphenyl)phosphate). Our findings documenting various hazardous chemicals in the e-liquids underscore the importance of awareness and education when handling or disposing of e-liquids/e-cigarettes and aim to inform strategies to prevent and reduce hazards from e-cigarettes. This includes any scenario where e-liquids can come into contact with people or the environment during e-liquid storage, manufacturing, use, and disposal practices. Overall, our study characterises the environmental hazards of e-liquid chemicals and provides regulators and researchers a readily available list for future ecological and health risk assessments.


Long-term efficacy of dexamethasone-cyclophosphamide pulse therapy in pemphigus.
Corticosteroids are used as a daily oral therapy or in a pulse form with or without various adjuvant drugs for the treatment of pemphigus. Our long-term experience with the use of dexamethasone-cyclophosphamide pulse therapy as a first-line treatment modality for pemphigus is presented. A retrospective analysis of records of pemphigus patients treated by dexamethasone-cyclophosphamide therapy was carried out. The treatment regimen consisted of the monthly administration of intravenous dexamethasone (136 mg) for 3 consecutive days with addition of intravenous cyclophosphamide (500 mg) on the second day. Oral cyclophosphamide (50 mg) daily and oral corticosteroids (low tapering doses) were given in the intervals between the pulses, till partial remission was achieved. Pulse therapy was then continued for another 6 months followed by daily oral cyclophosphamide (50 mg) for 1 year, which produced a complete remission. A total of 36 patients, 32 with pemphigus vulgaris and 4 with pemphigus foliaceus, were treated with this regimen. Two to 8 pulses were required to achieve a partial remission, while the total number of pulses given for complete remission ranged from 8 to 32. The duration of pulse therapy correlated with both the disease severity and the time to achieve remission. All patients are now in complete remission with a follow-up of 0.5-12 years. Four patterns of remission were observed, related to the severity of disease. The response to pulse therapy was faster in the milder form of disease. The severe form of disease required more pulses as well as higher doses of intervening oral corticosteroids. Dexamethasone-cyclophosphamide pulse therapy is an effective form of treatment in pemphigus and results in long-lasting remissions.


MR imaging of rotator cuff tendon tears: comparison of T2*-weighted gradient-echo and conventional dual-echo sequences.
Although MR imaging evaluation of the rotator cuff is usually done with proton density- and T2-weighted spin-echo techniques, interest also exists in T2*-weighted gradient-recalled echo techniques. The shorter scan times of T2*-weighted sequences can be used to increase the number of signal averages and thus improve the signal-to-noise ratio. Our purpose in this study was to compare the sensitivity and specificity of oblique coronal T2*-weighted MR image interpretations with conventional dual-echo T2-weighted MR image interpretations when diagnosing rotator cuff tears. Forty-seven consecutive patients who underwent both MR imaging and shoulder arthroscopy were included in this study. The MR examination included both a 7 min 20 sec acquisition time proton density- and T2-weighted oblique coronal sequence and a 7 min 5 sec T2*-weighted oblique coronal sequence. The oblique coronal dual-echo T2-weighted images were evaluated by two of the authors independently, who were unaware of the arthroscopic findings. Each of the two observers graded each cuff as being intact, having a partial-thickness tear, or having a full-thickness tear. After a 3-week interval, each of the two observers then interpreted the T2*-weighted oblique coronal MR images in the same manner. Sensitivity and specificity for the two sets of interpretations were calculated in terms of the ability of the observers to use the two sequences to distinguish an intact cuff from a rotator cuff tear and to distinguish a partial-thickness cuff tear from an intact cuff or full-thickness tear. The results were then compared using Student's t test calculations. For distinguishing an intact cuff from a torn cuff, the sensitivity of the observers' interpretations was lower for the T2*-weighted images than for the conventional dual-echo T2-weighted images. The specificity also decreased with interpretation of the T2*-weighted images for one observer and was unchanged for the second observer. For distinguishing a partial-thickness cuff tear from a non-partial-thickness cuff tear (intact or full-thickness tear), the sensitivity and specificity of both observers decreased with interpretations of the T2*-weighted images when compared with the conventional dual-echo T2-weighted images. The results did not reach statistical significance. In this small study evaluating the ability of observers to diagnose rotator cuff tears on oblique coronal MR images only, interpretations of T2*-weighted images tended to be less sensitive and specific than interpretations of standard dual-echo T2-weighted images.


Keratin8 Deficiency Aggravates Retinal Ganglion Cell Damage Under Acute Ocular Hypertension.
Keratin 8/18 (KRT8/18), paired members of the intermediate filament family, have shown vital functions in regulating physiological activities more than supporting the mechanic strength for cells and organelles. However, the KRT8/18 presence in retinal ganglion cells (RGCs) and functions on neuroprotection in a mouse model of acute ocular hypertension (AOH) are unknown and worthy of exploration. We identified the existence of KRT8/18 in normal human and mouse retinas and primary RGCs. KRT8/18 levels were detected after AOH modeling. The adeno-associated virus (AAV) system was intravitreally used for selective KRT8 knockdown in RGCs. The histological changes, the loss and dysfunction of RGCs, and the gliosis in retinas were detected. The markers of cell apoptosis and MAPK pathways were investigated. KRT8/18 existed in all retinal layers and was highly expressed in RGCs, and they increased after AOH induction. The KRT8 knockdown in RGCs caused no histopathological changes and RGC loss in retinas without AOH modeling. However, after the KRT8 deficiency, AOH significantly promoted the loss of whole retina and inner retina thickness, the reduction, apoptosis, and dysfunction of RGCs, and the glial activation. Besides, downregulated Bcl-2 and upregulated cleaved-Caspase 3 were found in the AOH retinas with KRT8 knockdown, which may be caused by the increased phosphorylation level of MAPK pathways (JNK, p38, and ERK). The KRT8 deficiency promoted RGC apoptosis and neurodegeneration by abnormal activation of MAPK pathways in AOH retinas. Targeting KRT8 may serve as a novel treatment for saving RCGs from glaucomatous injuries.


Bioinspired micrograting arrays mimicking the reverse color diffraction elements evolved by the butterfly Pierella luna.
Recently, diffraction elements that reverse the color sequence normally observed in planar diffraction gratings have been found in the wing scales of the butterfly Pierella luna. Here, we describe the creation of an artificial photonic material mimicking this reverse color-order diffraction effect. The bioinspired system consists of ordered arrays of vertically oriented microdiffraction gratings. We present a detailed analysis and modeling of the coupling of diffraction resulting from individual structural components and demonstrate its strong dependence on the orientation of the individual miniature gratings. This photonic material could provide a basis for novel developments in biosensing, anticounterfeiting, and efficient light management in photovoltaic systems and light-emitting diodes.


From Pixels to Pathology: Employing Computer Vision to Decode Chest Diseases in Medical Images.
Radiology has been a pioneer in the healthcare industry's digital transformation, incorporating digital imaging systems like picture archiving and communication system (PACS) and teleradiology over the past thirty years. This shift has reshaped radiology services, positioning the field at a crucial junction for potential evolution into an integrated diagnostic service through artificial intelligence and machine learning. These technologies offer advanced tools for radiology's transformation. The radiology community has advanced computer-aided diagnosis (CAD) tools using machine learning techniques, notably deep learning convolutional neural networks (CNNs), for medical image pattern recognition. However, the integration of CAD tools into clinical practice has been hindered by challenges in workflow integration, unclear business models, and limited clinical benefits, despite development dating back to the 1990s. This comprehensive review focuses on detecting chest-related diseases through techniques like chest X-rays (CXRs), magnetic resonance imaging (MRI), nuclear medicine, and computed tomography (CT) scans. It examines the utilization of computer-aided programs by researchers for disease detection, addressing key areas: the role of computer-aided programs in disease detection advancement, recent developments in MRI, CXR, radioactive tracers, and CT scans for chest disease identification, research gaps for more effective development, and the incorporation of machine learning programs into diagnostic tools.


Preferences of Iranian patients about style of labelling and calling of their physicians.
To document the performance of patients regarding label styles of their doctors and modes of addressing them. In this descriptive survey, 400 patients, at two teaching hospitals--Hajar and Kashani--with a mean age of 40.5 +/- 19.5 years were enrolled. Their demographic data, disorder type and duration were recorded. Photos demonstrating different label and attire styles based on Iranian culture were shown to the patients and they were asked to mark their performances about the necessity of wearing name badge. They were also requested to nominate the way they preferred to be addressed by the doctors. Of the participants, 180 (45%) were men; 307 (76.8%) were married; and the mean duration of hospitalisation was 2.5 +/- 2.1 days. Most of the patients, (n = 320; 80%) stated that the doctor should always wear a name badge; 301 (75.3%) preferred to call their physicians by title; and 227 (56.8%) preferred to be called by their surnames. Patients preferred to have female physicians wearing white coat, shirt and trousers as the preferred dress code. Patients in the study preferred to have the physicians professionally attired, with the only difference being the dark veil for female physicians. Name badge and white coat were also preferred by the patients.


Children as agents of their own health: exploratory analysis of child discourse in Spain.
The promotion of children's decision-making is one of the principles of health-promoting schools, and the empowerment of children means that they are enabled to influence their lifestyles and living conditions. The aim of this study was to find out the suggestions of Spanish school pupils in Year 3 and Year 6 of primary education to promote their own health and the health of the people closer to them, through their ideas about health. We analyse the discourse on health in the school environment from focus groups of primary school pupils aged around 8 and 12 of five schools in the town of Alicante (Spain). The groups were organized according to the type of school (public, private), the socioeconomic status of the neighbourhood (residential, working-class) and gender (single-sex, mixed groups) to ensure both the highest intergroup diversity and intra-group homogeneity. The findings show that primary school pupils have a wide and diverse notion of health. The application of the focus group technique has proved useful in eliciting information from groups of primary school pupils, and involving students in health-promoting programmes because it allows them to identify the social and interpersonal determinants of health. There is a firm basis to consider school pupils as health agents, particularly regarding interventions within the school environment itself. With the support of teachers, it is possible to train school pupils as community health agents, and increase their control over their own health.


DR typing in Australian Aborigines. An indication for a second locus in the HLA--D region defined by serology.
A group of 43 Australian Aborigines was typed for HLA--DR determinants and other antigens on B cells, using pregnancy sera from Caucasoid women. The group could not be considered as random, since a selection was made for an equal number of Au antigen positive and Au antigen negative individuals The typing results showed that the specificities DRw2, 4 and 8 were as well defined in this population as in Caucasoids, whereas the specificities DRw1, 3, 5 and 7 could not be defined. Even more interesting was the finding that a cluster of six sera, defining the local B cell specificity LB12, gave positive reactions in 41 out of 43 Aborigines. Although LB12 is found to be highly associated with DRw1, 2 and 6 in the Caucasoid population, in 36 cases the LB12 positive Aborigines could not be demonstrated to carry the specificities DRw1 or 2. The recognition of DRw6 is difficult at the moment and for the reason its presence or absence in this material is uncertain. However, three individuals typed positive for DRw4 and 8 and for LB12 as well. These findings strongly support the hypothesis that the genes coding for LB12 and its postulated allele LB13 are separate from the genes coding for the known DR determinants. LB12 is very likely identical to the recently described determinants DC1 (Tosi & Tanigaki 1979) and MB1 (Duquesnoy et al. 1979a).


Association Between a Dietary Inflammatory Index and Prostate Cancer Risk in Ontario, Canada.
Evidence exists showing that various aspects of diet are implicated in the etiology of prostate cancer, although results across studies remain inconsistent. We examined the ability of the dietary inflammatory index (DII) to predict prostate cancer in a case-control study conducted in Kingston, Ontario, Canada, between 1997 and 1999. The study included 72 cases of incident primary prostate cancer patients and 302 controls of urology clinic patients who had prostate conditions other than prostate cancer. The DII was computed based on intake of 18 nutrients assessed using a 67-item food frequency questionnaire. Univariate and multivariate logistic regression models were used to estimate odds ratios (ORs). Men with higher DII scores were at increased risk of prostate cancer using DII score fit both as a continuous [OR = 1.58, 95% confidence interval (CI) 1.05-2.38] and categorical variable [compared to men in the lowest DII quartile, men in the highest quartile were at elevated risk (OR = 3.50, 95% CI 1.25-9.80; ptrend = 0.02)]. There was no significant heterogeneity by weight status, but stronger association was observed in men with body mass index >25 kg/m2 versus <25 kg/m2. These findings suggest that a proinflammatory diet, as indicated by increasing DII score, is a risk factor for prostate cancer.


Preparation of fullerene-polyyne nanospheres via thermally induced solid-state polymerization.
A 1,3,5,7-octatetrayne-linked bis(fullerene) compound has been synthesized. Through a thermally induced solid-state polymerization reaction on a surface, the solid thin film of this compound was transformed into a highly uniform and well organized polymer nanosphere array. This finding suggests a simple and useful method for the preparation of carbon-rich, fullerene-containing nanoparticles.


[Kyoto Prefectural Hospital "Tenko-in" for the mentally disabled: its opening, development, and abolition].
The aim of this article is to investigate various attempts made at the first hospital for the mentally disabled in Japan. The prefectural government opened the hospital "Tenkyo-in" in the Nanzenji-Hojo, a temple in a residential area in Kyoto on 25 July, 1875. New rules on nursing, medical examination and medical fees, such as doctor's fees and hospital charges, were established. The doctors' services for Kyoto residents required no charge from 1876. The hospital's therapeutic concepts depended on the knowledge and opinions of Langegg Junker, a German teacher invited by the Kyoto Ryo-byoin. His idea adapted "moral treatment" which was popular in Britain. Diagnostic methods in this hospital were formed around the model based on the concept described in "insanity", an article written by Henry Maudsley in 1872. By promoting these ideas, the hospital was able to help many patients return to their lives in their own residences. The hospital was closed on 21 September, 1882, because the hospital faced a big financial deficit and because prefectural policies were changed. The hospital was founded as a facility of public health service in Kyoto in the age of modernization of Japan. It introduced a new idea for mental health and treatment, which had a strong impact on hospital care of psychiatric patients afterwards.


[On the etiology of epileptic seizures in children of the first year of life].
The paper presents the analysis of unfavourable ante- and intranatal factors as well as the data of neurosonography of 109 children with the fits during the first year of life and of 58 children with hypoxic-ischemic encephalopathy without convulsions. The high degree of the correlation was found between complications of the first half of pregnancy and the disturbances of growth and development of a child. Frequency of a trauma in the course of a delivery correlated with frequency of asphyxia. A persistence of a germinative matrix and signs of functional immaturity of the brain suggested the important role of both focal and multifocal cerebral dysplasias in the genesis of epileptic fits at the early stages of ontogenesis. In children with nonmalignant neonatal and idiopathic fits there were some nonvisualized cortical disorders that became pronounced under hypoxic-dysmetabolic conditions in the first case and during a period of the following maturation of axon-dendritic bounds and of the increase of neuronal activity in the second case.


Comparison of implant stability measurement devices for bone-anchored hearing aid systems.
The success of implants for bone-anchored hearing aids (BAHA) relies on proper osseointegration at the bone-implant interface. Clinical evaluation of implant stability is important in prescribing loading, identifying the risk of failure, and monitoring the long-term health of the implant. The purpose of this in vitro study was to evaluate 2 measurement systems for BAHA implant stability: the most commonly used, Osstell implant stability quotient (ISQ), and a newly developed advance system for implant stability testing (ASIST). BAHA implants (Oticon Medical Ponto and Cochlear BAHA Connect systems) were installed in plastic materials with adhesive to simulate implants integrated in bone with varying levels of interface stiffness. Different lengths of BAHA abutments were used with each implant specimen, and stability measurements were obtained with both the Osstell ISQ and the ASIST systems. The measurement systems were evaluated in terms of sensitivity to differences in interface stiffness and the effect of abutment length on the stability measurement. Repeated measures ANOVA followed by post hoc t tests were used for the comparisons with a Bonferroni adjusted alpha value of .05/15 = .003 to control for potential type 1 errors. Changing the abutment length of a single implant installation had minimal effect on the ASIST stability coefficient, whereas large variations were observed in the Osstell implant stability quotient (ISQ). The Osstell showed a clear relationship of decreasing ISQ with increasing abutment length for both the Oticon Medical and the Cochlear implant systems. Both the ASIST and the Osstell were found to be sensitive to changes in interface properties, with the ASIST being more sensitive to these changes. The ASIST system is more sensitive to changes in interface properties and shows smaller variation because of changes in abutment length than the Osstell ISQ system.


An RNA splice site mutation in the C1-inhibitor gene causes type I hereditary angio-oedema.
Restriction fragment length polymorphism analysis, the polymerase chain reaction and nucleotide sequencing have been used to characterise a single base substitution (G----T) at nucleotide 8863 in the C1-inhibitor gene. This destroys the 5' donor splice site recognition motif of the sixth intron. Family studies suggest that the mutation is responsible for type I hereditary angio-oedema in a studied kindred.


Synthesis and antimycobacterial activity of selected nitrobenzyloxylated benzotriazoles.
A series of 1-nitrobenzyloxybenzotriazoles was prepared by the benzylation of the respective halogenosubstituted 1-hydroxybenzotriazoles. The newly obtained compounds were tested against four Mycobacterium strains. Particularly high antimycobacterial activity, comparable with that of isoniazide, was found for 5,6-dichloro- 1-(3,5-dinitrobenzyloxy)- 1H-benzotriazole.


Solvent-Free Synthesis of a Pillared Three-Dimensional Coordination Polymer with Magnetic Ordering.
A new magnetic coordination polymer, [Fe(bipy)(im)2] (bipy = 4,4-bipyridine and im = imidazole), has been synthesized in a solvent-free reaction. Structural analysis reveals a pillared 3D coordination polymer composed by neutral layers, formed by iron(II) and imidazolate linkers, interconnected by bipy ligands which serve as pillars. Magnetic measurements show that the material magnetically orders at low temperatures (Tc = 14.5 K) as a weak ferromagnet, likely due to a spin canting.


The Sulfate Supply Maximizing Arabidopsis Shoot Growth Is Higher under Long- than Short-Term Exposure to Cadmium.
The processes involved in cadmium detoxification in plants deeply affect sulfate uptake and thiol homeostasis and generate increases in the plant nutritional request for sulfur. Here, we present an analysis of the dependence of Arabidopsis growth on the concentration of sulfate in the growing medium with the aim of providing evidence on how plants optimize growth at a given sulfate availability. Results revealed that short-term (72 h) exposure to a broad range of Cd concentrations (0.1, 1, and 10 μM) inhibited plant growth but did not produce any significant effects on the growth pattern of both shoots and roots in relation to the external sulfate. Conversely, long-term (22 days) exposure to 0.1 μM Cd significantly changed the pattern of fresh weight accumulation of the shoots in relation to the external sulfate, without affecting that of the roots, although their growth was severely inhibited by Cd. Moreover, under long-term exposure to Cd, increasing the sulfate external concentration up to the critical value progressively reduced the inhibitory effects exerted by Cd on shoot growth, indicating the existence of sulfate-dependent adaptive responses protecting the shoot tissues against Cd injury. Transcriptional induction of the high-affinity sulfate transporter genes (SULTR1; 1 and SULTR1; 2) involved in sulfate uptake by roots was a common adaptive response to both short- and long-term exposure to Cd. Such a response was closely related to the total amount of non-protein thiols accumulated by a single plant under short-term exposure to Cd, but did not showed any clear relation with thiols under long-term exposure to Cd. In this last condition, Cd exposure did not change the level of non-protein thiols per plant and thus did not alter the nutritional need for sulfur. In conclusion, our results indicate that long term-exposure to Cd, although it induces sulfate uptake, decreases the capacity of the Arabidopsis roots to efficiently absorb the sulfate ions available in the growing medium making the adaptive response of SULTR1; 1 and SULTR1; 2 "per se" not enough to optimize the growth at sulfate external concentrations lower than the critical value.


Resolvin E1 in Follicular Fluid Acts as a Potential Biomarker and Improves Oocyte Developmental Competence by Optimizing Cumulus Cells.
Metabolic profile of follicular fluid (FF) has been investigated to look for biomarkers for oocyte quality. Resolvin E1 (RvE1), a potent pro-resolving mediator, was reported to have protective action in cell function. The study aimed to examine the predictive value of RvE1 for oocyte quality and to explore the cellular mechanism of RvE1 in improving oocyte competence. Metabolic profiles of 80 FF samples showed a higher level of RvE1 in group A (blastocysts scored ≥ B3BC and B3CB according to Gardner's blastocyst scoring system, N = 36) than that of group B (blastocysts scored < B3BC and B3CB, N = 44, P = 0.0018). The receiver operating characteristic (ROC) curve analysis showed that RvE1 level in FF below 8.96 pg/ml (AUC:0.75; 95%CI: 0.64-0.86; P = 0.00012) could predict poor oocyte quality with specificity of 97.22%, suggesting RvE1 as a potential biomarker to exclude inferior oocytes. Besides, the level of RvE1 was found to be significantly lower in FF than in serum (57.49 to 17.62 pg/ml; P=.0037) and was gradually accumulated in the culture medium of cumulus cells (CCs) during cell culture, which indicated that RvE1 came from both blood exudates and local secretion. The in vitro experiment revealed thecellular mechanism of RvE1 in improvingoocyte qualityby decreasing the cumulus cellapoptotic rate and increasing cell viability and proliferation. It is the first time thatthe role of RvE1 in reproduction is explored. In conclusion, RvE1 is valuable as a potential exclusive biomarker for oocyte selection andplays a role in improving oocyte quality.


A Usability Study of 3 Radiotherapy Systems: A Comparative Evaluation Based on Expert Evaluation and User Experience.
BACKGROUND The complex user interface design of radiotherapy treatment delivery systems can lead to use error and patient harm. In this study, we present the results of a comparison of 3 radiotherapy treatment delivery systems now used in China. MATERIAL AND METHODS We conducted a comprehensive usability study of 3 radiotherapy treatment delivery systems. Expert evaluation was performed through heuristic evaluation with 3 human-factors experts and 1 experienced radiation therapist for each system. User experience was assessed through perceived system usability and workload, using the National Aeronautics and Space Administration Task Load Index and the Post-Study System Usability Questionnaire. RESULTS For the expert evaluation, 47 usability problems were identified for Varian Trilogy, 75 for Elekta Precise, and 37 for Shinva XHA600E. Most problems were classified as major and minor usability problems, and were found in the process of patient setup and setup verification. For the user experience, radiation therapists presented a lower workload for Varian Trilogy compared to Elekta Precise (P<0.01) and Shinva XHA600E (P<0.01), and a lower workload for Elekta Precise compared to Shinva XHA600E (P=0.020). Radiation therapists perceived a higher system usability for Varian Trilogy compared to Shinva XHA600E (P<0.01), and a higher system usability for Elekta Precise compared to Shinva XHA600E (P<0.01). CONCLUSIONS This research provides valuable data on how 3 radiotherapy treatment delivery systems compare. The results of this study may be useful for hospital equipment procurement decisions, and designing next-generation products to improve patient safety.


OBSERVATIONS ON STROKES AND CEREBRAL EDEMA WITH INTRACRANIAL TUMOURS.
Four patients who suffered strokes were found at autopsy to have intracranial tumours remote from the region responsible for the stroke, but the relevant cerebral white matter was swollen, pale yellow, and manifestly edematous. It is inferred from these observations that strokes in the presence of cerebral tumours may be caused by rapid fluctuations in the extent and intensity of the edema surrounding the cerebral tumour.A fifth patient is reported with recurrent strokes associated with a glioblastoma multiforme. He showed many dramatic remissions associated with treatment with adrenocorticotrophic hormone and equally prompt relapses when treatment was stopped. Similar cases in the literature are referred to. It is suggested that these hormones decrease the cerebral edema and thus produce the remissions.


Nutritional status of the elderly. II. Anthropometry, dietary and biochemical data of old pensioners in Perugia at the fifth year follow-up.
206 aged pensioners of the city of Perugia have been examined in a longitudinal study, with emphasis on body composition, diet, life habits and clinical-biochemical data. From the anthropometric data of the individuals examined in 1981 it is evident that both in men and women obesity is common especially among the women. The opposite is true for the arm muscle area. Comparing the same men examined in 1976 and 1981 body fatness decreased in the five years interval. Food and nutrient intakes are rather similar in the 1976 and 1981 surveys. Consumption of milk, eggs, fish and legumes is not high. The men, but not the women, tended to a high consumption of meat and alcoholic beverages. The intake in 1981 of thiamin, riboflavin and vitamin A seems in general to be inadequate according to our recommended values. The biochemical data show practically no difference in the two surveys. Serum cholesterol continued to be rather high for an Italian population.


Exploring potential roles for the interaction of MOM1 with SUMO and the SUMO E3 ligase-like protein PIAL2 in transcriptional silencing.
The CHD3-like chromatin remodeling protein MOM1 and the PIAS-type SUMO E3 ligase-like protein PIAL2 are known to interact with each other and mediate transcriptional silencing in Arabidopsis. However, it is poorly understood whether and how the interaction is involved in transcriptional silencing. Here, we demonstrate that, while the PIAL2 interaction domain (PIAL2-IND) is required for PIAL2 dimerization, MOM-PIAL2 interaction, and transcriptional silencing, a transgene fusing the wild-type MOM1 protein with the PIAL2 protein defective in PIAL2-IND can completely restore transcriptional silencing in the mom1/pial2 double mutant, demonstrating that the artificial fusion of MOM1 and PIAL2 mimics the in vivo interaction of these two proteins so that PIAL2-IND is no longer required for transcriptional silencing in the fusion protein. Further, our yeast two-hybrid assay identifies a previously unrecognized SUMO interaction motif (SIM) in the conserved MOM1 motif CMM3 and demonstrates that the SIM is responsible for the interaction of MOM1 with SUMO. Given that eukaryotic PIAS-type SUMO E3 ligases have a conserved role in chromatin regulation, the findings reported in this study may represent a conserved chromatin regulatory mechanism in higher eukaryotes.


Facility and Family Communication during the COVID-19 Visit Restriction: Early Perspectives of Family Members.
During the COVID-19 pandemic, family concerns regarding residents in long-term care facilities (LTCFs) increased due to a high proportion of COVID cases and deaths among residents and restrictions that made it impossible to visit. These changes created numerous challenges for facilities communicating with families, and between families and residents. However, little is known about how these facilities addressed these communication challenges and how those communication strategies were related to family perceptions about the facility. We implemented an online survey of family members or friends of residents in LTCFs from April 28 to June 19, 2020, using convenience sampling. A total of 174 responses nationwide reported the types of communications used, frequency of communication and alternative visits, and whether respondents had peace of mind, would recommend the facility, or were considering removing the resident from the facility. The results of our hierarchical logistic regression showed that respondents felt greater peace of mind when there were multiple communication channels to contact the resident. Also, respondents had more negative perceptions of a facility when they were not informed about confirmed COVID cases. Our findings suggest multiple communication channels and transparency about COVID status were effective in keeping positive family perceptions about the facility.


Human genetic variation: new challenges and opportunities for doping control.
Sport celebrates differences in competitors that lead to the often razor-thin margins between victory and defeat. The source of this variation is the interaction between the environment in which the athletes develop and compete and their genetic make-up. However, a darker side of sports may also be genetically influenced: some anti-doping tests are affected by the athlete's genotype. Genetic variation is an issue that anti-doping authorities must address as more is learned about the interaction between genotype and the responses to prohibited practices. To differentiate between naturally occurring deviations in indirect blood and urine markers from those potentially caused by doping, the "biological-passport" program uses intra-individual variability rather than population values to establish an athlete's expected physiological range. The next step in "personalized" doping control may be the inclusion of genetic data, both for the purposes of documenting an athlete's responses to doping agents and doping-control assays as well facilitating athlete and sample identification. Such applications could benefit "clean" athletes but will come at the expense of risks to privacy. This article reviews the instances where genetics has intersected with doping control, and briefly discusses the potential role, and ethical implications, of genotyping in the struggle to eliminate illicit ergogenic practices.


Effect of warfarin on survival in patients with concomitant left ventricular systolic dysfunction and pulmonary hypertension: a population cohort study.
The use of oral anticoagulation in patients with heart failure in sinus rhythm remains controversial as previous large randomized controlled trials (RCTs) have not shown a survival benefit. However, heterogeneity exists among heart failure patients and it is possible that high-risk subgroups may benefit from anticoagulation (warfarin). We hypothesize that one such subgroup are patients with heart failure and pulmonary hypertension (PH), conditions associated with coagulation abnormalities. We conducted a retrospective, population-based, longitudinal cohort study in patients with left ventricular systolic dysfunction (LVSD) and PH [defined as a right ventricular systolic pressure (RVSP) >35 mmHg] identified from echocardiograms performed between January 1994 to May 2011. This data was linked using a unique patient-specific identifier to community-dispensed prescriptions, hospital admissions, and mortality data. For comparison, we included patients with LVSD and no PH. A total of 2619 subjects with LVSD and a measurable RVSP were identified (mean ± SD age of 73 ± 12 years); 1606 out of 2619 had PH and 1013 out of 2619 had no PH. The overall mean follow-up period was 2.56 ± 3.0 years. In patients with LVSD and PH, the use of warfarin was associated with an improved survival [hazard ratio (HR) = 0.72 95% confidence interval (CI) 0.58-0.90, P = 0.0003], fewer non-cardiovascular disease-related deaths (HR = 0.65, 95%CI 0.49-0.87, P = 0.0033 and showed a trend towards reduced cardiovascular disease-associated mortality (HR = 0.72, 95%CI 0.51-1.02). Warfarin did not improve survival in those with LVSD with no PH. In patients with both LVSD and PH, the use of warfarin is associated with a 28% reduction in mortality. Further prospective trials are required to confirm our findings.


CSF Apo-E levels associate with cognitive decline and MRI changes.
Apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for Alzheimer's disease (AD) and it is thought to do so by modulating levels of its product, apolipoprotein E (Apo-E), and regulating amyloid-β (Aβ) clearance. However, information on clinical and biomarker correlates of Apo-E proteins is scarce. We examined the relationship of cerebrospinal fluid (CSF) and plasma Apo-E protein levels, and APOE genotype to cognition and AD biomarker changes in 311 AD neuroimaging initiative subjects with CSF Apo-E measurements and 565 subjects with plasma Apo-E measurements. At baseline, higher CSF Apo-E levels were associated with higher total and phosphorylated CSF tau levels. CSF Apo-E levels were associated with longitudinal cognitive decline, MCI conversion to dementia, and gray matter atrophy rate in total tau/Aβ1-42 ratio and APOE genotype-adjusted analyses. In analyses stratified by APOE genotype, our results were only significant in the group without the ε4 allele. Baseline CSF Apo-E levels did not predict longitudinal CSF Aβ or tau changes. Plasma Apo-E levels show a mild correlation with CSF Apo-E levels, but were not associated with longitudinal cognitive and MRI changes. Based on our analyses, we speculate that increased CSF Apo-E2 or -E3 levels might represent a protective response to injury in AD and may have neuroprotective effects by decreasing neuronal damage independent of tau and amyloid deposition in addition to its effects on amyloid clearance.


The effects of hydrogen sulfide under sevoflurane administration against ischemia and reperfusion injury in isolated rat heart.
Hydrogen sulfide (H(2)S) produces a protective effect against myocardial ischemia and reperfusion injury. Sevoflurane, which is used for anesthesia in cardiac problem patients, also has a protective effect. This study is designed to reveal the effects of H(2)S under sevoflurane using rat hearts. The hearts were Langendorff-perfused, subjected to 30 minutes ischemia and 60 minutes reperfusion. Group I was a control group. The other groups were pretreated for 15 minutes before ischemia as follows: 1.6% sevoflurane for group S; 18.5 µM H(2)S S for group H; and 1.6% sevoflurane and 18.5 µM H(2)S simultaneously for group HS. Hemodynamics and the infarct size were measured. Group HS presented depressed hemodynamics during pretreatment. LV function in group HS achieved better recovery than group I after reperfusion. The infarct size of groups S, H and HS was smaller than group I, while there were no differences between groups S, H and HS. Exogenous H(2)S did not enhance the preconditioning effects of sevoflurane. Rather, the results suggest that H(2)S under sevoflurane might depress hemodynamics.


Sleep-inducing effect of Rhynchophylline in EphA4 knockout mice.
We have recently demonstrated that the alkaloid rhynchophylline (RHY; purified from Uncaria plants) induces sleep and modifies electrocorticographic (ECoG) activity throughout the 24-h day in a vigilance state-dependent manner in wild-type mice. We here asked whether this alkaloid impacts wake/sleep variables in the absence of the cell adhesion protein EPHA4, via ECoG recording in EphA4 knockout (KO) mice submitted to the same RHY treatment contemporaneously to the wild-type mice (littermates). We uncover that RHY decreases time spent awake and increases time spent in slow wave sleep in EphA4 KO mice and alters the 24-h time course of ECoG activity during wakefulness and sleep states. These observations are similar to the reported effects of RHY in wild-type littermate animals, which strongly supports that RHY-driven sleep alterations are not dependent on the presence of EPHA4.


Child mental health in Jordanian orphanages: effect of placement change on behavior and caregiving.
To assess the mental health and behavioral problems of children in institutional placements in Jordan to inform understanding of current needs, and to explore the effects of placement change on functioning and staff perceptions of goodness-of-fit. An assessment was completed of 134 children between 1.5-12 years-of-age residing in Jordanian orphanages. The Child Behavior Checklist was used to assess prevalence rates of problems across externalizing and internalizing behavior and DSM-IV oriented subscales. Also included was caregiver perceived goodness-of-fit with each child, caregiving behavior, and two placement change-clock variables; an adjustment clock measuring time since last move, and an anticipation clock measuring time to next move. 28% were in the clinical range for the internalizing domain on the CBCL, and 22% for the externalizing domain. The children also exhibited high levels of clinical range social problems, affective disorder, pervasive developmental disorder, and conduct problems. Internalizing problems were found to decrease with time in placement as children adjust to a prior move, whereas externalizing problems increased as the time to their next age-triggered move drew closer, highlighting the anticipatory effects of change. Both behavioral problems and the change clocks were predictive of staff perceptions of goodness-of-fit with the children under their care. These findings add to the evidence demonstrating the negative effects of orphanage rearing, and highlight the importance of the association between behavioral problems and child-caregiver relationship pathways including the timing of placement disruptions and staff perceptions of goodness-of-fit.


Novel L-lactic acid biosensors based on conducting polypyrrole-block copolymer nanoparticles.
The development of advanced nanomaterials for the highly efficient electrical detection of biological species has attracted great attention. Here, novel polypyrrole-Pluronic F127 nanoparticles (PPy-F127 NPs) with conducting and biocompatibility properties were synthesized and used to construct a L-lactic acid biosensor that could be applied in biochemical assays. The PPy-F127 NPs were characterized by transmission electron microscopy (TEM), elemental analysis and UV-vis spectroscopy. Lactate oxidase (LOx) structure variation on the PPy-F127 NPs was investigated by circular dichroism (CD). The cyclic voltammetric results indicated that LOx immobilized on the PPy-F127 NPs exhibited direct electron transfer reaction with a formal potential value (E(0)') of 0.154 V vs. SCE. Moreover, the biosensor had good electrocatalytic activity toward L-lactic acid with a wide linear range (0.015-37.5 mM) and a low detection limit of 0.0088 mM. The regression equation was I (μA) = 0.02353c (mM) + 1.4135 (R(2) = 0.9939). The L-lactic acid biosensor had a good anti-interference property towards uric acid (UA), ascorbic acid (AA), glucose and cysteine. The idea and method provide a promising platform for the rapid development of biosensors that can be used in the detection of biological species.


Reconstruction of protein structures from a vectorial representation.
We show that the contact map of the native structure of globular proteins can be reconstructed starting from the sole knowledge of the contact map's principal eigenvector, and present an exact algorithm for this purpose. Our algorithm yields a unique contact map for all 221 globular structures of PDBselect25 of length N</=120. We also show that the reconstructed contact maps allow in turn for the accurate reconstruction of the three-dimensional structure. These results indicate that the reduced vectorial representation provided by the principal eigenvector of the contact map is equivalent to the protein structure itself. This representation is expected to provide a useful tool in bioinformatics algorithms for protein structure comparison and alignment, as well as a promising intermediate step towards protein structure prediction.


Is HOMA-IR a potential screening test for non-alcoholic fatty liver disease in adults with type 2 diabetes?
Non-alcoholic fatty liver disease (NAFLD) is the commonest hepatic disease in many parts of the World, with particularly high prevalence in patients with type 2 diabetes (T2DM). However, a good screening test for NAFLD in T2DM has not been established. Insulin resistance (IR) has been associated with NAFLD, and homeostatic model assessment of insulin resistance (HOMA-IR), a good proxy for IR, may represent an affordable predictive test which could be easily applied in routine clinical practice. We aimed to evaluate the diagnostic accuracy of HOMA-IR for NAFLD in T2DM and sought to estimate an optimal cut-off value for discriminating NAFLD from non-NAFLD cases. We conducted a retrospective analysis of 56 well-controlled patients with T2DM (HbAc1<7%, on oral anti-diabetic and/or glucagon-like peptide-1 agonist treatment), who had at least one glucose and insulin level determined, and at least one hepatic imaging test (ultrasonography or computed tomography scanning). The prevalence of NAFLD was 73.2% (95% CI: 59.7-84.2) in our population. An association between HOMA-IR and NAFLD was found (OR 1.5; 95% CI: 1.03-2.1; p=0.033), independently of transaminases, fat percentage, BMI and triglyceride levels. The AUROC curve of HOMA-IR for identifying NAFLD was 80.7% (95% CI: 68.9-92.5). A value of HOMA-IR of 4.5 was estimated to be an optimal threshold for discriminating NAFLD from non-NAFLD cases. HOMA-IR is independently associated with the presence of NAFLD in adults with T2DM, and might potentially be applied in clinical practice as a screen for this condition.


The incidence of childhood type 1 diabetes in Ireland and the National Childhood Diabetes Register.
The incidence of Type 1 diabetes (T1D) in childhood and adolescence is increasing globally with few exceptions. To date limited conflicting data has been available regarding diabetes epidemiology in Ireland. We sought to determine the incidence of T1D in those aged under 15 years in the ROI by establishing a prospective national register of incident cases (Irish Childhood Diabetes National Registry (ICDNR)) using a standardised protocol which includes a measure of case ascertainment using capture-recapture methodology. In the period, 489 new cases were identified. All paediatric centres nationally participated. The directly standardised incidence rate was 27.5 per 100,000 per year (95% CIs: 24.0, 30.9) and 26.0 (95% CIs: 22.7, 29.3) in 2008 and 2009 respectively. The ICDNR is widely acceptable, it has confirmed a high incidence of T1D and is vital to monitor changes in disease incidence, optimise resource utilisation and diabetes management in the Irish population.


Molecular characterization of antibiotic-resistant Staphylococcus aureus from livestock (bovine and swine).
The aim of this study was to figure the prevalence, phenotypic and genotypic antibiotic resistance (AR) pattern of Staphylococcus aureus isolated from bovine and swine nares. Colonies with typical morphology on Baird-Parker agar supplemented with egg-yolk tellurite emulsion were selected and biochemically/genotypically identified as S. aureus. These strains were further subjected to epsilometer test for their sensitivity to various clinically important antibiotics and antibiotic susceptibility testing for amoxicillin/clavulanic acid, and double-disk diffusion testing was performed by the standard disc diffusion method following CLSI guidelines. S. aureus strains were also tested for the presence of AR genes, viz., blaZ, mecA, aacA-aphD, erm (ermA, ermB, ermC), tet (efflux genes tetK and tetL, tetM and tetO of the ribosomal protection family), and vanA. The nasal cavities of 17 out of 47 randomly selected bovine and 20 out of 28 randomly selected swine were positive for S. aureus, representing the prevalence of 36.2% (95% confidence interval [CI]: 22.5-49.9) and 71.4% (95% CI: 54.7-88.1), respectively. Most of the S. aureus strains showed higher resistance to penicillin (94.6%, minimal inhibitory concentration [MIC] ≥1.5 µg/ml) followed by ciprofloxacin (56.7%, MIC ≥32 µg/ml) and tetracycline (18.9%, MIC ≥32 µg/ml). About 10-15% of the strains were resistant to gentamicin (MIC 16 µg/ml) and oxacillin (MIC 6-8 µg/ml). None of the strains were resistant to vancomycin (MIC 0.25-1.5 µg/ml). In this study, 32.4% strains were resistant to three or more than three antibiotics and prevalence of this multi-drug resistant S. aureus was 45% (95%CI: 26.6-63.4) and 17.6% (95%CI: 6.7-28.5) in swine and bovine nasal samples, respectively. Four strains from pigs were borderline oxacillin-resistant S. aureus MIC 6-8 µg/ml, but none were mecA positive. Two of these strains were β-lactamase hyperproducers. Among the resistance genes blaZ, tetK, tetL, tetM, ermB, and aacA-aphD were found. Our results demonstrated the absence of mecA and pvl gene, but the presence of multi-drug resistant S. aureus in the nares of healthy animals which has a potential to spread in a community.


[The influence of hemorrheology on the practice of clinical medicine].
Hemorheological considerations are beginning to alter routine clinical practice. A hemorheological defect may play a primary etiological role not only in classical diseases like polycythemia, but also in conditions such as essential hypertension and non-coronary angina. Hemorheological abnormalities may also play a part in arterial thrombosis through a number of mechanisms, and are a frequent accompaniment in many cases of atherosclerosis, where they carry a bad prognosis. Our new awareness of the dangers of a high hematocrit, even in the normal range, has had widespread consequences on the management of not only all kinds of ischemic disease, but also for instance on surgical practice in general. Finally, hemorheological treatment has much wider applications than simply in conditions where a hemorheological abnormality has been detected. Treatment aimed at improving the flow properties of blood, whether by drugs, hemodilution or plasmapheresis, may also be the most practical and effective therapy for ischemia due to insufficient blood flow down narrowed arteries.


[Compound Huang Gan delays chronic renal failure after 5/6 nephrectomy in rats].
To observe the effect of compound Huang Gan in delaying chronic renal failure in rats after 5/6 nephrectomy and explore the possible mechanisms. High-performance liquid chromatography was used to was used identify the components of compound Huang Gan extract. Rat models of 5/6 nephrectomy received a 12-week treatment with intragastric administration of Niaoduqing, Cozaar, or compound Huang Gan at low, moderate or high doses (n=10). After the treatments, the rats were sacrificed for detecting Scr, BUN, Ucr and 24h UPr , pathological examination of the renal tissues, and determination of FN, MCP-1, and ICAM-1 expression levels in the renal tissues using RT-PCR and immunohistochemistry. The major chemical components of compound Huang Gan extract included glycyrrhizin (0.61%), paeonol (1.2%), aloe emodin (0.72%), rhein (0.85%), emodin (0.87%), chrysophanol (0.79%) and physcion (0.8%). Treatment with compound Huang Gan at low, moderate and high doses significantly reduced Scr, BUN, Ucr , Ccr and 24 h UPr levels (P(P<0.05), improved interstitial fibrosis and glomerulosclerosis, and reduced FN and ICAM-1 expressions (P(P<0.05) in rats following nephrectomy. Compound Huang Gan can improve the renal function and lessen glomerulosclerosis and renal interstitial fibrosis to delay the progression of chronic renal failure in rat models of 5/6 nephrectomy.


Humans with chimpanzee-like major histocompatibility complex-specificities control HIV-1 infection.
Major histocompatibility complex (MHC) class I molecules allow immune surveillance by presenting a snapshot of the intracellular state of a cell to circulating cytotoxic T lymphocytes. The MHC class I alleles of an HIV-1 infected individual strongly influence the level of viremia and the progression rate to AIDS. Chimpanzees control HIV-1 viral replication and develop a chronic infection without progressing to AIDS. A similar course of disease is observed in human long-term non-progressors. To investigate if long-term non-progressors and chimpanzees have functional similarities in their MHC class I repertoire. We compared the specificity of groups of human MHC molecules associated with different levels of viremia in HIV-1 infected individuals with those of chimpanzee. We demonstrate that human MHC with control of HIV-1 viral load share binding motifs with chimpanzee MHC. Moreover, we find that chimpanzee and human MHC associated with low viral load are predicted to elicit broader Gag-specific immune responses than human MHC associated with high viral load, thus supporting earlier findings that Gag-specific immune responses are essential for HIV-1 control.


On the use of ultraviolet light to study protein-DNA crosslinking.
Irradiation of Ehrlich ascites chromatin with ultraviolet light (u.v.) leads to protein-DNA crosslinking as determined by CsCl isopycnic ultra-centrifugation and SDS-polyacrylamide gel electrophoresis. At the most 4.5% of the chromatin proteins labelled with (14C)-lysine and (14C)-arginine can be crosslinked to DNA at u.v. doses between 3.6 X 10(4) to 10.8 X 10(4) ergs/mm2. We find however that the crosslinking reaction is hindered by protein breakage induced by u.v. light of wave length of less than 2950 A. Our results point out that caution must be used in the interpretation of studies on protein-nucleic acid interactions using u.v. light.


Incidence, Prevalence, and Mortality Trends in Chronic Obstructive Pulmonary Disease over 2001 to 2011: A Public Health Point of View of the Burden.
Background. An increase of chronic obstructive pulmonary disease (COPD) prevalence was reported in Canada despite the decline of the main risk factor. Objectives. To estimate incidence, prevalence, and mortality of COPD from 2001 to 2011 and establish the COPD burden by the evaluation of the age-period-cohort effects on incidence trends and the comorbidities prevalence estimations. Methods. A retrospective population-based cohort was built using Quebec health administrative data. Change in trends was measured by relative percentage of changes and by joinpoint regression. After a descriptive analysis of the trends, an age-period-cohort analysis was performed on incidence rates. Results. Overall increase in prevalence along with a decrease of incidence and all-cause mortality was observed. Over time, all age-standardized trends were higher in men than women. Despite higher rates, the number of incident and prevalent cases in women exceeds men since 2004. The curve analysis by age groups showed over time a downshift for both sexes in incidence and all-cause mortality. Further analysis showed the presence of a cohort effect in women. Conclusion. The burden of COPD has risen over time. Women younger than 65 years old have been identified as at-risk group for healthcare planning.


Roles of fission yeast tea1p in the localization of polarity factors and in organizing the microtubular cytoskeleton.
The cylindrical shape of the fission yeast cell is generated by linear polarized growth from its cell ends. Using immunofluorescence and live imaging microscopy, we have investigated the roles of the cell end marker tea1p in generating linear polarized growth. We found that tea1p is primarily transported on plus ends of microtubules from the vicinity of the nucleus to the cell ends, and that its movement near the nucleus is independent of the kinesin tea2p. Deletion analysis identified a coiled-coil domain in tea1p essential for its retention at cell ends, and demonstrated that tea1p exerts different functions dependent on its location. On the tips of microtubules, tea1p prevents the curling of microtubules around the cell ends, whereas it is required for maintaining linear cell growth and for retention of polarity factors such as the Dyrk kinase pom1p, the CLIP170-like tip1p, and tea2p at the cell ends. We propose that tea1p has roles in organizing the microtubule cytoskeleton on the tips of microtubules, and in the retention of factors at the cell ends necessary for the cell to grow in a straight line.


The diagnosis of food allergy.
Food allergy is increasingly common; however, there is a discrepancy between the large number of people who believe they or their children are affected and the actual number with true food allergies. It is therefore imperative that physicians evaluating patients with possible adverse reactions to foods understand the current modalities used to diagnose food allergies. Simple tests including skin-prick testing (SPT) and serum food-specific IgE testing are the most commonly used diagnostic tests to evaluate for IgE-mediated food reactions. However, these tests have pitfalls and their usefulness must be appreciated to avoid over- and underdiagnosis. A firm diagnosis is imperative because a misdiagnosis could lead to life-threatening reactions and overdiagnosis will lead to unnecessary elimination diets with nutritional and social implications. Physician-supervised oral food challenges (OFC) remain the gold standard for food allergy diagnosis; however, a careful medical history and simple tests can often provide a reliable diagnosis. In this review, we examine the usefulness and pitfalls of SPT used by allergists and serum food-specific IgE levels that are available to all practitioners. We also review the OFC as a diagnostic modality in food allergy. Finally, we describe emerging tests, such as the basophil activation test, atopy patch testing, and component-resolved diagnostics, that may be of benefit in the future.


Intravenous busulfan and melphalan versus high-dose melphalan as a conditioning regimen for early autologous stem cell transplantation in patients with multiple myeloma: a propensity score-matched analysis.
We compared the efficacy and toxicity of busulfan and melphalan (BUMEL) and those of high-dose melphalan (HDMEL) as conditioning regimens for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) through a propensity score-matched analysis. No significant difference in the complete response and overall response rate after ASCT was observed between BUMEL and HDMEL. After a median follow-up of 37.3 months in the BUMEL group and 50.8 months in the HDMEL group, the median progression-free survival was calculated to be 32.9 months and 25.2 months (p = 0.995). With respect to non-hematologic toxicities, infections were more frequently reported in the BUMEL group (p < 0.001). Three patients who received BUMEL developed veno-occlusive disease (VOD), and all of them recovered without administration of defibrotide. In conclusion, BUMEL is an effective alternative conditioning regimen in terms of efficacy, but attention should be paid to toxicities.


Bone Mineralization in Rhythmic Gymnasts Entering Puberty: Associations with Jumping Performance and Body Composition Variables.
This study examined bone mineral density (BMD) accrual in prepubertal rhythmic gymnasts entering puberty and their age-matched untrained control girls, and associations with baseline jumping performance and body composition over the 3-year period. Whole body (WB) and femoral neck (FN) BMD, WB fat mass (FM) and fat free mass (FFM), countermovement jump (CMJ) and rebound jumps for 15 s (RJ15s) were assessed in 25 rhythmic gymnasts and 25 untrained controls at baseline and after 3-year period. The changes over this period were calculated (Δ scores). Pubertal maturation over the 3-year period was slower in rhythmic gymnasts compared to untrained controls, while no difference in bone age development was seen. WB BMD increased similarly in both groups, while the increase in FN BMD was higher in rhythmic gymnasts compared with untrained controls. In rhythmic gymnasts, baseline FFM was the most significant predictor of ΔWB BMD explaining 19.2% of the variability, while baseline RJ15s was the most significant predictor of ΔFN BMD explaining 18.5% of the variability. In untrained controls, baseline FM explained 51.8 and 18.9% of the variability in ΔWB BMD and ΔFN BMD, respectively. In conclusion, mechanical loading of high-intensity athletic activity had beneficial effect on BMD accrual in rhythmic gymnasts and may have counterbalanced such negative factors on bone development as slower pubertal maturation and lower body FM. Baseline FFM and repeated jumps test performance were related to BMD accrual in rhythmic gymnasts, while baseline FM was related to BMD accrual in untrained controls.


Methodological considerations for research in nocturnal home hemodialysis.
Nocturnal hemodialysis (NHD) is a form of frequent, intensive renal replacement therapy, which has been suggested to offer multiple physiological benefits over conventional hemodialysis (CHD). Though the evidence supporting these advantages is steadily increasing, significant methodological challenges exist in conducting research in this area. Our review highlights these important considerations and potential biases within the present NHD literature and suggests future research opportunities.


Are You Ready for Change?
Under the direction of the Journal's new Psychopharmacology Section Editor, a different approach will be taken: psychotropic drugs will be classified based on their neurobiological mechanism of action in the brain. This approach focuses on how the drug acts on brain cells and neurotransmitters involved in the specific symptoms presented by patients. The current article introduces the approach and will help clinicians think about medications as they relate to the neurobiological functions they are trying to correct. [Journal of Psychosocial Nursing and Mental Health Services, 56(2), 11-13.].


Recent advances in spectroelectrochemistry.
The integration of two quite different techniques, conventional electrochemistry and spectroscopy, into spectroelectrochemistry (SEC) provides a complete description of chemically driven electron transfer processes and redox events for different kinds of molecules and nanoparticles. SEC possesses interdisciplinary advantages and can further expand the scopes in the fields of analysis and other applications, emphasizing the hot issues of analytical chemistry, materials science, biophysics, chemical biology, and so on. Considering the past and future development of SEC, a review on the recent progress of SEC is presented and selected examples involving surface-enhanced Raman scattering (SERS), ultraviolet-visible (UV-Vis), near-infrared (NIR), Fourier transform infrared (FTIR), fluorescence, as well as other SEC are summarized to fully demonstrate these techniques. In addition, the optically transparent electrodes and SEC cell design, and the typical applications of SEC in mechanism study, electrochromic device fabrication, sensing and protein study are fully introduced. Finally, the key issues, future perspectives and trends in the development of SEC are also discussed.


Functional mimicry of tumor-associated antigens by antiidiotypic antibodies.
Antiidiotypic antibodies (Ab2) have been shown to induce specific immunity against murine and human tumors. Studies in murine tumor systems also have shown that Ab2 immunizations can induce protective immunity against a challenge with tumor cells. Antibodies and cytotoxic/regulatory T cells have been implicated as mediators of the antitumor effects induced by Ab2 immunization in mice. In recent clinical trials, cancer patients immunized with Ab2 that functionally mimic a gastrointestinal tumor-associated antigen developed highly specific antitumor immune responses. Thus Ab2 are promising vaccine candidates in immunotherapy approaches to cancer. The choice of Ab2 as well as optimization of immunization procedures with Ab2 are important considerations in future studies.


Breast health of US women religious (nuns).
Breast cancer is a major health problem and concern of women religious in the USA. Although they have been identified as a high-risk population, only a limited number of breast health studies have been conducted. The purpose of this study was to explore breast-related health practices (breast self-examination [BSE], clinical breast examination [CBE], and mammography) of women religious residing in the United States. A survey design was used to collect a national sample. The probability sample consisted of 1,615 women religious between the ages of 24 and 99 (mean age = 64.5). Nearly 71% of the respondents reported performing BSE; 22.7% monthly. Sixty-nine percent of participants reported having a mammogram within the past year. Nearly 70% of the respondents reported having had a CBE within the past year. Several factors for not performing BSE or having mammogram are described by this population. Findings suggest a need for increase engagement by women religious in breast-related health practices.


Impact of cytolysis following transarterial chemoembolization for hepatocellular carcinoma.
Transarterial chemoembolization (TACE) is increasingly used as a treatment of hepatocellular carcinoma. Cytolysis, which may occur within days following the procedure is due to either necrosis of the tumour or of the non-tumoral parenchyma. Therefore it may influence either tumour response or liver function or both. We evaluated the impact of cytolysis after TACE on tumour response, incidence of hepatobiliary complications and overall survival. We conducted a retrospective analysis of 157 patients with liver disease who underwent 271 treatments for hepatocellular carcinoma. Cytolysis was defined as an increase of AST value above 100 IU/L with at least doubling of the baseline value. The associations between cytolysis and radiologic tumor response two months following each treatment and adverse hepatobiliary events were estimated using generalized estimating equations models. Comparison of 18 months survival after a first treatment of chemoembolization between the groups with and without cytolysis was performed using the proportional hazards model. Cytolysis occurred in 198 out of 271 cases and was associated with a favourable radiological response (OR 1.90, 1.03-3.54) at two months compared to non-cytolysis with no difference in the occurrence of adverse hepatobiliary events. The adjusted hazard ratio for overall survival was 1.33 times greater in the group with cytolysis compared to non-cytolysis (0.45-3.90). The occurrence of cytolysis was associated with a favorable radiological response, but had no impact on short-term adverse events and on survival at 18 months.


Framing the public health of caregiving.
Caregiving has only recently been acknowledged by the nation as an important topic for millions of Americans. A psychological or sociological approach to care-giving services has been most often applied, with little attention to the population-based public health outcomes of caregivers. We conceptualize caregiving as an emerging public health issue involving complex and fluctuating roles. We contend that caregiving must be considered in the context of life span needs that vary according to the ages, developmental levels, mental health needs, and physical health demands of both caregivers and care recipients.


The epidemiologist's dilemma: a position paper on the role of epidemiology in Canadian research.
Canadian epidemiology is currently in transition from being primarily interested in infectious disease to becoming active in investigating causes of non-infectious disease. Generally, epidemiologists limit their work to "field", "basic", or "theoretical" epidemiology. In all three fields there appears to be a shortage of qualified personnel which is likely to become even more acute because of new roles that epidemiologists will probably play in the future. A minimum of 40 full-time epidemiologists is currently required in Canada.Departments other than departments of preventive medicine at medical schools and teaching hospitals are currently spending 79.5% of all funds allocated for non-microbiological epidemiological research in Canada. Since epidemiology is by its very nature population orientated, rather than clinically orientated, clinicians require consultative advice from epidemiologists at many stages of their research. Epidemiological facilities in departments of preventive medicine should therefore be strengthened in order to provide research training and didactic courses needed as the numbers of physicians, nurses and paramedical persons are increased.


Experimental transmission of infectious pancreatic necrosis virus from the blue mussel, Mytilus edulis, to cohabitating Atlantic Salmon (Salmo salar) smolts.
Integrated multitrophic aquaculture (IMTA) reduces the environmental impacts of commercial aquaculture systems by combining the cultivation of fed species with extractive species. Shellfish play a critical role in IMTA systems by filter-feeding particulate-bound organic nutrients. As bioaccumulating organisms, shellfish may also increase disease risk on farms by serving as reservoirs for important finfish pathogens such as infectious pancreatic necrosis virus (IPNV). The ability of the blue mussel (Mytilus edulis) to bioaccumulate and transmit IPNV to naive Atlantic salmon (Salmo salar) smolts was investigated. To determine the ability of mussels to filter and accumulate viable IPNV, mussels were held in water containing log 4.6 50% tissue culture infective dose(s) (TCID50) of the West Buxton strain of IPNV ml(-1). Viable IPNV was detected in the digestive glands (DGs) of IPNV-exposed mussels as early as 2 h postexposure. The viral load in mussel DG tissue significantly increased with time and reached log 5.35 ± 0.25 TCID50 g of DG tissue(-1) after 120 h of exposure. IPNV titers never reached levels that were significantly greater than that in the water. Viable IPNV was detected in mussel feces out to 7 days postdepuration, and the virus persisted in DG tissues for at least 18 days of depuration. To determine whether IPNV can be transmitted from mussels to Atlantic salmon, IPNV-exposed mussels were cohabitated with naive Atlantic salmon smolts. Transmission of IPNV did occur from mussels to smolts at a low frequency. The results demonstrate that a nonenveloped virus, such as IPNV, can accumulate in mussels and be transferred to naive fish.


BiPSim: a flexible and generic stochastic simulator for polymerization processes.
Detailed whole-cell modeling requires an integration of heterogeneous cell processes having different modeling formalisms, for which whole-cell simulation could remain tractable. Here, we introduce BiPSim, an open-source stochastic simulator of template-based polymerization processes, such as replication, transcription and translation. BiPSim combines an efficient abstract representation of reactions and a constant-time implementation of the Gillespie's Stochastic Simulation Algorithm (SSA) with respect to reactions, which makes it highly efficient to simulate large-scale polymerization processes stochastically. Moreover, multi-level descriptions of polymerization processes can be handled simultaneously, allowing the user to tune a trade-off between simulation speed and model granularity. We evaluated the performance of BiPSim by simulating genome-wide gene expression in bacteria for multiple levels of granularity. Finally, since no cell-type specific information is hard-coded in the simulator, models can easily be adapted to other organismal species. We expect that BiPSim should open new perspectives for the genome-wide simulation of stochastic phenomena in biology.


Identification of α-helix 4 (α4) of Rab11a as a novel Rab11-binding domain (RBD): Interaction of Rab11a with the Prostacyclin Receptor.
The cellular trafficking of numerous G protein-coupled receptors (GPCRs) is known to be regulated by Rab proteins that involves a direct protein:protein interaction between the receptor and the GTPase. In the case of the human prostacyclin receptor (hIP), it undergoes agonist-induced internalization and subsequent Rab11a-dependent recyclization involving an interaction between a Rab11-binding domain (RBD) localized within its carboxyl-tail domain with Rab11a. However, the GPCR-interacting domain on Rab11a itself is unknown. Hence, we sought to identify the region within Rab11a that mediates its interaction with the RBD of the hIP. The α4 helix region of Rab11 was identified as a novel binding domain for the hIP, a site entirely distinct from the Switch I/Switch II -regions that act as specific binding domain for most other Rab and Ras-like GTPase interactants. Specifically, Glu138 within α4 helix of Rab11a appears to contact with key residues (e.g. Lys304) within the RBD of the hIP, where such contacts differ depending on the agonist-activated versus -inactive status of the hIP. Through mutational studies, supported by in silico homology modelling of the inactive and active hIP:Rab11a complexes, a mechanism is proposed to explain both the constitutive and agonist-induced binding of Rab11a to regulate intracellular trafficking of the hIP. Collectively, these studies are not only the first to identify α4 helix of Rab11a as a protein binding domain on the GTPase but also reveal novel mechanistic insights into the intracellular trafficking of the hIP, and potentially of other members of the GPCR superfamily, involving Rab11-dependent mechanisms.


[Experience from palliative chemotherapy for advanced ovarian carcinoma - progress report on hospital with outpatient department at district level (author's transl)].
Reported in this paper is progress obtained from palliative treatment of patients with advanced ovarian carcinoma in an area under the control of a district hospital, between 1957 and 1978. Particular reference is made to the favourable effects of combination chemotherapy on survival rates and general condition. This study is intended to underline that the above therapeutic approach should not be restricted to few highly specialised centres and that it is practicable to the benefit of the patients concerned also under routine conditions at district hospitals. However, everything depends on high-continuity and persistent monitoring of these women on the basis of unity of hospital and outpatient attention.


[Non-Q infarct. Clinical and prognostic aspects].
Prognosis of on-Q wave myocardial infarction (nQMI) has been the subject of considerable controversy over the last few years and a systematically aggressive approach with PTCA or coronary by-pass surgery (CBS) has been advocated as a means to reduce subsequent coronary events rate. To investigate clinical outcome and possibly identify high-risk subgroups 131 consecutive patients (pts) meeting diagnostic criteria for nQMI, admitted to our CCU for their first myocardial infarction between January 1980 and June 1985, were followed-up for a mean period of 34 months (range 6-72). Mean age of pts was 59 +/- 7 yrs; 101 (76%) were males, 30 (24%) females. No pt was lost to follow-up. During the same period 684 pts were admitted for Q wave myocardial infarction. Major coronary events such as angina, reinfarction, CBS, cardiac death as well as overall early and late mortality were considered for statistical evaluation with uni-multivariate analysis taking into account multiple data from pts history and acute clinical presentation. Angina appeared or recurred in 71 pts (54%), reinfarction occurred in 14 (10.7%); 25 pts underwent CBC (19%). Early cardiac deaths were 7 (5.3%), late cardiac deaths 12 (9.2%); overall mortality rate 18.1%. Uni- and multivariate statistical analysis did not disclose significant criteria predicting major coronary events and no high-risk subgroup could be identified, confirming uncertainties and doubts from literature.


Effect of corticosteroids on estradiol and testosterone secretion by granulosa cells in culture.
Effect of corticosteroids on testosterone and estradiol secretion of FSH-primed pig granulosa cells were studied. Cortisol, corticosterone, deoxycorticosterone, deoxycorticosterone acetate and aldosterone enhanced testosterone synthesis, whereas cortisone and dexamethasone were found without effect. Maximal production of testosterone by granulosa cells cultured in delta-4-androstenedione supplemented medium was not further enhanced by addition of DOC. On the contrary, an inhibitory effect of corticosteroids on estradiol secretion in the presence of delta 4-androstenedione was observed. The inhibitory effect of corticosteroids on aromatisation was compared with that of the known aromatase inhibitor 4-androsten-17 beta-ol-3-one acetate. The addition of 4-androsten-17 beta-ol-3-one acetate and DOC to the culture medium supplemented with delta 4-androstenedione resulted in a marked decrease of estradiol synthesis. DOC decreased dbcAMP stimulated estradiol secretion. The results support the idea that corticosteroids may act as modulators of granulosa cell steroidogenesis and thus determine, at least partially, further follicular development or atresia.


A Comparison of Apical Bacterial Extrusion in Manual, ProTaper Rotary, and One Shape Rotary Instrumentation Techniques.
Apical extrusion of irrigants and debris is an inherent limitation associated with cleaning and shaping of root canals and has been studied extensively because of its clinical relevance as a cause of flare-ups. Many factors affect the amount of extruded intracanal materials. The purpose of this study was to assess the bacterial extrusion by using manual, multiple-file continuous rotary system (ProTaper) and single-file continuous rotary system (One Shape). Forty-two human mandibular premolars were inoculated with Enterococcus faecalis by using a bacterial extrusion model. The teeth were divided into 3 experimental groups (n = 12) and 1 control group (n = 6). The root canals of experimental groups were instrumented according to the manufacturers' instructions by using manual technique, ProTaper rotary system, or One Shape rotary system. Sterilized saline was used as an irrigant, and bacterial extrusion was quantified as colony-forming units/milliliter. The results obtained were statistically analyzed by using one-way analysis of variance for intergroup comparison and post hoc Tukey test for pair-wise comparison. The level for accepting statistical significance was set at P < .05. All the instrumentation techniques resulted in bacterial extrusion, with manual step-back technique exhibiting significantly more bacterial extrusion than the engine-driven systems. Of the 2 engine-driven systems, ProTaper rotary extruded significantly more bacteria than One Shape rotary system (P < .05). The engine-driven nickel-titanium systems were associated with less apical extrusion. The instrument design may play a role in amount of extrusion.