Sacral root injury during trans-sacral epiduroscopic laser decompression: A case report.
Trans-sacral epiduroscopic laser decompression (SELD) is reported to have strong positive short-term effects in controlling lower back pain (LBP) or radicular leg pain following herniated lumbar disc (HLD). However, little is known about the possible complications following SELD. A 36-year-old man received SELD with YAG laser for controlling LBP and radicular pain due to HLD on L5-S1. However, after SELD, voiding and defecation difficulties and sensory deficits on the S3-5 dermatome were presented. An areflexic neurogenic bladder was demonstrated by a urodynamic study four days after onset of sacral nerve root injury symptoms. In the electromyogram study, latency of electrically induced bulbocavernosus reflex (BCR) was delayed on both sides at four days after symptom onset. Based on the patient's symptoms and the results of the clinical evaluation, we diagnosed the patient as having an injury in the sacral nerve roots. The patient was observed without any specific medication. Three months after symptom onset, the patient's voiding and defecation difficulties were nearly completely recovered. In this study, we described a patient who showed neurogenic bladder and bowel and sensory deficits in the S3 to S5 dermatome due to sacral nerve root injury after SELD. During SELD, clinicians should be mindful of the possibility of injury to sacral nerve roots.


AICPA (American Institute of Certified Public Accountants) seeks comments on proposed accounting changes.
The American Institute of Certified Public Accountants has exposed for public comment a revised version of its accounting and auditing guide--Audits of Providers of Health Care Services. The guide covers accounting, auditing, and financial reporting in healthcare organizations and is being revised primarily to address the changing healthcare environment and changes mandated by the Financial Accounting Standards Board. This article provides an overview of some of the more significant proposed changes. The comment period ends August 14, 1995.


Prediction of diabetes with body mass index, oral glucose tolerance test and islet cell autoantibodies in a regional population.
Our aim was to test the hypothesis that a combination of markers for Type 1 diabetes (glutamate decarboxylase and IA-2 autoantibodies) and for Type 2 diabetes [oral glucose tolerance test (OGTT) and body mass index (BMI)], would predict clinical diabetes in a regional population. A population-based follow-up cohort study. Participants visited the primary health care centre in Lycksele, Sweden in 1988-92. A cohort of 2278 subjects (M/F 1149/1129) who were studied at follow-up in 1998. At base line there were 2314 subjects (M/F 1167/1147) who participated in the Västerbotten Intervention Program on their birthday when turning either 30, 40, 50 or 60 years of age. Main outcome measurements. A clinically diagnosed diabetes at follow-up when the medical records were reviewed for diagnosis of diabetes. At base line, the participants were subjected to a standard OGTT and their BMI determined along with the autoantibodies. At follow-up, 42/2278 (1.8%, 95% CI 1.2-2.3) (M/F 23/19) had developed diabetes: 41 subjects were clinically classified with Type 2 and one with Type 1 diabetes. There was no significant relation between autoantibody levels at base line and diabetes at follow-up. Stepwise multiple logistic regression showed that the odds ratio for developing diabetes was 10.8 (95% CI 6.3-18.9) in subjects in the fourth quartile of BMI (BMI > 27) compared with 7.8 (95% CI 4.8-12.6) in the fourth quartile of 2-h plasma glucose (>7.5 mmol L(-1)) and 7.2 (95% CI 4.8-11.4) in the fourth quartile of the fasting plasma glucose (>5.6 mmol L(-1)). Islet cell autoantibodies did not predict diabetes at follow-up. BMI measured at base line was as effective as 2-h plasma glucose and fasting plasma glucose to predict diabetes in this adult population.


Recent patents in the treatment and prevention of leishmaniasis.
Leishmaniasis, a neglected tropical disease, is caused by protozoal parasites of the genus Leishmania. Clinical manifestations vary from asymptomatic to lethal grade depending on the type of the disease. The currently available antileishmanial drugs suffer from considerable limitations. There is a dire need for better and safer drugs and/or vaccines to eradicate this disease. There are enormous developments ongoing in this field. Newer combinations of existing drugs and newer drugs targeting these intracellular parasites as well as their vectors are being tried to control the disease. Attempts to develop vaccines to enhance the immunity of the patient have shown some promise. This article is a peep into the recent patent developments in this field.


Pathways and contingencies linking road traffic noise to annoyance, noise sensitivity, and mental Ill-Health.
Traffic noise may contribute to depression and anxiety through higher noise annoyance (NA). However, little is known about noise sensitivity (NS) and mental health status as contextual factors. We tested three hypotheses: (1) Traffic noise is associated with mental ill-health through higher NA; (2) Mental ill-health and NS moderate the association between traffic noise and NA; and (3) NS moderates the indirect effect of traffic noise on mental ill-health. We used a convenience sample of 437 undergraduate students from the Medical University in Plovdiv, Bulgaria (mean age 21 years; 35% male). Residential road traffic noise (LAeq; day equivalent noise level) was calculated using a land use regression model. Depression and anxiety symptoms were measured with the Patient Health Questionnaire 9-item (PHQ-9) and the Generalized Anxiety Disorder 7-item (GAD-7) scale, respectively. NA was measured using a 5-point verbal scale. The Noise Sensitivity Scale Short Form (NSS-SF) was used to measure NS. To investigate how these variables intertwine, we conducted mediation, moderation and moderated mediation analyses. LAeq was indirectly associated with higher PHQ-9/GAD-7 scores through higher NA, but only in the low NS group. The relationship between LAeq and NA was stronger in students reporting depression/anxiety. While high NS was associated with high NA even at low noise levels, LAeq contributed to NA only in students low on NS. We found complex conditional relationships between traffic noise, annoyance and mental ill-health. Understanding respective vulnerability profiles within the community could aid noise policy and increase efficacy of interventions.


Allergic contact dermatitis caused by mushrooms. A case report and literature review.
The first author is allergic to skin contact with mushrooms of Suillus americanus, S. granulatus, S. grevillei, S. luteus, or S. neoalbidipes. Symptoms develop between one and two days after contact and last for approximately a week, disappearing completely without treatment. Symptoms consist of reddening, swelling, and itching, at the sites of contact with pileus cuticle mucilage of all five species. Pore layer tissues (tested for S. americanus and S. luteus) also produced strong reactions, as did pileus trama (tested for S. luteus). Spores from spore prints (tested for S. americanus and S. luteus) produced no reaction. The reaction can be avoided by wearing gloves when handling allergic species and by washing hands promptly after working with these species. Similar cases, reported from North America, Europe, and Russia, involve Agaricus, Boletus, Lactarius, Paxillus, Ramaria, and Suillus species. Several cases involve allergy to multiple species or genera. Symptom severity varies, presumably with intensity of exposure. In one case, symptoms were renewed following ingestion. Most cases demonstrate delayed allergic contact sensitivity.


Light field compression using disparity-compensated lifting and shape adaptation.
We propose disparity-compensated lifting for wavelet compression of light fields. With this approach, we obtain the benefits of wavelet coding, such as scalability in all dimensions, as well as superior compression performance. Additionally, the proposed approach solves the irreversibility limitations of previous light field wavelet coding approaches, using the lifting structure. Our scheme incorporates disparity compensation into the lifting structure for the transform across the views in the light field data set. Another transform is performed to exploit the coherence among neighboring pixels, followed by a modified SPIHT coder and rate-distortion optimized bitstream assembly. A view-sequencing algorithm is developed to organize the views for encoding. For light fields of an object, we propose to use shape adaptation to improve the compression efficiency and visual quality of the images. The necessary shape information is efficiently coded based on prediction from the existing geometry model. Experimental results show that the proposed scheme exhibits superior compression performance over existing light field compression techniques.


Disease specificity of autoantibodies to cytosolic 5'-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases.
The diagnosis of inclusion body myositis (IBM) can be challenging as it can be difficult to clinically distinguish from other forms of myositis, particularly polymyositis (PM). Recent studies have shown frequent presence of autoantibodies directed against cytosolic 5'-nucleotidase 1A (cN-1A) in patients with IBM. We therefore, examined the autoantigenicity and disease specificity of major epitopes of cN-1A in patients with sporadic IBM compared with healthy and disease controls. Serum samples obtained from patients with IBM (n=238), PM and dermatomyositis (DM) (n=185), other autoimmune diseases (n=246), other neuromuscular diseases (n=93) and healthy controls (n=35) were analysed for the presence of autoantibodies using immunodominant cN-1A peptide ELISAs. Autoantibodies directed against major epitopes of cN-1A were frequent in patients with IBM (37%) but not in PM, DM or non-autoimmune neuromuscular diseases (<5%). Anti-cN-1A reactivity was also observed in some other autoimmune diseases, particularly Sjögren's syndrome (SjS; 36%) and systemic lupus erythematosus (SLE; 20%). In summary, we found frequent anti-cN-1A autoantibodies in sera from patients with IBM. Heterogeneity in reactivity with the three immunodominant epitopes indicates that serological assays should not be limited to a distinct epitope region. The similar reactivities observed for SjS and SLE demonstrate the need to further investigate whether distinct IBM-specific epitopes exist.


Future trends in 3D medical imaging.
Areas where significant progress is needed are outlined. A unified conceptual framework based on generic tasks, showing the intricacies and the dependences that exist among completely distinct and intensive research lines, is defined. True 3-D volume imaging devices are then discussed, with the main emphasis on vascular network reconstruction. Segmentation issues are briefly reviewed. The fusion of information dealing with image, signal, and model is described. Simulation and planning problems are discussed.


Creating Fluorine-Doped MoS2 Edge Electrodes with Enhanced Hydrogen Evolution Activity.
The edge sites of MoS2 are catalytically active for hydrogen evolution reactions (HER). However, pristine edge sites usually contain only intrinsic atoms or defects, limiting the tuning of on-site hydrogen species adsorption and desorption, the critical steps for HER. In addition, the number of atoms on pristine edges is small compared to that of electrochemically inert atoms in bulk. Thus, it is desirable to develop a scalable technique of creating a large number of highly HER-active edge sites. Here, a plasma etching strategy is developed for creating MoS2 edge electrodes with a controllable number of active sites that enable the quantitative characterization of their HER activity using a local probe method. Fluorine atoms with large electronegativity are doped on the MoS2 edge sites that lead to a fivefold activity enhancement compared to that from pristine edges and is attributed to the more moderate binding energy for hydrogen species. The scalability of such a method is further demonstrated by activating MoS2 catalyst in macroscopic quantities with enhanced HER performance and stability. The work provides two-dimensional materials as a platform for understanding the doping effect on the edge sites at atomic-level, and offers a novel route for the design of efficient catalysts.


The place of spirituality and religion in mental health services.
Mental health professionals have raised concerns about the role of spirituality and religion in services for people with severe mental disorders, but this chapter offers compelling reasons for increased attention to spiritual issues in service delivery.


Effect of remdesivir on patients with COVID-19: A network meta-analysis of randomized control trials.
Several randomized controlled trials (RCTs) were conducted to investigate the effect of remdesivir for patients with COVID-19, but their results were conflicting. Thus, we conducted a network meta-analysis comparing the rate of clinical improvement among patients with COVID-19 who received 5-day course of remdesivir versus 10-day course of remdesivir versus standard care. Our network meta-analysis of 4 randomized controlled trials demonstrated that the rate of clinical improvement was significantly higher in the 5-day remdesivir group and 10-day remdesivir group compared to standard care group (OR [95% confidence interval [CI]] =1.89 [1.40-2.56], P <0.001, OR [95% CI] =1.38 [1.15-1.66], P <0.001, respectively). In addition, the rate of clinical improvement was significantly higher in the 5-day remdesivir group compared to the 10-day remdesivir group (OR [95% confidence interval [CI]] =1.37 [1.01-1.85], P =0.041). Our analysis demonstrated that the use of remdesivir for patients with COVID-19 was associated with the significantly higher clinical improvement rate compared with standard care alone.


Secular changes in functional disability, pain, fatigue and mental well-being in early rheumatoid arthritis. A longitudinal meta-analysis.
To conduct a systematic review and longitudinal meta-analysis of early rheumatoid arthritis (RA) cohorts with long-term data on pain, fatigue or mental well-being. Searches using PUBMED, EMBASE and PyscInfo were performed to identify all early RA cohorts with longitudinal measures of pain, fatigue or mental well-being, along with clinical measures. Using longitudinal meta-analyses, the progression of each outcome over the first 60-months was estimated. Cohorts were stratified based on the median recruitment year to investigate secular trends in disease progression. Of 7,319 papers identified, 75 met the inclusion criteria and 46 cohorts from 41 publications provided sufficient data on 18,046 patients for meta-analysis. The Disease Activity Scores (DAS28) and the Short-Form 36 (SF-36) Physical Component Score (PCS) indicated that post-2002 cohorts had statistically significant improvements over the first 60-months compared to pre-2002 cohorts, with standardised mean differences (SMD) of 0.86 (95% Confidence Intervals 0.34 to 1.37) and 0.76 (95% CI 0.25 to 1.27) respectively at month-60. However, post-2002 cohorts indicated statistically non-significant improvements in pain, fatigue, functional disability and SF-36 Mental Component Score (MCS) compared to pre-2002 cohorts, with SMD of 0.24 (95% CI -0.25 to 0.74), 0.38 (95% CI -0.11 to 0.88), 0.34 (95% CI -0.15-0.84) and -0.08 (95% CI -0.41 to 0.58) at month-60 respectively. Recent cohorts indicate improved levels of disease activity and physical quality of life, however this has not translated into similar improvements in levels of pain, fatigue and functional disability by 60-months.


Safety of balanced propofol and midazolam in upper gastrointestinal endoscopy for sedation in cirrhotic patients.
Sedation for upper gastrointestinal endoscopy (UGIE) in patients with cirrhosis is theoretically associated with high incidence of adverse events due to low levels of binding proteins and decreased hepatic clearance of drugs. The objective of the study was to assess the safety of combined propofol and midazolam sedation in cirrhotic patients undergoing UGIE. A total of 500 patients undergoing UGIE were divided in to two groups in a prospective observational study from Jan 1st 2018 to June 30th 2018. Group (I) consisted of cirrhotic patients who underwent the procedure with sedation and Group (II) consisted of non-cirrhotic patients who opted for sedation. The main outcome measurements included vitals monitoring before, during and after procedure, total sedation dose, time to initial and deep sedation, recovery time and complications. There was no significant difference between sedation safety and rate of complications for the cirrhotic and non-cirrhotic patients except for the recovery period during initial 10 minutes. The Modified Aldrete score for the cirrhotic patients was 9.5±0.5 min as compared to 9.8±0.4 min for non-cirrhotic patients (p<0.001) at 10 minutes. Grade 2 hepatic encephalopathy was seen in 0.8% of the cirrhotic patients who required hospitalization for 24 hours. Also balanced sedation was acceptable by the patients and the endoscopists equally with statistically significant scores on endoscopist's assessment of co-operation and assessment of patient's satisfaction scores. Balanced propofol and midazolam sedation has a good index of safety for both cirrhotic and non-cirrhotic patients and is acceptable by the patients and endoscopists equally.


Murine microenvironment metaprofiles associate with human cancer etiology and intrinsic subtypes.
Ionizing radiation is a well-established carcinogen in rodent models and a risk factor associated with human cancer. We developed a mouse model that captures radiation effects on host biology by transplanting unirradiated Trp53-null mammary tissue to sham or irradiated hosts. Gene expression profiles of tumors that arose in irradiated mice are distinct from those that arose in naïve hosts. We asked whether expression metaprofiles could discern radiation-preceded human cancer or be informative in sporadic breast cancers. Affymetrix microarray gene expression data from 56 Trp53-null mammary tumors were used to define gene profiles and a centroid that discriminates tumors arising in irradiated hosts. These were applied to publicly available human cancer datasets. Host irradiation induces a metaprofile consisting of gene modules representing stem cells, cell motility, macrophages, and autophagy. Human orthologs of the host irradiation metaprofile discriminated between radiation-preceded and sporadic human thyroid cancers. An irradiated host centroid was strongly associated with estrogen receptor-negative breast cancer. When applied to sporadic human breast cancers, the irradiated host metaprofile strongly associated with basal-like and claudin-low breast cancer intrinsic subtypes. Comparing host irradiation in the context of TGF-β levels showed that inflammation was robustly associated with claudin-low tumors. Detection of radiation-preceded human cancer by the irradiated host metaprofile raises possibilities of assessing human cancer etiology. Moreover, the association of the irradiated host metaprofiles with estrogen receptor-negative status and claudin-low subtype suggests that host processes similar to those induced by radiation underlie sporadic cancers.


Brain metastases of sarcoma: a rare phenomenon in rare tumours.
The usual site for distant metastases of sarcoma is lungs, while brain metastasis (BM) occurs much less frequently and usually late in the disease progression. Despite the advancement in cancer treatment, the outcome for patients with brain metastasis is poor, and their lifespan is short. The frequency of BM in sarcoma seems to be affected by the location and histology of the primary tumour. Sarcoma subtypes with a high propensity for brain metastasis are ASPS, leiomyosarcoma and osteosarcoma. There are no clear guidelines for the treatment of sarcoma brain metastasis. However, therapeutic options include surgery, radiotherapy and chemotherapy, and are often combined. Targeted therapies are a promising treatment option for sarcoma but require investigation in patients with BM. The following review presents the data on sarcoma brain metastasis incidence, treatment and prognosis.


NMR structural analysis of the yeast cytochrome c oxidase subunit Cox13 and its interaction with ATP.
Mitochondrial respiration is organized in a series of enzyme complexes in turn forming dynamic supercomplexes. In Saccharomyces cerevisiae (baker's yeast), Cox13 (CoxVIa in mammals) is a conserved peripheral subunit of Complex IV (cytochrome c oxidase, CytcO), localized at the interface of dimeric bovine CytcO, which has been implicated in the regulation of the complex. Here, we report the solution NMR structure of Cox13, which forms a dimer in detergent micelles. Each Cox13 monomer has three short helices (SH), corresponding to disordered regions in X-ray or cryo-EM structures of homologous proteins. Dimer formation is mainly induced by hydrophobic interactions between the transmembrane (TM) helix of each monomer. Furthermore, an analysis of chemical shift changes upon addition of ATP revealed that ATP binds at a conserved region of the C terminus with considerable conformational flexibility. Together with functional analysis of purified CytcO, we suggest that this ATP interaction is inhibitory of catalytic activity. Our results shed light on the structural flexibility of an important subunit of yeast CytcO and provide structure-based insight into how ATP could regulate mitochondrial respiration.


Big Data Privacy in Biomedical Research.
Biomedical research often involves studying patient data that contain personal information. Inappropriate use of these data might lead to leakage of sensitive information, which can put patient privacy at risk. The problem of preserving patient privacy has received increasing attentions in the era of big data. Many privacy methods have been developed to protect against various attack models. This paper reviews relevant topics in the context of biomedical research. We discuss privacy preserving technologies related to (1) record linkage, (2) synthetic data generation, and (3) genomic data privacy. We also discuss the ethical implications of big data privacy in biomedicine and present challenges in future research directions for improving data privacy in biomedical research.


Dying at home for terminal cancer patients: differences by level of education and municipality of residence in Spain.
To measure and assess differences by educational level in the place of death for cancer patients, and to determine whether patterns of geographical disparities are associated with access to palliative care services in the municipality of residence. We analysed the death certificates of adults (older than 24) who died of cancer (ICD-10 C00 to C97) in Spain during 2015, either at home, in hospital or in a long-term care centre. Of the 105,758 individuals included in the study population, 75.2% lived in one of the 746 identifiable municipalities (more than 10,000 inhabitants). This individual database was combined with three economic databases at municipal level and with a directory of palliative care resources published by the Sociedad Española de Cuidados Paliativos. Multilevel models were estimated to predict the place of death according to individual characteristics. Generalised least squares regression models were then applied to the municipal effects estimated in the first stage. The probability of dying in long-term care centre decreases as levels of education increase; the probability of dying at home, rather than in hospital, is higher for patients with higher education. Dying in hospital is an urban phenomenon. There are large differences between Spanish regions. Access to palliative services is only of marginal significance in accounting for the systematic differences observed between municipalities. Developing specific plans for palliative care, with an active role being played by primary care teams, may help improve end-of-life care in Spain.


[Clinical and epidemiological features of imported dengue in Spain].
Dengue is the most common imported arbovirus infection in Europe. International travel and an increasing incidence of dengue fever in tropical areas have defined the disease as an emerging infection in returning travellers. We describe the clinical and microbiological features of imported dengue in 3 referral hospitals in Spain. We included patients diagnosed with dengue infection during a 3-year period (2002--2005). We recorded clinical and epidemiological data and collected blood samples for serological and molecular studies of dengue infection. Data was analyzed with the statistical package Stata 9.2. We diagnosed 61 dengue cases, mostly European tourists who travelled to Latin America. Fever was found in 98.4% of patients and 80.3% presented with cutaneous eruption. Five patients had severe symptoms. Eighteen percent were considered to have secondary infections, although no patients met the WHO criteria for hemorrhagic dengue. In 26 cases, dengue was confirmed through viral genome detection and 35 cases through serology. Four patients were considered as <<probable>> dengue infection, and 57 as <<confirmed>>. Dengue is a common diagnosis for returning travellers, and it may present with severe manifestations. In our sample, there was an elevated percentage of secondary infections even though no previous history of dengue was reported by the patients. Hemorrhagic dengue and septic shock dengue are a risk for travellers returning from endemic areas.


Functional analysis of the nonstructural protein NSs of tomato zonate spot virus.
Tomato zonate spot virus (TZSV), a member of the genus orthotospovirus, causes severe damage to vegetables and ornamental crops in southwest China. The NSs protein is an RNA silencing suppressor in various orthotospovirus like TZSV, but its mechanism and role in virus infection are poorly understood. Here, we observed that an NSs-GFP fusion protein was transiently expressed on the plasma membrane and Golgi bodies in Nicotiana benthamiana plants. The TZSV NSs gene was silenced and infiltrated into N. benthamiana and N. tabacum cv. K326. RT-qPCR and Indirect enzyme-linked immunosorbent assay (ID-ELISA) showed that the transcription and the protein expression of the NSs gene were inhibited by more than 90.00%, and the symptoms on silenced plants were alleviated. We also found that the expression of the Zingipain-2-like gene significantly decreased when the NSs gene was silenced, resulting in co-localization of the NSs-GFP and the Zingipain-2-like-mCherry fusion protein. The findings of this study provide new insights into the mechanism of silencing suppression by NSs, as well as its effect on systemic virus infection, and also support the theory of disease resistance breeding and control and prevention of TZSV in the field.


Vocal dialects, sex-biased dispersal, and microsatellite population structure in the parrot Amazona auropalliata.
Geographic variation in microsatellite allele frequencies was assessed at nine sites in two regional vocal dialects of the parrot Amazona auropalliata (yellow-naped amazon) to test for correspondence between dialects and population structure. There was no relationship between the genetic distances between individuals and their dialect membership. High rates of gene flow were estimated between vocal dialects based on genetic differentiation. In addition, 5.5% of pairs of individuals compared across the dialect boundary were estimated to be related at the level of half siblings, indicating that dispersal is ongoing. The number of effective migrants per generation between dialects estimated with the microsatellite data was roughly one-seventh the number estimated with mitochondrial control region sequence data from the same individuals, suggesting that gene flow may be female-biased. Together, these results suggest that the observed mosaic pattern of geographic variation in vocalizations is maintained by learning of local call types by immigrant birds after dispersal. We found no evidence that ongoing habitat fragmentation has contributed to cryptic population structure.


Oxycodone, Morphine, and Fentanyl in Patients With Chronic Pain: Proposal of Dose-Specific Concentration Ranges.
Interpreting opioid concentrations is challenging because of the lack of reference ranges. Therefore, the authors aimed to propose dose-specific concentration ranges in serum for oxycodone, morphine, and fentanyl in patients with chronic pain, based on concentration measurements from a large number of patients and supported by theoretical pharmacokinetic calculations and previously published concentrations. The opioid concentrations in patients undergoing therapeutic drug monitoring (TDM) for various indications (TDM group) and patients with cancer (cancer group) were investigated. Patients were divided based on the daily opioid doses, and the 10th and 90th percentiles of the concentrations in each dose interval were evaluated. In addition, the expected average serum concentrations were calculated for each dose interval based on published pharmacokinetic data, and a targeted literature search for previously reported dose-specific concentrations was performed. The opioid concentrations in 1054 patient samples were included: 1004 in the TDM group and 50 in the cancer group. In total, 607 oxycodone, 246 morphine, and 248 fentanyl samples were evaluated. The authors proposed dose-specific concentration ranges based mainly on 10th-90th percentiles of the concentrations measured in patient samples, whereas the calculated average concentrations and previously published concentrations were used to adjust the ranges. In general, results from calculations and concentrations retrieved from previous literature were within the 10th-90th percentiles of concentrations from patient samples. However, the lowest calculated average concentrations of fentanyl and morphine were below the 10th percentiles of patient samples in all dose groups. The proposed dose-specific ranges may be useful for interpreting steady-state opioid serum concentrations in clinical and forensic settings.


Breast cancer and fertility.
Maintaining fertility and having children after treatment for breast cancer are a growing concern for women of childbearing age. There are many factors to be considered before a decision can be made. This article reviews the changes in breast cancer survival and treatment, epidemiology of pregnancy after breast cancer, and concerns during and after the pregnancy period. Specific nursing interventions aimed at improving quality of life and surviving illness are described.


S2 episome of maize mitochondria encodes a 130-kilodalton protein found in male sterile and fertile plants.
The mitochondrial genome of the S-type male-sterile cytoplasm of maize contains two linear episomes, S1 (6397 base pairs) and S2 (5453 base pairs). The S2 episome contains two large unidentified open reading frames, URF1 (3512 base pairs) and URF2 (1017 base pairs). We have demonstrated that a polypeptide with an apparent molecular mass of 130 kDa is the gene product of URF1. This polypeptide was first detected in Coomassie blue-stained protein gels of cms-S (where cms = cytoplasmic male sterile) but not in those of cms-T, cms-C, or normal mitochondrial proteins. The protein product of a translational fusion containing the 5' end of Escherichia coli lacZ and an internal segment from URF1 of S2 was recognized by antisera raised against the 130-kDa variant polypeptide. The mitochondria of fertile F(1) hybrids of cms-S x Ky21 (the male parent carrying nuclear fertility restoration genes) contain as much of the 130-kDa protein as is found in cms-S mitochondria of sterile plants. Spontaneous fertile cytoplasmic revertants from cms-S in a WF9 nuclear background also synthesized the 130-kDa polypeptide. Therefore, the mere presence or absence of the URF1 gene product of S2 does not determine the fertility status of maize plants, because male sterile and male fertile (nuclear restored and revertant) plants can contain equivalent amounts of the 130-kDa polypeptide.


Actin-propelled invasive membrane protrusions promote fusogenic protein engagement during cell-cell fusion.
Cell-cell fusion is critical for the conception, development, and physiology of multicellular organisms. Although cellular fusogenic proteins and the actin cytoskeleton are implicated in cell-cell fusion, it remains unclear whether and how they coordinate to promote plasma membrane fusion. We reconstituted a high-efficiency, inducible cell fusion culture system in the normally nonfusing Drosophila S2R+ cells. Both fusogenic proteins and actin cytoskeletal rearrangements were necessary for cell fusion, and in combination they were sufficient to impart fusion competence. Localized actin polymerization triggered by specific cell-cell or cell-matrix adhesion molecules propelled invasive cell membrane protrusions, which in turn promoted fusogenic protein engagement and plasma membrane fusion. This de novo cell fusion culture system reveals a general role for actin-propelled invasive membrane protrusions in driving fusogenic protein engagement during cell-cell fusion.


Interaction of brain areas of visual and vestibular simultaneous activity with fMRI.
Static body equilibrium is an essential requisite for human daily life. It is known that visual and vestibular systems must work together to support equilibrium. However, the relationship between these two systems is not fully understood. In this work, we present the results of a study which identify the interaction of brain areas that are involved with concurrent visual and vestibular inputs. The visual and the vestibular systems were individually and simultaneously stimulated, using flickering checkerboard (without movement stimulus) and galvanic current, during experiments of functional magnetic resonance imaging. Twenty-four right-handed and non-symptomatic subjects participated in this study. Single visual stimulation shows positive blood-oxygen-level-dependent (BOLD) responses (PBR) in the primary and associative visual cortices. Single vestibular stimulation shows PBR in the parieto-insular vestibular cortex, inferior parietal lobe, superior temporal gyrus, precentral gyrus and lobules V and VI of the cerebellar hemisphere. Simultaneous stimulation shows PBR in the middle and inferior frontal gyri and in the precentral gyrus. Vestibular- and somatosensory-related areas show negative BOLD responses (NBR) during simultaneous stimulation. NBR areas were also observed in the calcarine gyrus, lingual gyrus, cuneus and precuneus during simultaneous and single visual stimulations. For static visual and galvanic vestibular simultaneous stimulation, the reciprocal inhibitory visual-vestibular interaction pattern is observed in our results. The experimental results revealed interactions in frontal areas during concurrent visual-vestibular stimuli, which are affected by intermodal association areas in occipital, parietal, and temporal lobes.


Neutravidin micropatterning by deep UV irradiation.
We describe a novel approach for directly patterning neutravidin protein by exposure to deep UV irradiation. Neutravidin is physically absorbed onto the glass or quartz substrate, dehydrated in acetone and air-dried. Dry neutravidin-coated samples are patterned either by top-side or back-side exposure to 185 nm UV. Subsequent introduction of fluorescent biotinylated proteins clearly demonstrates binding to the masked neutravidin regions and no binding to exposed areas. Patterned samples retain their protein affinity for at least three months of storage at room temperature.


Mortality and quality of life 12 months after myocardial infarction: effects of depression and anxiety.
The purpose of this study was to determine the impact of symptoms of depression and anxiety on mortality and quality of life in patients hospitalized for acute myocardial infarction (MI). The Beck Depression Inventory and the State-Trait Anxiety Inventory were completed by 288 patients hospitalized for MI. Twelve-month survival status was ascertained, and quality of life among survivors was assessed at 12 months using the Dartmouth COOP charts. Thirty-one (10.8%) patients died, 27 of cardiac causes, during the 12-month follow-up. Symptoms of depression and anxiety predicted neither cardiac nor all-cause mortality. Severity of infarction and evidence of heart failure predicted both cardiac and all-cause mortality. The same findings emerged from supplementary analyses of data from patients who died after discharge from the hospital. Symptoms of depression and anxiety, measured at entry, predicted 12-month quality of life among survivors, as did gender, partner status, employment status, living alone, previous frequency of exercise, and indices of disease severity (Killip class and Peel Index). In a multiple regression model in which all of these variables were entered, initial depression scores provided the best independent prediction of quality of life, although living alone, severity of infarction, and state anxiety also entered the model. Symptoms of depression and anxiety did not predict either cardiac or all-cause mortality after MI, but they did predict quality of life among those who lived to 12 months.


Normal variation in cutaneous blood content and red blood cell velocity in humans.
This study was designed to determine normal variations in cutaneous blood content, red blood cell content and skin thickness in healthy human volunteers. The blood content (BC) of human skin and the velocity of red blood cells (RBV) has been comprehensively mapped over 30 anatomical sites in 28 volunteers between the age of 7 and 77 years using reflectance spectrophotometry (RFS) and laser Doppler (LD) techniques respectively. Total skin thickness, which may have a relationship with blood content, has been mapped at the same anatomical sites in six of the volunteers using two-dimensional array, 12 MHz ultrasound equipment. The major determinant of BC and RBV was found to be anatomical site. Regardless of age, gender or prior sun exposure, anatomical sites above the waist produced higher readings than below. BC and RBV were found to be dependent on age and gender at most sites with higher readings being observed in males and younger volunteers. The largest difference was seen in males under 55 years whose RFS readings above the waist were significantly higher than in older males or females of any age. Heavy prior sun exposure and skin thickness could not be demonstrated to impact on either RFS or LD readings independently of the effects of anatomical site, gender or age. In general, RFS and LD readings paralleled one another and correlated linearly at most anatomical sites. While RFS readings tended to decrease in the cranio-caudal direction, LD readings were relatively uniform across the body except for the head and groin where they were higher, and the abdomen where they were lower. The site-to-site variations in RFS readings observed in this study correspond well to capillary density variations noted in previous studies.


Coccoid forms of Helicobacter pylori are the morphologic manifestation of cell death.
Helicobacter pylori can transform from its normal helical bacillary morphology to a coccoid morphology. Since this coccoid form cannot be cultured in vitro, it has been speculated that it is a dormant form potentially involved in the transmission of H. pylori and in a patient's relapse after antibiotic therapy. In this study we determined the effects of aging, temperature, aerobiosis, starvation, and antibiotics on the morphologic conversion rate and culturability of H. pylori. Aerobiosis and the addition of a bactericidal antibiotic to the culture medium resulted in the highest conversion rate. During the conversion to coccoid forms, the cultures always lost culturability at the stage where 50% of the organisms were still in bacillary form; this result indicated that culturability and coccoid morphology are two separate but related entities. Independent of the conditions used to induce the conversion into coccoids, the morphological conversion was accompanied by several marked antigenic and ultrastructural changes. Also, both the total amounts and the integrity of RNA and DNA were significantly reduced in coccoid forms. With the potential-sensitive probe diOC(5)-3, a clear loss of membrane potential in coccoid forms was observed. Inhibition of protein or RNA synthesis by the addition of bacteriostatic antibiotics did not prevent the conversion to coccoid forms but resulted in an increased conversion rate. Hence, we conclude that conversion of H. pylori from the bacillary to the coccoid form is a passive process that does not require protein synthesis. Our data suggest that the coccoid form of H. pylori is the morphologic manifestation of bacterial cell death.


Soybean toxin (SBTX) impairs fungal growth by interfering with molecular transport, carbohydrate/amino acid metabolism and drug/stress responses.
Soybean toxin (SBTX) is an antifungal protein from soybeans with broad inhibitory activity against the growth and filamentation of many fungi, including human and plant pathogenic species such as Candida albicans, Candida parapsilosis, Aspergillus niger, Penicillium herquei, Cercospora sojina and Cercospora kikuchii. Understanding the mechanism by which SBTX acts on fungi and yeasts may contribute to the design of novel antifungal drugs and/or the development of transgenic plants resistant to pathogens. To this end, the polymorphic yeast C. albicans was chosen as a model organism and changes in the gene expression profile of strain SC5314 upon exposure to SBTX were examined. Genes that were differentially regulated in the presence of SBTX were involved in glucose transport and starvation-associated stress responses as well as in the control of both the induction and repression of C. albicans hyphal formation. Transmission electron microscopy showed that C. albicans cells exposed to SBTX displayed severe signs of starvation and were heavily granulated. Our data were indicative of C. albicans cell starvation despite sufficient nutrient availability in the medium; therefore, it can be speculated that SBTX blocks nutrient uptake systems. Because neither the starvation signal nor the alkaline response pathway lead to the induction of hyphae, we hypothesise that conflicting signals are transmitted to the complex regulatory network controlling morphogenesis, eventually preventing the filamentation signal from reaching a significant threshold.


Synthesis, crystal structure, cytotoxicity and action mechanism of a Rh(iii) complex with 8-hydroxy-2-methylquinoline as a ligand.
A rhodium(iii) complex, [Rh(MQ)(DMSO)2Cl2] (1), with 8-hydroxy-2-methylquinoline as the ligand was synthesized and characterized. Complex 1 exhibited cytotoxicity against BEL-7404, Hep-G2, NCI-H460, T-24, and A549 cell lines with IC50 values in the micromolar range (6.52-17.86 μM). Various experiments on the Hep-G2 cells showed that complex 1 caused cell cycle arrest at the S phase, downregulation of cdc25 A, cyclin A, cyclin B and CDK2, and upregulation of p21, p27 and p53. Furthermore, cytotoxicity mechanism studies suggested that complex 1-induced apoptosis was achieved via disruption of the mitochondrial function, which led to a significant loss of the mitochondrial membrane potential, an increase in the cellular levels of reactive oxygen species, cytochrome c, and apaf-1, and a fluctuation of the intracellular Ca2+ concentration. Taken altogether, complex 1 can trigger cancer cell death by inducing apoptosis through a mitochondrial dysfunction pathway.


PR_b functionalized stealth liposomes for targeted delivery to metastatic colon cancer.
A gene delivery system was designed to carry a payload to integrin overexpressing cells. Branched-polyethyleneimine (bPEI) condensed plasmid DNA was encapsulated into targeted stealth liposomes, thereby combining the condensing and transfection properties of bPEI with the stealth and targeting properties of the liposomal carrier system. PR_b was used as a targeting ligand - a peptide we designed to bind specifically to the cancer cell surface marker α5β1 integrin - and such a robust receptor-ligand interaction achieved higher specificity than what has been previously reported for targeted delivery systems. In the process of formulating the PR_b functionalized gene delivery vehicle, we developed a protocol to fully encapsulate condensed DNA in liposomes and accurately quantify the total DNA in the system. We demonstrate that compared to non-targeted stealth liposomes and non-encapsulated condensed DNA, the PR_b functionalized stealth liposomes mediated improved in vitro transfection specifically to colon cancer cells overexpressing the α5β1 integrin. Furthermore, when administered in vivo to metastatic tumor bearing mice, PR_b functionalized stealth liposomes outperformed non-targeted liposomes and delivered genes specifically to the tumor site.


Interreality in the management of psychological stress: a clinical scenario.
The term "psychological stress" describes a situation in which a subject perceives that environmental demands tax or exceed his or her adaptive capacity. According to the Cochrane Database of Systematic Reviews, the best validated approach covering both stress management and stress treatment is the Cognitive Behavioral (CBT) approach. We aim to design, develop and test an advanced ICT based solution for the assessment and treatment of psychological stress that is able to improve the actual CBT approach. To reach this goal we will use the "interreality" paradigm integrating assessment and treatment within a hybrid environment, that creates a bridge between the physical and virtual worlds. Our claim is that bridging virtual experiences (fully controlled by the therapist, used to learn coping skills and emotional regulation) with real experiences (allowing both the identification of any critical stressors and the assessment of what has been learned) using advanced technologies (virtual worlds, advanced sensors and PDA/mobile phones) is the best way to address the above limitations. To illustrate the proposed concept, a clinical scenario is also presented and discussed: Paola, a 45 years old nurse, with a mother affected by progressive senile dementia.


Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group.
To assess the effect of low-dose, diuretic-based antihypertensive treatment on major cardiovascular disease (CVD) event rates in older, non-insulin-treated diabetic patients with isolated systolic hypertension (ISH), compared with nondiabetic patients. Double-blind, randomized, placebo-controlled trial: the Systolic Hypertension in the Elderly Program (SHEP). Multiple clinical and support centers in the United States. A total of 4736 men and women aged 60 years and older at baseline with ISH (systolic blood pressure [BP], > or = 160 mm Hg; diastolic BP, <90 mm Hg) at baseline, 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients (4 additional patients not so classifiable were randomized but not included in these analyses). Diabetes mellitus defined as physician diagnosis, taking oral hypoglycemic drugs, fasting glucose level of 7.8 mmol/L or more (> or = 140 mg/dL), or any combination of these characteristics. The active treatment group received a low dose of chlorthalidone (12.5-25.0 mg/d) with a step-up to atenolol (25.0-50.0 mg/d) or reserpine (0.05-0.10 mg/d) if needed. The placebo group received placebo and any active antihypertensive drugs prescribed by patient's private physician for persistently high BP. The 5-year rates of major CVD events, nonfatal plus fatal stroke, nonfatal myocardial infarction (MI) and fatal coronary heart disease (CHD), major CHD events, and all-cause mortality. The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients, with few adverse effects. For both diabetic and nondiabetic patients, all outcome rates were lower for participants randomized to the active treatment group than for those randomized to the placebo group. Thus, 5-year major CVD rate was lower by 34% for active treatment compared with placebo, both for diabetic patients (95% confidence interval [CI], 6%-54%) and nondiabetic patients (95% CI, 21%-45%). Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients (101/1000 vs 51/1000 randomized participants at the 5-year follow-up), reflecting the higher risk of diabetic patients. Low-dose diuretic-based (chlorthalidone) treatment is effective in preventing major CVD events, cerebral and cardiac, in both non-insulin-treated diabetic and nondiabetic older patients with ISH.


Does nonnutritive tree gouging in a rainforest-dwelling lemur convey resource ownership as does loud calling in a dry forest-dwelling lemur?
Nonhuman primates may defend crucial resources using acoustic or chemical signals. When essential resources are limited, ownership display for a resource may be enhanced. Defending resources may depend on population density and habitat characteristics. Using the Milne Edwards' sportive lemurs (Lepilemur edwardsi) and weasel sportive lemurs (L. mustelinus) as models, we tested whether two cryptic nocturnal lemur species differing in population density and habitat show differences in their vocal and chemical communication for signaling ownership of resources. L. edwardsi inhabits a western dry deciduous forest in a high-density population, whereas L. mustelinus is found in an eastern rainforest in low density. We followed ten L. edwardsi (six males and four females) and nine L. mustelinus (four males and five females) for 215 hr during the early evening (06:00-10:00 p.m.) and the early morning (02:00-05:00 a.m.) and recorded their behavior using focal animal sampling. We found that both species differed in their vocal and chemical communication. L. edwardsi was highly vocal and displayed loud calling in the mornings and evenings while feeding or in the vicinity of resting places. In contrast, L. mustelinus never vocalized during observations, but displayed tree-gouging behavior that was never observed in L. edwardsi. Tree gouging occurred more often during early evening sessions than early morning sessions. Subjects gouged trees after leaving their sleeping hole and before moving around. We suggest that, in weasel sportive lemurs, non-nutritive tree gouging is used as a scent-marking behavior in order to display ownership of sleeping sites. Altogether, our findings provide first empirical evidence on the evolution of different communication systems in two cryptic nocturnal primate species contrasting in habitat quality and population density. Further investigations are needed to provide more insight into the underlying mechanisms.


The association between periodontal disease and age-related macular degeneration in the Korea National health and nutrition examination survey: A cross-sectional observational study.
Periodontal disease (PD) is associated with various systemic diseases. We investigated the association between PD and age-related macular degeneration (AMD).For this population-based, cross-sectional study, we enrolled 13,072 adults at least 40 years of age with gradable retinal fundus photographs and community periodontal index (CPI) data from the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2010 and 2012). Participants were divided into a middle age group (age ≤62 years) and old age group (age >62 years). PD was divided into 2 categories of mild and severe. Logistic regression analysis was used to evaluate the association between PD and AMD (early and late).The prevalence of PD and AMD in the study population was 37.4% ± 0.8% and 5.6% ± 0.2%, respectively. Overall, there was no significant difference in the proportion of participants with PD between those with and without AMD. Only participants with AMD in the middle age group had more any PD than those without AMD (P = 0.031). Multivariate logistic regression model after adjusting for all confounding factors showed that PD was not significantly associated with AMD (odds ratio [OR] 1.03, 95% confidence interval [CI] 0.86-1.22). However, according to degree of PD, participants with severe PD in the middle age group were 1.61 times more likely to have AMD (OR 1.61, 95% CI 1.02-2.54).Our data, collected from an Asian population, showed that only severe PD is independently associated with AMD in individuals aged 62 years or younger.


Mechanistic Insights into the cis- and trans-Acting DNase Activities of Cas12a.
CRISPR-Cas12a (Cpf1) is an RNA-guided DNA-cutting nuclease that has been repurposed for genome editing. Upon target DNA binding, Cas12a cleaves both the target DNA in cis and non-target single-stranded DNAs (ssDNAs) in trans. To elucidate the molecular basis for both DNase cleavage modes, we performed structural and biochemical studies on Francisella novicida Cas12a. We show that guide RNA-target strand DNA hybridization conformationally activates Cas12a, triggering its trans-acting, non-specific, single-stranded DNase activity. In turn, cis cleavage of double-stranded DNA targets is a result of protospacer adjacent motif (PAM)-dependent DNA duplex unwinding, electrostatic stabilization of the displaced non-target DNA strand, and ordered sequential cleavage of the non-target and target DNA strands. Cas12a releases the PAM-distal DNA cleavage product and remains bound to the PAM-proximal DNA cleavage product in a catalytically competent, trans-active state. Together, these results provide a revised model for the molecular mechanisms of both the cis- and the trans-acting DNase activities of Cas12a enzymes, enabling their further exploitation as genome editing tools.


Which components of processing speed are affected in ADHD subtypes?
The term "processing speed" (PS) encompasses many components including perceptual, cognitive and output speed. Despite evidence for reduced PS in Attention-Deficit/Hyperactivity Disorder (ADHD), little is known about which component(s) is most impacted in ADHD, or how it may vary by subtypes. Participants included 151 children, ages 8-12 years, with ADHD Predominantly Inattentive Type, ADHD Combined Type and typically developing controls using DSM-IV criteria. All children completed four measures of processing speed: Symbol Search, Coding, Decision Speed, and simple reaction time. We found children with ADHD-PI and ADHD-C had slower perceptual and psychomotor/incidental learning speed than controls and that ADHD-PI had slower decision speed than controls. The subtypes did not differ on any of these measures. Mean reaction time was intact in ADHD. Hence, at a very basic output level, children with ADHD do not have impaired speed overall, but as task demands increase their processing speed becomes less efficient than controls'. Further, perceptual and psychomotor speed were related to inattention, and psychomotor speed/incidental learning was related to hyperactivity/impulsivity. Thus, inattention may contribute to less efficient performance and worse attention to detail on tasks with a higher perceptual and/or psychomotor load; whereas hyperactivity/impulsivity may affect psychomotor speed/incidental learning, possibly via greater inaccuracy and/or reduced learning efficiency. Decision speed was not related to either dimension. Results suggest that PS deficits are primarily linked to the inattention dimension of ADHD but not exclusively. Findings also suggest PS is not a singular process but rather a multifaceted system that is differentially impacted in ADHD.


Site-directed mutagenesis in Escherichia coli of a stable R772::Ti cointegrate plasmid from Agrobacterium tumefaciens.
The host range of an octopine Ti plasmid is limited to Rhizobiaceae. This has been extended also to Escherichia coli in the form of a stable cointegrate with the wide-host-range plasmid R772. Its structure was studied by constructing a physical map of R772 and of the R772::pTiB6 cointegrate. An insertion sequence present in R772, called IS70, turned out to be involved in cointegrate formation. We found one intact copy of IS70 and a small segment of IS70, respectively, at the junctions of R772 and Ti DNA. The absence of a complete second copy of IS70 is a likely explanation for the stability of the cointegrate plasmid. A procedure for site-directed mutagenesis of this cointegrate plasmid in E. coli is described. The effect of mutations in the Ti plasmid part can be studied subsequently by transferring the cointegrate into Agrobacterium tumefaciens. The advantage of this procedure for Ti plasmids over other methods used at present is discussed.


Interferon-gamma increases IL-12 mRNA expression and attentuates allergic late-onset airway responses in the Brown Norway rat.
Interferon gamma is a T-helper cell (Th)-1-type cytokine that has been suggested to inhibit the development of an atopic Th2-type profile of cytokine expression. The aim of this study was to investigated the effect of exogenous rat interferon gamma on antigen-induced airway responses, and on Th1 and Th2-type cytokine messenger ribonucleic acid (mRNA) expression in the Brown Norway rat. Rats were actively sensitized to ovalbumin and 14 days later underwent an aerosolized ovalbumin challenge. Animals were intratracheally administered either interferon gamma (3,000 U) or control solvent 30 min prior to, and 2 and 4 h following, antigen challenge. Lung resistance was monitored over an 8-h time period. Using in situ hybridization and immunocytochemistry, the levels of Th1- (interleukin-12) and Th2-type (interleukin4 and -5) cytokine mRNA, and major basic protein expression in the bronchoalveolar lavage fluid of these rats 8 h after ovalbumin challenge were also determined. Administration of interferon gamma attenuated the development of the late-onset airways response in ovalbumin-sensitized antigen-challenged rats (p<0,05). The expression of interleukin-4 and -5 mRNA in the bronchoalveolar lavage fluid of interferon gamma treated rats was significantly attenuated compared to ovalbumin-challenged saline-treated controls (p<0.001). This was accompanied by a significant increase in the expression of interleukin-12 mRNA, and a reduction in eosinophil numbers. Intratracheal administration of interferon gamma modulates the allergic late-onset airways response in rats, and this is associated with a reduction in the expression of T-helper cell 2-type cytokines and an increase in interleukin-12 messenger ribonucleic acid expression within the airways. The present results support a role for interferon gamma in the pathophysiology of acute allergic airway responses, possibly by virtue of its ability to modulate T-helper cell 1- 2-type cytokine expression within the lungs.


Non-invasive estimation of arterial blood pressure fluctuations using a peripheral photoplethysmograph inside the MRI scanner.
The blood-oxygen-level-dependent (BOLD) signal measured by functional magnetic resonance imaging (fMRI) is modulated by neural activity through the neurovascular coupling effect, as well as non-neural factors of physiological origin such as heart rate, respiration, and arterial blood pressure (ABP). While the former two effects have been previously characterized, the modulation of the BOLD signal by ABP fluctuations is still poorly understood. This is largely due to the difficulty of obtaining reliable ABP measurements in the MRI environment. Here, we propose a combined experimental and mathematical modeling framework to estimate ABP fluctuations inside the MRI scanner using photoplethysmography (PPG). Specifically, we used concurrent PPG and ABP measurements obtained outside the scanner to train the mathematical model and applied it to PPG measurements obtained inside the MRI scanner. Our results suggest good agreement between the model-predicted and experimentally measured ABP fluctuations and region specific correlations with the BOLD fluctuations.


Non-specific spondylodiscitis: a new perspective for surgical treatment.
Pyogenic spondylodiscitis is a relatively rare spinal disease; non-specific spondylodiscitis (NSS) cases are increasing. This study aims to identify if changes of inflammatory markers under antibiotic therapy can be used to determine which NSS patients can benefit from surgical indication earlier than others. Two groups of patients with NSS were examined. Group A underwent surgery, while Group B was treated conservatively. Group B was also subdivided in patients undergoing antibiotic therapy for > 6 weeks (B1) and < 6 weeks (B2). Groups were compared for age, gender, BMI, blood levels of ESR and CRP and VAS scale. There were no differences (P = 0.06) in reduction in ESR at 4 weeks between two main groups. A reduction in CRP, with < 2.7 mg/dl at 4 weeks, was observed in Group A (P = 0.01). Comparing Group B1 to B2, a reduction (P = 0.0001) in VAS, ESR and CRP at 4 weeks was observed in Group B2. It was possible to isolate the pathogen in 52.8% of Group B, without any differences on VAS, ESR and CRP values and on length of the antibiotic therapy. The surgical treatment should be considered for patients who, after 4 weeks of conservative therapy, do not show a reduction in the ESR < 50 mm/h and of the CRP < 2.7 g/dl. The comparison between groups underwent surgically and those treated conservatively showed a reduction in the CRP at 4 weeks and better VAS for pain at 3 months in Group A.


A novel approach to assessing the drug susceptibility and replication of human immunodeficiency virus type 1 isolates.
Human immunodeficiency virus type 1 (HIV-1) drug susceptibility testing is often curtailed because such testing is expensive and time consuming. A colorimetric tetrazolium dye method previously used for high-throughput antiviral drug screening was adapted to assess the susceptibility of 16 HIV-1 isolates to zidovudine, didanosine, lamivudine, and nevirapine in MT-2 cells. Cell viability was assessed colorimetrically, and all measurements and calculations were automated. Each HIV-1 isolate was tested in > or = 5 assays to determine the reproducibility of the assay in HIV-1 isolates with known reverse-transcriptase mutations. The drug susceptibility of several mutant HIV-1 strains whose drug susceptibilities had not previously been well defined was also determined. Data on HIV-1 replication from the susceptibility assays indicated that some mutant HIV-1 isolates may have been less cytopathic in MT-2 cells than wild type HIV-1 isolates.


Correlates of Perceptual Orientation Biases in Human Primary Visual Cortex.
Vision can be considered as a process of probabilistic inference. In a Bayesian framework, perceptual estimates from sensory information are combined with prior knowledge, with a stronger influence of the prior when the sensory evidence is less certain. Here, we explored the behavioral and neural consequences of manipulating stimulus certainty in the context of orientation processing. First, we asked participants to judge whether a stimulus was oriented closer to vertical or the clockwise primary oblique (45°) for two stimulus types (spatially filtered noise textures and sinusoidal gratings) and three manipulations of certainty (orientation bandwidth, contrast, and duration). We found that participants consistently had a bias toward reporting orientation as closer to 45° during conditions of high certainty and that this bias was reduced when sensory evidence was less certain. Second, we measured event-related fMRI BOLD responses in human primary visual cortex (V1) and manipulated certainty via stimulus contrast (100% vs 3%). We then trained a multivariate classifier on the pattern of responses in V1 to cardinal and primary oblique orientations. We found that the classifier showed a bias toward classifying orientation as oblique at high contrast but categorized a wider range of orientations as cardinal for low-contrast stimuli. Orientation classification based on data from V1 thus paralleled the perceptual biases revealed through the behavioral experiments. This pattern of bias cannot be explained simply by a prior for cardinal orientations.SIGNIFICANCE STATEMENT Our perception of the world around us is biased through prior expectations rather than necessarily reflecting the true state of our environment. Here, we investigate biases in the visual processing of spatial orientation to understand how prior expectations and current sensory information interact to generate a percept. By degrading visual input in various ways, we are able to quantify the extent to which prior experience affects both perceptual judgments and neural responses in the human visual system. We observe systematic biases in the perception of orientation that correlate with the pattern of activity in the primary visual cortex of the human brain. These results indicate that prior expectations influence neural processing right from the earliest stage of the cortical hierarchy.


Molecular, neuromuscular, and recovery responses to light versus heavy resistance exercise in young men.
Recent evidence suggests that resistance training with light or heavy loads to failure results in similar adaptations. Herein, we compared how both training modalities affect the molecular, neuromuscular, and recovery responses following exercise. Resistance-trained males (mean ± SE: 22 ± 2 years, 84.8 ± 9.0 kg, 1.79 ± 0.06 m; n = 15) performed a crossover design of four sets of leg extensor exercise at 30% (light RE) or 80% (heavy RE) one repetition maximum (1RM) to repetition failure, and heavy RE or light RE 1 week later. Surface electromyography (EMG) was monitored during exercise, and vastus lateralis muscle biopsies were collected at baseline (PRE), 15 min (15mPOST), and 90 min following RE (90mPOST) for examination of molecular targets and fiber typing. Isokinetic dynamometry was also performed before (PRE), immediately after (POST), and 48 h after (48hPOST) exercise. Dependent variables were analyzed using repeated measures ANOVAs and significance was set at P ≤ 0.05. Repetitions completed were greater during light RE (P < 0.01), while EMG amplitude was greater during heavy RE (P ≤ 0.01). POST isokinetic torque was reduced following light versus heavy RE (P < 0.05). Postexercise expression of mRNAs and phosphoproteins associated with muscle hypertrophy were similar between load conditions. Additionally, p70s6k (Thr389) phosphorylation and fast-twitch fiber proportion exhibited a strong relationship after both light and heavy RE (r > 0.5). While similar mRNA and phosphoprotein responses to both modalities occurred, we posit that heavy RE is a more time-efficient training method given the differences in total repetitions completed, lower EMG amplitude during light RE, and impaired recovery response after light RE.


Decentralized control of discrete event systems with specializations to local control and concurrent systems.
The decentralized supervisory control problem of discrete event systems under partial observation is studied in this paper. The main result of the paper is a necessary and sufficient condition for the existence of decentralized supervisors for ensuring. That the controlled behavior of the system lies in a given range. The contribution of the paper is (1) our setting of decentralized control generalizes the prior ones; (2) we present an alternative approach for solving the decentralized control problem, which leads to computational saving for concurrent systems and certain other systems; and (3) our generalized formulation and its solution lets us extend several of the existing results reported previously. The results of our paper are illustrated by an example of a simple manufacturing system.


Actuation means for the mechanical stimulation of living cells via microelectromechanical systems: A critical review.
Within a living body, cells are constantly exposed to various mechanical constraints. As a matter of fact, these mechanical factors play a vital role in the regulation of the cell state. It is widely recognized that cells can sense, react and adapt themselves to mechanical stimulation. However, investigations aimed at studying cell mechanics directly in vivo remain elusive. An alternative solution is to study cell mechanics via in vitro experiments. Nevertheless, this requires implementing means to mimic the stresses that cells naturally undergo in their physiological environment. In this paper, we survey various microelectromechanical systems (MEMS) dedicated to the mechanical stimulation of living cells. In particular, we focus on their actuation means as well as their inherent capabilities to stimulate a given amount of cells. Thereby, we report actuation means dependent upon the fact they can provide stimulation to a single cell, target a maximum of a hundred cells, or deal with thousands of cells. Intrinsic performances, strengths and limitations are summarized for each type of actuator. We also discuss recent achievements as well as future challenges of cell mechanostimulation.


[Non-mutagenic non-targeted radiation effects. Determined decrease of cells viability in populations induced by low dose radiation].
Experimental data obtained from studies on the objects with different organization were analyzed. These data expand the ideas about the phenomenon of "viability determinate decrease in offspring of irradiated cells" discovered in the 1970s. This phenomenon was evaluated according to the standpoint of modern radiobiology. It is postulated that the studied effects, which are associated with the cytoplasmic structures damage and are clearly manifested in mammalian low proliferative tissues, can be significant for humans in connection with the delayed somatic consequences of low dose irradiation, as well as with a more general problem of longevity reduction. Possibility of inheritance ofthese alteration in protozoa asexual reproduction and metazoan sexual reproduction (generation F1) is demonstrated.


Scoliosis and bronchial obstruction.
Severe scoliosis may have a significant effect on respiratory function. The effect is most often restrictive due to severe anatomical distortion of the chest, leading to reduced lung volumes, limited diaphragmatic excursion and chest wall muscle inefficiency. Bronchial compression by the deformed spine may also occur but is more unusual. Management options include a conservative approach using bracing and physiotherapy in mild cases, as well as surgical correction of the scoliosis in more severe cases. Bronchial stenting has also been used successfully as an alternative to surgical correction, and in cases in which spinal surgery was either unsuccessful or not feasible. The authors present a case involving a 52-year-old woman who exhibited symptomatic compression of the bronchus intermedius by severe residual scoliosis despite previous corrective surgery. She was treated with an indwelling bronchial stent.


Under-reporting of Parkinson's disease on death certificates: a population-based study (NEDICES).
Parkinson's disease is frequently omitted as a cause of death from death certificates. A limitation of previous studies that attempted to assess the validity of death certificates is that population-dwelling cases, with milder, undiagnosed Parkinson's disease were likely excluded. As a result, those studies likely overestimated the validity of death certificates because they did not include these milder cases. We assessed the validity of death certificates in a prospective population-based study (NEDICES), which includes previously undiagnosed Parkinson's disease cases detected during the assessment. 3926 community-dwelling elderly subjects with and without Parkinson's disease were followed during a median of 12.6 years, after which the death certificates of those who died were examined. We calculated the proportion of cases of clinically diagnosed Parkinson's disease for whom a diagnosis of Parkinson's disease was certified as the basic cause of death on death certificates. 1791 (45.6%) of the 3926 participants died over a median follow-up of 7.1 years, including 82 (73.9%) deaths among 111 participants with Parkinson's disease. Parkinson's disease was rarely certified as the basic cause of death (14.6%). Gender, disease stage and the period during which the study was conducted (i.e., 1994 to 2007) did not influence the likelihood that Parkinson's disease would be reported. Our findings reinforce the notion that the reporting of Parkinson's disease on death certificates remains poor. This suggests a lack of awareness of the importance of Parkinson's disease as a cause of death.


Exchange donor program in kidney transplantation.
The donor organ shortage has been one of the major barriers to kidney transplantation in Korea, even though there has been a small but steady flow of cadaveric kidney donations for the last decade. To expand the donor pool in kidney transplantation, we have developed the exchange donor program at our institution and in Korea. The donor exchange program was first started for end-stage renal disease patients who had willing but incompatible related donors due to positive lymphocyte cross-match. The kidney transplantations were performed using exchanged kidneys between two families with successful results. Since this success, we have expanded the donor pool by accepting close relatives, spouses, friends of recipients, and willing voluntary donors as candidates for exchange donors with careful donor screening procedures. It helps relieve stress on donor supply. Particularly in those countries where brain death has not been socially or legally accepted, living donors including related, unrelated, and exchange donors should be considered as potential donors for kidney transplantation to relieve the pressure on donor organ shortage.


The effects of vowels on voice perturbation measures.
This study examines voice perturbation parameters of the sustained [a] in English and of the eight vowels in Turkish to discover whether any difference exists between these languages, and whether a correlation exists between voice perturbation parameters and articulatory and acoustic properties of the Turkish vowels. Eight Turkish vowels uttered by 26 healthy nonsmoker volunteer males who are native Turkish speakers were compared with a voice database that includes samples of normal and disordered voices belonging to American English speakers. Fundamental frequencies, the first and second formants, and perturbation parameters, such as jitter percent, pitch perturbation quotient, shimmer percent, and amplitude perturbation quotient of the sustained vowels, were measured. Also, the first and second formants of the sustained [a] in English were measured, and other parameters have been obtained from the database. When the voice perturbation parameters in Turkish and English were compared, statistically significant differences were not found. However, when Turkish vowels compared with each other, statistically significant differences were found among perturbation values. Categorical comparisons of the Turkish vowels like high-low, rounded-unrounded, and front-back revealed significant differences in perturbation values. In correlation analysis, a weak linear inverse relation between jitter percent and the first formant (r=-0.260, p<0.05) was found.


Dissecting the contribution of host genetics and the microbiome in complex behaviors.
The core symptoms of many neurological disorders have traditionally been thought to be caused by genetic variants affecting brain development and function. However, the gut microbiome, another important source of variation, can also influence specific behaviors. Thus, it is critical to unravel the contributions of host genetic variation, the microbiome, and their interactions to complex behaviors. Unexpectedly, we discovered that different maladaptive behaviors are interdependently regulated by the microbiome and host genes in the Cntnap2-/- model for neurodevelopmental disorders. The hyperactivity phenotype of Cntnap2-/- mice is caused by host genetics, whereas the social-behavior phenotype is mediated by the gut microbiome. Interestingly, specific microbial intervention selectively rescued the social deficits in Cntnap2-/- mice through upregulation of metabolites in the tetrahydrobiopterin synthesis pathway. Our findings that behavioral abnormalities could have distinct origins (host genetic versus microbial) may change the way we think about neurological disorders and how to treat them.


Management of complicated ptosis with contralateral levator recession.
We describe a unique approach to complicated unilateral minimal ptosis. Three cases of unilateral ptosis were successfully managed with the technique of contralateral levator recession. Contralateral levator recession is a useful procedure heretofore undescribed, to our knowledge, for the management of ptosis.


Surgical Treatment of Iatrogenic Ventral Glottic Stenosis Using a Mucosal Flap Technique.
To describe a novel surgical technique for correcting postoperative ventral glottic stenosis (cicatrix or web formation) and the outcome in 2 Thoroughbred racehorses. Retrospective case report. Thoroughbreds diagnosed with ventral glottic stenosis (n=2). Horses presenting with iatrogenic ventral glottic stenosis and resultant exercise intolerance and abnormal exercise-related noise were anesthetized and a midline sagittal skin incision was made over the ventral larynx and between the sternohyoideus muscles overlying the cricothyroid notch. The cricothyroid ligament, attached laryngeal cicatrix, and overlying mucosa were sagittally sectioned at the dorsal aspect of the cicatrix on the left side. The laryngeal mucosa, cicatrix, and underlying cricothyroid ligament immediately rostral and caudal to the cicatrix were sectioned in a medial (axial) direction as far as the right side of the cricothyroid notch. After resection of the majority of the attached cicatrix tissue, the residual mucosal flap (attached to the right side of the larynx) was reflected ventrally and sutured to the attachment of the cricothyroid ligament on the right side of the cricothyroid notch, creating an intact mucosal layer on the right side of the ventral larynx. Both horses had good intralaryngeal wound healing with minimal redevelopment of ventral glottic stenosis at 5 and 9 months postoperatively and were successfully returned to racing with complete absence of abnormal respiratory noise. The unique laryngeal anatomy of horses, with a cartilage-free ventral laryngeal area (cricothyroid notch), allowed the use of this novel surgical technique to successfully treat ventral glottic stenosis.


Thyroid autoimmunity in Type 1 diabetes: systematic review and meta-analysis.
To review the incidence and evidence for screening for thyroid autoimmunity and thyroid dysfunction in Type 1 diabetes. Systematic review and meta-analysis. Inclusion criteria were prospective cohort studies screening for thyroid autoimmunity and/or dysfunction (defined as an abnormal thyroid-stimulating hormone level) in Type 1 diabetes. Exclusion criteria included pregnancy and thyroid dysfunction before diabetes onset. Outcomes examined were: incidence of thyroid autoimmunity and/or dysfunction; association between thyroid autoimmunity and dysfunction; and cost-effectiveness. Data sources were MEDLINE, EMBASE, the Cochrane Library, manual searching and contact with authors, with limitations to English language and human studies. Meta-analysis was performed using random effects models. We identified 14 eligible studies, involving 2972 young people and 789 adults with Type 1 diabetes. Follow-up ranged from 1-18 years. None of the studies were of good methodological quality (Newcastle Ottowa Scale score > 7). The incidence of thyroid dysfunction (11 studies) ranged from 27 (95% CI 15-45) to 246 (95% CI 118-453) per 10 000 patient-years and thyroid autoimmunity (four studies) from 13 (95% CI 0.3-71) to 326 (95% CI 194-510). The risk of thyroid dysfunction was higher in those with thyroid autoimmunity: summary risk ratio 25 (95% CI 9-71) and was higher in children (49, 95% CI 16-150) compared with adults (7, 95% CI 3-13). No studies examined cost-effectiveness of screening. There is a markedly increased risk of thyroid dysfunction in people with Type 1 diabetes and thyroid autoimmunity. The optimal method or frequency of screening could not be determined from available data. Future studies should examine whether screening improves clinical outcomes in this population.


A phase 1 study of azacitidine with high-dose cytarabine and mitoxantrone in high-risk acute myeloid leukemia.
In this phase 1 study, azacitidine (AZA) was given before high-dose cytarabine (HiDAC) and mitoxantrone (mito) based on the hypothesis that epigenetic priming with a hypomethylating agent before cytotoxic chemotherapy would improve response rates in patients with high-risk acute myeloid leukemia (AML), including relapsed/refractory disease. The primary objective was to establish the recommended phase 2 dose of AZA given before standard HiDAC/mito. In a dose escalation scheme, 46 patients (median age, 66 years) received AZA at 37.5, 50, or 75 mg/m2 subcutaneously or IV once daily on days 1 to 5 followed by HiDAC (3000 mg/m2) and mitoxantrone (30 mg/m2) once each on days 6 and 10 (the HiDAC/mito dose was reduced 33% in elderly subjects). Two dose-limiting toxicities occurred (both in the same patient): acute liver failure and kidney injury at the 50 mg/m2 dose. The 30-day induction death rate was 2.2% (1 of 46). The overall response rate, including complete remission and complete remission with incomplete count recovery, was 61% (28 of 46). Previously untreated patients aged ≥60 years with therapy-related AML and de novo AML were more likely to respond than untreated patients with AML progressing from an antecedent hematologic disorder (myelodysplastic syndrome and chronic myelomonocytic leukemia). Patients with favorable European Leukemia Network risk (P = .008), NPM1 mutations (P = .007), or IDH2 mutations (P = .03) were more likely to respond, and those with TP53 mutations (P = .03) were less likely to respond. The recommended phase 2 dose of AZA is 75 mg/m2 per day on days 1 to 5 followed by HiDAC (3000 mg/m2) and mitoxantrone (30 mg/m2) once each on days 6 and 10. This trial was registered at www.clinicaltrials.gov as #NCT01839240.


Predictive factors for acute esophageal toxicity in thoracic radiotherapy.
Acute esophageal toxicity (AET) is a common complication and dose-limiting toxicity in thoracic radiotherapy. Previous studies demonstrated several clinical and dosimetric parameters of AET in patients with lung cancer. However, there are few reports dealing with these variables in intra-thoracic malignancies, including lung cancer and other thoracic malignancy. The purpose of this study was to evaluate the clinical and dosimetric factors associated with AET in patients with intra-thoracic malignancies. We examined 61 patients with intra-thoracic malignancies treated with radiotherapy: 34 patients with non-small-cell lung cancer (55%), 9 cases with small-cell lung cancer (15%), 7 cases with thymic cancer (11%), 4 thymomas (7%), 2 malignant lymphomas (3%), one seminoma (2%), one liposarcoma (2%), and 3 cases of other malignancies (5%). Radiotherapy was performed with a median dose of 60 Gray (Gy) (range 40-67 Gy). AET was graded according to the Radiation Therapy Oncology Group (RTOG) criteria. The following parameters were analyzed with respect to associations with AET by univariate and multivariate analyses: age, gender, thoracic surgery before radiotherapy, concurrent chemotherapy, duration of radiotherapy, maximum esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving from 10 Gy (V10) to 65 Gy (V65), in 5-Gy increments. 43 patients (70%) developed AET: 36 patients (59%) with AET of RTOG Grade 1, 7 patients (11%) with Grade 2, and no patients (0%) with Grade 3 or worse. On multivariate analysis, V35 > 30% was the most statistically significant factor associated with mild AET (p = 0.013). Our findings provide a better understanding of the factors related to AET, and might be useful in designing a treatment plan to prevent severe esophageal toxicity.


Geminin is required for zygotic gene expression at the Xenopus mid-blastula transition.
In many organisms early development is under control of the maternal genome and zygotic gene expression is delayed until the mid-blastula transition (MBT). As zygotic transcription initiates, cell cycle checkpoints become activated and the tempo of cell division slows. The mechanisms that activate zygotic transcription at the MBT are incompletely understood, but they are of interest because they may resemble mechanisms that cause stem cells to stop dividing and terminally differentiate. The unstable regulatory protein Geminin is thought to coordinate cell division with cell differentiation. Geminin is a bi-functional protein. It prevents a second round of DNA replication during S and G2 phase by binding and inhibiting the essential replication factor Cdt1. Geminin also binds and inhibits a number of transcription factors and chromatin remodeling proteins and is thought to keep dividing cells in an undifferentiated state. We previously found that the cells of Geminin-deficient Xenopus embryos arrest in G2 phase just after the MBT then disintegrate at the onset of gastrulation. Here we report that they also fail to express most zygotic genes. The gene expression defect is cell-autonomous and is reproduced by over-expressing Cdt1 or by incubating the embryos in hydroxyurea. Geminin deficient and hydroxyurea-treated blastomeres accumulate DNA damage in the form of double stranded breaks. Bypassing the Chk1 pathway overcomes the cell cycle arrest caused by Geminin depletion but does not restore zygotic gene expression. In fact, bypassing the Chk1 pathway by itself induces double stranded breaks and abolishes zygotic transcription. We did not find evidence that Geminin has a replication-independent effect on transcription. We conclude that Geminin is required to maintain genome integrity during the rapid cleavage divisions, and that DNA damage disrupts zygotic gene transcription at the MBT, probably through activation of DNA damage checkpoint pathways.


Translation and validation of hindi version of oral health impact profile-14, a measure of oral health-related quality of life of geriatrics.
The oral health impact profile-14 (OHIP-14) scale developed originally in English has been translated from time to time in different languages revealing to be valid and reliable instruments. The present study was carried out with an aim to translate and validate Hindi Version of OHIP-14 instrument among geriatrics to measure the oral health-related quality of life. This was a descriptive cross-sectional study, which employed 400 individuals aged 60 years and above who were residents of Durg, Chhattisgarh India. Participants were selected through convenient sampling method. The English version of the OHIP-14 was translated into Hindi, pretested and subsequently administered to the participants by a trained interviewer. Each patient signed informed consent and responded to the Hindi version of the questionnaire. Cronbach's alpha of the translated scale was 0.89-0.90 when words were deleted individually. Comparison of English and translated Hindi version of OHIP-14 by unpaired t-test showed no significant difference (P = 0.562). Pearson correlation coefficient test showed very strong positive correlation (0.892). Furthermore, a very strong positive correlation was observed between the recorded OHIP-14 scores and Decayed Missing Filled Teeth (DMFT) scores of examined geriatric individuals (Pearson correlation coefficient = 0.952 and P = 0.001). The Hindi translation of the OHIP-14 is a valid and reliable instrument to measure the oral health-related quality of life in older adults of India.


Efficiency and accuracy of numerical solutions to the time-dependent Schrödinger equation.
Recent significant improvements of the numerical solutions of the time-dependent Schrödinger equation beg the question as to whether these recent methods are comparable in efficacy (in terms of accuracy and computational time) to the current "method of choice," i.e., the Chebyshev expansion of the time-evolution operator and the fast-Fourier-transform method of determining the kinetic energy. In this paper we review the methods in question and, by studying the time development of a coherent wave packet in an oscillator well, we are able to assess the effectiveness of the various methods. It turns out that the new generalizations come close (to within an order of magnitude) to being able to generate solutions as precisely and efficiently as the Chebyshev-fast-Fourier-transform method. The strict unitarity of the generalized methods may be an advantage. We also show that the fast-Fourier-transform approach to calculating the kinetic energy can be replaced by straightforward numerical differentiation to obtain the same precision.


Is Sentinel Node Biopsy of the Internal Mammary Lymph Nodes Relevant in the Management of Breast Cancer?
The aim of this study was to review the outcomes of a series of breast cancer patients who underwent sentinel node biopsy inclusive of lymphoscintigraphy, and to assess the incidence of internal mammary node (IMN) metastatic positivity at exploration and whether these findings influenced treatment. Between April 2001 and December 2012, 581 breast cancer patients at Princess Alexandra Hospital underwent preoperative lymphoscintigraphy in the course of the performance of sentinel node biopsy. Analysis was performed of those patients who demonstrated radio-isotope uptake to the IMN chain, and who had sentinel node biopsy of the IMN's and were found to have metastatic involvement. Assessment was made to determine whether the finding of IMN metastases changed the adjuvant systemic management of these patients, and to review complication rates. 95 of 581 (16.4%) patients with preoperative breast lymphoscintigraphy had lymphatic mapping to the IMN chain. 51 (54%) of these patients had IMN chain surgically explored and IMN nodes were found in 35 of these patients (success rate of 69%). Of these, three patients (3/35 = 8.6%) had metastatic involvement of the IMN sentinel node group. All three IMN positive patients received adjuvant breast radiotherapy, chemotherapy, and hormonal therapy. In four patients (7.8%) IMN surgical exploration was complicated by pneumothorax. Only a small proportion of breast cancer patients were found to have metastasic involvement of the IMN chain and which did not significantly change their adjuvant therapy management. These findings suggest that the benefits of exploration of the IMN chain in breast cancer patients are limited and may be outweighed by the risk of complications.


Lymphocyte subpopulations anomalies in lung cancer patients and relationship to the stage of disease.
The host immune response is important in the natural history of neoplastic disease. In order to evaluate alterations of immune function associated with cancer we analyzed the nyctohemeral profile of lymphocyte subpopulations in peripheral blood of cancer patients. The study was carried out on seven healthy volunteers (mean age +/- s.e. 68.8 +/- 1.92), seven patients with I and II stage lung cancer (mean age +/- s.e. 67.2 +/- 0.80), seven patients with III and IV stage lung cancer (mean age +/- s.e. 69.5 +/- 2.26). The area under the curve (AUC) and the presence of circadian rhythmicity were evaluated. The most striking differences were a statistically significant decrease of CD8 (T suppressor/cytotoxic subset) and CD8bright (T suppressor subset) in cancer patients, with a loss of normal circadian rhythmicity, and a statistically significant increase of CD16 (natural killer cells) in cancer patients, especially with I and II stage disease, with a clear circadian rhythm present in all the groups. A statistically significant decrease of delta TcS1 (epitope of the variable domain of delta chain of T-cell receptor 1) was observed in the subjects with I and II stage lung cancer, with a loss of circadian rhythmicity in the two groups of cancer patients. TcR delta 1 (epitope of the constant domain of delta chain of T-cell receptor 1) was significantly decreased in cancer patients, but a clear circadian rhythm was present in these subjects. No significant differences among the groups were found in the values of CD2 (total T cells), CD4 (T helper/inducer subset), CD8dim (T cytotoxic subset), CD4/CD8 ratio, HLA-DR (B cells and activated T cells), CD20 (total B cells) and CD25 (T activated lymphocytes with expression of the alpha chain of interleukin-2 receptor). Nyctohemeral variations of CD2 in control subjects and in I-II stage cancer patients and of CD4 and CD20 in III-IV stage cancer patients presented circadian rhythmicity. The results suggest that lung cancer is associated with alterations in the proportions and nyctohemeral profiles of various lymphocyte subsets, related to the stage of disease and probably the expression of an altered immune function.


Work ability in rheumatoid arthritis patients: a register study on the prospective risk of exclusion and probability of returning to work.
The aim was to study work ability in patients with RA compared with the general population by investigating the rates and risks of long-term sickness absence, unemployment and disability pension, and the chance of returning to work and the changes in these risks over time (1994-2011). This was a cohort study with up to 17 years of follow-up (mean 6.95 years/person) including 6677 RA patients of working age (identified in the nationwide DANBIO registry) and 56 955 matched controls from the general population. A multi-state model was used to analyse all shifts between the work-related states (long-term sickness absence, unemployment and disability pension, as well as the chance of returning to work) and calculate hazard rates (HRs). Analyses were stratified by disease duration and controlled for socio-demographic factors, physical job exposure and somatic and psychiatric co-morbidities. RA patients had increased risk of long-term sickness absence (e.g. early RA: HR = 4.00, 95% CI: 3.64, 4.30) and disability pension (e.g. established RA: HR = 2.75, 95% CI: 2.54, 2.98) relative to controls. From 1994-99 to 2006-11, a decrease in the effect of established RA was observed [long-term sickness absence: from HR = 2.25 (95% CI: 1.99, 2.54) to 1.63 (95% CI: 1.51, 1.75); and disability pension: from HR = 3.49 (95% CI: 2.83, 4.32) to 2.40 (95% CI: 2.15, 2.69)]. RA patients had a lower chance of returning to work from long-term sickness absence or unemployment (HR = 0.60, HR=0.80), and this did not change over time. RA patients remain at high risk for long-term sickness absence and disability pension, despite a positive development between 1996-99 and 2006-11. Returning to work after sick leave or unemployment remains a challenge for RA patients.


A novel multiscale nonlinear thresholding method for ultrasonic speckle suppressing.
This paper presents a novel speckle suppression method for medical B-scan ultrasonic images. An original image is first separated into two parts with an adaptive filter. These two parts are then transformed into a multiscale wavelet domain and the wavelet coefficients are processed by a soft thresholding method, which is a variation of Donoho's soft thresholding method. The processed coefficients for each part are then transformed back into the space domain. Finally, the denoised image is obtained as the sum of the two processed parts. A computer-simulated image and an in vitro B-scan image of a pig heart have been used to test the performance of this new method. This technique effectively reduces the speckle noise, while preserving the resolvable details. It performs well in comparison to the multiscale thresholding technique without adaptive preprocessing and two other speckle-suppression methods.


[Clinical features of Eosinophilic Colitis in infants with persistent rectal bleeding].
The most common presentation of cow's milk protein allergy (CMP) in infants is known as eosinophilic colitis (EC). The aim of this study is to evaluate EC characteristics in infants evaluated with colonoscopy due to the presence of rectorrhagia. A retrospective case-control study. Left-sided colonoscopy records of infants with persistent rectal bleeding, conducted between January 2006 and March 2011, were reviewed. The cases corresponded to infants with rectal biopsy compatible with EC and controls with negative biopsy. Telephone questionnaires to parents were conducted, evaluating personal and family history. Complete records were obtained in 61 (79%) of the 77 procedures. 33 (54%) of them were males. Examination average age was 6.3 ± 5.9 months. 25 (41%) patients had EC on their histology. Between cases and controls, no significant difference in gestational age, birth weight and gender, only regarding age at the time of rectal bleeding, were observed. There was also no difference in personal history regarding obstructive bronchitis, allergic rhinitis, family history of asthma, allergic rhinitis or other food allergies. Those who received artificial feeding did not presented greater risk of EC. The most common symptoms in the cases did not differ significantly from the controls. The prevalence of EC in the children studied was 40.9%. Our results show that there are groups of patients with persistent rectal bleeding in which there is no personal or family history that helps diagnosing EC. An endoscopic study could be considered in these patients to establish a correct diagnosis of this condition, avoid unnecessary diets and not to delay the detection of other diseases.