Mass spectrometry and proteomics in hematology.
Mass spectrometry-based techniques now enable the unbiased identification of proteins in complex mixtures including proteins isolated from cells and tissues. These powerful tools permit near-complete annotation of proteins expressed in cells, tissues or organs. Further, these techniques permit the interrogation of the numerous posttranslational modifications that govern cell-specific responses to signaling cues and underlie the functional heterogeneity of cellular composition and contribute to biological complexity. Parallel developments in technologies such as mass cytometry and multicolor ion-beam imaging which permit multi-parameter detection of numerous proteins at the single-cell and in situ level respectively, are poised to radically impact our understanding of the functional and translational importance of proteins in hematologic conditions. Importantly, the field of proteomics is poised to realize the immensely powerful opportunities in integration with genomic information that is being discovered at an unprecedented pace for many hematologic conditions.


Regulated chromatin domain comprising cluster of co-expressed genes in Drosophila melanogaster.
Recently, the phenomenon of clustering of co-expressed genes on chromosomes was discovered in eukaryotes. To explore the hypothesis that genes within clusters occupy shared chromatin domains, we performed a detailed analysis of transcription pattern and chromatin structure of a cluster of co-expressed genes. We found that five non-homologous genes (Crtp, Yu, CK2betates, Pros28.1B and CG13581) are expressed exclusively in Drosophila melanogaster male germ-line and form a non-interrupted cluster in the 15 kb region of chromosome 2. The cluster is surrounded by genes with broader transcription patterns. Analysis of DNase I sensitivity revealed 'open' chromatin conformation in the cluster and adjacent regions in the male germ-line cells, where all studied genes are transcribed. In contrast, in somatic tissues where the cluster genes are silent, the domain of repressed chromatin encompassed four out of five cluster genes and an adjacent non-cluster gene CG13589 that is also silent in analyzed somatic tissues. The fifth cluster gene (CG13581) appears to be excluded from the chromatin domain occupied by the other four genes. Our results suggest that extensive clustering of co-expressed genes in eukaryotic genomes does in general reflect the domain organization of chromatin, although domain borders may not exactly correspond to the margins of gene clusters.


Trends and Characteristics of Industry Payments for Ophthalmology Research From 2014 to 2020.
Characterizing industry-ophthalmology collaborations in research can highlight current areas of focus, improve transparency, and identify potential sources for conflicts of interest. To assess the trends and characteristics in research payments reported from industry to ophthalmologists from 2014 to 2020. This cross-sectional study used data from the Centers of Medicare & Medicaid Services' Open Payments database (OPD), which contains public records of payments between industry and physicians, to identify all ophthalmologists who received industry payments for research purposes between 2014 and 2020. Industry funding was compared with public research funding by the National Eye Institute. The value and distribution of payments, sponsoring manufacturers, and research products were assessed. Changes in aggregate and per individual-level funding were characterized using formal trend analysis. From 2014 to 2020, 2102 ophthalmologists were reported to have received $825 417 233 in industry research payments. Industry funding increased 203% from $62 924 525 in 2014 to $190 714 508 in 2020 (P = .01). Comparatively, total National Eye Institute research funding during the same period was $5 003 407 764 and increased 6.6% from $701 313 262 in 2014 to $747 929 556 in 2020 (P = .04). The share of all medical research funding from industry directed specifically toward ophthalmology research increased from 1.2% in 2014 to 3.2% in 2020 (P = .04). The distribution of industry payments was skewed, with the top 15 of 108 manufacturers accounting for 93.9% of funding. The top 10% of ophthalmologists (210) were reported to have received 65.7% of all research dollars ($542 299 121). The highest funded research products were anti-vascular endothelial growth factor agents, glaucoma treatments, and intraocular lenses. Although unequal in distribution, industry-funded research in ophthalmology is extensive and increasing in scope. Industry funding for research is less than that of public funding; however, industry funding increased faster between 2014 and 2020. Results of this study highlight the increasing importance of industry funding in ophthalmology research, but it may also present ethical challenges for clinicians collaborating with industry.


Epidemic of cutaneous leishmaniasis: 109 cases in a population of 500.
In February 2004, 4 patients aged 10-15 years presented at the Pakistan Institute of Medical Sciences with non-healing multiple ulcers on exposed parts. On the basis of history, clinical assessment and fine needle aspiration cytology, they were diagnosed as having cutaneous leishmaniasis. We were informed that several similar cases were present in their village. A team of doctors and technicians visited the area. A survey was conducted and another 105 cases with various morphological presentations were identified. The area was visited several times to find the vector, reservoirs and source of infection and to advise on controlling the epidemic.


Down-regulation of c-Ki-ras2 gene expression associated with morphologic differentiation in human embryonal carcinoma cells treated with berberine.
A pluripotent human embryonal carcinoma (EC) clone, NT2/D1, which was derived from the Tera-2 cell line, was induced to differentiate into cells with neuronal-like cell morphology by treatment with berberine, an alkaloid derived from a Chinese herbal medicine (Huang Lien). As early as one day after 24-hour treatment of cells with berberine at a nontoxic dose of 0.1 mg/ml in culture medium, the cells started to show morphologic changes, developing into terminally differentiated neuronal-like cells with long, inter-connecting network cellular structures. This process was much faster as compared with that induced by treatment with retinoic acid (RA), which took at least several days to develop. Unlike RA, berberine could not induce murine EC cell line, F9, to differentiate into endodermal cells. It was also found that although the NT2/D1 cell clone exhibited amplification and enhanced mRNA expression of c-Ki-ras2 gene as did the parent cell line, a marked down-regulation of c-Ki-ras2 mRNA expression was observed. However, there was no change in actin mRNA expression even after differentiation had occurred. Thus, morphologic differentiation of EC cells into neuronal-like cells was found to be associated with down-regulation of a protooncogene which plays some definite role in oncogenesis. The mechanism by which berberine induces differentiation in these cells needs further investigation.


Negative feedback control of hunger circuits by the taste of food.
The rewarding taste of food is critical for motivating animals to eat, but whether taste has a parallel function in promoting meal termination is not well understood. Here we show that hunger-promoting AgRP neurons are rapidly inhibited during each bout of ingestion by a signal linked to the taste of food. Blocking these transient dips in activity via closed-loop optogenetic stimulation increases food intake by selectively delaying the onset of satiety. We show that upstream leptin receptor-expressing neurons in the dorsomedial hypothalamus (DMH LepR ) are tuned to respond to sweet or fatty tastes and exhibit time-locked activation during feeding that is the mirror image of downstream AgRP cells. These findings reveal an unexpected role for taste in the negative feedback control of ingestion. They also reveal a mechanism by which AgRP neurons, which are the primary cells that drive hunger, are able to influence the moment-by-moment dynamics of food consumption.


Systematic analysis of bicistronic reporter assay data.
Bicistronic reporter assay systems have become a mainstay of molecular biology. While the assays themselves encompass a broad range of diverse and unrelated experimental protocols, the numerical data garnered from these experiments often have similar statistical properties. In general, a primary dataset measures the paired expression of two internally controlled reporter genes. The expression ratio of these two genes is then normalized to an external control reporter. The end result is a 'ratio of ratios' that is inherently sensitive to propagation of the error contributed by each of the respective numerical components. The statistical analysis of this data therefore requires careful handling in order to control for the propagation of error and its potentially misleading effects. A careful survey of the literature found no consistent method for the statistical analysis of data generated from these important and informative assay systems. In this report, we present a detailed statistical framework for the systematic analysis of data obtained from bicistronic reporter assay systems. Specifically, a dual luciferase reporter assay was employed to measure the efficiency of four programmed -1 frameshift signals. These frameshift signals originate from the L-A virus, the SARS-associated Coronavirus and computationally identified frameshift signals from two Saccharomyces cerevisiae genes. Furthermore, these statistical methods were applied to prove that the effects of anisomycin on programmed -1 frameshifting are statistically significant. A set of Microsoft Excel spreadsheets, which can be used as templates for data generated by dual reporter assay systems, and an online tutorial are available at our website (http://dinmanlab.umd.edu/statistics). These spreadsheets could be easily adapted to any bicistronic reporter assay system.


Stable propagation of non-Gaussian beams in a multiple-pass cell.
To apply annular output beams emitted from an unstable resonator to a multiple-pass cell (MPC) for Raman conversion, we studied the mode-matching condition of non-Gaussian beams to a MPC using beam propagation analysis based on Laguerre-Gaussian functions. During transits of the MPC, the radial profile of an annular beam changes between annular and Airy patterns. Although such behavior indicates that it is impossible to achieve complete mode matching of an annular beam, we found a quasi-mode-matching condition under which the variation of beam size was minimized. The above theoretical analysis was verified experimentally using a CO(2) laser beam prepared for a para-hydrogen Raman laser.


A probabilistic model for cell cycle distributions in synchrony experiments.
Synchronized populations of cells are often used to study dynamic processes during the cell division cycle. However, the analysis of time series measurements made on synchronized populations is confounded by the fact that populations lose synchrony over time. Time series measurements are thus averages over a population distribution that is broadening over time. Moreover, direct comparison of measurements taken from multiple synchrony experiments is difficult, as the kinetics of progression during the time series are rarely comparable. Here, we present a flexible mathematical model that describes the dynamics of population distributions resulting from synchrony loss over time. The model was developed using S. cerevisiae, but we show that it can be easily adapted to predict distributions in other organisms. We demonstrate that the model reliably fits data collected from populations synchronized by multiple techniques, and can accurately predict cell cycle distributions as measured by other experimental assays. To indicate its broad applicability, we show that the model can be used to compare global periodic transcription data sets from different organisms: S. cerevisiae and S. pombe.


Complications of cleft palate repair in large animals.
Seven foals, 2 horses, and 2 calves were presented to the George D. Widener Hospital for Large Animals at New Bolton Center and the Large Animal Clinic at Auburn University for surgical repair of cleft palate. All animals had preexisting pneumonia. Initial repair of cleft palate in 6 foals, 2 horses, and 2 calves was performed via mandibular symphysiotomy. Primary repair of cleft soft palate in a foal was attempted through a pharyngotomy incision after fracture of the basal hyoid bone; however, exposure was inadequate and mandibular symphysiotomy had to be done. Dehiscence of a portion of the cleft palate occurred in all cases (10 of 11) that survived the immediate postoperative period. A 2nd repair was attempted in 3 foals; however, dehiscence of the palate recurred. Osteomyelitis of the mandibular symphysis developed in 6 animals; dehiscence of the lower lip occurred in 3 animals. Serious complications after surgery led to euthanasia or death of 5 animals. Of the 6 surviving animals, 4 did not grow normally. All survivors experienced chronic nasal discharge often contaminated with food material. Although mandibular symphysiotomy provided adequate exposure for surgical repair of cleft palate, serious complications have not been overcome.


Soft Cysteine Signaling Network: The Functional Significance of Cysteine in Protein Function and the Soft Acids/Bases Thiol Chemistry That Facilitates Cysteine Modification.
The unique biophysical and electronic properties of cysteine make this molecule one of the most biologically critical amino acids in the proteome. The defining sulfur atom in cysteine is much larger than the oxygen and nitrogen atoms more commonly found in the other amino acids. As a result of its size, the valence electrons of sulfur are highly polarizable. Unique protein microenvironments favor the polarization of sulfur, thus increasing the overt reactivity of cysteine. Here, we provide a brief overview of the endogenous generation of reactive oxygen and electrophilic species and specific examples of enzymes and transcription factors in which the oxidation or covalent modification of cysteine in those proteins modulates their function. The perspective concludes with a discussion of cysteine chemistry and biophysics, the hard and soft acids and bases model, and the proposal of the Soft Cysteine Signaling Network: a hypothesis proposing the existence of a complex signaling network governed by layered chemical reactivity and cross-talk in which the chemical modification of reactive cysteine in biological networks triggers the reorganization of intracellular biochemistry to mitigate spikes in endogenous or exogenous oxidative or electrophilic stress.


Posterior transverse plication of the internal carotid artery to correct for kinking.
The occasional need for shortening of the internal carotid artery (ICA) following carotid endarterectomy (CEA) to correct for kinking is still controversial. Although several technical options have been suggested, the impact on perioperative outcome remains unclear, and long-term clinical follow-up is lacking. Shortening by resection has a theoretical risk for a twisted anastomosis and subsequent ICA thrombosis. Posterior transverse plication (PTP) offers an alternative shortening technique without the need for a new anastomosis. We aimed to assess the safety and patency of CEA with concomitant PTP. Secondly, we aimed to provide an overview of different technical modalities for shortening of the carotid artery in current literature. Within the time frame of 2000 through 2011, 29 patients (mean age, 73.4 years) undergoing CEA with additional PTP of the ICA and standardized patchplasty were retrospectively identified. Patient characteristics, surgical procedural details, and both short- (<30 days) and long- (>30 days) term clinical and duplex ultrasound follow-up were retrieved. Restenosis was defined as ≥50% stenosis on duplex ultrasound. In addition, a literature search was performed on different techniques for ICA shortening. Thirty-day outcome revealed no deaths or strokes. No postprocedural thrombosis or narrowing of the ipsilateral ICA was observed. During follow-up (mean, 34.3 months; range, 3-125 months), one patient (4%) died of a noncardiovascular cause. Three patients (11%) developed ipsilateral neurological symptoms (1 stroke, 2 transient ischemic attacks) after 5, 19, and 66 months follow-up, respectively. Of these, two patients (7%) had restenosis at the site of PTP. Asymptomatic restenosis occurred in one other patient (4%) after 16 months. Although the indications for additional shortening procedures following CEA need to be defined, in this small series, PTP as an additional shortening procedure of the ICA following CEA seems feasible and safe with no additional periprocedural risk for narrowing at the plicature or thrombosis of the endarterectomy plane. However, restenosis at the plicature may hamper the long term benefit of carotid reconstruction.


An Unusual Association of Idiopathic Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) With Interstitial Lung Disease (ILD).
Although the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is commonly associated with many lung conditions and drugs used for treating them, no literature describes a direct association between SIADH and interstitial lung disease. This case report discusses a 79-year-old male patient who presented to the emergency department (ED) with altered mental status following a fall. The patient had clinical symptoms and imaging findings concerning interstitial lung disease (ILD), and laboratory tests from the ER indicated severe hyponatremia and an increased white blood cell count, suggesting an unusual clinical picture. Detailed workup and medication reconciliation revealed no other medical conditions or intake of drugs associated with SIADH; however, the patient's low serum osmolality, high urine osmolality, high urine sodium, and improvement in serum sodium level with the initiation of 0.9% saline, salt tablets, and tolvaptan verify the presence of SIADH. While the association between SIADH and ILD is not well documented in medical literature, a few case reports from different regions have indicated a potential link, either through drug-induced ILD or SIADH resolution coinciding with ILD improvement. Hence, we describe a case of idiopathic SIADH, possibly associated with interstitial lung disease. This case demonstrates the importance of recognizing the coexistence of SIADH and ILD, as severe hyponatremia can lead to potential life-threatening neurological consequences.


Distance sets for shape filters and shape recognition.
We introduce a novel rich local descriptor of an image point, we call the (labeled) distance set, which is determined by the spatial arrangement of image features around that point. We describe a two-dimensional (2D) visual object by the set of (labeled) distance sets associated with the feature points of that object. Based on a dissimilarity measure between (labeled) distance sets and a dissimilarity measure between sets of (labeled) distance sets, we address two problems that are often encountered in object recognition: object segmentation, for which we formulate a distance sets shape filter, and shape matching. The use of the shape filter is illustrated on printed and handwritten character recognition and detection of traffic signs in complex scenes. The shape comparison procedure is illustrated on handwritten character classification, COIL-20 database object recognition and MPEG-7 silhouette database retrieval.


Psychophysiological responses to Salsa dance.
Speculation exists whether dance provides physiological stimuli adequate to promote health and fitness benefits. Unfortunately, research to date has not addressed the affective and exertional responses to dance. These responses are of interest as positive affective and exertional responses experienced during physical activity may play an important role in predicting adherence. The present study aims to examine the psychophysiological responses of different Salsa dance styles. Ten pairs of dancers performed two different structured lessons of Salsa dance, including Typical Salsa and Rueda de Casino lessons, and a non-structured Salsa dance at a night club. Physiological responses (i.e., percent of heart rate reserve; %HRR) were continuously assessed and perceived exertion and affective valence were rated every 15 min throughout the trials. %HRR responses differed between the Salsa dance styles (%HRR from 41.3 to 51.9%), and participants were dancing at intensities near their ventilatory threshold. Specifically, Typical Salsa lesson elicited lower %HRR responses than Rueda de Casino lesson (p < 0.05), but similar %HRR responses to Salsa dance at a night club condition (p > 0.05). Surprisingly, exertional (from 8 to 11) and affective (from +3 to +5) responses were unaffected by Salsa dance styles (p > 0.05). These data support that different Salsa dance styles provide physiological stimuli adequate to promote health and fitness benefits, and perhaps more importantly, produce pleasurable experiences, which in turn might lead to an increase in adherence to Salsa dancing which likely provides exercise-like health benefits.


[Inapparent charges for the assistance to nephropathic patient on dialysis].
The increasing technological effectiveness has undoubtedly produced an improvement in clinical parameters of dialysis patients, but this satisfactory therapeutic result did not follow an adequate improvement in mortality or in the perception of quality of life as per patients. Furthermore, dialysis treatment is often associated with "inapparent charges" that reduce the perception of well-being, independently of clinical changes. Thirty years ago, we carried out a national survey on inapparent charges, which represent frustrating aspects that negatively affect patients' perception of their quality of life. Thirty years later, it seemed important for us to repeat the survey to understand if Italian legislative remodeling have introduced changes in procedures and social aspects of dialysis, as preservation of quality of life is an important aspect of the replacement treatment.


No effect of adding brief dynamic therapy to pharmacotherapy in the treatment of obsessive-compulsive disorder with concurrent major depression.
Until now no studies have investigated the benefits of adding brief dynamic therapy (BDT) to medication in obsessive-compulsive disorder (OCD), while a number of recent investigations have demonstrated the efficacy of supplemental BDT among patients with major depressive disorders (MDD). The objective of the present study was to explore the efficacy of BDT combined with pharmacotherapy in comparison with pharmacotherapy alone in the treatment of OCD with concurrent MDD. A 12-month randomized clinical trial compared a standard selective serotonin reuptake inhibitor treatment with (n = 27) or without (n = 30) supplemental BDT in patients with OCD and concurrent MDD. Supplemental BDT was added during the first 16-week trial; all patients continued to be treated with only pharmacotherapy in the following continuation phase. The primary efficacy assessments were the Yale-Brown Obsessive Compulsive Scale and the 17-item Hamilton Rating Scale for Depression; the secondary efficacy measures included the Clinical Global Impression scale and the Global Assessment of Functioning. The data analysis was conducted on the 'intent-to-treat (ITT) efficacy patient sample'. Fifty patients completed the study. No difference between the 2 treatment groups was found at any point by any assessment method in the ITT study sample. Supplemental BDT in the treatment of patients with OCD with concurrent MDD who are receiving effective medication has no significant clinical effect on both obsessive and depressive symptoms.


Rapid absorbing gut suture versus 2-octylethylcyanoacrylate tissue adhesive in the epidermal closure of linear repairs.
While a variety of epidermal wound closure techniques are utilized, there are few evidence based studies comparing techniques in head-to-head studies. To compare the aesthetic outcomes and wound healing properties of 2 epidermal closure mechanisms: 2-octylethylcyanoacrylate adhesive and rapid absorbing gut suture in skin closures. A total of 8 patients were enrolled in this randomized right-left comparative trial. Patients were randomized for epidermal closure with one half of their wounds (chest [n=6] and upper extremities [n=2]) with tissue adhesive and the contralateral with rapid absorbing gut suture. Three months following wound closure, overall cosmetic outcome was slightly greater on the half closed with rapid absorbing gut suture (mean=3.56) relative to the tissue adhesive (mean=3.19, P=.05). For dyspigmentation, the half of the scar treated with the suture had a better outcome (mean=3.50) relative to tissue adhesive (mean=2.75) (P<.05). All other variables (i.e., scar thickness, wound approximation, patient outcome, and preference) were highly equivalent. Both rapid absorbing gut suture and tissue adhesive appear to be highly efficacious techniques for epidermal closure. It appears that tissue adhesive may not be as effective in achieving optimal cosmesis for defects after Mohs micrographic surgery on the trunk and extremities in follow-up at 3 months.


Evaluating the correspondence between face-, scene-, and object-selectivity and retinotopic organization within lateral occipitotemporal cortex.
The organization of human lateral occipitotemporal cortex (lOTC) has been characterized largely according to two distinct principles: retinotopy and category-selectivity. Whereas category-selective regions were originally thought to exist beyond retinotopic maps, recent evidence highlights overlap. Here, we combined detailed mapping of retinotopy, using population receptive fields (pRF), and category-selectivity to examine and contrast the retinotopic profiles of scene- (occipital place area, OPA), face- (occipital face area, OFA) and object- (lateral occipital cortex, LO) selective regions of lOTC. We observe striking differences in the relationship each region has to underlying retinotopy. Whereas OPA overlapped multiple retinotopic maps (including V3A, V3B, LO1, and LO2), and LO overlapped two maps (LO1 and LO2), OFA overlapped almost none. There appears no simple consistent relationship between category-selectivity and retinotopic maps, meaning category-selective regions are not constrained spatially to retinotopic map borders consistently. The multiple maps that overlap OPA suggests it is likely not appropriate to conceptualize it as a single scene-selective region, whereas the inconsistency in any systematic map overlapping OFA suggests it may constitute a more uniform area. Beyond their relationship to retinotopy, all three regions evidenced strongly retinotopic voxels, with pRFs exhibiting a significant bias towards the contralateral lower visual field, despite differences in pRF size, contributing to an emerging literature suggesting this bias is present across much of lOTC. Taken together, these results suggest that whereas category-selective regions are not constrained to consistently contain ordered retinotopic maps, they nonetheless likely inherit retinotopic characteristics of the maps from which they draw information.


Malignant hypertension in a patient with primary aldosteronism with elevated active renin concentration.
A 40-year-old male, with a past history of hypertension but receiving no medical treatment, was referred. He manifested malignant hypertension (190/130 mmHg; Keith-Wagener III), renal dysfunction (serum creatinine, 3.8 mg/dl), and elevated plasma aldosterone (450 pg/ml) and active renin concentration (ARC, 104 pg/ml). His blood pressure was controlled with multiple antihypertensive agents and ARC thus decreased (4.3 pg/ml), but aldosterone remained elevated. Abdominal magnetic resonance imaging (MRI) revealed a right adrenal adenoma, and aldosterone-producing adenoma was confirmed by adrenal venous sampling. Primary aldosteronism very rarely develops to malignant hypertension, and even in that case ARC is suppressed. Therefore this is a rare case of primary aldosteronism complicated with malignant hypertension and high ARC.


[The stress-limiting action of low-intensity laser radiation in patients with ischemic heart disease].
In 20 patients with exercise-induced angina, the cold test brought about activated lipid peroxidation, modified the lipid phase of a red cell membrane, which correlated with systolic changes. Following a month laser therapy, it did not cause no activation of lipid peroxidative processes, significant changes in the organization of a cell membrane lipid bilayer, or any profound cardiac performance abnormalities, which gives grounds to state that laser radiation exerts membrane-stabilizing and antistress effects. The findings suggest that laser therapy should be used in coronary heart disease patients having a functional component of coronary insufficiency.


Immunostimulant properties of a cell wall-modified whole Saccharomyces cerevisiae strain administered by diet to seabream (Sparus aurata L.).
The possible differences in the immunostimulant effects between whole wild Saccharomyces cerevisiae and a mutant strain (fks-1) administered in the diet to gilthead seabream (Sparus aurata L.) were studied. Fish were fed diets containing 0 (control) or 10 g whole wild yeast or fks-1 strain per kilogram feed for 2, 4 or 6 weeks. After each sampling, the innate humoral (complement, lysozyme and peroxidases) and cellular (intracellular peroxidases, phagocytosis, respiratory burst activity and cytotoxicity) responses were determined. Among the humoral responses, serum peroxidases and complement activity were significantly decreased after 6 weeks of feeding with the fks-1 strain-supplemented diet, while lysozyme activity increased after 2 and 4 weeks of feeding the fks-1 strain. Of the cellular responses studied, phagocytosis was increased to a significant degree at all the assayed times but only by the fks-1 strain-supplemented diet, while respiratory burst activity (after 4 weeks) and natural cytotoxicity (after 4 and 6 weeks) increased with either yeast strain. The intracellular peroxidase content was not affected by the dietary supplementation of either yeast strain. These results are discussed with a view to assessing the possible use of wild and/or mutant yeast strains for immunostimulant purposes in aquaculture.


Cementless total hip arthroplasty for primary osteoarthritis in patients aged 55 years and older.
Cemented total hip arthroplasty has been the treatment of choice for elderly patients with osteoarthritis. We analyzed survival rates of the most common cementless designs used in this age group in Finland. Inclusion criteria permitted 10,310 replacements (8 designs) performed in patients aged 55 years or older to be selected for evaluation. The risk of revision of each of the 8 implants was compared with that of a group comprising 3 cemented designs as the reference (9,549 replacements). Survival analyses were performed overall and separately for 3 age cohorts: 55-64 years (6,781 replacements), 65-74 years (8,821 replacements), and 75 years or older (4,257 replacements). In all patients aged 55 years or more, the Bi-Metric stem had a higher survival rate for aseptic loosening at 15 years than the cemented reference group: 96% (95% CI: 94-98) vs. 91% (CI: 90-92). However, the 15-year survival rates of the Bi-Metric/Press-Fit Universal (71% (CI: 67-75)) and the Anatomic Mesh/Harris-Galante II (72% (CI: 67-78)) total hip replacements were lower than that of the reference group (86% (CI: 84-87)). Information was scarce for patients aged 75 years or more. Cementless proximal porous-coated stems are a good option for elderly patients. Even though biological fixation is a reliable fixation method in THA, polyethylene wear and osteolysis remain a serious problem for cementless cup designs with unplugged screw holes and low-quality liners.


Properties and sensing characteristics of surface-plasmon resonance in infrared light.
Conditions of surface-plasmon resonance (SPR) production with use of IR pumping light (800-2300 nm) in the Kretschmann-Raether prism arrangement were investigated. Both calculations and experimental data showed that SPR characteristics in the IR are strongly influenced by the properties of the coupling prism material. Indeed, quite different regularities of plasmon excitation, polarity of sensing response, and sensitivity are observed for two different glasses and silicon. The observed differences in SPR properties are related to essentially different behavior of dispersion characteristics of materials near the SPR coupling point. Methods for improving sensor performance and miniaturizing the SPR technique using novel coupling materials (silicon) are discussed.


Supraventricular pacemaker underdrive in the absence of sinus nodal influences in the conscious dog.
The ability to reduce and maintain heart rate by electrical stimulation (underdrive) was tested in three groups of chronically instrumented dogs: sinoatrial node intact, ectopic atrial pacemaker produced by injection of rapidly hardening latex into the sinoatrial nodal artery, and idioventricular pacemaker produced by injection of formalin into the atrioventricular node. In the conscious unsedated state, underdrive of sinoatrial or idioventricular pacemakers resulted in competition between driven and intrinsic foci. However, the cycle length of ectopic atrial pacemakers could be increased by 148.4 +/- 30.7 msec (P less than 0.001) and maintained at that value. Cessation of underdrive resulted in a period of pacemaker suppression similar to that produced following overdrive. Single premature stimuli produced marked cycle length prolongations in dogs with ectopic atrial foci. Total autonomic blockade had no significant effect on the production of underdrive. Thus, the results of the present experiments provide evidence for maintained capture of cardiac pacemakers at rates significantly below intrinsic control and indicate that underdrive varies as a function of pacemaker site. Underdrive may explain the failure of junctional escape in the presence of slower atrial rhythms.


Socket preservation and implant insertion in a smoker with a 10-year history of bisphosphonate use: a case report.
A 63-year-old woman was seen as self-referred at the School of Dental Medicine, State University of New York at Buffalo, for the evaluation and management of a root perforation on a maxillary premolar (or bicuspid). The tooth was diagnosed as untreatable and extraction was indicated. Simultaneously, the patient was advised that tooth number 14 was missing and offered options for replacing the missing tooth. The patient was informed about the risks associated with both smoking habits and bisphosphonate intake. Amoxicillin was started the day prior to extraction and continued for 10 days. The tooth was extracted without raising the flaps, and the socket was degranulated and filled with calcium sulfate (DentoGen) and 50% cortical/50% cancellous bone allograft (AlloOss). The orifice was protected with a collagen barrier (Conform). The patient applied chlorhexidine over the wound site (bid) for 14 days; follow-up visits were at 2, 7, 14 and 21 days. Although the patient continued smoking, healing was uneventful. After 4 months, 2 implants (Nobel Biocare) were inserted to replace missing teeth. The full thickness flap was raised and completely repositioned after insertion. Healing was uneventful. Three months later, implants were exposed using a diode laser and were prepared for restoration. Implants were clinically stable and no soft/hard tissues deficiencies were noted. This clinical case may indicate that a minimally invasive surgical extraction combined with regenerative techniques and antibiotic/antimicrobial therapy, followed by implant placement with complete wound closure, may be considered when treating patients with known health risk factors.


Fatty Acids in Blue-Green Algal Mat Communities.
The concentrations of the major fatty acids were determined for the varied layers of an algal mat community. The living mat contains substantial amounts of the unsaturated acids, while the underlying layers become progressively depleted in unsaturated molecules. A similar progressive increase in the ratio of saturated to unsaturated acids was detected in a sediment core from a hypersaline lagoon.


Epidemiology and diagnosis of health care-associated infections in the NICU.
Health care-associated infections in the NICU are a major clinical problem resulting in increased morbidity and mortality, prolonged length of hospital stays, and increased medical costs. Neonates are at high risk for health care-associated infections because of impaired host defense mechanisms, limited amounts of protective endogenous flora on skin and mucosal surfaces at time of birth, reduced barrier function of neonatal skin, the use of invasive procedures and devices, and frequent exposure to broad-spectrum antibiotics. This statement will review the epidemiology and diagnosis of health care-associated infections in newborn infants.


Inotropes and vasopressors use in cardiogenic shock: when, which and how much?
Data and interventional trials regarding vasopressor and inotrope use during cardiogenic shock are scarce. Their use is limited by their side-effects and the lack of solid evidence regarding their effectiveness in improving outcomes. In this article, we review the current use of vasopressor and inotrope agents during cardiogenic shock. Two recent Cochrane analyses concluded that there was not sufficient evidence to prove that any one vasopressor or inotrope was superior to another in terms of mortality. A recent RCT and a meta-analysis on individual data suggested that norepinephrine may be preferred over epinephrine in patients with cardiogenic shock . For inotrope agents, when norepinephrine fails to restore perfusion, dobutamine represents the first-line agent. Levosimendan is a calcium sensitizer agent, which improves acute hemodynamics, albeit with uncertain effects on mortality. When blood pressure needs to be restored, norepinephrine is a reasonable first-line agent. Dobutamine is the first-line inotrope agent wheraes levosimendan can be used as a second-line agent or preferentially in patients previously treated with beta-blockers. Current information regarding comparative effective outcomes is nonetheless sparse and their use should be limited as a temporary bridge to recovery, mechanical circulatory support or heart transplantation.


Opiate agonists and antagonists modulate taste perception in opiate-maintained and recently detoxified subjects.
Heroin addicts consume large quantities of refined sugars. This study investigated the effect of opiate use and antagonism on sweet taste in opiate-maintained drug users and detoxified former chronic opiate users, using a within-subject design. Seven opiate users received methadone and seven buprenorphine maintenance. Six detoxified subjects received naltrexone. Sucrose recognition thresholds and measurements of pleasantness and intensity were determined before and four hours after 1) a single dose of methadone or buprenorphine or 2) naltrexone. Control data were taken from a cohort of healthy volunteers including smokers. All measures of sweet and salt taste perception were significantly greater in opiate users and recently detoxified subjects compared to control subjects, with the exception of sweet pleasantness, which returned to control level after detoxification. Acute methadone administration reduced salt thresholds and unpleasantness to control levels. Increased sweet thresholds and salt unpleasantness in detoxified subjects were reversed by acute opioid antagonism, returning to control levels. These results suggest that opiate use and antagonism alters taste perception. Some of the alterations reverse on detoxification (sweet pleasantness), and others can be reversed by opioid antagonism (sweet threshold, salt unpleasantness). Changes in taste perception may underlie altered consumption of refined sugars in opiate users.


Influence of GATC sequences on Escherichia coli DNA mismatch repair in vitro.
The effect of the number and position of DNA adenine methylation (dam) sites, i.e., d(GATC) sequences, on mismatch repair in Escherichia coli was investigated. The efficiency of repair was measured in an in vitro assay which used an f1 heteroduplex containing a G/T mismatch within the single EcoRI site. Both an increase in the number of dam sites and a shortened distance between dam site and mismatched site increased the efficiency of mismatch repair. The sequences adjacent to d(GATC) also affected the efficiency of methylation-directed mismatch repair. Furthermore, heteroduplexes with one extra dam site located close to either the 5' or 3' end of the excised base increased the repair efficiency to about the same extent. The findings suggest that the mismatch repair pathway has no preferred polarity.


[Corrective action of bacillary probiotic on the immune system of animals in experimential dysbacteriosis].
Is established that at intestinal dysbacteriosis in the organism of experimental animals develop reactions of inflammatory type (early and late), leading to an accumulation in the blood serum of humoral immunity factors, blocking reactions mediated by lymphocytes ormacrophages, while maintaining their cytotoxic activity. Introduction of animals of tne probiotic endosporin promotes restoration of quantitative and qualitative indicators of intestinal microbiocenosis and the normalization of the immune system.


Linguistically complex recognition prompts in pre-recorded cross-examinations.
This study examined the effects of pre-trial preparation and pre-recorded cross-examinations on the linguistic complexity of recognition prompts (i.e., option-posing or suggestive questions) used when questioning child victims in English criminal courts. The study also compared the linguistic complexity of recognition prompts that did and did not contain suggestive content. Analyses compared 43 cases that involved pre-recorded cross-examinations with pre-trial preparation and 44 cases that did not, which occurred between 2012 and 2016. Cases utilizing the "special measures" contained fewer linguistically complex prompts with and without suggestive content than did their counterparts, demonstrating the benefits of those special measures. Overall, linguistically complex recognition prompts were more likely to contain suggestive content than other recognition prompts. However, linguistically complex prompts with and without suggestive content were still frequently used despite the special measures, demonstrating the need for further professional training to improve the quality of children's evidence.


3D bioprinting of conductive hydrogel for enhanced myogenic differentiation.
Recently, hydrogels have gained enormous interest in three-dimensional (3D) bioprinting toward developing functional substitutes for tissue remolding. However, it is highly challenging to transmit electrical signals to cells due to the limited electrical conductivity of the bioprinted hydrogels. Herein, we demonstrate the 3D bioprinting-assisted fabrication of a conductive hydrogel scaffold based on poly-3,4-ethylene dioxythiophene (PEDOT) nanoparticles (NPs) deposited in gelatin methacryloyl (GelMA) for enhanced myogenic differentiation of mouse myoblasts (C2C12 cells). Initially, PEDOT NPs are dispersed in the hydrogel uniformly to enhance the conductive property of the hydrogel scaffold. Notably, the incorporated PEDOT NPs showed minimal influence on the printing ability of GelMA. Then, C2C12 cells are successfully encapsulated within GelMA/PEDOT conductive hydrogels using 3D extrusion bioprinting. Furthermore, the proliferation, migration and differentiation efficacies of C2C12 cells in the highly conductive GelMA/PEDOT composite scaffolds are demonstrated using various in vitro investigations of live/dead staining, F-actin staining, desmin and myogenin immunofluorescence staining. Finally, the effects of electrical signals on the stimulation of the scaffolds are investigated toward the myogenic differentiation of C2C12 cells and the formation of myotubes in vitro. Collectively, our findings demonstrate that the fabrication of the conductive hydrogels provides a feasible approach for the encapsulation of cells and the regeneration of the muscle tissue.


Irreversible Adsorption Governs the Equilibration of Thin Polymer Films.
We demonstrate that the enhanced segmental motion commonly observed in spin cast thin polymer films is a nonequilibrium phenomenon. In the presence of nonrepulsive interfaces, prolonged annealing in the liquid state allows, in fact, recovering bulk segmental mobility. Our measurements prove that, while the fraction of unrelaxed chains increases upon nanoconfinement, the dynamics of equilibration is almost unaffected by the film thickness. We show that the rate of equilibration of nanoconfined chains does not depend on the structural relaxation process but on the feasibility to form an adsorbed layer. We propose that the equilibration of the thin polymer melts is driven by the slow relaxation of interfacial chains upon irreversible adsorption on the confining walls.


An indirubin derivative, E804, exhibits potent angiosuppressive activity.
Angiogenesis, the development of neovessels from pre-existing vessels, is obligatory for solid tumors survival, growth, invasion, and metastasis. Many anti-angiogenic agents are small molecules originated from natural sources. Recently, angiosuppressive effects of indirubin and its derivatives, the active components in indigo-producing herbs, have been shown to possess anti-viral and anti-inflammatory potentials. In this study, we identified another indirubin derivative, indirubin-3'-(2,3 dihydroxypropyl)-oximether (E804), could exhibit potent angiosuppressive effects. In vitro study showed that E804 could significantly inhibit human umbilical vein endothelial cells proliferation, migration, and tube formation in a concentration-dependent manner (0.4-40 μM); at the concentration of 1 μmol or above, angiosuppressive potency of E804 was found to be more significant than indirubin-3'-oxime. Using in vivo Matrigel plug model and directed-in vivo-angiogenesis-assay (DIVAA), E804 was shown more effective to attenuate the VEGF/bFGF-induced neovessel formation. The hemoglobin content and the invaded endothelial cells in the implants were also greatly reduced. Results from the aortic ring assay indicated E804 (4 μM) could completely suppress ex vivo sprouting of endothelial cells from the rat aorta fragments; with concomitant reduction of gelatinolytic activities of matrix metalloproteinase-2 and -9. E804 also concentration-dependently (0.04-10 μM) inhibited the subintestinal vessels formation in zebrafish embryos. This study provides the first evidence that E804, a novel indirubin derivative, could more effectively inhibit angiogenesis. With the improved anti-angiogenic potency when compared with indirubin-3'oxime, E804 would be a new potential candidate in the treatment of angiogenesis-dependent diseases.


NG-DTA: Drug-target affinity prediction with n-gram molecular graphs.
Drug-target affinity (DTA) prediction is crucial to speed up drug development. The advance in deep learning allows accurate DTA prediction. However, most deep learning methods treat protein as a 1D string which is not informative to models compared to a graph representation. In this paper, we present a deep-learning-based DTA prediction method called N-gram Graph DTA (NG-DTA) that takes molecular graphs of drugs and n-gram molecular sub-graphs of proteins as inputs which are then processed by graph neural networks (GNNs). Without using any prediction tool for protein structure, NG-DTA performs better than other methods on two datasets in terms of concordance index (CI) and mean square error (MSE) (CI: 0.905, MSE: 0.196 for the Davis dataset; CI: 0.904, MSE: 0.120 for Kiba dataset). Our results showed that using n-gram molecular sub-graphs of proteins as input improves deep learning models' performance in DTA prediction.


Thirteenth Annual Lenna Frances Cooper Memorial Lecture: Nutrition education-what comes next?
Education for normal nutrition must include preventive measures against the principal health problems of the day, namely cardiovascular and gastrointestinal diseases. Preventive nutrition denotes a sufficiency of all nutrients for normal metabolic processes and the avoidance of excesses of calories, salurated fat, cholesterol, simple carbohydrates, and refined foods. The dietitian is uniquely qualified to interpret nutritional science and to apply it to daily food choices by people and must assume leadership in all program development for nutrition education, including nutrition education programs in the nation's schools. For effective, preventive nutrition education, new perspectives are needed to overcome the limitations of the simplistic, traditional approach.


Criminal legal involvement among recently separated veterans: Findings from the LIMBIC study.
This study investigated individual-level and neighborhood-level predictors of criminal legal involvement of veterans during the critical transition period from military to civilian life. We hypothesized that substance use, mental health, and personality disorders will increase the incidence of criminal legal involvement, which will be highest among veterans living in socioeconomically disadvantaged neighborhoods after military discharge. We analyzed data from a longitudinal cohort study of 418,624 veterans who entered Department of Veterans Affairs (VA) health care after leaving the military. Department of Defense (DoD) data on clinical diagnoses, demographics, and military history were linked to VA data on neighborhood of residence and criminal legal involvement. Criminal legal involvement in the 2 years following military discharge was most strongly predicted by younger age, substance use disorder, and being male. Other predictors included the military branch in which veterans served, deployment history, traumatic brain injury, serious mental illness, personality disorder, having fewer physical health conditions, and living in socioeconomically disadvantaged neighborhoods. These factors combined in multivariable analysis yielded a very large effect size for predicting criminal legal involvement after military separation (area under the curve = .82). The incidence of criminal legal involvement was 10 times higher among veterans with co-occurring substance use disorder, serious mental illness, and personality disorder than among veterans with none of these diagnoses, and these rates were highest among veterans residing in more socioeconomically disadvantaged neighborhoods. To our knowledge, this is the largest longitudinal study of risk factors for criminal legal involvement in veterans following military discharge. The findings supported the hypothesis that veterans with co-occurring mental disorders living in socioeconomically disadvantaged neighborhoods were at higher risk of criminal legal involvement, underscoring the complex interplay of individual-level and neighborhood-level risk factors for criminal legal involvement after veterans leave the military. These results can inform policy and programs, such as the DoD Transition Assistance Program (TAP) and the VA Military to Civilian Readiness Pathway program (M2C Ready), to enhance community reintegration and prevent criminal legal involvement among veterans transitioning from military to civilian life. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Update on phase II studies of erythropoietin in acute myocardial infarction. Rationale and design of Exogenous erythroPoietin in Acute Myocardial Infarction: New Outlook aNd Dose Association Study (EPAMINONDAS).
Erythropoietin (Epo) is a hematopoietic hormone produced mainly by the kidneys in response to hypoxia. Recent acquisitions in the fields of hematology, neurology, cardiology, and experimental medicine show cytoprotective, angiogenetic and antiinflammatory effects of Epo. Exogenous erythroPoietin in Acute Myocardial Infarction: New Outlook aNd Dose Association Study (EPAMINONDAS, EudraCTno. 200500485386) is one of four ongoing randomized controlled trials, each testing the effects of Epo in >or=100 patients with STEMI. EPAMINONDAS is a multicenter, prospective, double-blind, placebo-controlled, dose-finding study assessing intravenous moderate doses of human recombinant Epo (epoietin-alpha, 100 or 200 IU/kg/die) versus placebo, given on the first 3 days, in 102 patients with first ST-segment elevation myocardial infarction. Initial dosing is within 12 h of primary percutaneous coronary revascularization. The primary endpoint is infarct size, quantified by CK-MB time-concentration curve, left ventricular wall motion score index, and pattern of contrast-enhanced magnetic resonance imaging. Secondary endpoints are ischemic recurrences, ventricular remodelling, and safety events, assessed in-hospital and at 12 months' follow-up. The results of current phase II studies will help define the safety/efficacy profile of Epo for patients with STEMI.


Cognition-Mortality Associations Are More Pronounced When Estimated Jointly in Longitudinal and Time-to-Event Models.
With aging populations worldwide, there is growing interest in links between cognitive decline and elevated mortality risk-and, by extension, analytic approaches to further clarify these associations. Toward this end, some researchers have compared cognitive trajectories of survivors vs. decedents while others have examined longitudinal changes in cognition as predictive of mortality risk. A two-stage modeling framework is typically used in this latter approach; however, several recent studies have used joint longitudinal-survival modeling (i.e., estimating longitudinal change in cognition conditionally on mortality risk, and vice versa). Methodological differences inherent to these approaches may influence estimates of cognitive decline and cognition-mortality associations. These effects may vary across cognitive domains insofar as changes in broad fluid and crystallized abilities are differentially sensitive to aging and mortality risk. We compared these analytic approaches as applied to data from a large-sample, repeated-measures study of older adults (N = 5,954; ages 50-87 years at assessment; 4,453 deceased at last census). Cognitive trajectories indicated worse performance in decedents and when estimated jointly with mortality risk, but this was attenuated after adjustment for health-related covariates. Better cognitive performance predicted lower mortality risk, and, importantly, cognition-mortality associations were more pronounced when estimated in joint models. Associations between mortality risk and crystallized abilities only emerged under joint estimation. This may have important implications for cognitive reserve, which posits that knowledge and skills considered well-preserved in later life (i.e., crystallized abilities) may compensate for declines in abilities more prone to neurodegeneration, such as recall memory and problem solving. Joint longitudinal-survival models thus appear to be important (and currently underutilized) for research in cognitive epidemiology.


[Mechanism of magnetosensitive binding of ions by certain proteins].
For the first time a consistent physical model is proposed that explains a weak ELF magnetic fields effect on biological systems. The probability density changes are calculated in the context of an idealized quantum model for an ion within a protein under the magnetic field modulated on the magnitude. The dissociation probability of an ion-protein complex is shown to depend on the magnetic field parameters. It is the consequence of an interference of angular modes of an ion wave function.


δ-Valerolactamic Quaternary Amino Acid Derivatives: Enantiodivergent Synthesis and Evidence for Stereodifferentiated β-Turn-Inducing Properties.
Enantiopure (R) and (S) cyclic α,α-disubstituted amino acid derivatives displaying a δ-valerolactam side chain were prepared from a common isoxazolidine precursor. The (R)-configured δ-valerolactam 11 was converted into diastereoisomeric pseudopeptides to investigate its ability to induce secondary structures in peptidomimetics. Conformational studies of these pseudopeptides were carried out in the solid state (X-ray diffraction), in solution (NMR analyses), and in silico (computer-aided conformational analysis), which demonstrated that such quaternary amino acids induce β-turn conformations stable enough to be retained in polar media (DMSO). Incorporation of this new type of α,α-disubstituted amino acid into a representative pseudopeptidic sequence by N- then C-elongation and N-debenzylation is also described herein and could serve for the synthesis of various structured peptidomimetics.


Photon scattering measurement of calcaneal bone density: result of in vivo cross-sectional studies.
The density of trabecular bone in the os calcis has been measured in 321 subjects using a gamma ray scattering technique. In normal subjects it was shown that density could be predicted from body weight and age with a standard error of 5.6%. It was also shown that the dependence of density upon weight and age was the same for both sexes. When the os calcis had been subjected to a greater than normal mechanical stress by either increased physical activity or excessive body weight, trabecular bone density was increased. Density was measured in 128 patients in whom the incidence of skeletal demineralization was expected to be greater than that in control subjects. Some significant reductions in density were observed. It is projected that density measurements might be of value in those situations where, in response to metabolic stress, the rate of loss of mineral from trabecular bone is greater than that from cortical bone.


Microreactor array device.
We report a device to fill an array of small chemical reaction chambers (microreactors) with reagent and then seal them using pressurized viscous liquid acting through a flexible membrane. The device enables multiple, independent chemical reactions involving free floating intermediate molecules without interference from neighboring reactions or external environments. The device is validated by protein expressed in situ directly from DNA in a microarray of ~10,000 spots with no diffusion during three hours incubation. Using the device to probe for an autoantibody cancer biomarker in blood serum sample gave five times higher signal to background ratio compared to standard protein microarray expressed on a flat microscope slide. Physical design principles to effectively fill the array of microreactors with reagent and experimental results of alternate methods for sealing the microreactors are presented.


Measuring energy expenditure in cardiac patients using the Body Media Armband versus indirect calorimetry. A validation study.
The purpose of this study was to compare differences in energy expenditure using the newly developed SenseWear Armband body monitor to indirect calorimetry in cardiac rehabilitation patients. Twenty-four (62+/-8.1 years) patients completed steady state exercise for 8 minutes on 4 modes of exercise (arm ergometry, treadmill walking, recumbent stepping and rowing ergometry). Total cumulative kilojoules were recorded simultaneously by indirect calorimetry and the SenseWear Armband. Statistical analyses assessed the degree of agreement between the 2 measurement methods and 3 different versions of the SenseWear software. The correlations between indirect calorimetry and version 2.2 of the SenseWear armband for arm and rowing ergometry, the treadmill and recumbent stepper were r=0.90, r=0.67, r=0 .80 and r=0.74, respectively. There were no between method differences during arm ergometry (p<1.000) and the recumbent stepper (p<0.102). Bland and Altman plots revealed the greatest spread of scores for the rower and the treadmill. Between method differences were minimal when using the preliminary cardiac software. The correlations for arm and rowing ergometry, the treadmill and recumbent stepper were r=0.90, r=0.84, r=0.78 and r=0.82, respectively. The accuracy of the BodyMedia SenseWear Armband appears to be exercise modality dependent in those with heart disease when using software developed for the general population. Therefore, the information should be interpreted cautiously, particularly during treadmill walking and rowing. Initial experiments with cardiac-focused software are promising, but preliminary.


Antigenic promotion. Increase in hapten-specific plaque-forming cells after pre-injection with structurally unrelated macromolecules.
Rabbits were immunized with p-azobenzene arsonic acid derivatives of human serum albumin (HA-As) or of dissociated keyhole limpet hemocyanin. The IgM response to the hapten was evaluated in terms of the number of hapten-specific plaque-forming cells in the lymph node draining the injection site. In some experiments, antibody was measured by agglutination of tanned and sensitized erythrocytes. The hapten response of animals immunized with HA-As was increased (promoting effect) when the animals were injected with one of several structurally unrelated macromolecules: keyhole limpet hemocyanin (KLH), horse spleen ferritin (HSF), lysozyme (Lys), alum-precipitated human gamma globulin (alum-precipitated HGG). Different macromolecules differed in the magnitude of the promoting effect they induced, e.g., promotion by the associated form of KLH was greater than that by the dissociated form; alum-precipitated HGG was a better promoter than was soluble HGG. The relative magnitude of promotion by different macromolecules (associated vs. dissociated KLH, alum-precipitated vs. soluble HGG) correlated with the relative magnitude of the carrier effect, as judged by the hapten response induced by p-azobenzene arsonic acid conjugated to various proteins. Promotion was detected by agglutination assay of circulating antibody, by plaque assay of cells from the popliteal lymph node draining the site of preinjection, but not by plaque assay of cells from the contralateral lymph node. Promotion was dependent on the dose of the promoting macromolecule and on the dose of the hapten-protein conjugate. It was not observed in animals tolerant to the promoting macromolecule. Inhibition (i.e. antigenic competition), rather than promotion, was observed upon a secondary response to the preinjected macromolecule or when the hapten-protein conjugate was incorporated in Freund's adjuvant.


Whole genome sequencing identifies a deletion in protein phosphatase 2A that affects its stability and localization in Chlamydomonas reinhardtii.
Whole genome sequencing is a powerful tool in the discovery of single nucleotide polymorphisms (SNPs) and small insertions/deletions (indels) among mutant strains, which simplifies forward genetics approaches. However, identification of the causative mutation among a large number of non-causative SNPs in a mutant strain remains a big challenge. In the unicellular biflagellate green alga Chlamydomonas reinhardtii, we generated a SNP/indel library that contains over 2 million polymorphisms from four wild-type strains, one highly polymorphic strain that is frequently used in meiotic mapping, ten mutant strains that have flagellar assembly or motility defects, and one mutant strain, imp3, which has a mating defect. A comparison of polymorphisms in the imp3 strain and the other 15 strains allowed us to identify a deletion of the last three amino acids, Y313F314L315, in a protein phosphatase 2A catalytic subunit (PP2A3) in the imp3 strain. Introduction of a wild-type HA-tagged PP2A3 rescues the mutant phenotype, but mutant HA-PP2A3 at Y313 or L315 fail to rescue. Our immunoprecipitation results indicate that the Y313, L315, or YFLΔ mutations do not affect the binding of PP2A3 to the scaffold subunit, PP2A-2r. In contrast, the Y313, L315, or YFLΔ mutations affect both the stability and the localization of PP2A3. The PP2A3 protein is less abundant in these mutants and fails to accumulate in the basal body area as observed in transformants with either wild-type HA-PP2A3 or a HA-PP2A3 with a V310T change. The accumulation of HA-PP2A3 in the basal body region disappears in mated dikaryons, which suggests that the localization of PP2A3 may be essential to the mating process. Overall, our results demonstrate that the terminal YFL tail of PP2A3 is important in the regulation on Chlamydomonas mating.


Can Ciprofloxacin be Used for Precision Treatment of Gonorrhea in Public STD Clinics? Assessment of Ciprofloxacin Susceptibility and an Opportunity for Point-of-Care Testing.
Background: Given the lack of new antimicrobials to treat Neisseria gonorrhoeae (NG) infections, reusing previously recommended antimicrobials has been proposed as a strategy to control the spread of multi-drug-resistant NG. We assessed ciprofloxacin susceptibility in a large sample set of NG isolates and identified correlates associated with ciprofloxacin-resistant NG infections. Methods: NG isolates collected in Baltimore, Maryland between 2014 and 2016 were evaluated by Gyrase A (gyrA) PCR and E-test for susceptibility to ciprofloxacin. Clinical characteristics and demographics were evaluated by multivariate regression analysis to identify correlates of ciprofloxacin-resistant NG infections. Results: 510 NG isolates from predominately African American (96.5%), heterosexual (85.7%), and HIV-negative (92.5%) male subjects were included in the study. The overall percentage of isolates with mutant gyrA sequences, indicative of ciprofloxacin resistance, was 32.4%, and significantly increased from 24.7% in 2014 to 45.2% in 2016 (p < 0.001). Participants older than 35 years of age were 2.35 times more likely to have a gyrA mutant NG infection than younger participants (p < 0.001). Race, sexual orientation, symptomology, or co-infection the HIV or syphilis were not associated with a particular NG gyrA genotype. Conclusions: Resistance to ciprofloxacin in Baltimore is lower than other regions and indicates that in this environment, use of ciprofloxacin may be appropriate for targeted treatment provided utilization of enhanced surveillance tools. The targeted use of ciprofloxacin may be more beneficial for individuals under 35 years of age. Point-of-care tests for NG diagnosis and susceptibility testing are urgently needed to identify individuals who can be treated with this targeted approach.


Response of pregnant and lactating sows to reduced protein content in complete compound feed.
The experimental material consisted of 42 sows divided into 3 feeding groups, each containing 14 sows fed complete compound feed varying in protein content. Protein and amino acid content of the feed fed to the control group was in compliance with Polish standards. Protein content in the experimental groups was reduced by 10% and 20%, respectively. At the same time, lysine, methionine, threonine and tryptophane content was supplemented to the level of the control group. All pregnant and lactating sows were fed individually. The condition of the sows was determined by measuring the thickness of backfat at the P2 position on days 30 and 105 of pregnancy and on day 25 of lactation. The data analyzed in the study included: the total number of piglets born, their body weight gain, milk composition, weaning-to-estrus interval and the farrowing rate. Protein content of the compound feed did not have a significant impact on the increment in backfat during pregnancy and losses during lactation. The sows fed compound feed with reduced protein content gave birth to 0.7 and 0.6 less piglets per litter than the control animals. However, due to lower losses, they bred 0.3 and 0.4 more piglets than the control sows. Average body weight of a piglet on day 21 was 0.5 kg lower in the experimental than in the control group. Dry matter, protein, fat and lactose content of the sow's milk did not depend on protein content of the feed. The weaning-to-estrus interval in the experimental groups was one day longer than in the control group. The reproductive rate accounted for 86% and was comparable in all the groups.


Vertical stiffness and muscle strain in professional Australian football.
Abstract The purpose of this study was to establish if vertical stiffness was greater in professional Australian rules footballers who sustained a lower limb skeletal muscle strain compared to those who did not, and to establish if a relationship between age, or training history, and vertical stiffness existed. Thirty-one participants underwent weekly rebound jump testing on a force platform over two seasons. Vertical stiffness was calculated for injured players and the uninjured cohort 1 and 3 weeks prior to sustaining an injury and at the end of preseason. Eighteen athletes were in the "uninjured" cohort and 13 in the "injured" cohort. No significant difference in vertical stiffness was observed between groups (P = 0.18 for absolute stiffness; P = 0.08 for stiffness relative to body mass), within groups (P = 0.83 and P = 0.88, respectively) or for a time*cohort interaction (P = 0.77 and P = 0.80, respectively). No relationship between age and vertical stiffness existed (r = -0.06 for absolute and relative stiffness), or training history and vertical stiffness (r = -0.01 and 0.00 for absolute and relative stiffness, respectively) existed. These results and others lend to suggest that vertical stiffness is not related to lower limb muscle strain injury.


Characterizing interface shape evolution in immiscible polymer blends via 3D image analysis.
The coordinate transformation (CT) method was applied to measure the local curvature of the interface of an immiscible polymer blend made of fluorescently labeled polystyrene (FLPS) and styrene-ran-acrylonitrile copolymer (SAN). The CT method involves the local parametrization of the interface by a quadratic polynomial to compute the local values of the mean (H) and the Gaussian (K) curvatures. Distributions of the curvatures at different annealing times were obtained by measuring H and K at many (typically 10(7)) points on the interface. Coarsening of a symmetric (50/50 w/w FLPS/SAN) and a nonsymmetric (35/65 w/w) blend was monitored. For the symmetric blend, two regimes of surface evolution were identified: in the early stage, the probability densities of the curvatures at various times were successfully scaled by a time-dependent characteristic length, i.e., interface area per unit volume (Q). This behavior has been previously observed in blends with morphologies created by a different mechanism, namely spinodal decomposition. In the late stage, the dynamic scaling failed and the time evolution of the interface slowed down. For the nonsymmetric blend, the domains of the minor phase (FLPS) were more elongated and they eventually broke up producing a composite microstructure with islands of drops within cocontinuous domains. We defined a "scaled" genus (G) to quantify the topology evolution of the blends during coarsening. Loss of connectivity was evidenced by a decrease of G with time for the nonsymmetric blend, while a constant value of this parameter indicated no change in topology during coarsening for the symmetric blend.


Variance Spectroscopy.
Spectroscopic analysis and study of nanoparticle samples is often hampered by structural diversity that presents a complex superposition of spectral signatures. By probing the spectra of small volumes within dilute samples, we can expose statistical variations in composition to obtain information unavailable from bulk spectroscopy. This new approach is demonstrated using fluorescence spectra of unsorted single-walled carbon nanotube samples to deduce structure-specific abundances and emissive efficiencies. Furthermore, correlations between intensity variations at different wavelengths provide two-dimensional covariance maps that isolate the spectra of homogeneous subpopulations. Covariance analysis is also a sensitive probe of particle aggregation. It shows that well-dispersed nanotube samples can spontaneously form loose aggregates of a type not previously recognized. Variance spectroscopy is a simple and practical technique that should find application in many nanoparticle studies.


How much diffusion lesion reversal occurs after treatment within three-hours of stroke onset?
In this issue of the journal, Sakamoto et al. present an analysis of diffusion lesion evolution in acute ischemic stroke patients first imaged less than three-hours from stroke onset. Although temporary lesion volume reduction was observed following reperfusion, the affected regions were generally abnormal on follow-up fluid attenuated inversion recovery imaging, indicating lack of tissue salvage. Taken in conjunction with other recent articles, it seems that temporary postreperfusion 'reversal' of diffusion lesions is quite common but usually does not translate to permanent tissue salvage. A minority of patients demonstrate permanent reversibility of a component of the acute diffusion lesion. This is dependent on early reperfusion and is more frequent when patients are treated within three-hours. Early reperfusion is clearly associated with a reduction in infarct growth through salvage of ischemic penumbra, and this probably contributes more to the favorable neurological outcomes in these patients than the relatively small volumes of diffusion reversal. It is currently unknown whether future therapeutic advances that increase the speed and success rates of reperfusion will increase the proportion of reversibility further and lead to clinically relevant salvage within the diffusion lesion. For the present, it appears that intravenous tissue plasminogen activator rarely achieves substantial permanent reversal of diffusion lesions, even when administered within three-hours.


Quantitative aspects of the spatial distribution and morphological characteristics of the sea bass (Dicentrarchus labrax L.; Teleostei, Serranidae) trunk lateral line neuromasts.
The results presented herein report quantitative data relative to the distribution and morphological characteristics of both types of neuromasts encountered on the trunk lateral line of the sea bass (Dicentrarchus labrax, L.). These data were obtained from scanning electron micrographs. They indicate that, as expected, each modified scale of the sea bass possessed a single canal neuromast with long axis oriented parallel to the fish's long axis. In contrast to several fish species, two thirds of superficial neuromasts observed herein were oriented perpendicular to the fish's long axis. However, whatever the main orientation of superficial neuromasts, two thirds of their hair bundles were oriented parallel to the long axis of the animal with approximately half of them in the direction of the head. Similar ratios were observed for canal neuromasts whatever the area of the maculae: central or peripheral. For both types of neuromasts it was not possible to clearly distinguish a paired organization of hair bundles with opposing polarities. Superficial neuromasts on each trunk canal scale were located on either the dorsal or ventral side of the canal and appeared to be distributed along the trunk lateral line with a higher probability to be encountered closer to the operculum. The frequency of presence and the average number of superficial neuromasts per scale increased with fish size. We observed a size gradient for canal neuromasts between the operculum and caudal peduncle. This gradation was correlated with a reduction of the width of the central area of the canal segment. Canal neuromasts were always localized in the larger portions of the canal segments. Taken together, these results point out some specific features associated with the sea bass trunk lateral line. With the previous report, they establish the first full description of the trunk lateral line of sea bass and will be useful for upcoming experiments regarding the function of the two types of neuromasts.


Parenteral nutrition in the septic patient: nitrogen balance, limiting plasma amino acids, and calorie to nitrogen ratios.
A series of eight septic patients was provided varying levels of beef fibrin protein hydrolysate by central vein in the presence of adequate calories for evaluation of nitrogen retention under septic conditions. The mean nitrogen intake to achieve nitrogen equilibrium was 240 mg/kg of body wt per day. This represents a 40% increase over that required to produce nitrogen equilibrium in normal adults. The mean caloric intake of these patients was 43.3 kcal/kg of body wt per day. The calorie to nitrogen ratio based on the above intake was calculated to be 180:1. In order to utilize effectively calorie to nitrogen ratios in the nutritional care of patients, it is suggested that ratios be standardized using daily total coloric expenditures. Correcting the mean measured resting calorie expenditures of these patients for minimal daily activity, a caloric to nitrogen ratio of 138:1 was obtained. The plasma amino acid ratios in these septic patients confirm the finding that valine and phenylalnine are limiting amino acids in a beef fibrin hydrolysate at infusion levels below 240 mg of N/kg of body wt per day. Analysis of the urinary excretion of total nitrogen, urea, and amino acids in two patients suggests that 30 to 50% of the infused peptides of a beef fibrin hydrolysate are lost in the urine in these septic patients.


Short- and long-term morbidity and mortality in the population exposed to dioxin after the "Seveso accident".
The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies. Chloracne was the only effect linked with sufficient certainty to dioxin exposure. The possible long-term consequences were investigated with mortality and cancer incidence studies. Mortality and morbidity findings during the 20-year period following the accident showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in males, and biliary tract among females, in particular) and respiratory system cancer (lung, among males). In the incidence analyses, also thyroid gland and pleura cancer appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects with dioxin exposure were corroborated by findings in the Seveso population: this was the case with cardiovascular effects (possibly linked to both chemical exposure and stressful disaster experience), endocrine effects (diabetes among females) and reproductive effects: exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring. The results of many Seveso studies point to possible gender effects, in accordance with animal models. Notwithstanding the acknowledged study limitations (lack of individual exposure markers, short latency, and small population size for certain cancer types), results of previous experimental and epidemiological studies, along with mechanistic knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be associated with dioxin exposure. The mortality and cancer incidence follow-up of the Seveso cohort are continuing.


Assessing and Managing Unintentional Weight Loss: A Global Survey of Geriatrician Practice and Their Use of Ice Cream to Address It.
Unintentional weight loss (UIWL) is common among older adults but lacks standardized methods for its diagnosis and management. With a limited understanding on how geriatricians actually address UIWL, we conducted a survey to examine how they diagnose and manage it, and their opinions regarding the use of ice cream to address it. An international descriptive, cross-sectional, online survey conducted over a 16-week period in 2019 involving 1131 geriatricians in clinical practice across 51 countries. We collected information around respondent demographics, use of screening tools and diagnostic investigations, and pharmacological and non-pharmacological approaches to address UIWL. 89.1% of respondents reported frequently seeing UIWL. The most common methods reportedly used to evaluate UIWL were performing a comprehensive history and physical examination (97.4%) and assessing for cognitive impairment (86.5%). 74.2% noted that they routinely prescribed oral nutritional supplements and 71.6% involved non-medical professional(s) to help manage UIWL. While 50.4% reported recommending ice cream to their patients with UIWL, only 30.6% reported being aware of other colleagues recommending it. Geriatricians in practice for 30+ years were significantly more likely to recommend ice cream (P < 0.05). A thematic analysis of qualitative responses identified that prescribing ice cream tended to align both with patient preferences and socio-economic realities. While a majority of geriatricians surveyed routinely prescribe ONS and involve others to manage UIWL, at least half are also recommending ice cream. A key practice amongst experienced geriatricians, the use of ice cream could be better acknowledged as a practical and cost-effective way to address UIWL.


Enhanced tubular reabsorption of phosphate.
Individual kidney functions were studied during water diuresis in eight patients, following the relief of unilateral ureteral obstruction. Fractional excretion of phosphate was diminished in four of the patients, presumably due to enhanced tubular reabsorption of phosphate in the diseased side. Glomerular underperfusion may be the main factor responsible for the hypophosphaturia in the postobstructive kidney. Fractional excretion of sodium and water was increased in the obstructed side in six of the eight patients. In two of the four patients with hypophosphaturia, there was enhanced fractional sodium excretion, suggesting a dissociation of renal handling of sodium and phosphate in some patients with this condition.


New cytotoxic oxygenated fucosterols from the brown alga Turbinaria conoides.
Fucosterol (1), 24xi-hydroperoxy-24-vinylcholesterol (2), 29-hydroperoxystigmasta-5,24(28)-dien-3beta-ol (3), 24-ethylcholesta-4,24(28)-dien-3-one (4), 24xi-hydroperoxy-24-ethylcholesta-4,28(29)-dien-3-one (5), 24-ethylcholesta-4,24(28)-dien-3,6-dione (6), 24xi-hydroperoxy-24-ethylcholesta-4,28(29)-dien-3,6-di one (7), 6beta-hydroxy-24-ethylcholesta-4,24(28)-dien-3-one (8), and 24xi-hydroperoxy-6beta-hydroxy-24-ethylcholesta-4,28(2 9)-dien-3-one (9) were isolated from the marine brown alga Turbinaria conoides. The structures of these compounds were established by spectral analysis. Isolated for the first time from a natural source, the oxygenated fucosterols 4-9 exhibit cytotoxicity against various cancer cell lines.


[Analysis of diadochokinetic movement. Electronic data processing-aided diadochometry--a contribution to developmental neurologic diagnosis].
A method of objective registration and analysis of diadochokinetic arm movement was tested in normal children and those with signs of minimal cerebral dysfunction (MCD). 44 children aged 4-10 yrs. (9 with the diagnosis of MCD, 31 controls) were investigated. By means of a special device 270 deg. twisting of the forearms were transduced linearly by foam-cushioned clamps at the wrists and a potentiometer into a direct current of 0-2,7 V, respectively. The analog DC signal was digitalized by 0.7 kHz and stored in a calculator, the identification of the first and last sectors were performed on monitor. After removing artificial currents by a special filtering program, the remaining sinus-like curves could be analyzed by a special program (BEWESI). Mathematical analysis was performed by 11 factors respecting right and left arm, unilateral or bilateral twisting. Statistical analysis showed significant differences in some parameters between normal and MCD-children. In addition, a significant difference between the velocity of pronation and supination was evident. The fact that a clear age relation of parameters was found, proves the practicability of this diagnostical method in developmental neurology.


Extreme polyploidy in a large bacterium.
Cells rely on diffusion to move metabolites and biomolecules. Diffusion is highly efficient but only over short distances. Although eukaryotic cells have broken free of diffusion-dictated constraints on cell size, most bacteria and archaea are forced to remain small. Exceptions to this rule are found among the bacterial symbionts of surgeonfish; Epulopiscium spp. are cigar-shaped cells that reach lengths in excess of 600 mum. A large Epulopiscium contains thousands of times more DNA than a bacterium such as Escherichia coli, but the composition of this DNA is not well understood. Here, we present evidence that Epulopiscium contains tens of thousands of copies of its genome. Using quantitative, single-cell PCR assays targeting single-copy genes, we have determined that copy number is positively correlated with Epulopiscium cell size. Although other bacteria are known to possess multiple genomes, polyploidy of the magnitude observed in Epulopiscium is unprecedented. The arrangement of genomes around the cell periphery may permit regional responses to local stimuli, thus allowing Epulopiscium to maintain its unusually large size. Surveys of the sequences of single-copy genes (dnaA, recA, and ftsZ) revealed genetic homogeneity within a cell consistent with only a small amount ( approximately 1%) of the parental DNA being transferred to the next generation. The results also suggest that the abundance of genome copies in Epulopiscium may allow for an unstable genetic feature, a long mononucleotide tract, in an essential gene. With the evolution of extreme polyploidy and large cell size, Epulopiscium has acquired some of the advantages of eukaryotic cells.


A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction.
For the treatment of myocardial infarction with ST-segment elevation, primary angioplasty is considered superior to fibrinolysis for patients who are admitted to hospitals with angioplasty facilities. Whether this benefit is maintained for patients who require transportation from a community hospital to a center where invasive treatment is available is uncertain. We randomly assigned 1572 patients with acute myocardial infarction to treatment with angioplasty or accelerated treatment with intravenous alteplase; 1129 patients were enrolled at 24 referral hospitals and 443 patients at 5 invasive-treatment centers. The primary study end point was a composite of death, clinical evidence of reinfarction, or disabling stroke at 30 days. Among patients who underwent randomization at referral hospitals, the primary end point was reached in 8.5 percent of the patients in the angioplasty group, as compared with 14.2 percent of those in the fibrinolysis group (P=0.002). The results were similar among patients who were enrolled at invasive-treatment centers: 6.7 percent of the patients in the angioplasty group reached the primary end point, as compared with 12.3 percent in the fibrinolysis group (P=0.05). Among all patients, the better outcome after angioplasty was driven primarily by a reduction in the rate of reinfarction (1.6 percent in the angioplasty group vs. 6.3 percent in the fibrinolysis group, P<0.001); no significant differences were observed in the rate of death (6.6 percent vs. 7.8 percent, P=0.35) or the rate of stroke (1.1 percent vs. 2.0 percent, P=0.15). Ninety-six percent of patients were transferred from referral hospitals to an invasive-treatment center within two hours. A strategy for reperfusion involving the transfer of patients to an invasive-treatment center for primary angioplasty is superior to on-site fibrinolysis, provided that the transfer takes two hours or less.


The optimal surgical management of the super-obese patient: the debate. Presented at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons, Hollywood, Florida, USA, April 13-16, 2005.
Optimal management of the super-obese patient (body mass index>50 kg/m2) undergoing weight loss surgery in the new era of laparoscopic treatment is more controversial than ever before. Newer laparoscopic options for treatment of the super obese, including laparoscopic adjustable gastric banding, sleeve gastrectomy, and staging of gastric bypass, are technically easier and may be safer. Concerns that weight loss may be suboptimal or that the procedures will require revision, or both, make these choices controversial. Open access/conversion for established procedures such as long-limb gastric bypass and biliopancreatic diversion with or without duodenal switch are the traditional alternatives when laparoscopic access fails or is deemed too difficult to undertake. The following debate was presented by invited experts in laparoscopic and open bariatric surgery at the 2005 Annual Meeting of the Society of American Gastrointestinal and Endoscopic Surgeons in Florida. The presenters put forth arguments for the various modern options for treatment of the super obese, which are presented in written form. Interactive audience response technology provided a mechanism for polling the audience before and after the presentations. A review of the audience's responses provides insight into the decision-making considerations of a population of laparoscopically oriented bariatric surgeons.


Wearable sensors-based postural analysis and fall risk assessment among patients with diabetic foot neuropathy.
To investigate the cross-sectional association between deep and superficial diabetic neuropathy, postural impairment assessed by wearable inertial sensors, and the risk of fall among patients with diabetic foot. Diabetic patients attending a University Podiatric Clinic were evaluated for the presence of deep and superficial peripheral neuropathy in sensory tests. Postural impairment was assessed using a wearable inertial sensor, and the evaluation of balance/gait and risk of fall was determined by the Tinetti Scale and Downton Index, respectively. Glycemic control was measured by glycated haemoglobin concentration and fasting glycaemia. The postural parameters measured were the anteroposterior and medio-lateral sway of the center of mass (CoM) and the sway area (area traveled by the CoM per second). The results were analyzed through a logistic regression model to assess those posture variables mostly significantly associated with neuropathy and risk of fall scales. A total of 85 patients were evaluated. Spearman's rank correlation coefficients showed a strong and significant relationship (p < 0.05) between deep diabetic neuropathy assessed by Semmes-Weinstein monofilament, diapason and biothensiometer and postural alterations, whereas no significant correlations between superficial (painful sensitivity) neuropathy and the postural parameters. The sway path of the displacement along the anterior-posterior axis recorded during tests performed with eyes open and feet close together were significantly (p < 0.05) correlated with a poor glycemic (glycated haemoglobin concentration) control and each other with all diabetic neuropathy tests, fall risk scales, muscular weakness, ankle joint limitation and history of ulcers. The results support the existence of a strong association between alterations of the deep somato-sensitive pathway (although depending on the tool used to measure peripheral neuropathy), glycemic control and balance impairments assessed using a wearable sensors. Wearable-based postural analysis might be part of the clinical assessment that enables the detection of balance impairments and the risk of fall in diabetic patients with diabetic peripheral neuropathy.


Gender differences in poor outcome patients with lifelong schizophrenia.
Gender effects have been reported quite consistently in schizophrenia, with male patients having an earlier age of onset, poorer functional outcome, greater negative symptoms and cognitive impairment, and less severe positive symptoms. Because age of onset, cognitive impairments, and negative symptoms are all correlated with poorer functional status, it is not clear if previously reported gender differences in symptoms are just recapturing gender differences in functional outcome. In this study, 205 geriatric patients with lifelong poor-outcome schizophrenia (43% male) were examined for the severity of schizophrenic symptoms, cognitive impairments, and specific deficits in adaptive skills, as well as for demographic differences such as age at first psychiatric admission, premorbid education, and current treatment status. Previously reported gender differences were replicated in these patients with a uniformly poor functional outcome, with male patients having more severe negative symptoms and an earlier age of first psychiatric admission. No differences in cognitive functioning or specific functional deficits were found, however. These findings suggest that negative symptom severity is greater in male patients regardless of functional outcome and that the association of cognitive deficits with gender may be found only in patients with better functional outcome. The study of gender-related differences in brain structure or function and their interaction with overall course of illness might help understand these differences in symptom presentation.


Detection and typing of maize streak virus and other distantly related geminiviruses of grasses by polymerase chain reaction amplification of a conserved viral sequence.
The application of the polymerase chain reaction DNA amplification technique to the detection and typing of isolates of maize streak virus (MSV) and other related geminiviruses of grasses is described. The oligonucleotide primers used for amplification were 17-mers which contained a number of degeneracies. An approximately 250 base pair fragment was amplified from all geminivirus-infected grass and cereal samples tested. The amplification reaction was specific, working down to a concentration of 50 fg/ml of MSV-specific plasmid-cloned DNA and with a 10(-9) dilution of MSV-infected maize DNA extract. DNA could also be amplified from distantly related geminiviruses, including two different sugarcane viruses, digitaria streak virus and another as yet uncharacterized virus of a Panicum sp. Amplified DNA from a Mauritian sugarcane isolate (SSV-M) was cloned and sequenced. Sequence comparison and phylogenetic analysis showed that this sequence differed sufficiently from the analogous region of other geminiviruses for SSV-M to be considered a distinct virus. The use of the polymerase chain reaction for the amplification of gemini- and other virus genomes or genomic fragments for typing, mapping, phylogenetic analysis and taxonomy is discussed.


Angular under-sampling effect on VMAT dose calculation: An analysis and a solution strategy.
Most VMAT algorithms compute the dose on discretized apertures with small angular separations for practical reasons. However, machines deliver the VMAT dose with a continuously moving MLC and gantry and a continuously changing dose rate. The computed dose can deviate from the delivered dose, especially if no, or loose, MLC movement constraints are applied for the VMAT optimization. The goal of this paper is to establish a simplified mathematical model to analyze the discrepancy between the VMAT plan calculation dose and the delivered dose and to provide a reasonable solution for clinical implementation. A simplified metric is first introduced to describe the discrepancy between doses computed with discretized apertures and a continuous delivery model. The delivery fluences were formed separately for six different leaf movement scenarios. The formula was then rewritten in a more general form. The correlation between discretized and continuous fluence is summarized using this general form. The Fourier analysis for the impacts from three separate factors - dose kernel width, aperture width, aperture distance - to the dose discrepancy is also presented in order to provide insight into the dose discrepancy caused by under-sampling in the frequency domain. Finally, a weighting-based interpolation (WBI) algorithm, which can improve the aperture interpolation efficiency, is proposed. The associated evaluation methods and criteria for the proposed algorithm are also given. The comparisons between the WBI algorithm and the equal angular interpolation (EAI) method suggested that the proposed algorithm has a great advantage with regard to aperture number efficiency. To achieve a 90% gamma passing rate using the dose computed with apertures generated with 0.5° EAI, with the initial optimization apertures as the standard for the comparison, the WBI needs only 66% and 54% of the aperture numbers that the EAI method needs for a 2° and a 4° angular separation of the VMAT optimization, respectively. The results also suggested that the weighted dose error index value, Θ, can be used as a stopping criterion for an interpolation algorithm, e.g., WBI or EAI, or as an indicator for sampling level evaluations. The phantom results indicate that the gamma passing rate decreases with increasing depth, from the phantom surface to the iso center, for the plans computed with under-sampled apertures. No obvious variation trends were observed for the plans computed with well-sampled apertures. The mathematical analysis suggests that the dose discrepancies due to under-sampling are strongly correlated with the aperture width, the distance between apertures, and the width of the dose kernel. The WBI algorithm proves to be an efficient aperture interpolation strategy and is useful for dose computation of VMAT plans.