[Choice of anesthesia in operations on the spine and spinal cord].
It was found that in patients with spinal and cerebrospinal lesions considerable circulatory disorders occur that are depended on the character of the disease and related homeostasis disturbances. As evidenced by the authors' findings the main causes of circulatory disturbances may be as follows: altered innervation below the focus of cerebrospinal lesion, the development of insufficiency of the myocardiac contractility, a changed general vascular resistance, a decrease of total circulatory volume.


Once-daily treatment of essential hypertension with captopril.
After a 4- to 6-week placebo lead-in period, 382 mild-to-moderate hypertensive patients with diastolic blood pressures remaining between 92 and 109 mmHg were randomized to double-blind treatment with captopril (50 mg q.d.) (94), captopril (50 mg b.i.d.) (97), captopril (50 mg q.d.) plus hydrochlorothiazide (97), and placebo (94). After 4 weeks the captopril dosage was doubled, whereas the hydrochlorothiazide dose remained at 25 mg for an additional 4 weeks. Response to treatment was evaluated by means of blood pressure determinations at the end of 4 and 8 weeks. All three active treatment regimens reduced diastolic blood pressure more than placebo did (p less than or equal to 0.01). Patients receiving captopril with diuretic had a greater decrease in pressure than those receiving captopril alone. The once-daily captopril regimen was as effective as the twice-daily regimen, although the latter employed double the daily dose. Increasing the captopril dosage during the second 4-week period resulted in a minimal addition reduction in blood pressure. Full 24-hour monitoring confirmed that the blood pressure was controlled by once-daily captopril therapy. Captopril given once daily, alone or in combination with hydrochlorothiazide, is efficacious treatment for patients with mild-to-moderate hypertension. The once-daily regimen should further enhance patient compliance.


Celecoxib for Management of Refractory Back Pain Secondary to Vertebral Osteomyelitis: A Case Report.
Back pain is the most common symptom of vertebral osteomyelitis and can be difficult to manage. Pain may persist despite appropriate antibiotic medications and may be refractory to common analgesic treatments. We present a case of a 53-year-old man with acute onset severe low back pain. Clinical evaluation and diagnostic workup were consistent with L1 osteomyelitis. The patient continued to report pain following treatment with intravenous antibiotics and typical analgesic therapy. Opioids were discontinued and low-dose celecoxib was initiated with appreciable improvement in pain and activity tolerance. Celecoxib may be a good option and alternative to opioids in the pain management of this population.


When to vaccinate a fluctuating wildlife population: Is timing everything?
Wildlife vaccination is an important tool for managing the burden of infectious disease in human populations, domesticated livestock and various iconic wildlife. Although substantial progress has been made in the field of vaccine designs for wildlife, there is a gap in our understanding of how to time wildlife vaccination, relative to host demography, to best protect a population.We use a mathematical model and computer simulations to assess the outcomes of vaccination campaigns that deploy vaccines once per annual population cycle.Optimal timing of vaccination is an important consideration in animals with short to intermediate life spans and a short birthing season. Vaccines that are deployed shortly after the birthing season best protect the host population.The importance of timing is greater in wildlife pathogens that have a high rate of transmission and a short recovery period. Vaccinating at the end of the birthing season best reduces the mean abundance of pathogen-infected hosts. Delaying vaccination until later in the year can facilitate pathogen elimination. Policy Implications. Tuning wildlife vaccination campaigns to host demography and pathogen traits can substantially increase the effectiveness of a campaign. Our results suggest that, for a fluctuating population, vaccinating at, or shortly after, the end of the birthing season, best protects the population against an invading pathogen. If the pathogen is already endemic, delaying vaccination until after the birthing season is over can help facilitate pathogen elimination. Our results highlight the need to better understand and predict host demography in wildlife populations that are targeted for vaccination.


The teaching of legal medicine in Australasia.
The interface of medicine and law highlights the difference between doctors and lawyers. It is the doctor's role to determine his or her adversary (diagnosing an illness) and to decide the optimal means for overcoming same, such that the doctor assumes the role which is analogous to not only the lawyer but also the judge and jury when dealing with illness and it is the doctor who prescribes the appropriate remedy. Conversely, the lawyer only represents the objectives of his/her client, thereby only representing a single focus within the complexity of the problem. It is the duty of the system to reach the proper conclusion and prescribe the appropriate remedy. It follows that doctors and lawyers operate under a different set of standard operating procedures and expectations. This paper describes the evolution of the Australian College of Legal Medicine (ACLM) and its contribution to the teaching of legal medicine in Australasia. The ACLM was formed in 1995 and in its first decade of existence has established a range of programs, including the expert witness program, basic law intensive, the advanced law intensive, annual scientific meetings and further educative programs in forensic medicine. The Australian & New Zealand Forensic Medicine Society has been incorporated into the ACLM and the College has formed a partnership with Griffith University to provide the first Master of Legal Medicine course provided from within a School of Medicine, at university level, rather than offering health law from within a legal program. The College has been approached by other medical colleges within Australia to offer training for their Fellows and organised its first offshore training program in 2006.


A systematic review of psychoeducational intervention trials for the management of chronic stable angina.
Chronic stable angina (CSA) is a cardinal symptom of coronary artery disease and has a major impact on health-related quality of life (HRQOL). There are few data on the effectiveness of psychoeducational interventions for CSA patients that target HRQOL-related outcomes. To determine the effectiveness of psychoeducational interventions for CSA management based on the best available evidence. A systematic review of randomized controlled trials (RCTs) testing the effects of psychoeducational interventions on angina symptoms, angina symptom-related distress, and physical functioning was conducted. Four primary studies (1994-97) were included that had (a) specified treatment and control conditions, (b) participants with anigna class I-III (Canadian Cardiovascular Society) and (c) psychoeducational interventions. These studies were reviewed for methodological rigour. A pooled common effect could not be determined because of heterogeneity of outcomes, measures and analyses. While positive effects were reported, methodological problems with respect to sampling, randomization, controls and measurement precluded generalization. The effectiveness of psychoeducation interventions for improving angina outcomes is inconclusive. Future RCTs of psychoeducational programmes require methodologically robust methods to reduce biases and random error, and to enhance the generalizability of findings for CSA management.


[Radiotherapy in the treatment of children with Itsenko-Cushing's disease].
Forty children with Icenko-Cushing's disease were subjected to radiotherapy. Radiation of the pituitary with a proton beam in a dose of 70-100 Gy (7000-10000 rad) performed according to the indicated technique appeared highly effective. It was not associated with local or total radiation injuries and was safe. X-ray therapy conducted according to the fractionally intensive technique in a dose of 3000-3500 rad was less effective and produced disease relapses more frequently as compared with proton therapy.


Intra-specific comparison of mitochondrial genomes reveals host gene fragment exchange via intron mobility in Tremella fuciformis.
Mitochondrial genomic sequences are known to be variable. Comparative analyses of mitochondrial genomes can reveal the nature and extent of their variation. Draft mitochondrial genomes of 16 Tremella fuciformis isolates (TF01-TF16) were assembled from Illumina and PacBio sequencing data. Mitochondrial DNA contigs were extracted and assembled into complete circular molecules, ranging from 35,104 bp to 49,044 bp in size. All mtDNAs contained the same set of 41 conserved genes with identical gene order. Comparative analyses revealed that introns and intergenic regions were variable, whereas genic regions (including coding sequences, tRNA, and rRNA genes) were conserved. Among 24 introns detected, 11 were in protein-coding genes, 3 in tRNA genes, and the other 10 in rRNA genes. In addition, two mobile fragments were found in intergenic regions. Interestingly, six introns containing N-terminal duplication of the host genes were found in five conserved protein-coding gene sequences. Comparison of genes with and without these introns gave rise to the following proposed model: gene fragment exchange with other species can occur via gain or loss of introns with N-terminal duplication of the host genes. Our findings suggest a novel mechanism of fungal mitochondrial gene evolution: partial foreign gene replacement though intron mobility.


Progressive Minimal Path Method for Segmentation of 2D and 3D Line Structures.
We propose a novel minimal path method for the segmentation of 2D and 3D line structures. Minimal path methods perform propagation of a wavefront emanating from a start point at a speed derived from image features, followed by path extraction using backtracing. Usually, the computation of the speed and the propagation of the wave are two separate steps, and point features are used to compute a static speed. We introduce a new continuous minimal path method which steers the wave propagation progressively using dynamic speed based on path features. We present three instances of our method, using an appearance feature of the path, a geometric feature based on the curvature of the path, and a joint appearance and geometric feature based on the tangent of the wavefront. These features have not been used in previous continuous minimal path methods. We compute the features dynamically during the wave propagation, and also efficiently using a fast numerical scheme and a low-dimensional parameter space. Our method does not suffer from discretization or metrication errors. We performed qualitative and quantitative evaluations using 2D and 3D images from different application areas.


Surface enhanced Raman spectroscopy (SERS) for the discrimination of Arthrobacter strains based on variations in cell surface composition.
Surface enhanced Raman spectroscopy (SERS) is a rapid and highly sensitive spectroscopic technique that has the potential to measure chemical changes in bacterial cell surface in response to environmental changes. The objective of this study was to determine whether SERS had sufficient resolution to differentiate closely related bacteria within a genus grown on solid and liquid medium, and a single Arthrobacter strain grown in multiple chromate concentrations. Fourteen closely related Arthrobacter strains, based on their 16S rRNA gene sequences, were used in this study. After performing principal component analysis in conjunction with Linear Discriminant Analysis, we used a novel, adapted cross-validation method, which more faithfully models the classification of spectra. All fourteen strains could be classified with up to 97% accuracy. The hierarchical trees comparing SERS spectra from the liquid and solid media datasets were different. Additionally, hierarchical trees created from the Raman data were different from those obtained using 16S rRNA gene sequences (a phylogenetic measure). A single bacterial strain grown on solid media culture with three different chromate levels also showed significant spectral distinction at discrete points identified by the new Elastic Net regularized regression method demonstrating the ability of SERS to detect environmentally induced changes in cell surface composition. This study demonstrates that SERS is effective in distinguishing between a large number of very closely related Arthrobacter strains and could be a valuable tool for rapid monitoring and characterization of phenotypic variations in a single population in response to environmental conditions.


Creating Space for Large Acceptors: Rational Biocatalyst Design for Resveratrol Glycosylation in an Aqueous System.
Polyphenols display a number of interesting properties but their low solubility limits practical applications. In that respect, glycosylation offers a solution for which sucrose phosphorylase has been proposed as a cost-effective biocatalyst. However, its activity on alternative acceptor substrates is too low for synthetic purposes and typically requires the addition of organic (co-)solvents. Here, we describe the engineering of the enzyme from Thermoanaerobacterium thermosaccharolyticum to enable glycosylation of resveratrol as test case. Based on docking and modeling studies, an active-site loop was predicted to hinder binding. Indeed, the unbolted loop variant R134A showed useful affinity for resveratrol (K(m)=185 mM) and could be used for the quantitative production of resveratrol 3-α-glucoside in an aqueous system. Improved activity was also shown for other acceptors, introducing variant R134A as promising new biocatalyst for glycosylation reactions on bulky phenolic acceptors.


Marker-assisted introgression of quantitative trait loci.
The use of molecular markers for the introgression of one or several superior QTL alleles into a recipient line is investigated using analytic and simulation results. The positions of the markers devoted to the control of the genotype at the QTLs in a "foreground selection" step are optimized given the confidence interval of the QTL position. Results demonstrate that using at least three markers per QTL allows a good control over several generations. Population sizes that should be recommended for various numbers of QTLs are calculated and are used to determine the limit in the number of QTLs that can be monitored simultaneously. If "background selection" devoted to accelerate the return to the recipient parent genotype outside the QTL regions is applied, the positions of the markers devoted to the control of the QTLs have to be reconsidered. When several QTLs are monitored simultaneously, background selection among the limited number of individuals resulting from the foreground selection step accelerates the increase in genomic similarity with the recipient parent, with only limited costs. Background selection is even more efficient in a pyramidal backcross program where QTLs are first monitored one by one.


A double-blinded randomised dietary supplement crossover trial design to investigate the short-term influence of medium chain fatty acid (MCT) supplement on canine idiopathic epilepsy: study protocol.
Epilepsy is the most common brain disease in dogs. Recently, diets have been reported to have a positive impact on seizure activity and behaviour in various species including dogs with idiopathic epilepsy (IE). Historically, classic high fat ketogenic diets (KD) and medium chain triglycerides (MCT) KD have been successfully used to manage drug-resistant epilepsy. Similarly, an MCT enriched diet has been shown to improve seizure control and behavioural comorbidities in some dogs with IE. However, it is unknown whether an MCT dietary supplement (DS) may provide similar positive effects. A 6-month prospective, randomised, double-blinded, placebo-controlled, crossover, multicentre dietary trial is designed comparing a 9% metabolic energy based calculated medium-chain triglyceride (MCT) oil supplement to a conventional 'control' DS. Only dogs which will have an International Veterinary Epilepsy Task Force Tier II level like diagnosis of IE which satisfied the following inclusion criteria are included: age between 6 months and ≤ 12 years; weighing between 4 and ≤ 65 kg; unremarkable interictal neurological examinations; no clinically significant findings on routine laboratory diagnostics; unremarkable brain MRI scan; have had at least 3 seizures in the previous 3 months prior to enrolment; treated with at least one ASD and being classified as resistant. All dogs are fed initially for 90 ± 2 days with either the control oil or the MCT oil alongside their normal diet, followed by 97 ± 2 days with the other supplement including a 7-day washout period. Overall, the aim is to recruit thirty-six patients at five different centres and to investigate the effect of MCTs as DS on seizure activity, tolerability, behavioural comorbidities and quality of life (QoL). Dietary interventions are rarely studied in a standardised form in veterinary medicine. The background diet, the cohort of animals and ASD received is standardised in this prospective diet trial to ensure representative data about the potential effect of MCT DS. If the study data confirms former findings, this would provide further evidence for the efficacy of MCTs as a management option for canine epilepsy. This publication should offer a repository of trial conditions and variable description with forecasted statistical analysis.


A neurocomputational model of the mismatch negativity.
The mismatch negativity (MMN) is an event related potential evoked by violations of regularity. Here, we present a model of the underlying neuronal dynamics based upon the idea that auditory cortex continuously updates a generative model to predict its sensory inputs. The MMN is then modelled as the superposition of the electric fields evoked by neuronal activity reporting prediction errors. The process by which auditory cortex generates predictions and resolves prediction errors was simulated using generalised (Bayesian) filtering--a biologically plausible scheme for probabilistic inference on the hidden states of hierarchical dynamical models. The resulting scheme generates realistic MMN waveforms, explains the qualitative effects of deviant probability and magnitude on the MMN - in terms of latency and amplitude--and makes quantitative predictions about the interactions between deviant probability and magnitude. This work advances a formal understanding of the MMN and--more generally--illustrates the potential for developing computationally informed dynamic causal models of empirical electromagnetic responses.


[Typology of the non-psychotic form of psychogenic fantasizing].
Non-morbid forms of fantasy were studied in 120 individuals with psychopathy (n = 80) and psychopath-like manifestations of traumatic genesis (n = 40) in psychogenic conditions. The authors identified such variants of fantasy at a non-psychotic level as "expansive-sthenic" and "paraphrenia-like" which are considered as manifestations of adaptive psychological mechanisms.


Interferons Induce STAT1-Dependent Expression of Tissue Plasminogen Activator, a Pathogenicity Factor in Puumala Hantavirus Disease.
Hantaviruses are zoonotic viruses that show various degrees of vasculopathy in humans. In this study, we analyzed the regulation of 2 fibrinolytic parameters, tissue plasminogen activator (tPA) and its physiological inhibitor, plasminogen activator inhibitor 1 (PAI-1), in Puumala hantavirus (PUUV)-infected patients and in human microvascular endothelial cells. We detected strong upregulation of tPA in the acute phase of illness and in PUUV-infected macaques and found the tPA level to positively correlate with disease severity. The median levels of PAI-1 during the acute stage did not differ from those during the recovery phase. In concordance, hantaviruses induced tPA but not PAI-1 in microvascular endothelial cells, and the induction was demonstrated to be dependent on type I interferon. Importantly, type I and II interferons directly upregulated tPA through signal transducer and activator of transcription 1 (STAT1), which regulated tPA gene expression via a STAT1-responsive enhancer element. These results suggest that tPA may be a general factor in the immunological response to viruses.


Hemodynamic response to featural changes in the occipital and inferior temporal cortex in infants: a preliminary methodological exploration.
Over the past 30 years researchers have learned a great deal about the development of object processing in infancy. In contrast, little is understood about the neural mechanisms that underlie this capacity, in large part because there are few techniques available to measure brain functioning in human infants. The present research examined the extent to which near-infrared spectroscopy (NIRS), an optical imaging technique, could be used to assess the relation between object processing and brain functioning. Infants aged 6.5 months were presented with an occlusion event involving objects that differed on many feature dimensions (multi-featural change), differed on shape only (shape change) or color only (color change), or did not differ (control). NIRS data were collected in the occipital and inferior temporal cortex. In the occipital cortex, a significant increase in oxyhemoglobin (HbO(2)) was observed in response to all four events and these responses did not differ significantly from each other. In the inferior temporal cortex, a significant increase in HbO(2 )was observed in the multi-featural and the shape change condition but not in the control condition. An increase was also observed in the color change condition but this increase did not differ significantly from baseline nor did it differ significantly from the response obtained in the control condition. These data were discussed in terms of (a) what they suggest about the neural basis of feature processing in infants and (b) the viability of using NIRS to study brain-behavior relations in infants.


Co-ordinated multidisciplinary approaches for inpatient rehabilitation of older patients with proximal femoral fractures.
Hip fracture is a major cause of morbidity in older people and its impact, both on the individual and to society, is substantial. To examine the effects of co-ordinated multidisciplinary inpatient rehabilitation, compared with usual orthopaedic care, for older patients with hip fracture. We searched the Cochrane Musculoskeletal Injuries Group trials register, Medline (up to August 1999), and reference lists of published papers and books. We also contacted colleagues and trialists. Randomised and quasi-randomised trials of post surgical care using specialised rehabilitation of mainly older patients (aged 65 years or over) with hip fracture. Trial assignment to included, excluded and awaiting assessment categories, was by consensus. Two reviewers independently assessed trial quality and extracted data. Limited additional information was sought from most trialists. As well as pooling of data from primary outcomes, supplementary analyses were performed to combine clinically relevant outcomes and investigate possible explanatory factors. In this substantive update, three new trials have been included. The eight included trials involved 1609 patients. The combined outcomes of death or requiring institutional care showed no significant difference between intervention and control groups (relative risk 0.91; 95% confidence interval 0.80 to 1.03). There was considerable heterogeneity in length of stay and cost data. Using death and deterioration in function as a further combined outcome variable yielded a relative risk of 0.90 (95% confidence interval 0.81 to 1.01). This should be interpreted with caution due to heterogeneity. No quality of life measures were reported and the two trials investigating carer burden showed no detrimental effect from the intervention. The review update did not result in any new data for these outcomes. The trials reviewed had different aims, interventions and outcomes. As a consequence, results were heterogeneous and the question of effectiveness of different types of co-ordinated inpatient rehabilitation after hip fracture cannot be answered conclusively. There is a trend to effectiveness when combined outcome variables (death and institutional care, death and deterioration in function) are considered. Future trials of post surgical care involving inpatient rehabilitation, or other models such as 'early supported discharge' and 'hospital at home' schemes, should aim to establish both effectiveness and cost effectiveness of multidisciplinary rehabilitation overall, rather than attempt to evaluate its components.


Reuse of fresh water sludge in cement making.
With the increasing demand for high quality water, a large quantity of chemical agent must be added in the water purification process, which in turn generates enormous amount of fresh water sludge. Of all the options for sludge disposal, sludge reuse has been considered most economical and environmentally sound. This study evaluated the possibility of incorporating fresh water sludge in the making of Portland cement through the sintering process. The goal was to search for the optimal condition to maximize the replacement of clay with the fresh water sludge. Characteristics of fresh water sludge were collected and analyzed. The analysis showed that water source and water treatment process dominate th characteristics, particularly the chemical composition of the fresh water sludge. The fresh water sludge was mixed with the cement clay in various percentages, from 0% to 100%, as raw material for cement-making. The effects of its addition on the sintering condition and the quality of cement were evaluated. The analysis of the clinkers showed that the addition of the fresh water sludge did not change the phase form and the f-CaO content of the cement. The compressive strength of the masonry increased with the increasing addition of fresh water sludge. All cement products made from various replacement ratios met the Chinese National Standard of first degree Portland cement.


Anastomotic-vaginal fistula (AVF) after anterior resection of the rectum for cancer--occurrence and risk factors.
The aim of the study was to assess recto-vaginal fistula (RVF) after anterior resection of the rectum for cancer with regard to occurrence and risk factors. All female patients [median age 69.5 years, Union Internationale centre le Cancer (UICC) cancer stage IV in 10%] who developed a symptomatic RVF (n = 20) after anterior resection of the rectum for cancer from three separate cohorts of patients were identified and compared with those who developed conventional symptomatic leakage (n = 32), and those who did not leak (n = 338). Patient demography and perioperative data were compared between these three groups. Fourteen patient-related and surgery-related variables thought to be possible risk factors for RVF (anastomotic-vaginal fistula) were analysed. Symptomatic anastomotic leakage occurred in 52 (13.3%) of 390 patients. Twenty (5.1%) had an anastomotic-vaginal fistula (AVF) and 32 (8.2%) conventional leakage (CL). Patients with AVF required unscheduled re-operation and defunctioning stoma as often as those with CL. AVF was diagnosed later and more often after discharge from hospital compared with CL. Patients with AVF had lower anastomoses and decreased BMI compared with those with CL. Risk factors for AVF in multivariate analysis were anastomosis < 5 cm above the anal verge (P = 0.001), preoperative radiotherapy (P = 0.004), and UICC cancer stage IV (P = 0.005). Previous hysterectomy was a risk factor neither for AVF nor for CL. Anastomotic-vaginal fistula forms a significant part of all symptomatic leakages after low anterior resection for cancer in women. Although diagnosed later, the need for abdominal re-operation and defunctioning stoma was not different from patients with CL. Risk factors for AVF included low anastomosis, preoperative radiotherapy and UICC cancer stage IV.


Influence of phonological expectations during a phoneme deletion task: evidence from event-related brain potentials.
Several studies have identified a negativity [the phonological mismatch negativity (PMN)] preceding the N400 during auditory sentence comprehension. The present study investigated whether the PMN reflects a prelexical or lexical stage of spoken word recognition. Event-related brain potentials (ERPs) were recorded to investigate phonological processing independently from lexical/semantic influences during a task requiring metalinguistic analysis of speech stimuli. Participants were instructed to omit the initial phoneme from a word ("clap" without the/k/) after which they heard a correct (lap) or incorrect (cap, ap, nose) answer. The PMN (peaking at 270 ms) was largest to incorrect items and did not differentiate between items that shared the same rime and items that were phonologically unrelated to the correct choice. Further, the PMN did not differ between word (cap) and nonword (ap) choices. The P300 was largest to correct items but was also seen to choices that rhymed with the correct answer. It is concluded that the PMN serves as a neural marker for the analysis of acoustic input merging with prelexical phonemic expectations.


Asymptotic judgment of cause in a relative validity paradigm.
We report three experiments in which we tested asymptotic and dynamic predictions of the Rescorla-Wagner (R-W) model and the asymptotic predictions of Cheng's probabilistic contrast model (PCM) concerning judgments of causality when there are two possible causal candidates. We used a paradigm in which the presence of a causal candidate that is highly correlated with an effect influences judgments of a second, moderately correlated or uncorrelated cause. In Experiment 1, which involved a moderate outcome density, judgments of a moderately positive cause were attenuated when it was paired with either a perfect positive or perfect negative cause. This attenuation was robust over a large set of trials but was greater when the strong predictor was positive. In Experiment 2, in which there was a low overall density of outcomes, judgments of a moderately correlated positive cause were elevated when this cause was paired with a perfect negative causal candidate. This elevation was also quite robust over a large set of trials. In Experiment 3, estimates of the strength of a causal candidate that was uncorrelated with the outcome were reduced when it was paired with a perfect cause. The predictions of three theoretical models of causal judgments are considered. Both the R-W model and Cheng's PCM accounted for some but not all aspects of the data. Pearce's model of stimulus generalization accounts for a greater proportion of the data.


Generalized spatial structural equation models.
It is common in public health research to have high-dimensional, multivariate, spatially referenced data representing summaries of geographic regions. Often, it is desirable to examine relationships among these variables both within and across regions. An existing modeling technique called spatial factor analysis has been used and assumes that a common spatial factor underlies all the variables and causes them to be related to one another. An extension of this technique considers that there may be more than one underlying factor, and that relationships among the underlying latent variables are of primary interest. However, due to the complicated nature of the covariance structure of this type of data, existing methods are not satisfactory. We thus propose a generalized spatial structural equation model. In the first level of the model, we assume that the observed variables are related to particular underlying factors. In the second level of the model, we use the structural equation method to model the relationship among the underlying factors and use parametric spatial distributions on the covariance structure of the underlying factors. We apply the model to county-level cancer mortality and census summary data for Minnesota, including socioeconomic status and access to public utilities.


Step Tests Are Safe for Assessing Functional Capacity in Patients Hospitalized With Acute Lung Diseases.
To investigate the safety of the Chester step test (CST) and the modified incremental step test (MIST) to assess functional capacity in patients hospitalized with acute lung diseases. Seventy-seven hospitalized patients (46 men) performed the CST and the MIST on the same day in random order and the 6-minute walk test (6MWT) the following day. A control group of 20 healthy volunteers performed the same procedures. No adverse events were observed during the step tests. Mean exercise-induced desaturation was similar between the CST (-2%; 95% CI, -6 to 0), the MIST (-2%; 95% CI, -6 to -1), and the 6MWT (-2%; 95% CI, -5 to 0). Significant correlations were found between the number of steps on the CST and the MIST and lung function (forced vital capacity: r = 0.52 and r = 0.57, respectively), dyspnea (r =-0.54 and r =-0.41, respectively), and the distance walked on the 6MWT (r = 0.59 and r = 0.64, respectively). In addition, a significant correlation was observed between the number of steps and the length of hospitalization. Patients performed poorer on the step tests compared with healthy subjects (P < .05). The CST and the MIST are safe and can be used as an alternative test to assess functional capacity in patients hospitalized for acute lung diseases. The worse the performance on the step tests, the lower the pulmonary function and the distance walked on the 6MWT, the greater the dyspnea, and the longer the hospitalization.


[Dissemination of medical knowledge to the public in Iceland by a country doctor 1782-1834].
Jón Pétursson (1733-1801) was an apprentice af the first Chief Medical Officer of Iceland. In 1765 Pétursson enrolled in the Medical Faculty at the University of Copenhagen. In 1769 with the Faculties approval he published a monograph on the so called Icelandic Scurvy. In 1770-71 Pétursson served as ship's surgeon in the Royal Danish Navy on an expedition to the Mediterranean. In 1772-1775 he served as an assistant to the Chief Medical Officer and the newly appointed apothecary, who shared premises at Nes, Reykjavík. In 1775 he was appointed surgeon (chirurgeon) to the Northern District. Pétursson wrote two medical book while serving his district, both being prepared now for republication. A. The Lækningabók fyrir almúga (Leechbook for common people) published posthumously 1834, edited by Sveinn Pálsson surgeon. It was undoubtedly inspired by the Swiss physician Tissot and his book Avis au peuple sur sa santé ou traité des maladies plus fréquentes 1761. B. A treatise on rheumatism or dirorder of the joints (Stutt ágrip um iktsýki edur lidaveiki, 1782). In Scand J Rheumatol 1996: 25; 134-7 the authors point out that Péturssons description of what he calls arthritis vaga encompasses these essential features: It is common, chronic, destructive, inflammatory polyarthritis, sometimes with systemic manifestations. It affects peope of all ages and has a female preponderance. They state that only rheumatoid arthritis fulfills these specifications. They conclude that medical history should give Pétursson credit for the first definite description of rheumatoid arthritis.


Factors associated with first antenatal care (ANC) attendance within 12 weeks of pregnancy among women in Lira City, Northern Uganda: a facility-based cross-sectional study.
This study aimed at assessing factors associated with first antenatal care (ANC) attendance within 12 weeks of pregnancy among women in Lira City. A cross-sectional study. The study was conducted in health facilities offering ANC services in Lira City, Northern Uganda. The study was among 368 pregnant mothers attending their first ANC in the three selected facilities (Lira Regional Referral Hospital, Ober Health Center IV and Pentecostal Assembly of God Mission Health Center IV) in Lira City. Level of first ANC attendance within 12 weeks of pregnancy and associated factors. Early ANC attendance was 36.1%. Women who were: unmarried (adjusted OR (aOR): 0.40, 95% CI: 0.16 to 0.99), took >2 hours to reach a health facility (aOR: 0.21, 95% CI: 0.07 to 0.62), or not visited by village health teams or healthcare workers at home (aOR: 0.33, 95% CI: 0.12 to 0.92) were less likely to attend their first ANC early. On the other hand, women who were: not knowing first that ANC guides parents on infant care (aOR: 2.22, 95% CI: 1.06 to 4.67); pregnant without consent of spouse (aOR: 4.29, 95% CI: 1.75 to 10.55); attending ANC from a private facility (aOR: 2.89, 95% CI: 1.27 to 6.15); and having two to three healthcare workers present at the ANC clinic (aOR: 1.79, 95% CI: 1.03 to 3.13) were more likely to attend ANC early. Despite the fact that the WHO recommends that all women begin ANC within 12 weeks after conception, Lira City in Northern Uganda had a low overall incidence of timely ANC initiation. Being unmarried, distance to reach a health facility, and being visited by village health teams or healthcare workers at home were all linked to timely ANC commencement. As a result, intervention efforts should concentrate on the highlighted determinants in order to promote ANC initiation in Lira City, Northern Uganda. This can be accomplished by providing information and education to the community on the timing and necessity of ANC in Northern Uganda.


Therapeutic Potential of ω-3 Polyunsaturated Fatty Acids in Human Autoimmune Diseases.
The recognition of ω-3 polyunsaturated acids (PUFAs) as essential fatty acids to normal growth and health was realized more than 80 years ago. However, the awareness of the long-term nutritional intake of ω-3 PUFAs in lowering the risk of a variety of chronic human diseases has grown exponentially only since the 1980s (1, 2). Despite the overwhelming epidemiological evidence, many attempts of using fish-oil supplementation to intervene human diseases have generated conflicting and often ambiguous outcomes; null or weak supporting conclusions were sometimes derived in the subsequent META analysis. Different dosages, as well as the sources of fish-oil, may have contributed to the conflicting outcomes of intervention carried out at different clinics. However, over the past decade, mounting evidence generated from genetic mouse models and clinical studies has shed new light on the functions and the underlying mechanisms of ω-3 PUFAs and their metabolites in the prevention and treatment of rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and type 1 diabetes. In this review, we have summarized the current understanding of the effects as well as the underlying mechanisms of ω-3 PUFAs on autoimmune diseases.


Protoporphyrin IX formation after application of methyl aminolevulinate on the face and scalp with and without prior curettage.
Pulse photodynamic therapy (PDT) is carried out as classical PDT except that methyl aminolaevulinate (MAL) is removed after 30 min. Protoporphyrin IX (PpIX) accumulation becomes lower after 3 h in pulse-PDT than in classical PDT, but pulse-PDT still has full treatment effect on actinic keratosis (AK). The present study aimed to investigate when PpIX formation in classical PDT without curettage reaches the PpIX level in pulse-PDT with curettage in the skin of the face and scalp. Fourteen patients with AKs in the face and scalp were included in this pilot study. Each patient had two fields randomly allocated to two different regimes: (i) continuing MAL incubation without prior curettage (-Cur) and (ii) 30 min MAL incubation after curettage (+Cur). The PpIX level in each field was measured with a hand-held fluorescence photometer every 30 min for 6 h after MAL application. No illumination was performed. The median PpIX level in the +Cur field after 3 h was 22 arbitrary units (AU), which represents the amount of PpIX that could have been photobleached after pulse-PDT with maximal treatment effect. After 3 h the median PpIX level in the -Cur field was 20 AU, which was not significantly different from the level in the +Cur field (p = 0.9). We propose PDT without curettage as follows: 3 h of MAL incubation and subsequently sufficient illumination. The treatment effect of this regime should be tested to verify if curettage of the face and scalp area may be omitted in PDT.


Bonding and spectroscopic analyses of N2O-CS2 and N2O-OCS heterodimer complexes and their atmospheric consequences.
Different isomers of the valence isoelectronic pairs of the heterodimers N2O-SCS and N2O-OCS were investigated using MP2 and CCSD(T) methods with the aug-cc-pVXZ (X = D, T) basis set with anharmonic frequency calculations. Interaction energies of both the heterodimers were estimated at the CBS limit and for CCSD(T)/aug-cc-pVTZ. One isomer was located for the N2O-SCS heterodimer. In the case of the N2O-OCS heterodimer, three planar slipped-parallel isomers were characterized. There was no significant change in electron density at the bond critical points (BCPs) of various intra-bonds but the presence of inter-bonds with a weak electron density at the BCPs in the complexes was found as per the results from the quantum theory of atoms in molecules (QTAIM) analysis. The interorbital interactions of the monomer in the heterodimers are discussed herein in terms of the natural bond orbital (NBO) charge transfer. Symmetry-adapted perturbation analysis was performed for all the isomers. In the case of the stable complex of N2O-SCS, induction dominated over the dispersion energy. Among the N2O-OCS isomers, the dispersion effect predominates for the most stable isomer, while for the other two isomers, the induction effect is dominant. Frequency calculations for these complexes showed a number of interactions induced by the low frequency modes in the far IR region. The atmospheric implications are also discussed for these complexes.


Black-White Racial Disparities in Disabilities Among Older Americans Between 2008 and 2017: Improvements in Cognitive Disabilities but no Progress in Activities of Daily Living or Functional Limitations.
The objectives of this study were to examine the prevalence of race-based disparities in cognitive problems, functional limitations (FLs), and activity of daily living (ADL) limitations between US Black and White older adults in 2008 and 2017, to explore how age, sex, income, and education attenuate these racial disparities, and to determine if Black-White health disparities are narrowing. Secondary analysis of the nationally representative American Community Surveys including 423,066 respondents aged ≥65 (388,602 White, 34,464 Black) in 2008 and 536,984 (488,483 White, 48,501 Black) in 2017. Findings indicate that Black-White racial disparities were apparent for all three outcomes in 2008 and 2017. Approximately half of the racial disparities was attenuated when adjustments were made for education and income. Racial disparities in cognition declined between 2008 and 2017 (p < .001) but persisted unabated in FLs and ADL limitations. Further exploration on the mechanisms of racial disparities is warranted.


From the stage to the laboratory: magicians, psychologists, and the science of illusion.
In 1894, French psychologist Alfred Binet published an article on the psychology of conjuring. By observing five magicians perform in his laboratory, he was hoping to gain a better understanding of the psychological processes responsible for inducing illusions in an audience. This article focuses on the subjects of these experiments and their world. It attempts to explain why five men belonging to a profession in which secrecy was vital agreed to enter the laboratory and reveal their tricks. It argues that magicians saw themselves as men of science and that, by entering Binet's laboratory, they were responding to an opportunity to participate in a world to which they wished to belong.


Switch in the transposition products of Mu DNA mediated by proteins: Cointegrates versus simple insertions.
Bacteriophage Mu is a self-contained mobile unit encoding functions that mediate its movement. There appear to be two alternate pathways for Mu DNA transposition that differ with respect to the end products they generate. During the lytic cycle of phage Mu growth the end products of transposition are predominantly cointegrates in an experimental system in which the induced Mu prophage is located on pSC101, a low-copy-number plasmid. On the other hand, Mu insertions into the host genome during lysogenization contain Mu DNA as simple insertions. Two Mu functions, encoded by the A and B genes, are required for Mu DNA transposition during its lytic growth. However, during lysogeny the product of gene B is not required for integration of Mu DNA. Evidence is presented here which shows that in the absence of the B gene product the majority of transposition events are simple insertions. This is in striking contrast to the situation in which the majority of the products are cointegrates in the presence of both A and B gene products. Additional evidence also suggests that these simple insertions do not arise through the resolution of cointegrate structures.


Colic in equine neonates: 137 cases (2000-2010).
To document causes of colic in equine neonates, evaluate clinical features of neonates managed medically versus surgically, determine short- and long-term survival rates for neonates with specific medical and surgical lesions, and assess ability of patients to achieve intended use. Retrospective case series. 137 client-owned equine neonates (< 30 days old) with a history of colic or signs of colic within 1 hour after hospital admission examined between 2000 and 2010. Signalment, history, results of physical examination, laboratory data, ancillary diagnostic tests, details of treatment, primary diagnosis, concurrent diseases and short-term survival rate were obtained from the medical records. Long-term follow-up information was obtained through phone survey. 137 neonates with colic were included. The majority (122 [89%]) of neonates were managed medically. The 3 most common diagnoses associated with colic were enterocolitis (37 [27%]), meconium-associated colic (27 [20%]), and transient medical colic (26 [19%]). The most common reason for surgery was small intestinal strangulating obstruction, and these neonates were more likely to have severe, continuous pain and were less responsive to analgesics. Concurrent diseases were common (87 [64%]) but did not significantly impact survival rate. Short-term survival rate was not significantly different between medically (75%) and surgically (73%) managed neonates. Long-term survival rate was excellent (66/71 [93%]) for horses that survived to hospital discharge. Most neonates surviving to maturity were used as intended (49/59 [83%]). Most neonates examined for signs of colic can be managed medically. Short-term survival rate in medically and surgically treated neonates was good. Long-term survival rate of foals discharged from the hospital was excellent, with most achieving intended use.


Mapping MHC genes in river buffalo.
The major histocompatibility complex (MHC) contains a set of genes necessary for antigen presentation in the immune system. This gene dense and polymorphic region of the mammalian genome is of considerable interest due to the role of MHC genes in immune function and animal health. Previous cytogenetic studies have indicated that the MHC in river buffalo resides on the short arm of chromosome 2 (BBU2). A 5000-rad radiation hybrid mapping panel was recently generated to enable construction of a whole genome map of river buffalo. To this end, the aims of this project were to elucidate the general organization of the MHC on BBU2, and to compare gene order within this region to the MHC in cattle. PCR primers were selected from the bovine gene map and used with the BBURH5000 panel to map a set of ten MHC class II genes in river buffalo. Analysis indicates that these genes fall into two linkage groups, consistent with organization of the MHC in cattle. This comparison of buffalo and bovine MHC gene order provides the first insight into the organization of the MHC on river buffalo chromosome 2.


Thermosensitive visible-light-excited visible-/NIR-luminescent complexes with lanthanide sensitized by the π-electronic system through intramolecular H-bonding.
Visible-luminescent lanthanide (LnL) complexes with a highly planar tetradentate ligand were successfully developed for a visible-light solid-state excitation system. L was designed by using two 2-hydroxy-3-(2-pyridinyl)-benzaldehyde molecules bridged by ethylenediamine, which was then coordinated to a series of Ln ions (Ln = Nd, Sm, Eu, Gd, Tb, Dy, and Yb). From the measurement of single-crystal X-ray analysis of EuL, two phenolic O atoms and two imine N atoms in L were coordinated to the Eu ion, and each π-electronic system took coplanar with the edged-pyridine moiety through an intramolecular hydrogen bond. The enol group on the phenolic skeleton changed to the keto form, and the pyridine was protonated. Thus, intramolecular proton transfer occurred in L after the complexation. Other complexes take isostructure. The space group is P-1, and the c-axis shrinks with decreasing temperature without a phase transition in EuL. The yellow color caused by the planar structure of L can sensitize ff emission by visible light, and the luminescence color of each complex depends on central Ln ions. Furthermore, a phosphorescence band also appeared at rt with ff emission in LnL. Drastic temperature dependence of luminescence was clarified quantitatively.


Development of a Brief Psychoanalytic Group therapy (BPG) and its application in an asbestos national priority contaminated site.
The aim of the present paper is to describe the development of a Brief Psychoanalytic Group therapy for contaminated sites and its application in the National Priority Contaminated Site of Casale Monferrato. Before presenting the core of the clinical intervention, a brief examination of some clinical features encountered working with malignant mesothelioma patients and their caregivers is offered. These aspects have been pivotal elements in the construction of a psychoanalytically oriented time-limited (i.e., 12 sessions) group therapy. This model of intervention was designed by one of the Authors (AG) and is aimed at reducing the impact of living in a threatening place where both physical well-being and health are put to the test. At a psychological level, in fact, living in contaminated sites arouses death anxieties, which can deeply compromise the quality of time remaining to live together with loved ones after a fatal cancer diagnosis.


SNP and haplotype mapping for genetic analysis in the rat.
The laboratory rat is one of the most extensively studied model organisms. Inbred laboratory rat strains originated from limited Rattus norvegicus founder populations, and the inherited genetic variation provides an excellent resource for the correlation of genotype to phenotype. Here, we report a survey of genetic variation based on almost 3 million newly identified SNPs. We obtained accurate and complete genotypes for a subset of 20,238 SNPs across 167 distinct inbred rat strains, two rat recombinant inbred panels and an F2 intercross. Using 81% of these SNPs, we constructed high-density genetic maps, creating a large dataset of fully characterized SNPs for disease gene mapping. Our data characterize the population structure and illustrate the degree of linkage disequilibrium. We provide a detailed SNP map and demonstrate its utility for mapping of quantitative trait loci. This community resource is openly available and augments the genetic tools for this workhorse of physiological studies.


Inhibition of in vivo lymphocyte migration to inflammation and homing to lymphoid tissues by the TA-2 monoclonal antibody. A likely role for VLA-4 in vivo.
The adhesion receptors, LFA-1 and VLA-4, on lymphocytes mediate lymphocyte adherence to cytokine-activated endothelial cells (EC) in vitro. Based on our previous data, which suggested that the mAb TA-2 reacted with rat VLA-4, the effect of TA-2 on lymphocyte migration out of the blood was examined. Small peritoneal exudate lymphocytes (sPEL) preferentially migrate to cutaneous inflammatory reactions, whereas lymphocytes from peripheral lymph nodes (PLN) migrate poorly to inflammatory sites but home avidly to PLN. Treatment of sPEL with TA-2 inhibited sPEL migration to DTH, LPS, poly I:C, IFN-gamma, IFN-alpha/beta, and TNF-alpha by 35 to 65% and their accumulation in PLN by 50%. The homing of PLN lymphocytes to PLN was not inhibited by TA-2. Spleen T cell migration to cutaneous inflammatory sites was inhibited but homing to PLN was not affected. Systemic treatment with TA-2 inhibited sPEL migration to inflamed or cytokine-injected skin by up to 70%. Similarly, TA-2 strongly inhibited the migration of Ag-stimulated PLN lymphoblasts to skin and to PLN. The migration of lymphocytes from all sources, including the peritoneum, spleen, PLN, mesenteric nodes, and Peyer's patches, to mesenteric lymph nodes and Peyer's patches was inhibited by 80% and 95%, respectively. In conclusion, our results suggest that VLA-4 and possibly other alpha 4 integrins mediate the migration of the inflammation-seeking sPEL and Ag-activated lymphoblasts to cutaneous inflammatory sites and lymph nodes but do not affect the homing of PLN lymphocytes to PLN. These integrins also appear to be necessary for the migration of all types of lymphocytes to Peyer's patches and mesenteric lymph nodes.


Residency Training and Hand Surgery Practice Patterns: A National Surgical Quality Improvement Program Database Analysis.
Introduction Fellowship-trained hand surgeons may have residency training in either orthopedic, plastic, or general surgery, generating significant variability in education background. To study the effect of different training backgrounds on practice pattern variations, we utilized the NSQIP (National Surgical Quality Improvement Database) database to assess hand surgery volumes and case variety by specialty. Materials and Methods NSQIP years 2008 to 2017 was queried with hand surgery current procedural terminology codes defined by the American Board of Orthopedic Surgery. Procedures were grouped according to type and specialty, and relative rates calculated. Hand society membership data were used to determine if procedural volume for each specialty in each category and overall contribution to the volume of hand surgery performed nationally was distributed in accordance with membership data. Results A total of 145,015 hand surgeries were performed; 13,267 (9.1%) by general surgeons, 28,402 (19.6%) by plastic surgeons, and 103,346 (71.3%) by orthopedic surgeons. Orthopedic surgeons performed significantly more bone, fracture, joint, and tendon cases. General surgeons and plastic surgeons performed higher than expected numbers of soft tissue coverage and cases overall with respective excesses of 183 and 22%. Conclusion Hand surgery is an available fellowship pathway from multiple residencies. Fellowship training does not level the field of real-world practice patterns. Residency training experiences significantly impact practice.


Tracking structural solvent reorganization and recombination dynamics following e- photoabstraction from aqueous I- with femtosecond x-ray spectroscopy and scattering.
We present a sub-picosecond resolved investigation of the structural solvent reorganization and geminate recombination dynamics following 400 nm two-photon excitation and photodetachment of a valence p electron from the aqueous atomic solute, I-(aq). The measurements utilized time-resolved X-ray Absorption Near Edge Structure (TR-XANES) spectroscopy and X-ray Solution Scattering (TR-XSS) at the Linac Coherent Light Source x-ray free electron laser in a laser pump/x-ray probe experiment. The XANES measurements around the L1-edge of the generated nascent iodine atoms (I0) yield an average electron ejection distance from the iodine parent of 7.4 ± 1.5 Å with an excitation yield of about 1/3 of the 0.1M NaI aqueous solution. The kinetic traces of the XANES measurement are in agreement with a purely diffusion-driven geminate iodine-electron recombination model without the need for a long-lived (I0:e-) contact pair. Nonequilibrium classical molecular dynamics simulations indicate a delayed response of the caging H2O solvent shell and this is supported by the structural analysis of the XSS data: We identify a two-step process exhibiting a 0.1 ps delayed solvent shell reorganization time within the tight H-bond network and a 0.3 ps time constant for the mean iodine-oxygen distance changes. The results indicate that most of the reorganization can be explained classically by a transition from a hydrophilic cavity with a well-ordered first solvation shell (hydrogens pointing toward I-) to an expanded cavity around I0 with a more random orientation of the H2O molecules in a broadened first solvation shell.


Intensity-modulated radiation therapy (IMRT) vs. 3D conformal radiotherapy (3DCRT) in locally advanced rectal cancer (LARC): dosimetric comparison and clinical implications.
To compare target dose distribution, comformality, normal tissue avoidance, and irradiated body volume (IBV) in 3DCRT using classic anatomical landmarks (c3DCRT), 3DCRT fitting the PTV (f3DCRT), and intensity-modulated radiation therapy (IMRT) in patients with locally advanced rectal cancer (LARC). Fifteen patients with LARC underwent c3DCRT, f3DCRT, and IMRT planning. Target definition followed the recommendations of the ICRU reports No. 50 and 62. OAR (SB and bladder) constraints were D5 < or = 50 Gy and Dmax < 55 Gy. PTV dose prescription was defined as PTV95 > or = 45 Gy and PTVmin > or = 35 Gy. Target coverage was evaluated with the D95, Dmin, and Dmax. Target dose distribution and comformality was evaluated with the homogeneity indices (HI) and Conformity Index (CI). Normal tissue avoidance of OAR was evaluated with the D5 and V40. IBV at 5 Gy (V5), 10 Gy (V10), and 20 Gy (V20) were calculated. The mean GTV95, CTV95, and PTV95 doses were significantly lower for IMRT plans. Target dose distribution was more inhomogeneous after IMRT planning and 3DCRTplans had significantly lower CI. The V40 and D5 values for OAR were significantly reduced in the IMRT plans .V5 was greater for IMRT than for f3DCRT planning (p < 0.05) and V20 was smaller for IMRT plans(p < 0.05). IMRT planning improves target conformity and decreases irradiation of the OAR at the expense of increased target heterogeneity. IMRT planning increases the IBV at 5 Gy or less but decreases the IBV at 20 Gy or more.


Involvement of heparanase in the pathogenesis of acute kidney injury: nephroprotective effect of PG545.
Despite the high prevalence of acute kidney injury (AKI) and its association with increased morbidity and mortality, therapeutic approaches for AKI are disappointing. This is largely attributed to poor understanding of the pathogenesis of AKI. Heparanase, an endoglycosidase that cleaves heparan sulfate, is involved in extracellular matrix turnover, inflammation, kidney dysfunction, diabetes, fibrosis, angiogenesis and cancer progression. The current study examined the involvement of heparanase in the pathogenesis of ischemic reperfusion (I/R) AKI in a mouse model and the protective effect of PG545, a potent heparanase inhibitor. I/R induced tubular damage and elevation in serum creatinine and blood urea nitrogen to a higher extent in heparanase over-expressing transgenic mice vs. wild type mice. Moreover, TGF-β, vimentin, fibronectin and α-smooth muscle actin, biomarkers of fibrosis, and TNFα, IL6 and endothelin-1, biomarkers of inflammation, were upregulated in I/R induced AKI, primarily in heparanase transgenic mice, suggesting an adverse role of heparanase in the pathogenesis of AKI. Remarkably, pretreatment of mice with PG545 abolished kidney dysfunction and the up-regulation of heparanase, pro-inflammatory (i.e., IL-6) and pro-fibrotic (i.e., TGF-β) genes induced by I/R. The present study provides new insights into the involvement of heparanase in the pathogenesis of ischemic AKI.Our results demonstrate that heparanase plays a deleterious role in the development of renal injury and kidney dysfunction,attesting heparanase inhibition as a promising therapeutic approach for AKI.


Coding exon detection using comparative sequences.
We introduce a new system, called shortHMM, for predicting exons, which predicts individual exons using two related genomes. In this system, we build a hidden semi-Markov model to identify exons. In the hidden Markov model, we propose joint probability models of nucleotides in introns, splice sites, 5'UTR, 3'UTR, and intergenic regions by exploiting the homology between related genomes. In order to reduce the false positive rate of the hidden Markov model, we develop a screening process which is able to identify intergenic regions. We then build a classifier by combining the statistics from the hidden Markov model and the screening process. We implement shortHMM on human-mouse sequence alignments. The source codes are available at < www.stat.purdue.edu/ jingwu/hmm >. Compared to TWINSCAN and SLAM, shortHMM is substantially more powerful in identifying AT-rich RefSeq exons (8% more AT-rich RefSeq exons were predicted), as well as slightly more powerful in identifying RefSeq exons (3-10% more RefSeq exons were predicted), at a similar or lower false positive rate, with less computing time and with less memory usage. Last, shortHMM is also capable of finding new potential exons.


Medical aspects of ambulance design.
Various observations have shown that the interior layout of many ambulances leaves much to be desired. The lighting levels are inadequate, heat loss could be prevented, vehicle identification and passage through traffic could be improved, and measurable differences exist between the ride characteristics of commercially available ambulances, a prototype purpose-built ambulance, and a private car. Moreover the condition of some patients may be affected by the motion of the vehicle either directly or indirectly. Even though they form a small percentage of the total number carried, they represent a very considerable financial risk. A personally conducted survey of ambulance chief officers showed a deep interest and involvement in the upgrading of the service with a general dissatisfaction with many of the vehicles currently available. Hence there is a market for the purpose-built ambulance, which would benefit the patient and the ambulanceman alike.The inadequacies of many vehicles currently in use as ambulances have been shown to work against the interests of the patient requiring life support treatment, and it is suggested that this warrants urgent attention and action. A more extensive research project involving medical observations on the supine sick and injured, attendant task performance, and instrumentation analysis of linear and angular vehicle motions should enable the harmful effects of ride motion to be identified.None of these investigations, however, will be of any value unless they are used in developing future ambulances. Such development must also parallel an increase in the awareness of the importance of ambulance design and its relation to the increased comfort and chance of survival of the patients carried.


Relationship between employment status and obesity in a Korean elderly population, based on the 2007-2009 Korean National Health and Nutrition Examination Survey (KNHANES).
We investigated the relationship between employment status and obesity prevalence in an elderly Korean, using a nationally representative sample. This cross-sectional study included 2991 participants (1396 men and 1595 women) aged 60 years or older. Employment status was categorized into full-time employees, part-time employees, and an unemployed group, based on a self-reported questionnaire. According to Asia Pacific regional guidelines from the World Health Organization (WHO) and International Obesity Task Force (IOTF), obesity was defined as a body mass index (BMI)≥25kg/m(2). Mean BMI in women was highest in the unemployed group, whereas the mean BMI in men did not differ significantly between employment groups. The obesity prevalence in full-time employees, part-time employees, and the unemployed group were 25.1%, 25.5%, and 27.1% in men and 36.0%, 37.9%, and 40.4% in women, respectively. Compared to the full-time employees, the odds ratios (ORs) (95% confidence intervals) for obesity were 1.172 (0.765-1.795) and 1.164 (0.843-1.609) in the part-time employees, and 1.451 (1.054-1.999) and 1.399 (1.090-1.795) in the unemployed group, for men and women, respectively, after adjusting for age, lifestyle factors (physical activity, alcohol consumption, smoking status, daily calorie intake), socioeconomic factors (education level and household income), and inflammatory factor (white blood cell (WBC) counts). Unemployment appears to be significantly related to a higher prevalence risk of obesity in an elderly Korean population, regardless of age, lifestyle, socioeconomic factors, and inflammatory factor.


Efficacy of a brief behavioral intervention to promote condom use among female sex workers in Tijuana and Ciudad Juarez, Mexico.
We examined the efficacy of a brief behavioral intervention to promote condom use among female sex workers in Tijuana and Ciudad Juarez, Mexico. We randomized 924 female sex workers 18 years or older without known HIV infection living in Tijuana and Ciudad Juarez who had recently had unprotected sex with clients to a 30-minute behavioral intervention or a didactic control condition. At baseline and 6 months, women underwent interviews and testing for HIV, syphilis, gonorrhea, and chlamydia. We observed a 40% decline in cumulative sexually transmitted illness incidence (P = .049) in the intervention group. Incidence density for the intervention versus control groups was 13.8 versus 24.92 per 100 person-years for sexually transmitted illnesses combined (P = .034) and 0 versus 2.01 per 100 person-years for HIV (P < .001). There were concomitant increases in the number and percentage of protected sex acts and decreases in the number of unprotected sex acts with clients (P < .05). This brief behavioral intervention shows promise in reducing HIV and sexually transmitted illness risk behaviors among female sex workers and may be transferable to other resource-constrained settings.


β-Polymorph of phenazepam: a powder study.
THE TITLE COMPOUND [SYSTEMATIC NAME: 7-bromo-5-(2-chloro-phen-yl)-1H-1,4-benzodiazepin-2(3H)-one] (β-polymorph), C(15)H(10)BrClN(2)O, has been obtained via cryomodification of the known α-polymorph of phenazepam [Karapetyan et al. (1979 ▶). Bioorg. Khim.5, 1684-1690]. In both polymorphs, the mol-ecules, which differ only in the dihedral angles between the aromatic rings [75.4 (2)° and 86.2 (3)° in the α- and β-polymorphs, respectively], are linked into centrosymmetric dimers via N-H⋯O hydrogen bonds. In the crystal structure of the β-polymorph, weak inter-molecular C-H⋯O hydrogen bonds further link these dimers into layers parallel to bc plane.


Pharmaceutical policy in China.
Contradictory goals plague China's pharmaceutical policy. The government wants to develop the domestic pharmaceutical industry and has used drug pricing to cross-subsidize public hospitals. Yet the government also aims to control drug spending through price caps and profit-margin regulations to guarantee access even for poor patients. The resulting system has distorted market incentives, increased consumers' costs, and financially rewarded inappropriate prescribing, thus undermining public health. Pharmaceuticals account for about half of total health spending in China, representing 43 percent of spending per inpatient episode and 51 percent of spending per outpatient visit. Yet some essential medicines are unavailable or of questionable quality.


IoT and Interpretable Machine Learning Based Framework for Disease Prediction in Pearl Millet.
Decrease in crop yield and degradation in product quality due to plant diseases such as rust and blast in pearl millet is the cause of concern for farmers and the agriculture industry. The stipulation of expert advice for disease identification is also a challenge for the farmers. The traditional techniques adopted for plant disease detection require more human intervention, are unhandy for farmers, and have a high cost of deployment, operation, and maintenance. Therefore, there is a requirement for automating plant disease detection and classification. Deep learning and IoT-based solutions are proposed in the literature for plant disease detection and classification. However, there is a huge scope to develop low-cost systems by integrating these techniques for data collection, feature visualization, and disease detection. This research aims to develop the 'Automatic and Intelligent Data Collector and Classifier' framework by integrating IoT and deep learning. The framework automatically collects the imagery and parametric data from the pearl millet farmland at ICAR, Mysore, India. It automatically sends the collected data to the cloud server and the Raspberry Pi. The 'Custom-Net' model designed as a part of this research is deployed on the cloud server. It collaborates with the Raspberry Pi to precisely predict the blast and rust diseases in pearl millet. Moreover, the Grad-CAM is employed to visualize the features extracted by the 'Custom-Net'. Furthermore, the impact of transfer learning on the 'Custom-Net' and state-of-the-art models viz. Inception ResNet-V2, Inception-V3, ResNet-50, VGG-16, and VGG-19 is shown in this manuscript. Based on the experimental results, and features visualization by Grad-CAM, it is observed that the 'Custom-Net' extracts the relevant features and the transfer learning improves the extraction of relevant features. Additionally, the 'Custom-Net' model reports a classification accuracy of 98.78% that is equivalent to state-of-the-art models viz. Inception ResNet-V2, Inception-V3, ResNet-50, VGG-16, and VGG-19. Although the classification of 'Custom-Net' is comparable to state-of-the-art models, it is effective in reducing the training time by 86.67%. It makes the model more suitable for automating disease detection. This proves that the proposed model is effective in providing a low-cost and handy tool for farmers to improve crop yield and product quality.


What Domains of Belgian Euthanasia Practice are Governed and by Which Sources of Regulation: A Scoping Review.
Multiple sources of regulation seek to shape euthanasia practice in Belgium, including legislation and training. This study comprehensively mapped which of these sources govern which domains of euthanasia practice, such health professionals' obligations, or managing patient requests. Scoping review methodology was used to search for scholarly records which discussed Belgian euthanasia regulation. Template analysis was used to generate themes describing the domains of euthanasia practice governed by sources of regulation. Of 1364 records screened, 107 records were included. Multiple sources of regulation govern each domain, which are: the permissible scope of euthanasia; the legal status of a euthanasia death; the euthanasia process; the rights, obligations, and roles of those involved; system workings; and support for health professionals who provide euthanasia. Domains with significant yet fragmented regulation may lead to inconsistent care provision. Policymakers should develop coherent guidance to support health professionals to navigate this regulatory landscape.


Topoisomerase II-alpha expression increases with increasing Gleason score and with hormone insensitivity in prostate carcinoma.
To investigate and compare topoisomerase II-alpha expression in benign prostatic hyperplasia (BPH), prostate cancer of varying Gleason scores and hormone-insensitive prostate cancer. The immunohistochemical expression of topoisomerase II-alpha antibody in the above-mentioned diagnostic categories was investigated and compared. Increased expression of topoisomerase II-alpha was seen in the prostate cancers of Gleason scores 7 and 8-10 (p = 0.000) compared with prostate cancers of Gleason score 6 and BPH (p = 0.245). Statistically significant differences were found in the topoisomerase II-alpha gene expression between prostate cancers categorised by Gleason Score. Also, increased expression of topoisomerase II-alpha was seen in the known hormone-resistant prostate carcinomas compared with prostate cancers with no hormone treatment in the subgroup with Gleason scores 8-10, which approached statistical significance (p = 0.081). No statistically significant difference was observed in topoisomerase II-alpha expression between the groups with BPH and prostate carcinoma of Gleason score 6 (p = 0.245). Topoisomerase II-alpha expression was found to increase with the known prognostic marker Gleason score and with hormone insensitivity. Objective evidence is provided for clinical trials with drugs targeting topoisomerase II-alpha to be targeted to patients with prostate cancers of Gleason Score >6 and, in particular, prostate cancers of Gleason Scores 8-10.


[Hypogrowth. General considerations].
Growth is a basic indicator of the state of health of a child. Many pathologies that occur during childhood can have an incidence and affect final height in an evident way. The evolution and periodic follow up in the examination of the health of height and weight is a compulsory control for paediatricians, who must detect early alterations that might correspond to responsible pathologies and make possible a correct diagnosis and treatment as early as possible. The time of growth in the life of a person is not long, and the importance of a careful follow up derives from this. In this paper we review the factors that interact in growth, the methodology to follow in primary health consultation in order to establish a diagnosis, and the follow up when dealing with a low height. We include the classification of growth retardation that makes it possible to differentiate the low height denominated idiopathic from the pathological.


BAFF- and APRIL-dependent maintenance of antibody titers after immunization with T-dependent antigen and CD1d-binding ligand.
CD1d-restricted invariant NKT (iNKT) cells boost humoral immunity to T-dependent Ags that are coadministered with the CD1d-binding glycolipid Ag α-galactosylceramide (α-GC). Observations that mice lacking iNKT cells have decaying Ab responses following vaccination have led to the hypothesis that iNKT cells express plasma cell (PC) survival factors that sustain specific Ab titers. Bone marrow chimeric mice in which the entire hematopoietic compartment or iNKT cells selectively lacked BAFF, a proliferation-inducing ligand (APRIL), or both BAFF and APRIL were created and immunized with nitrophenol hapten-conjugated keyhole limpet hemocyanin adsorbed to Imject aluminum hydroxide-containing adjuvant or mixed with α-GC. In comparison with BAFF- or APRIL-sufficient bone marrow chimeras, absence of hematopoietic compartment- and iNKT-derived BAFF and APRIL was associated with rapidly decaying Ab titers and reduced PC numbers. The iNKT cell-derived BAFF or APRIL assumed a greater role in PC survival when α-GC was used as the adjuvant for immunization. These results show that iNKT cell-derived BAFF and APRIL each contribute to survival of PCs induced by immunization. This study sheds new light on the mechanisms through which iNKT cells impact humoral immunity and may inform design of vaccines that incorporate glycolipid adjuvants.


A phylogenomic perspective on diversity, hybridization and evolutionary affinities in the stickleback genus Pungitius.
Hybridization and convergent evolution are phenomena of broad interest in evolutionary biology, but their occurrence poses challenges for reconstructing evolutionary affinities among affected taxa. Sticklebacks in the genus Pungitius are a case in point: evolutionary relationships and taxonomic validity of different species and populations in this circumpolarly distributed species complex remain contentious due to convergent evolution of traits regarded as diagnostic in their taxonomy, and possibly also due to frequent hybridization among taxa. To clarify the evolutionary relationships among different Pungitius species and populations globally, as well as to study the prevalence and extent of introgression among recognized species, genomic data sets of both reference genome-anchored single nucleotide polymorphisms and de novo assembled RAD-tag loci were constructed with RAD-seq data. Both data sets yielded topologically identical and well-supported species trees. Incongruence between nuclear and mitochondrial DNA-based trees was found and suggested possibly frequent hybridization and mitogenome capture during the evolution of Pungitius sticklebacks. Further analyses revealed evidence for frequent nuclear genetic introgression among Pungitius species, although the estimated proportions of autosomal introgression were low. Apart from providing evidence for frequent hybridization, the results challenge earlier mitochondrial and morphology-based hypotheses regarding the number of species and their affinities in this genus: at least seven extant species can be recognized on the basis of genetic data. The results also shed new light on the biogeographical history of the Pungitius-complex, including suggestion of several trans-Arctic invasions of Europe from the Northern Pacific. The well-resolved phylogeny should facilitate the utility of this genus as a model system for future comparative evolutionary studies.


Association of autistic spectrum disorder and the measles, mumps, and rubella vaccine: a systematic review of current epidemiological evidence.
To systematically review the evidence for and against the existence of an association between autistic spectrum disorder (ASD) and the measles, mumps, and rubella (MMR) vaccine. We conducted a systematic review of the medical literature to identify all controlled epidemiological articles examining for an association between ASD and the MMR vaccine. We extracted data from the articles on the characteristics and objectives of the study as well as evidence of an association. Twelve articles met the inclusion criteria. One study found no difference in the rates of ASD and the MMR vaccine in children who were vaccinated and those who were not. Six studies examined for evidence of an increase in ASD associated with an increase in the MMR vaccine coverage, none of which showed evidence of an association. Four studies examined if a variant form of ASD was associated with the MMR vaccine, none of which showed evidence of an association. Eight studies attempted to determine if there was a temporal association between developing ASD and receiving the MMR vaccine. Of these, 1 study identified an increase in parental concern in the 6-month period following vaccination with MMR in one of its analyses. The results of all other studies showed no association between ASD and the MMR vaccine. The current literature does not suggest an association between ASD and the MMR vaccine; however, limited epidemiological evidence exists to rule out a link between a rare variant form of ASD and the MMR vaccine. Given the real risks of not vaccinating and that the risks and existence of variant ASD remain theoretical, current policies should continue to advocate the use of the MMR vaccine.


Anticipation of smoking sufficiently dampens stress reactivity in nicotine-deprived smokers.
Most smokers attempting to quit will relapse, even when using evidence-based cessation treatment. This illustrates the need for better understanding of the relapse process to thereby improve cessation treatments. Although the impact of stress sensitivity on relapse is clear, little research has precisely examined stress reactivity in addicted individuals. Further, most research on relapse focuses on affect surrounding self-administration, and does not address potentially important preconsumption processes such as anticipation of use. We examined the effects of anticipation and actual smoking on stress reactivity in 34 deprived smokers withdrawn for 24 hr and 37 nondeprived smokers, with 37 nonsmoker controls. Using a cued shock stressor task, we measured stress reactivity via startle potentiation and self-reported anxiety. After completing the task once, smokers anticipated smoking a cigarette resting in front of them while they completed the task a second time. Smokers then smoked before completing the task a third and final time. Nonsmokers anticipated and drank water as a control. Anticipation of smoking significantly attenuated both startle potentiation and self-reported anxiety to shock cues for deprived smokers relative to nondeprived smokers. Smokers' stress reactivity was not reduced by smoking beyond the prior effect of anticipation. These results suggest that anticipation, rather than actual drug consumption, may drive the primary reinforcing effect of reduced stress reactivity in smoking. Future research is needed to understand this effect of anticipation on drug use and to determine whether anticipation would make an effective intervention target for addiction and other psychopathology that exhibits increased stress sensitivity.


[Comparative clinical and x-ray evaluation of osteosynthesis methods in patients with posttraumatic defects and deformations of the upper and middle zones of the face].
The results of treatment are compared in three groups of patients treated by various methods of osteosynthesis. In group 1 (n = 203) osteosynthesis was carried out using wire suture. In group 2 (n = 231) titanic miniplates and screws were used. In group 3 (n = 21) combined methods were used (simultaneous fixation by wire sutures and titanium miniplates). Indications to the use of different osteosynthesis methods are defined, errors and complications in osteosynthesis in the upper and middle zones of the face are analyzed.


[The German Health Survey. 1997/98].
The first German Health Survey, a representative study of the health status of the population in unified Germany, was started in October 1997. In this project which is being carried out by the Robert Koch Institute on behalf of the Federal Ministry of Health about 7,200 study participants aged between 18 and 79 are going through a medical check-up and are interviewed as to health-relevant issues. The German National Health Survey consists of a core survey and supplementary modules. These modules are, for the most part, carried out in subsamples of the study population. They partially have been designed and co-financed by cooperating institutions of the RKI. This time, the opportunity given to the individual Länder to increase the size of the sample was realized by Bavaria. This practised principle of a modular structure and co-financing may be regarded as a model and serve as an example for the cost effective implementation of such extensive health surveys. As a result, the German National Health Examination Survey will yield information enabling the RKI to deliver relevant health reports on a federal level and, therefore, to support decisions in health policy. The demand for representative population-based data will be met by supply of survey data as a file for public use.


[Effect of combined anesthetics on the activity of various myocardium enzymes].
It is demonstrated by experiments with rabbits that the Ca2+-ATP-ase activity is stabilized when using combined anesthetics (diacetylcholine + halothane + N2O) as distinct from application of halothane. A decrease in the cholinesterase activity is less pronounced than under the halothane action but more than with the diacetylcholine application. A decrease in the Na+, K+-ATP-ase activity is observed with all types of anesthesia. A considerable inhibition of creatine kinase under the action of combined anesthesia and halothane and an increase of the lactate dehydrogenase activity under diacetylcholine application in mitochondria are shown. Reliable differences in the succinic dehydrogenase activity are not detected.


A population-based study examining the influence of a specialized rapid-access cancer clinic on initial treatment choice in localized prostate cancer.
Treatment decisions in localized prostate cancer are complicated by the available choices. A rapid-access cancer clinic (RAC) has been unique to Calgary, AB, since 2007. This RAC offers multidisciplinary prostate cancer education by a urologist, medical oncologist, and radiation oncologist. It is hypothesized that treatment utilization data from decisions taken at RAC may serve to benchmark the appropriateness of treatment decisions on a population level. Records of patients with clinically localized prostate cancer in Alberta between October 1, 2007 and September 30, 2009 were reviewed with ethics approval. Records were linked to the Alberta Cancer Registry database. Clinical, treatment, and health services characteristics pertaining to patients attending RAC were compared to the general population. The primary endpoint was utilization rates of each initial treatment. During this two-year period, 2838 patients were diagnosed with localized prostate cancer; 375 attended RAC. The utilization rates among RAC patients vs. the whole Alberta population were: prostatectomy 60.3% (95% confidence interval [CI] 55.3-65.2) vs. 48.0% (95% CI 47.1-50.7; χ2 p<0.001); active surveillance 16.0% (95% CI 12.3-19.7%) vs. 13.5% (95% CI 12.2-15.8; χ2 p=0.214); radiotherapy 11.7% (95% CI 8.5-15.0) vs. 18.0% (95% CI 16.9-20.5; χ2 p=0.002); and hormone therapy 8.0% (95% CI 5.2-10.8) vs. 17.4% (95% CI 16.1-18.9; χ2 p<0.001). A specialized clinic for localized prostate cancer may be associated with a higher likelihood of receiving surgery or active surveillance as initial treatment compared to the prostate cancer population in Alberta.


Stakeholder expectations in practice-based medicine.
Competitive pressures are forcing physicians from solo practice into new organizational structures. These new structures and the technologies supporting them have generated suggestions for improving medical practice. This article examines the unspoken assumption often accompanying these suggestions that practice improvement can come about through a closer alignment of the practice's goals and values with its stakeholders' expectations. Because conflict among competing goals is inevitable in a resource-scarce environment, an important question for each practice, and for each individual physician in a practice, is how to adjudicate conflicts of value when the goals of the practice appear to collide. This essay concludes with a proposal for an adjudicating process to help resolve these conflicts in practice-based medicine.


CXCL11 is involved in leucocyte recruitment to the central nervous system in neuroborreliosis.
We investigated the role of the CXCR3 chemokine CXCL11 (I-TAC) for leukocyte recruitment to the CSF in neuroborreliosis (NB). CXCL11 levels in the CSF of 17 patients with acute NB were elevated compared with 20 non-inflammatory controls (100.1 vs. 54.1 pg/ml, p = 0.002). Using a modified Boyden chamber chemotaxis-assay, the CSF of patients with acute NB was more chemotactic than the control CSF-samples (p = 0.001). A strong correlation (p < 0.001) between CXCL11 levels, chemotactic activity and CSF-white cell count was detected. Though the chemotactic activity of CSF from NB patients was only partially reduced by a human recombinant CXCL11 antibody, these findings suggest that, among other chemotactic factors, CXCL11 may play a role in the chemotaxis of mononuclear cells in NB.


IMGT (ImMunoGeneTics) locus on focus. A new section of Experimental and Clinical Immunogenetics.
IMGT, the international ImMunoGeneTics database (http:/(/)imgt.cnusc.fr:8104) is an integrated database specialising in immunoglobulins (Ig), T-cell receptors (TcR) and major histocompatibility complex (MHC) of all vertebrate species, created by Marie-Paule Lefranc, CNRS, Montpellier II University, Montpellier, France (firstname.lastname@example.com). IMGT includes three databases: LIGM-DB for Ig and TcR, MHC/HLA-DB, and PRIMER-DB (the last two in development). The new section of Experimental and Clinical Immunogenetics, 'IMGT locus on focus', will give the more updated and extensive overview of the current status of the different Ig, TcR and MHC genes in IMGT, with standardization of gene nomenclature, functionality, and allele polymorphism according to the IMGT rules and unique numbering.


Homodinuclear lanthanide {Ln2} (Ln = Gd, Tb, Dy, Eu) complexes prepared from an o-vanillin based ligand: luminescence and single-molecule magnetism behavior.
Four dinuclear lanthanide complexes [Gd2 (H2L)2 (µ-piv)2 (piv)2]·2CHCl3 (1), [Tb2 (H2L)2 (µ-piv)2 (piv)2]·2CHCl3 (2), [Dy2 (H2L)2 (µ-piv)2 (piv)2]·2CHCl3 (3) and [Eu2 (H2L)2 (µ-piv)2 (piv)2]·2CHCl3 (4) were synthesized by the reaction of appropriate Ln(III) chloride salts and a multidentate ligand, 2,2'-(2-hydroxy-3-methoxy-5-methylbenzylazanediyl)diethanol (H3L) in the presence of pivalic acid. 1-4 are neutral and are held by two monoanionic, [H2L](-) ligands. The two lanthanide ions are doubly bridged to each other via two phenolate oxygen atoms. Both the lanthanide ions are nine coordinated and possess a distorted capped square antiprism geometry. Photophysical studies reveal that Tb(3+) (2) and Dy(3+) (3) complexes display strong ligand-sensitized lanthanide-characteristic emission. The Tb(3+) complex (2) shows a very high overall quantum yield of 76.2% with a lifetime of 1.752 ms. Magnetic studies reveal single-molecule magnet behavior for 3 which shows in its ac susceptibility studies a two-step slow relaxation yielding two effective relaxation energy barriers of ΔE = 8.96 K and 35.51 K.


Rickettsia felis in Ctenocephalides felis from Guatemala and Costa Rica.
Rickettsia felis is an emerging human pathogen associated primarily with the cat flea Ctenocephalides felis. In this study, we investigated the presence of Rickettsia felis in C. felis from Guatemala and Costa Rica. Ctenocephalides felis were collected directly from dogs and cats, and analyzed by polymerase chain reaction for Rickettsia-specific fragments of 17-kDa protein, OmpA, and citrate synthase genes. Rickettsia DNA was detected in 64% (55 of 86) and 58% (47 of 81) of flea pools in Guatemala and Costa Rica, respectively. Sequencing of gltA fragments identified R. felis genotype URRWXCal(2) in samples from both countries, and genotype Rf2125 in Costa Rica. This is the first report of R. felis in Guatemala and of genotype Rf2125 in Costa Rica. The extensive presence of this pathogen in countries of Central America stresses the need for increased awareness and diagnosis.


Diagnostic value of a chemistry test profile.
Serum chemistry test results were correlated with discharge diagnoses of 4,295 persons admitted to an acute care general hospital in a seven-month period. The diagnostic value of the test results, separately and in combinations of up to 12 tests, were calculated at each of ten levels as measured from the mean of normal in standard deviations. All patients had a serum profile consisting of total calcium, inorganic phosphorus, glucose, urea nitrogen, uric acid, cholesterol, total protein, albumin, total bilirubin, alkaline phosphatase, lactic dehydrogenase, and glutamic oxaloacetic transaminase levels. Analysis by manual and computer technics is illustrated. Computerized analysis of a chemistry profile is reported as a list of diagnostic possibilities in ranking order, with the calculated probability for each. In this preliminary report individual diseases are replaced by categories of disease taken from The International Classification of Diseases, Adapted (ICDA).


Domestic exposure to irritant cleaning agents and asthma in women.
An adverse role of frequent domestic use of cleaning agents, especially in spray form, on asthma has been reported. However, sparse studies have investigated respiratory health effects of chronic domestic exposure to irritant cleaning agents. This study aims to investigate associations between weekly use of irritant domestic cleaning products and current allergic and non-allergic asthma in a large cohort of elderly women. We used data from the Asthma-E3N nested case-control study on asthma (n = 19,404 women, response rate: 91%, 2011), in which participants completed standardized questionnaires on asthma and on the use of domestic cleaning products including irritants (bleach, ammonia, solvents and acids). Allergic multimorbidity in asthma was assessed from allergic-related medications recorded in drug refunds database. The association between use of irritants and current asthma was estimated by logistic regression (current vs. never asthma) and multinomial logistic regression (never asthma, non-allergic asthma, allergic asthma) adjusted on age, smoking status and body mass index (BMI). In the 12,758 women included in the analysis (mean age: 70 years, current smokers: 4%, BMI ≥ 25 kg/m2: 32%, low education: 11%, current asthma: 23%), 47% reported weekly use of at least one irritant cleaning product at home. Weekly use of irritant products was associated with a higher risk of current asthma (adjusted Odds-Ratio: 1.17, 1.07-1.27). A statistically significant dose-response association was reported (p trend < 0.0001), with both the number of irritant products used weekly (1 irritant: 1.12, 1.02-1.23; 2 irritants: 1.21, 1.05-1.39; 3 irritants or more: 2.08, 1.57-2.75) and the frequency of use (1-3 days/week: 1.12, 1.02-1.23; 4-7 days/week: 1.41,1.22-1.64). A dose-response association was observed with the frequency of products used (p trend < 0.05), for both non-allergic (4-7 days/week: 1.27, 1.02-1.57) and allergic asthma (1.52, 1.27-1.82). In conclusion, weekly use of common cleaning irritants was associated with an increased risk of current asthma, whatever the allergic status.


Molecular and Clinical Epidemiology of SARS-CoV-2 Infection among Vaccinated and Unvaccinated Individuals in a Large Healthcare Organization from New Jersey.
New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations, from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOCs) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOCs, including Alpha (n = 714), Delta (n = 1877), and Omicron (n = 1802). Omicron isolates were further sub-typed as BA.1 (n = 899), BA.2 (n = 853), or BA.4/BA.5 (n = 50); the remaining 614 isolates were classified as "Other". Approximately 31.5% (1577/5007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p < 0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p < 0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p < 0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.


The diversity of HIV-1 fights against vaccine efficacy: how self-assembling protein nanoparticle technology may fight back.
An efficacious HIV-1 vaccine has remained an elusive target for almost 40 years. The sheer diversity of the virus is one of the major roadblocks for vaccine development. HIV-1 frequently mutates and various strains predominate in different geographic regions, making the development of a globally applicable vaccine extremely difficult. Multiple approaches have been taken to overcome the issue of viral diversity, including sequence optimization, development of consensus and mosaic sequences and the use of different prime-boost approaches. To develop an efficacious vaccine, these approaches may need to be combined. One way to potentially synergize these approaches is to use a rationally designed protein nanoparticle that allows for the native-like presentation of antigens, such as the self-assembling protein nanoparticle.