A prospective self-controlled phase II study of imiquimod 5% cream in the treatment of infantile hemangioma.
Imiquimod has been reported to be efficacious in the topical treatment of uncomplicated infantile hemangiomas (IH). However, due to the natural tendency of IH to involute spontaneously, prior uncontrolled efficacy and safety studies have been called into question. We conducted a prospective self-controlled phase II study of imiquimod initially applied to uncomplicated, proliferative superficial or mixed IHs treating half of each IH once every other night for 16 weeks, leaving the other half untreated. After 16 weeks, an independent dermatologist evaluated the color, area, and volume of each half of the hemangioma. Of the 44 patients treated, the total effective rate was 80% (n = 35), with an overall resolution rated as excellent or good rate in 39% of lesions (n = 17/44). The relapse rate was 2% (n = 1). Side effects were noted in 61% (n = 27) including erythema or/and edema (n = 16%, 7), local itching (n = 7%, 3), peeling (n = 7%, 3), erosion (n = 5%, 2), crusting (n = 55%, 24), ulceration (n = 9%, 4), and scarring (n = 5%, 2). Some patients had two or more side effects. Most were judged to be mild to moderate and did not result in treatment being interrupted. Crusting or ulceration was noted to cause post-treatment skin reactions, such as texture change, whereas cases without crusting involuted to almost normal skin. No local infection or systemic reaction was observed. The difference in effective rate and side effect incidence between superficial and mixed IH was not statistically significant. Imiquimod 5% cream can be an effective and safe treatment option for superficial mixed IH in which the superficial component predominates. The recurrence rate is low, but local reactions including crusting can develop and result in post-treatment skin changes.


[Heterosynaptic facilitation in giant neurons of the cerebral ganglion of the horned Planorbis].
Heterosynaptic facilitation evoked in the giant neuron of the Planorbis corneus cerebral ganglion by stimulation of the remote visceral nerve was more effective than facilitation achieved by paired stimulation of cerebral nerves. Its effectiveness depended not on the efficacy of the heterosynaptic input to the giant neuron, but on the strength of the connections between the chosen heterosynaptic input with neurons surrounding the giant cell. This finding as well as prolonged latency and slow rise-time of facilitation may indicate that the latter is of neurosecreory origin. The existence of a mechanism of drastic increase in the efficacy of synaptic connections may play an important role in animal habituation and during conditioning in particular, though such plasticsynaptic changes do not reflect the specificity of the conditioned reflex.


The destroyed elbow.
Surgeons need an advanced knowledge of upper extremity anatomy and function to care for the destroyed elbow. This paper describes strategies for evaluating and treating this severe injury. Outcomes can be optimized with contemporary techniques and technologies. Surgeons need to instill realistic expectations in patients with advanced compromise.


[Aspects of quality of life associated with self-rated health: a study of elderly women from a physical activity program in low-income neighborhoods in Curitiba in the state of Paraná, Brazil].
This study sought to analyze which aspects of quality of life (QoL; Physical, Psychological, Social Relationships and Environmental) are associated with the perception of health among elderly women from low-income neighborhoods in Curitiba in the state of Paraná. The sample comprised 450 elderly participants of the Elderly in Motion Program of the Boqueirão, Pinheirinho and Bairro Novo neighborhoods. The question "How do you rate your general health?" was used to assess the perceived health in the elderly, and the Whoqol-Bref questionnaire was used to identify the aspects of QoL. Descriptive statistics, the Mann-Whitney U test, Spearman's correlation test and binary logistic regression were used for data analysis. All aspects were significantly associated with perceived health (p < 0.05). However, after adjusting for confounding variables, only the Physical and Environmental aspects revealed significant associations. In other words, elderly women with a negative perception of these aspects were twice as likely to have a negative perception of health. The conclusion reached is that programs aimed at promoting health and QoL in low-income elderly women ought to concentrate their actions on the physical and environmental aspects of QoL.


[Still a small problem with the mad cow disease? Creutzfeldt-Jakob disease and other prion diseases: current status].
This review is based on recent published research on the BSE/CJD/vCJD problem mainly from UK, Germany and France. The situation in Sweden seems to be fortunate for several reasons. The use of meat and bonemeal as animal fodder was forbidden in this country 13 years ago. Sweden has not had any sheep with scrapie for many years. No animals with BSE have so far been found in our country. The incidence of sporadic CJD in this country followed retrospectively from 1985 to 1996 and prospectively from 1997 to 1999 has been around 1.2 per million per year with no significant increase. Only few cases of familial CJD are known. No patient with iatrogenic CJD has ever been found. The use of growth hormone derived from human pituitary glands was abandoned in 1985 when recombinant human growth hormone became available. So far there is no indication that any of the CJD cases diagnosed in Sweden has been of the vCJD type, the one linked to BSE. However, as the incubation period for prion diseases is very long and the Swedes are frequent travellers there is a risk that people from our country could have contracted vCJD through consuming meat products in countries with BSE. As a precaution the consumption of brain, spinal cord, lymphatic tissue, lungs, and gastrointestinal tract should be avoided. Human pituitary derived growth hormone is still available in some countries and might be illegally imported into Sweden.


[Pregnancy after treated breast cancer. Results of a case-control study].
Sixty-eight cases of pregnancy after carcinoma of the breast were collected during a survey conducted by the Société Française de Gynécologie: 27 patients had one or several pregnancies interrupted at an early stage; 41 patients had at least one uninterrupted pregnancy. The fate of these patients was compared to that of 136 controls similar in all respects, except for the absence of post-cancer pregnancy. There was no significant difference in survival curves: the 10-year survival rate in our 68 patients was 71% (90% in those with N- cancer; 71% in those with N+ cancer, with no significant difference between cases and controls in each group). The patients whose pregnancies were interrupted had the same prognosis as those who delivered at term. The survival of 14 patients who conceived within 6 months of the breast cancer treatment was not significantly different from that of the corresponding controls. Pregnancy after breast cancer does not seem to alter the prognosis of the disease. In women with good prognosis cancer, the survival rate is excellent whatever the delay between cancer and pregnancy, and women should not be discouraged from having children; in women with poor prognosis cancer (N+), the outcome is not modified by pregnancy, and it remains lethal in about 50% of cases.


Therapy in prion diseases: from molecular and cellular biology to therapeutic targets.
Prion diseases are infectious and fatal neurodegenerative disorders of man and animals which are characterized by spongiform degeneration in the central nervous system. In human diseases, the manifestation can be sporadic, familial or acquired by infection. Prion disorders are caused by the accumulation of an aberrantly folded isoform of the cellular prion protein (PrP(c)), commonly named PrP(Sc). Although prion diseases are usually rare, they have the potential to be transferred within and also between species by infection processes, giving then raise even to epidemic scenarios. As pathology is obviously restricted to the central nervous system pre-mortem diagnosis is usually hard to achieve. Promising approaches towards the development of therapeutic and even prophylactic anti-prion regimens were recently made. However, only a profound knowledge of the infectious agent and its replication strategy enables the design of effective anti-prion strategies. Cell culture models were highly instrumental in uncovering fundamental aspects of prion propagation. In this chapter, the cellular and molecular biology of prion proteins in general is discussed and prophylactic and therapeutic concepts derived thereof are introduced. In particular, emphasis is put on strategies targeting PrP(c) which is absolutely needed as substrate for prion conversion, and on intrinsic cellular clearance mechanisms for prions.


Obelionic cranial deformation in the Puebloan Southwest.
As a form of cranial deformation, obelionic flattening is rare. Originally named and described by Stewart (J Wash Acad Sci 29 (1939) 460-465), based on a small sample from Florida, it has been little noted since. Previously [Nelson and Madimenos, Paper presented at the Paleopathology Association annual meeting (2007)], we reported the discovery of two individuals from the Pueblo III Gallina site of Cañada Simon I who exhibit flattening of this type. Although technically undescribed in the Southwest before now, there are tantalizing clues in the literature that it occurred in low frequencies throughout the Ancestral Pueblo world. To determine whether the obelionic flattening found at Cañada Simon I was isolated or an indication of a more widespread phenomenon, we undertook a survey of crania from other Gallina sites, Chaco Canyon, and the literature (type of deformation can be determined on lateral photographs of crania properly positioned along the Frankfort Horizontal). We examined 146 crania (78 firsthand) of which seven exhibit obelionic flattening. Our results indicate that obelionic flattening should be added to the suite of cranial deformations that occur in the Southwest. Here, we propose parameters by which obelionic flattening can be described and differentiated from the more common lambdoidal and occipital forms and suggest that the three types of flattening form a continuum of cradleboard induced deformation, although the exact mechanism for obelionic flattening remains elusive. Am J Phys Anthropol, 2010. © 2010 Wiley-Liss, Inc.


[Roentgenographic study of the duodenal juice components in the dog].
It is shown that X-ray pattern rich in reflections that we have received earlier from concentrated canine duodenal juice is the sum of the patterns arising from both mucin macromolecules and from unknown component of the juice. The functional role of the duodenal juice regularity observed is discussed.


In situ generation of superoxide anion radical in aqueous medium under ambient conditions.
In the recent decades superoxide [O(2-.) ] has become the subject of considerable interest. Nonetheless, generation of superoxide compounds is still a substantial challenge. The standard methods for synthesis of superoxide derivatives are either through the oxidation of molten alkali metals with hot air or by using electrolytic reduction of oxygen in aprotic solvent such as dimethylformamide. No methodology is available for the generation of superoxides in protic solutions and particularly not in water. We propose a new in situ method for alkali superoxide preparation by using sodium hydroxide and hydrogen peroxide at room temperature and in aqueous solution.


Contribution of the flexible loop region to the function of staphylococcal enterotoxin B.
Staphylococcal enterotoxin B (SEB), a toxin produced by Staphylococcus aureus, causes food poisoning and other fatal diseases by inducing high levels of pro-inflammatory cytokines. These cytokines are released from CD4+ T cells and major histocompatibility complex (MHC) class II antigen-presenting cells, which are activated through binding of wild-type (WT) SEB to both the MHC class II molecule and specific T-cell receptor Vbeta chains. Here, we focused on a trypsin/cathepsin cleavage site of WT SEB, which is known to be cleaved in vivo between Lys97 and Lys98, located within the loop region. To know the function of the cleavage, an SEB mutant, in which both of these Lys residues have been changed to Ser, was examined. This mutant showed prolonged tolerance to protease cleavage at a different site between Thr107 and Asp108, and structural analyses revealed no major conformational differences between WT SEB and the mutant protein. However, differential scanning calorimetric analysis showed an increase in enthalpy upon thermal denaturation of the mutant protein, which correlated with the speed of cleavage between Thr107 and Asp108. The mutant protein also had slightly increased affinity for MHC. In the in vivo experiment, the SEB mutant showed lower proliferative response in peripheral blood mononuclear cells and had lower cytokine-induction activity, compared with WT SEB. These results highlight the importance of the flexible loop region for the functional, physical and chemical properties of WT SEB, thus providing insight into the nature of WT SEB that was unrevealed previously.


Fatty acid uptake is preserved in chronically dysfunctional but viable myocardium.
Glucose uptake appears preserved or even enhanced in the chronically dysfunctional but viable myocardium. However, the use of other fuels such as free fatty acids (FFA) remains unknown. We studied FFA uptake in the chronically dysfunctional but viable myocardium in seven patients with an occluded major coronary artery and a corresponding chronic wall motion abnormality but no previous infarction. Myocardial FFA uptake kinetics in the fasting state were measured with positron emission tomography (PET) and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA). The FFA uptake index was calculated by multiplying the fractional [18F]FTHA uptake with serum FFA concentration. Myocardial blood flow (MBF) was measured with [15O]H2O and PET. Myocardial viability was confirmed with a static 18F-labeled 2-fluoro-2-deoxy-D-glucose PET imaging and a follow-up echocardiography in the revascularized patients. Regional MBF was slightly but not significantly lower in the dysfunctional compared with normal myocardial segments (0.76 +/- 0.18 vs. 0.81 +/- 0.14 ml.min-1.g-1, means +/- SD; P = 0.16). The fractional [18F]FTHA uptake rates [0.11 +/- 0.03 vs. 0.11 +/- 0.04 ml.g-1.min-1; not significant (NS)], and the FFA uptake indexes (5.8 +/- 1.7 vs. 5.8 +/- 2.1 mumol.100g-1.min-1; NS) were similar in the dysfunctional but viable and in the normal myocardial regions. Thus, in the chronically dysfunctional but viable (collateral-dependent) myocardium, the fatty acid uptake probed by [18F]FTHA appears preserved. Taken together with preserved glucose uptake, the results indicate that there is uncoupling of substrate uptake and mechanical function in the chronically dysfunctional but viable myocardium.


High-Intensity Acute Exercise and Directed Forgetting on Memory Function.
Despite accumulating research demonstrating that acute exercise may enhance memory function, very little research has evaluated whether acute exercise can effectuate intentional directed forgetting (DF), an adaptative strategy to facilitate subsequent memory performance. A three-arm parallel-group randomized controlled intervention was employed. Participants were randomized into one of three groups, including: (1) exercise plus DF (Ex + DF), (2) DF (directed forgetting) only (DF) and (3) R (remember) only (R). The acute bout of exercise included 15 min of high-intensity treadmill exercise. The memory assessment involved the presentation of two-word lists. After encoding the first word list, participants were either instructed to forget all of those words (DF) or to remember them. Following this, participants encoded the second word list. We observed a statistically significant main effect for list F(1, 57) = 12.27, p < 0.001, η2p = 0.18, but no main effect for group F(2, 57) = 1.32, p = 0.27, η2p = 0.04, or list by group interaction, F(2, 57) = 2.89, p = 0.06, η2p = 0.09. This study demonstrates a directed forgetting effect in that cueing an individual to forget a previously encoded list of items facilitates memory performance on a subsequent list of items. However, we failed to demonstrate any beneficial effect of acute exercise in facilitating directed forgetting. These findings are discussed in the context of directed forgetting theories, particularly the attention inhibition mechanism, as well as the timing of the acute bout of exercise.


Urinary tract infection prophylaxis in children with neurogenic bladder with cranberry capsules: randomized controlled trial.
Objectives. The aim of this randomized controlled prospective study is to evaluate the efficacy of cranberry capsules for prevention of UTI in children with neurogenic bladder caused by myelomeningocele. Patients and Methods. To be eligible for this study, patients had to be diagnosed as neurogenic bladder caused by myelomeningocele, evaluated urodynamically, followed up with clean intermittent catheterization and anticholinergic drugs. Intervention. Six months of treatment with placebo; after a week of wash-out period treatment of cranberry extract tablets (1 capsule/day) for an additional 6 months. Randomization was performed sequentially. Patients and care givers were blinded to drug assignment. Main outcome measure was infection rate. Group comparisons were performed with Wilcoxon test. Results. The study population included 20 (F/M: 13/7) patients with neurogenic bladder with the mean age of 7.25 ± 3.49 (4, 18) years. The median UTI rate was 0.5/year during placebo usage whereas 0/year during cranberry capsule usage. Decrease in infection rate was significant with cranberry capsule usage (P = 0.012). Decrease in the percentage of the pyuria was also recorded as significant (P = 0.000). Any adverse events or side effects were not recorded. Conclusion. We concluded that cranberry capsules could be an encouraging option for the prevention of recurrent UTI in children with neurogenic bladder caused by myelomeningocele.


Evaluating the Effectiveness of Cooling Vest in a Hot and Humid Environment.
This study aims to evaluate the effectiveness of a newly designed hybrid cooling vest for construction workers in alleviating heat stress. Two types of cooling vests, namely, a commonly worn Vest A and a newly designed Vest B, were tested in a climatic chamber environment (34.0°C temperature, 60% relative humidity, and 0.4 m s-1 air velocity) using a sweating thermal manikin. Four test scenarios were included: fan off with no phase change materials (PCMs) (Fan-off), fan on with no PCMs (Fan-on), fan off with completely solidified PCMs (PCM + Fan-off), and fan on with completely solidified PCMs (PCM + Fan-on). Test results showed that Vests A and B provided a continuous cooling effect during the 3-h test. The average cooling power for the torso region of Vest B was 67 W, which was higher than that of Vest A (56 W). The addition of PCMs offered a cooling effect of approximately 60 min. Ventilation fans considerably improved the evaporative heat loss compared with the Fan-off condition. The newly designed hybrid cooling vest (Vest B) may be an effective means to reduce heat strain and enhance work performance in a hot and humid environment.


Prostaglandin: release from the rat phrenic nerve--diaphragm preparation.
Release of a substance that stimulates smooth muscle was detected from a phrenic nerve-diaphragm preparation from the rat upon direct and indirect stimulation. On thin-layer chromatography most of the active material behaved as a mixture of prostaglandins. The effect of electrical stimulation was mimicked by catecholamines but not by acetylcholine or eserine. The effect of nerve stimulation was not antagonized by d-tubocurarine.


Proactive management of penicillin and other antibiotic allergies.
Background: Antibiotic allergies, especially penicillin, are the most frequent drug allergy listed in the medical record. Proactive evaluations of antibiotic allergies, particularly penicillin allergies, have been recommended by various specialty societies. Objective: To review the history of the discovery of penicillin, implications of the penicillin allergy label, various delabeling strategies as well as a brief overview of the approach to cephalosporin, fluoroquinolone, and macrolide allergy. Methods: Recent studies on penicillin allergy delabeling and on cephalosporin and fluoroquinolone allergies were reviewed. Results: Although Alexander Fleming is often solely credited with the discovery of penicillin, other scientists were critical to the development of penicillin as a life-saving antibiotic. The vast majority of patients with a penicillin allergy label are not allergic; however, this label results in increased morbidities and mortality. A variety of penicillin delabeling strategies can be used in both the outpatient and the inpatient settings. The role of direct penicillin challenge in patients at low risk is emerging and is the method of choice for children. Patients with an unconfirmed penicillin allergy have a low risk of reacting to cephalosporins. The R1 side chain largely dictates cephalosporin allergy and cross-reactivity. Drug challenge is the preferred method for evaluation of both fluoroquinolone and macrolide allergy. Conclusion: Multiple effective methods are available to delabel patients of common antibiotic allergies. Delabeling patients in a proactive manner can reduce patient morbidity.


Emission and transmission brain tomography.
Comparative emission and transmission brain tomograms were obtained in 209 patients to establish the diagnostic accuracy of a new emission tomographic scanner in detecting space-occupying disease in the brain. Concordant results were obtained in 169 patients (81%). Computed transmission tomography (transmission CT) yielded an overall rate of false-positive results of 0.48% and a false-negative rate of 6%. Emission CT yielded a false-positive rate of 0% and false-negative rates of 2.4% for malignant disease and 10% for vascular disease. The higher rate of false-negative results for vascular disease with emission CT occurs because transmission CT can detect old infarction. The rates of detection of recent vascular disease with emission and trnasmission CT are identical. Thus emission CT is highly sensitive in detecting space-occupying disease in the brain. It represents an ideal screening procedure.


Long-range RNA interactions between structural domains of the aphthovirus internal ribosome entry site (IRES).
Internal initiation of translation is promoted by internal ribosome entry site (IRES) cis-acting elements. Using transcripts that correspond to the structural domains of the foot-and-mouth disease virus (FMDV) IRES, we have identified RNA-RNA interactions between separated domains (1-2, 3, 4-5, or HH) of the IRES structure. All the assayed domains were able to interact with the full-length IRES as well as with domain 3, although to a different extent, with the most efficient interactions being those occurring between domains 3 and 4-5, and domains 3 and 1-2. RNA-RNA complexes were stable over 1 h of incubation at 37 degrees C, and depended on Mg2+ and RNA concentration. Neither the antisense domain 1-2 nor tRNA interacted with domain 3, providing experimental evidence of the specificity for the sense strand of the IRES sequence. Additionally, domain 1-2 did not interact with 4-5, leading to the suggestion that domain 3 acts as a scaffold structure where the other domains bind. The thermal disassociation profile of these complexes indicated different strength in these interactions. Whereas 50% of the complexes between domains 3 and 4-5 were destabilized at 45 degrees C, those formed by domain 1-2 and 3 required temperatures higher than 51 degrees C. Efficient self-dimerization of domains 3 and 4-5 was found in the absence of other transcripts. Formation of domain 3 homodimer competed with formation of heterocomplexes with other domains, and conversely, domain 3 homodimers were competed out by the presence of the other domains. RNA interactions were also observed at physiological concentrations of Mg2+ and K1+. The identification of the RNA-RNA complexes reported here provide direct experimental evidence of tertiary interactions within IRES elements.


Foldamers reveal and validate therapeutic targets associated with toxic α-synuclein self-assembly.
Parkinson's disease (PD) is a progressive neurodegenerative disorder for which there is no successful prevention or intervention. The pathological hallmark for PD involves the self-assembly of functional Alpha-Synuclein (αS) into non-functional amyloid structures. One of the potential therapeutic interventions against PD is the effective inhibition of αS aggregation. However, the bottleneck towards achieving this goal is the identification of αS domains/sequences that are essential for aggregation. Using a protein mimetic approach, we have identified αS sequences-based targets that are essential for aggregation and will have significant therapeutic implications. An extensive array of in vitro, ex vivo, and in vivo assays is utilized to validate αS sequences and their structural characteristics that are essential for aggregation and propagation of PD phenotypes. The study aids in developing significant mechanistic and therapeutic insights into various facets of αS aggregation, which will pave the way for effective treatments for PD.


Value-based medicine in oncology: the importance of perspective in the emerging value frameworks.
Recently, professional and healthcare-related entities have launched frameworks designed to assess the value of cancer innovations in multistakeholder decision processes. Among the most visible entities that propose and implement value frameworks in oncology are the European Society of Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), the Memorial Sloan Kettering Cancer Center (MSKCC) and the National Comprehensive Cancer Network (NCCN). However, these value frameworks have been criticized for conceptual inconsistencies, inability to include a greater variety of value criteria, and inadequate explanation of the uncertainty approach used in the modeling process. On the other hand, Multi-Criteria Decision Analysis (MCDA) is a set of methods and processes that allow the multiple criteria involved in a decision to be explicitly addressed. This approach allows the identification of relevant decision criteria, gathering of evidence based on scientific literature, attribution of weights to the criteria and scores to the evidence raised, and aggregation of the weighted scores to constitute a global metric of value. The purpose of this article is to review the main features of these value frameworks in oncology and the importance of perspective for framework readiness to support healthcare decision-making based on MCDA methodology.


A new genus and species of philometrid (Nematoda) from the subcutaneous tissue of the crevalle jack, Caranx hippos (Osteichthyes), from the southern Gulf of Mexico.
A new genus and species of nematode, Caranginema americanum n. gen., n. sp. (Philometridae), are described from gravid, subgravid, and nongravid female specimens collected from the subcutaneous tissue of the fish (crevalle jack) Caranx hippos (Carangidae, Perciformes) from the coral reef El Cabezo, southern Gulf of Mexico, Mexico. Caranginema, assigned to the Philometrinae, differs from other genera of this subfamily mainly in the presence of 2 conspicuous parallel cordons on either side, extending along nearly the entire body length and demarcating narrow smooth lateral fields and in having the remaining body surface with numerous ornamentations forming irregularly scattered, transversely elongated narrow cuticular molds. The new species is characterized mainly by the presence of 3 large, sclerotized esophageal teeth protruded out of the mouth, the number and arrangement of cephalic papillae (8 papillae in 4 pairs of external circle and 4 single papillae of internal circle), the length and structure of the esophagus, and by the body length of gravid and subgravid females (267 and 258 mm, respectively). Caranginema americanum is the seventh philometrid species reported from marine and brackish water fishes in Mexico.


Laminin N-terminus α31 protein distribution in adult human tissues.
Laminin N-terminus α31 (LaNt α31) is a netrin-like protein derived from alternative splicing of the laminin α3 gene. Although LaNt α31 has been demonstrated to influence corneal and skin epithelial cell function, its expression has not been investigated beyond these tissues. In this study, we used immunohistochemistry to characterise the distribution of this protein in a wide-array of human tissue sections in comparison to laminin α3. The data revealed widespread LaNt α31 expression. In epithelial tissue, LaNt α31 was present in the basal layer of the epidermis, throughout the epithelium of the digestive tract, and in much of the epithelium of the reproductive system. LaNt α31 was also found throughout the vasculature of most tissues, with enrichment in reticular-like fibres in the extracellular matrix surrounding large vessels. A similar matrix pattern was observed around the terminal ducts in the breast and around the alveolar epithelium in the lung, where basement membrane staining was also evident. Specific enrichment of LaNt α31 was identified in sub-populations of cells of the kidney, liver, pancreas, and spleen, with variations in intensity between different cell types in the collecting ducts and glomeruli of the kidney. Intriguingly, LaNt α31 immunoreactivity was also evident in neurons of the central nervous system, in the cerebellum, cerebral cortex, and spinal cord. Together these findings suggest that LaNt α31 may be functionally relevant in a wider range of tissue contexts than previously anticipated, and the data provides a valuable basis for investigation into this interesting protein.


Synergism between Wnt3a and heparin enhances osteogenesis via a phosphoinositide 3-kinase/Akt/RUNX2 pathway.
A new strategy has emerged to improve healing of bone defects using exogenous glycosaminoglycans by increasing the effectiveness of bone-anabolic growth factors. Wnt ligands play an important role in bone formation. However, their functional interactions with heparan sulfate/heparin have only been investigated in non-osseous tissues. Our study now shows that the osteogenic activity of Wnt3a is cooperatively stimulated through physical interactions with exogenous heparin. N-Sulfation and to a lesser extent O-sulfation of heparin contribute to the physical binding and optimal co-stimulation of Wnt3a. Wnt3a-heparin signaling synergistically increases osteoblast differentiation with minimal effects on cell proliferation. Thus, heparin selectively reduces the effective dose of Wnt3a needed to elicit osteogenic, but not mitogenic responses. Mechanistically, Wnt3a-heparin signaling strongly activates the phosphoinositide 3-kinase/Akt pathway and requires the bone-related transcription factor RUNX2 to stimulate alkaline phosphatase activity, which parallels canonical beta-catenin signaling. Collectively, our findings establish the osteo-inductive potential of a heparin-mediated Wnt3a-phosphoinositide 3-kinase/Akt-RUNX2 signaling network and suggest that heparan sulfate supplementation may selectively reduce the therapeutic doses of peptide factors required to promote bone formation.


Does a 30-minute introductory visit to the operating room reduce patients' anxiety before elective surgery? a prospective controlled observational study.
Patients scheduled for elective surgery typically suffer from preoperative anxiety related to the unknown environment and unclear expectations. We hypothesized that a virtual or in-person introductory visit to the operating room one day before surgery may decrease the extent of preoperative anxiety by familiarizing patients and their families with the operating room environment. So, this study aimed to evaluate the impact of operating room visits, conducted both in-person and virtual reality, on patients' preoperative anxiety. This prospеctivе controllеd obsеrvational study еxaminеd patiеnts who wеrе candidatеs for gеnеral surgеry in a tеaching hospital in Iran. All patiеnts agеd bеtwееn 18-60 yеars, who wеrе undеrgoing gеnеral surgеry bеtwееn April and Sеptеmbеr 2022 and had prеopеrativе anxiеty basеd on thе Spiеlbеrgеr quеstionnairе, wеrе sеlеctеd. Patients who had emergency surgery or were taking anti-anxiety drugs were excluded from the study. Patiеnts wеrе thеn randomly assignеd to thе in-pеrson visit, virtual rеality visit, and control groups. In thе in-pеrson group, individuals visitеd thе opеrating room for 30 minutеs on thе day bеforе surgеry. In contrast, in thе virtual rеality group, visits wеrе conductеd via a 'livе' virtual vidеo tour of thе opеrating room for thе samе duration on thе day bеforе surgеry. The control group received routine care such as prе-surgеry hospitalization and mеdication. All participants completed the Spielberger questionnaire before the intervention (the day before surgery) and again two hours before surgery. Data were analyzed using variance analysis, t-tests, and Chi-square tests in SPSS 22 software. Wе idеntifiеd 105 patiеnts undеrgoing gеnеral surgеry who wеrе dividеd into thrее groups of 35 pеoplе еach. Thе rеsults showеd that, bеforе thе intеrvеntion, thеrе wеrе no statistically significant diffеrеncеs among thе thrее groups in tеrms of dеmographic data and prеopеrativе anxiеty (p > 0.05). Aftеr thе intеrvеntion, thе mеan scorеs of prеopеrativе anxiеty in thе in-pеrson visit, virtual rеality visit, and control groups wеrе 52.82 ± 4.51, 54.48 ± 5.04, and 53.42 ± 4.62, rеspеctivеly, with no significant statistical diffеrеncе (p = 0.33). Furthermore, there was no significant difference in preoperative anxiety scores before and after the intervention in the in-person visit (p = 0.13), virtual reality visit (p = 0.10), and control (p = 0.33) groups. A 30-minute visit to familiarize patients with the operating room environment, equipment, and staff, whether conducted in-person or virtually, does not significantly affect patients' preoperative anxiety or reduce their anxiety levels.


A new genus and species of Philopteridae (Phthiraptera: Ischnocera) from the trumpeters (Aves: Gruiformes: Psophiidae).
A new chewing louse genus and species belonging to the Philopteridae, namely, Palmaellus inexpectatus n. gen., n. sp., is described. The new genus is distinguished from the other ischnoceran genera hitherto described by its peculiar characters of the dorsal anterior head plate with 2 postero-lateral projections, pterothorax and abdomen with scarce chaetotaxy, male genitalia with simple mesomere and paramere lacking inner digitiform projection, and the genital region of female with postero-vulvar plates bearing setae. It is a parasite of the trumpeters, an avian family endemic to South America's Amazon Basin.


Sexual development and fertility of Jamaican female patients with homozygous sickle cell disease.
Results of a questionnaire study of 91 Jamaican patients with homozygous sickle cell (SS) disease and 59 Jamaican control subjects of similar socioeconomic status indicated a mean delay of 2.3 years in age at menarche and of 3.9 years in age at first pregnancy in Ss disease. The mean interval between first sexual exposure and pregnancy was similar in the two groups. The delay in age at first pregnancy in SS disease resulted partly from the delay in puberty, but it also resulted from a further delay in first sexual exposure, with a mean interval between menarche and first sexual exposure of 2.6 and 4.4 years in control subjects and patients, respectively. Physical and social factors that related to this delay were reflected in the higher prevalence of casual unions in patients; this finding implied lesser sexual exposure. Although the similar interval between first sexual exposure and pregnancy did not suggest a lesser fertility in patients with SS disease, the number of infants born to patients with SS disease was less at all ages compared with Jamaican standards. This finding might reflect lesser fertility subsequent to the first pregnancy.


Bacteriological and clinical profile of Community acquired pneumonia in hospitalized patients.
The aim of our study was to obtain comprehensive insight into the bacteriological and clinical profile of community-acquired pneumonia requiring hospitalization. The patient population consisted of 100 patients admitted with the diagnosis of community-acquired pneumonia (CAP), as defined by British Thoracic society, from December 1998 to Dec 2000, at the Sher- i-Kashmir institute of Medical Sciences Soura, Srinagar, India. Gram negative organisms were the commonest cause (19/29), followed by gram positive (10/29). In 71 cases no etiological cause was obtained. Pseudomonas aeruginosa was the commonest pathogen (10/29), followed by Staphylococcus aureus (7/29), Escherichia coli (6/29), Klebsiella spp. (3/29), Streptococcus pyogenes (1/29), Streptococcus pneumoniae (1/29) and Acinetobacter spp. (1/29). Sputum was the most common etiological source of organism isolation (26) followed by blood (6), pleural fluid (3), and pus culture (1). Maximum number of patients presented with cough (99%), fever (95%), tachycardia (92%), pleuritic chest pain (75%), sputum production (65%) and leucocytosis (43%). The commonest predisposing factors were smoking (65%), COPD (57%), structural lung disease (21%), diabetes mellitus (13%), and decreased level of consciousness following seizure (eight per cent) and chronic alcoholism (one per cent). Fourteen patients, of whom, nine were males and five females, died. Staphylococcus aureus was the causative organism in four, Pseudomonas in two, Klebsiella in one, and no organism was isolated in seven cases. The factors predicting mortality at admission were - age over 62 years, history of COPD or smoking, hypotension, altered sensorium, respiratory failure, leucocytosis, and staphylococcus pneumonia and undetermined etiology. The overall rate of identification of microbial etiology of community-acquired pneumonia was 29%, which is very low, and if serological tests for legionella, mycoplasma and viruses are performed the diagnostic yield would definitely be better. This emphasizes the need for further studies (including the serological tests for Legionella, mycoplasma and viruses) to identify the microbial etiology of CAP.


Preclinical and clinical evaluation of autonomic function in humans.
This review focuses on how to assess autonomic function in humans including various ways to measure heart rate, catecholamines, and sympathetic neural activity. The need to assess autonomic function is paramount in many experimental paradigms because of the following. (1) Autonomic dysfunction is present in common diseases like hypertension, diabetes and heart failure, and the magnitude of this dysfunction is broadly related to morbidity and mortality in these disorders. (2) The relationship between autonomic dysfunction and morbidity and mortality can be causal. (3) Interventions that modulate or reverse autonomic dysfunction can improve outcomes in the affected patients. The techniques discussed are also frequently used to understand the autonomic response to sympathoexcitatory manoeuvres like exercise, the cold pressor test or mental stress. Because these manoeuvres can engage a variety of sensory and efferent pathways, under some circumstances the physiological responses measured by many of the techniques are directionally similar, in others they are divergent. Thus any investigator seeking to study the autonomic nervous system or its contribution to either normal physiology or pathophysiological conditions must carefully balance a number of considerations to ensure that the right technique is used to address the question of interest.


Examining health care access disparities in Hispanic populations with peripheral artery disease and diabetes.
This study investigated disparities in health care access for Hispanic adults with diabetes and peripheral artery disease (PAD) who are at risk of lower-extremity amputation and other cardiovascular morbidities and mortalities. We utilized the health care access survey data from the All of Us research program to examine adults (⩾ 18 years) with either diabetes and/or PAD. The primary associations evaluated were: could not afford medical care and delayed getting medical care in the past 12 months. Multivariable logistic regression models were used to assess the association of Hispanic ethnicity and survey responses, adjusting for age, sex, income, health insurance, and employment status. Among 24,104 participants, the mean age was 54.9 years and 67% were women. Of these, 8.2% were Hispanic adults. In multivariable analysis, Hispanic adults were more likely to be unable to afford seeing a health care provider, and receiving emergency care, follow-up care, and prescription medications (p < 0.05) than non-Hispanic adults. Furthermore, Hispanic adults were more likely to report being unable to afford medical care due to cost (odds ratios [OR] 1.72, 95% CI 1.50-1.99), more likely to purchase prescription drugs from another country (OR 2.20, 95% CI 1.69-2.86), and more likely to delay getting medical care due to work (OR 1.46, 95% CI 1.22-1.74) and child care (OR 1.80, 95% CI 1.35-2.39) issues than non-Hispanic White adults. The Hispanic population with diabetes and PAD faces substantial barriers in health care access, including a higher likelihood of delaying medical care and being unable to afford it.


Bone regeneration and repair.
In the face of mounting clinical demand, and armed with reconstructive techniques that are technically challenging and frequently result in suboptimal patient outcomes, increasing focus is being placed on tissue engineering and regenerative medicine as a potential source of novel skeletal reconstructive approaches. Specifically, evidence is accumulating that highlights the promise of osteoprogenitor cell-based reconstructive strategies to meet the needs of an expanding patient population. Historically, the study of cell and molecular biology guiding physiologic and pathologic skeletal development, as well as endogenous bone regeneration following injury, has provided a wealth of information that lends insight toward potential parallel processes that may regulate the osteogenic differentiation of progenitor cells. Multiple progenitor cell populations are now known to possess a capacity to undergo robust osteogenic differentiation in the presence of appropriate environmental cues (hESC, BMSC, ASC, etc.) Recent investigations have put forth multiple advantages of ASC relative to BMSC. Of note, ASC exist in relative abundance, lack the need for in vitro expansion prior to utilization, and can be harvested with relative ease and reduced donor morbidity. Collectively, these factors, paired with promising in vitro and in vivo observations that speak toward the substantial osteogenic potential of ASC, have spurred enthusiasm to pursue the application of ASC in the maturation of skeletal tissue engineering applications. Yet, elucidating what structural and functional properties of scaffolds designed for ASC-mediated skeletal tissue engineering applications (porosity, pore size, composition, mechanical stability, degradation kinetics, etc.), as well as evolving our understanding and capacity to deliver spatiotemporally specific pro-osteogenic targeted molecular manipulation to progenitor cells, remain important hurdles to clear. The scope of this review encompasses the current state of ongoing investigations along these fronts, as well as what future direction will be critical to the transition of cell-based skeletal tissue engineering strategies to the bedside.


The Primate EAE Model Points at EBV-Infected B Cells as a Preferential Therapy Target in Multiple Sclerosis.
The remarkable clinical efficacy of anti-CD20 monoclonal antibodies (mAb) in relapsing-remitting multiple sclerosis points at the critical involvement of B cells in the disease. However, the exact pathogenic contribution of B cells is poorly understood. In this publication we review new data on the role of CD20+ B cells in a unique experimental autoimmune encephalomyelitis (EAE) model in common marmosets (Callithrix jacchus), a small-bodied neotropical primate. We will also discuss the relevance of these data for MS. Different from rodent EAE models, but similar to MS, disease progression in marmosets can develop independent of autoantibodies. Progressive disease is mediated by MHC class Ib (Caja-E) restricted cytotoxic T cells, which are activated by γ-herpesvirus-infected B cells and cause widespread demyelination of cortical gray matter. B-cell directed monoclonal antibody therapies (anti-CD20 versus anti-BLyS and anti-APRIL) have a variable effect on EAE progression, which we found associated with variable depletion of the Epstein Barr virus (EBV)-like γ-herpesvirus CalHV3 from lymphoid organs. These findings support an important pathogenic role of CD20+ B cell in MS, especially of the subset infected with EBV.


Production of eosinophil chemotactic factor by CD8+ T-cells in Toxocara canis-infected mice.
Production of eosinophil chemotactic factor by T-lymphocytes (ECF-L) was examined in Toxocara canis-infected mice. When spleen cells from T. canis-infected mice were cultured in serum-free RPMI1640, ECF-L production was detectable in an antigen-specific manner. The ECF-L production peaked at day 9 post-infection and then decreased. Depletion of Thy 1.2+ cells or CD8+ cells completely abrogated ECF-L production, whereas depletion of CD4+ cells did not, indicating that CD8+ T-cells are involved in the production of ECF-L. When bone marrow eosinophils obtained from T. canis-infected mice were preincubated with ECF-L, their chemotactic reactivity to parasite-derived ECFs was enhanced, whereas that of peritoneal cavity-derived eosinophils was not. Thus, ECF-L seems to be important not only as a chemoattractant but also as an activator of the chemotactic reactivity of naive eosinophils to the parasite-derived ECF in T. canis infection.


Pharmacotherapy of cerebral ischemia.
Ischemic stroke remains one of the leading causes of death and disability in the developed world. Despite many promising preclinical results, the only pharmacologic treatments proven effective in improving clinical outcome following ischemic stroke until now are administration of aspirin and acute thrombolysis using tissue-plasminogen activator. To review currently approved pharmacologic therapies as well as promising future treatment strategies for acute ischemic stroke. We performed an exhaustive PubMed search for articles published from 1950 through 2009 describing pharmacotherapy of acute ischemic stroke, focusing on agents that are currently in Phase III trials or approved for clinical use. Following this review, we present our interpretation of the existing literature and our vision of the future of pharmacotherapy for ischemic stroke. Since the clinical success of the first intravenous thrombolytic, many studies have sought to further characterize the ideal patient population and to extend the therapeutic time window for pharmacologic thrombolysis. Additionally, despite the many failures of neuroprotective trials, several promising agents are currently undergoing Phase III investigation. With the advent of interventional techniques enabling local delivery of therapeutics into the region of the thrombus, the future of pharmacotherapy for ischemic stroke will probably include a combination of interventional techniques and pharmacotherapy.


[The malaria situation in Afghanistan].
Malaria is endemic throughout the country at altitude below 1500 m. About 80-90% of malaria cases belongs to P. vivax, the rest to P. falciparum. Malaria has gone out of control in Afghanistan in the past 20 years. The annual number of cases is estimated at 2-3 million, the number of officially reported was 288,070 in 1998. Out of the 20.5 million population of Afghanistan (1998 estimates), more than 12 million are to be living in malaria endemic areas. A field study to evaluate the susceptibility of P. vivax and P. falciparum to chloroquine was conducted in four sites of the eastern region. The study revealed 100% susceptibility of P. vivax while P. falciparum indicated an alarming degree of resistance.


Unusual Presentation of a Testicular Lymphoma Mimicking a Missed Testicular Torsion: A Case Report.
Testicular lymphoma is an uncommon testicular tumor that usually presents as a painless mass. It usually shows hypervascularity on color Doppler ultrasound (US) and a mild enhancement on enhanced CT or MRI. We present an unusual case of a testicular lymphoma mimicking a missed testicular torsion in a 67-year-old male patient with right scrotal swelling and intermittent pain for 2 months. Color Doppler US demonstrated the absence of vascularity in the enlarged right testis, and the initial diagnosis was a missed testicular torsion. CT demonstrated a poorly enhancing mass rather than a missed testicular torsion with enhanced small nodular foci at the periphery. The final pathological diagnosis was testicular lymphoma.


Early and multiple PSA bounces can occur following high-dose prostate stereotactic body radiation therapy: Subset analysis of a phase 1/2 trial.
We hypothesized that high-dose stereotactic body radiation therapy (SBRT) would lead to faster time to nadir and lower nadir values compared with conventional radiation therapy experiences. We now report prostate-specific antigen (PSA) kinetics following high-dose SBRT in patients treated with radiation alone. Ninety-one patients were enrolled on the phase 1/2 dose escalation study of SBRT for localized prostate cancer. All patients with at least 36 months of follow-up and without hormone therapy were included in this analysis (n = 47). Treatment response parameters evaluated include time to nadir, nadir value, occurrence of PSA bounces (rise of ≥0.2 ng/mL followed by a subsequent fall), magnitude of bounces, duration of bounces, and correlation of bounces with clinical outcomes. Median follow-up was 42 months (range, 36-78 months). Treatment dose levels were 45 Gy (n = 10), 47.5 Gy (n = 8), and 50 Gy (n = 29) in 5 fractions. Biochemical control rate was 98%. Median PSA at follow-up was 0.10 ± 0.20 ng/mL. Median time to nadir was 36 ± 11 months. A total of 24/47 (51.1%) patients had ≥1 PSA bounce. Median magnitude of PSA rise during bounce was 0.50 ± 1.2 ng/mL. Median time to first bounce was 9 ± 7.0 months. Median bounce duration was 3 ± 2.3 months for the first bounce and 6 ± 5.2 months for subsequent bounces. Prostate volumes <30 mL were associated with a decreased likelihood of bounce (P = .0202), and increasing prostate volume correlated with increasingly likelihood of having ≥2 bounces (P = .027). Patients reaching PSA nadir of ≤0.1 ng/mL were less likely to experience any bounce (P = .0044). Compared with other SBRT experiences, our study demonstrated a higher PSA bounce rate, a similar or shorter median time to bounce, and a very low nadir. Prostate volume appears correlated with bounce.


In Situ Visualization of the Structural Evolution and Alignment of Lyotropic Liquid Crystals in Confined Flow.
Self-assembled materials such as lyotropic liquid crystals offer a wide variety of structures and applications by tuning the composition. Understanding materials behavior under flow and the induced alignment is wanted in order to tailor structure related properties. A method to visualize the structure and anisotropy of ordered systems in situ under dynamic conditions is presented where flow-induced nanostructural alignment in microfluidic channels is observed by scanning small angle X-ray scattering in hexagonal and lamellar self-assembled phases. In the hexagonal phase, the material in regions with high extensional flow exhibits orientation perpendicular to the flow and is oriented in the flow direction only in regions with a high enough shear rate. For the lamellar phase, a flow-induced morphological transition occurs from aligned lamellae toward multilamellar vesicles. However, the vesicles do not withstand the mechanical forces and break in extended lamellae in regions with high shear rates. This evolution of nanostructure with different shear rates can be correlated with a shear thinning viscosity curve with different slopes. The results demonstrate new fundamental knowledge about the structuring of liquid crystals under flow. The methodology widens the quantitative investigation of complex structures and identifies important mechanisms of reorientation and structural changes.


miRNA‑34a‑5p downregulation of VEGFA in endometrial stem cells contributes to the pathogenesis of endometriosis.
Endometrial-derived stem cells (EnSCs) serve an important role in the development of endometriosis via retrograde menstruation. Abnormal expression of miRNAs in EnSCs is involved in the etiology of endometriosis, however, the mechanisms remain unclear. The aim of the present study was to investigate the expression of miR‑34a‑5p and VEGFA in endometrial samples from patients with or without endometriosis, and then examine the underlying mechanism of microRNA‑34a‑5p regulation of VEGFA in EnSCs. Endometrial samples from patients with or without endometriosis were collected, and miR‑34a‑5p expression in the two groups was measured using RT‑PCR. Human endometrial‑derived stem cells (hEnSCs) were isolated from these endometrial samples, and hEnSCs were transfected with the miR‑34a‑5p mimics or control miRNAs. qPCR and western blotting were performed to assess the effects of miR‑34a‑5p on the expression of VEGFA in hEnSCs, and cell growth was assessed by an MTT assay. miR‑34a‑5p was significantly downregulated in patients with endometriosis when compared with that of those without endometriosis. VEGFA expression levels in hEnSCs with an overexpression of miR‑34a‑5p were significantly reduced when compared with those in the negative control (P<0.01). In addition, the upregulation of miR‑34a‑5p suppressed EnSCs proliferation by targeting the 3' untranslated region of VEGFA. miR‑34a‑5p provides a novel avenue for the understanding of the development of endometriosis, and may facilitate the development of potential therapeutics against endometriosis.


The influence of corporate structure and quality improvement activities on outcome improvement in residential care homes.
To examine the impact of corporate structure and quality improvement (QI) activities on improvements in client-reported and professional indicators between 2007 and 2009. A cross-sectional study using organizational survey and indicator multilevel modelling to test relationships between corporate structure, QI activities and performance improvements on indicators. In total, 169 residential care homes for the elderly in the Netherlands. Change between 2007 and 2009 in client-reported and professional indicators. A middle-size corporate structure was associated with QI. The QI activity 'multidisciplinary team meetings' was positively correlated with the indicator 'safety environment' for somatic and psycho-geriatric care. The QI activities 'educational material' and 'direct work instructions' were associated negatively with the indicator 'availability of personnel' for somatic clients, but positively for psycho-geriatric clients. QI activities such as 'health plan activities', 'clinical lessons' and 'financial activities' had no relationship to improved performance. For psycho-geriatric clients mainly organizational QI activities were positively associated with QI. The mediating role of the corporate structure for performing QI activities appeared stronger for the change in client-reported than for professional indicators. This study reveals associations between QI activities and corporate structure and changes in indicator performance. A corporate structure was associated with improvement in client-reported indicators, but less on professional indicators, which assumes a central policy at corporate level with impact on client-reported indicators, in contrast to a more local level approach towards activities that result in QI on professional indicators. Tailoring QI activities at the right managerial level may be important to achieve improvement.


Surgical treatment of parietal lobe epilepsy.
Parietal lobe epilepsy (PLE) accounts for a small percentage of extratemporal epilepsies, and only a few and mostly smaller series have been reported. Preoperative findings, surgical strategies, pathological bases, and postoperative outcomes for PLE remain to be elucidated. Patients with PLE were identified by screening a prospective epilepsy surgery database established in 1989 at the University of Bonn. Charts, preoperative imaging studies, surgical reports, and neuropathological findings were reviewed. Seizure outcome was classified according to Engel class (I-IV). Forty patients (23 females and 17 males) with PLE were identified and had a mean age of 25.0 years and a mean preoperative epilepsy duration of 13.7 years. Nine patients had a significant medical history (for example, trauma, meningitis/encephalitis, or perinatal hypoxia). Preoperative MR imaging abnormalities were identified in 38 (95%) of 40 patients; 26 patients (65%) underwent invasive electroencephalography evaluation. After lesionectomy of the dominant (in 20 patients) or nondominant (in 20 patients) parietal lobe and additional multiple subpial transections (in 11 patients), 2 patients suffered from surgical and 12 from neurological complications, including temporary partial Gerstmann syndrome. There were no deaths. Histopathological analysis revealed 16 low-grade tumors, 11 cortical dysplasias, 9 gliotic scars, 2 cavernous vascular malformations, and 1 granulomatous inflammation. In 1 case, no histopathological diagnosis could be made. After a mean follow-up of 45 months, 27 patients (67.5%) became seizure free or had rare seizures (57.5% Engel Class I; 10% Engel Class II; 27.5% Engel Class III; and 5% Engel Class IV). Parietal lobe epilepsy is an infrequent cause of extratemporal epilepsy. Satisfactory results (Engel Classes I and II) were obtained in 67.5% of patients in our series. A temporary partial hemisensory or Gerstmann syndrome occurs in a significant number of patients.


Estimating the administrative cost of regulatory noncompliance: a pilot method for quantifying the value of prevention.
Routine regulatory inspections provide a valuable independent quality assurance review of radiation protection programs that ultimately serves to improve overall program performance. But when an item of non-compliance is noted, regardless of its significance or severity the ensuing notice of violation (NOV) results in an added cost to both the permit holder and the regulatory authority. Such added costs may be tangible, in the form of added work to process and resolve the NOV, or intangible, in the form of damage to organizational reputation or worker morale. If the portion of the tangible costs incurred by a regulatory agency for issuing NOVs could be quantified, the analysis could aid in the identification of agency resources that might be dedicated to other areas such as prevention. Ideally, any prevention activities would reduce the overall number of NOVs issued without impacting the routine inspection process. In this study, the administrative costs of NOV issuance and resolution was estimated by obtaining data from the professional staff of the Texas Department of Health, Bureau of Radiation Control (TDH-BRC). Based a focus group model, the data indicate that approximately $106,000 in TDH-BRC personnel resources were expended to process and resolve the 6,800 NOVs issued in Texas during 1997 inspection activities. The study's findings imply that an incremental decrease in the number of NOVs issued would result in corresponding savings of agency resources. Suggested prevention activities that might be financed through any resource savings include the dissemination of common violation data to permit holders or training for improving correspondence with regulatory agencies. The significance of this exercise is that any savings experienced by an agency could enhance permittee compliance without impacting the routine inspection process.


Water-compatible halloysite-imprinted polymer by Pickering emulsion polymerization for the selective recognition of herbicides.
A water-compatible molecularly imprinted polymer was prepared by Pickering emulsion polymerization using halloysite nanotubes as stabilized solid particles. During polymerization, we used 4-vinylpyridine as monomer, divinylbenzene as cross-linking agent, toluene as porogen, 2,2-azobisisobutyronitrile as initiator, 2,4-dichlorophenoxyacetic acid as template to form the oil phase, and Triton X-100 aqueous solution to form the water phase. The halloysite nanotubes molecularly imprinted polymer was characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. Kinetic and equilibrium bindings were also employed to evaluate the adsorption properties of the imprinted polymer. The imprinted polymer showed better selectivity, more rapid kinetic binding (60 min) for 2,4-dichlorophenoxyacetic acid in pure water compared with rebinding in toluene. The imprinted polymer was used as a sorbent to enrich and separate 2,4-dichlorophenoxyacetic acid from water, and was detected by high-performance liquid chromatography with UV detection.


Anti-angiogenic treatment strategies for malignant brain tumors.
The use of angiogenesis inhibitors may offer novel strategies in brain tumor therapy. In contrast to traditional cancer treatments that attack tumor cells directly, angiogenesis inhibitors target at the formation of tumor-feeding blood vessels that provide continuous supply of nutrients and oxygen. With respect to brain tumor therapy, inhibitors of angiogenesis display unique features that are unknown to conventional chemotherapeutic agents. The most important features are independence of the blood-brain barrier, cell type specificity, and reduced resistance. Malignant brain tumors, especially malignant gliomas, are among the most vascularized tumors known. Despite multimodal therapeutic approaches, the prognosis remains dismal. Thus, angiogenesis inhibitors may be highly effective drugs against these tumors. In a clinical setting, they could be applied in the treatment of multiple tumors or postsurgically as an adjuvant therapy to prevent recurrence. This article provides an overview of current anti-angiogenic treatment strategies with emphasis on substances already in clinical trials or candidate substances for clinical trials. The cellular and molecular basis of these substances is reviewed.


[Epidemiological features of Candida infections detected in intensive care units and risk factors affecting mortality].
The aim of this study was to describe the epidemiological features of nosocomial Candida infections in intensive care units and to detect the risk factors which increase the mortality rate. A total of 940 patients hospitalized in ICUs of Gulhane Military Medical Academy Haydarpasa Training Hospital, Istanbul, between January 01 and December 31, 2006 were prospectively enrolled into this study. Candida spp. were isolated from various clinical specimens (blood, urine, respiratory tract, wound) in 48 patients. Of these patients, 50% were male and 50% were female, and the mean age was 63.66 +/- 22.72 (age range: 8-92) years. The mean duration of hospital stay was 36.25 +/- 44.51 (min: 1, max: 90) days. Thirty five Candida infection attacks were observed in 29 of 48 patients. C. albicans was isolated in 18 infections and non-albicans Candida spp. in 17 infections. Nosocomial infection rate due to Candida spp. was 3.22 per 1000 patient-days. The most common Candida infections were bloodstream (42.9%) and urinary tract infections (37.1%). At the time of diagnosis, 89.6% of patients were being hospitalized for more than ten days and 69% of the patients were using three or more wide spectrum antibiotics. Diabetes mellitus and cardiovascular diseases were the most frequently detected co-morbid diseases. The overall mortality rate was 55.2%. Predictors of adverse outcome were diabetes mellitus (p= 0.016), need for mechanical ventilation (p= 0.010) and infection with non-albicans Candida spp. (p= 0.002). In conclusion, Candida infections in the intensive care patients are associated with high mortality. Mortality due to Candida infections could be reduced by defining the risk factors and starting preemptive antifungal treatment to patients who are under risk.


Effect of educational intervention on medication timing in Parkinson's disease: a randomized controlled trial.
Medicine usage in Parkinson's disease patients is often imperfect, in particular irregular timing of medication. The effect of informing Parkinson's disease patients about the continuous dopaminergic hypothesis (to encourage regular medicine intake) on medication adherence and motor control was tested. Patients were randomised either to the active group (receiving the intervention) or control group (no extra information). Antiparkinson medicine usage was monitored for 3 months before and after the intervention using electronic pill bottles which record the date and time of opening (MEMS, Aardex, Switzerland) and data used to calculate the percentage of doses taken at correct time intervals. 43 patients (52%) were randomised to active counselling, and 40 (48%) were controls (standard management). The intervention effect (difference in timing adherence pre- to post-intervention between the 2 groups) was 13.4% (CI 5.1 to 21.7), p = 0.002. Parkinson motor scores did not change significantly (active group 0.1, CI -3.4 to 3.7) versus controls (4.5, CI 1.6 to 7.1), p = 0.06. Timing adherence, but not motor scores, improves by providing patients with extra information. Therapy timing is of potential importance in Parkinson's disease management. NCT00361205.


The impact of shifting demographics, variants of concern and vaccination on outcomes during the first 3 COVID-19 waves in Alberta and Ontario: a retrospective cohort study.
In Canada, published outcome data for COVID-19 come largely from the first 2 waves of the pandemic. We examined changes in demographics and 30-day outcomes after SARS-CoV-2 infection during the first 3 pandemic waves in Alberta and Ontario; for wave 3, we compared outcomes between those infected with a variant of concern and those infected with the original "wild-type" SARS-CoV-2. We conducted a population-based retrospective cohort study using linked health care data sets in Alberta and Ontario. We identified all-cause hospitalizations or deaths within 30 days after a positive result on a reverse transcription polymerase chain reaction test for SARS-CoV-2 in individuals of any age between Mar. 1, 2020, and June 30, 2021, with genomic confirmation of variants of concern. We compared outcomes in wave 3 (February 2021 to June 2021) with outcomes in waves 1 and 2 combined (March 2020 to January 2021) after adjusting for age, sex and Charlson Comorbidity Index score. Using wave 3 data only, we compared outcomes by vaccination status and whether or not the individual was infected with a variant of concern. Compared to those infected with SARS-CoV-2 during waves 1 and 2 (n = 372 070), we found a shift toward a younger and healthier demographic in those infected during wave 3 (n = 359 079). In wave 3, patients were more likely to be hospitalized (adjusted odds ratio [aOR] 1.57, 95% confidence interval [CI] 1.46-1.70) but had a shorter length of hospital stay (median 6 days v. 7 days, p < 0.001) and lower 30-day mortality (aOR 0.73, 95% CI 0.65-0.81). The 217 892 patients in wave 3 who were infected with a variant of concern (83.5% confirmed to have the Alpha variant, 1.7% confirmed to have the Delta variant) had a higher risk of death (Alpha: aOR 1.29, 95% CI 1.16-1.44; Delta: aOR 2.05, 95% CI 1.49-2.82) and hospitalization (Alpha: aOR 1.59, 95% CI 1.53-1.66; Delta: aOR 1.88, 95% CI 1.64-2.15) than those infected with wild-type SARS-CoV-2. We observed a shift among those infected with SARS-CoV-2 toward younger patients with fewer comorbidities, a shorter length of hospital stay and lower mortality risk as the pandemic evolved in Alberta and Ontario; however, infection with a variant of concern was associated with a substantially higher risk of hospitalization or death. As variants of concern emerge, ongoing monitoring of disease expression and outcomes among vaccinated and unvaccinated individuals is important to understand the phenotypes of COVID-19 and the anticipated burdens for the health care system.


Development of a questionnaire to measure heart disease risk knowledge in people with diabetes: the Heart Disease Fact Questionnaire.
This paper describes a paper and pencil questionnaire that measures heart disease risk knowledge in people with diabetes. The Heart Disease Fact Questionnaire (HDFQ) is a 25-item questionnaire that was developed to tap into respondents' knowledge of major risk factors for the development of CHD. Approximately half of these items specifically address diabetes-related CHD risk factors. Based on extensive pilot data, the current study analyzed responses from 524 people with diabetes to assess the psychometric properties. The HDFQ is readable to an average 13-year old and imposes little burden. It shows good content and face validity. It demonstrates adequate internal consistency, with Kuder-Richardson-20 formula = 0.77 and good item-total correlations. Item analysis showed a desirable range in P-values. In discriminant function analyses, HDFQ scores differentiated respondents by knowledge of their own cardiovascular health, use of lipid lowering medications, health insurance status, and educational attainment, thus indicating good criterion related validity. This measure of heart disease risk knowledge is brief, understandable to respondents, and easy to administer and score. Its potential for use in research and practice is discussed. Future research should establish norms as well as investigate its test-retest reliability and predictive validity.


[The influence of a shot distance on a profile of a wound canal in flat bones].
Experimental shots were made from rifled weapons, from different distances, at isolated flat bones. There was established a significantly increased angle of the axial section of the cone-shaped defect due to the expanding sizes of the exit part of the wound canal (WC) and of the outlet opening as the shot distances increased. An expert's evaluation is offered to assess a shot distance involving the WC profile and by calculating an angle of the axial section of the cone-shaped defect on the basis of the inlet and outlet sizes and of the flat-bone thickness.


From the present to the future. Commentary on Luszcz and Bryan.
Recent research on aging and memory is admirably reviewed in the article by Luszcz and Bryan. In particular, they clearly describe the major theoretical perspectives proposed to account for the relations between age and memory at the current time. This commentary focuses on several issues that seem likely to emerge as important themes in future research in this area, such as construct validity and multivariate analytical procedures.


Learning contracts in clinical education.
This study explored the outcomes of using learning contracts in a radiologic science program. Telephone surveys of contract learning participants and other radiologic science graduates provided data regarding graduate career satisfaction, lifelong learning habits and attitudes toward learning. Statistical comparison data found that contract learning participants reported higher job satisfaction, participated more in continuing education, demonstrated more self-motivation and independence, felt less competitive and anxious about courses and grades and felt more involved in their clinical courses.


Biogenesis of mitochondria. The effects of physiological and genetic manipulation of Saccharomyces cerevisiae on the mitochondrial transport systems for tricarboxylate-cycle anions.
1. Kinetic and equilibrium parameters for the uptake of l-malate, succinate, citrate and alpha-oxoglutarate by fully functional mitochondria of Saccharomyces cerevisiae were determined. 2. The uptake of l-malate and succinate is mediated by a common carrier, and two other distinct carriers mediate the uptake of citrate and alpha-oxoglutarate. 3. The properties of the carrier systems for l-malate, succinate and citrate closely resemble those of mammalian mitochondria, but the alpha-oxoglutarate carrier differs from the mammalian system in minor respects. 4. The composition of the yeast mitochondria was extensively manipulated by (a) anaerobiosis, (b) catabolite repression, (c) inhibition of mitochondrial protein synthesis and (d) elimination of mitochondrial DNA by mutation. 5. The carrier systems for l-malate, succinate, citrate and alpha-oxoglutarate are essentially similar in the five different types of mitochondria. 6. It is concluded that all the protein components of the carrier systems for l-malate, succinate, citrate and alpha-oxoglutarate are coded by nuclear genes and synthesized extramitochondrially by cell-sap ribosomes.


Alternative splicing events as peripheral biomarkers for motor learning deficit caused by adverse prenatal environments.
Severity of neurobehavioral deficits in children born from adverse pregnancies, such as maternal alcohol consumption and diabetes, does not always correlate with the adversity's duration and intensity. Therefore, biological signatures for accurate prediction of the severity of neurobehavioral deficits, and robust tools for reliable identification of such biomarkers, have an urgent clinical need. Here, we demonstrate that significant changes in the alternative splicing (AS) pattern of offspring lymphocyte RNA can function as accurate peripheral biomarkers for motor learning deficits in mouse models of prenatal alcohol exposure (PAE) and offspring of mother with diabetes (OMD). An aptly trained deep-learning model identified 29 AS events common to PAE and OMD as superior predictors of motor learning deficits than AS events specific to PAE or OMD. Shapley-value analysis, a game-theory algorithm, deciphered the trained deep-learning model's learnt associations between its input, AS events, and output, motor learning performance. Shapley values of the deep-learning model's input identified the relative contribution of the 29 common AS events to the motor learning deficit. Gene ontology and predictive structure-function analyses, using Alphafold2 algorithm, supported existing evidence on the critical roles of these molecules in early brain development and function. The direction of most AS events was opposite in PAE and OMD, potentially from differential expression of RNA binding proteins in PAE and OMD. Altogether, this study posits that AS of lymphocyte RNA is a rich resource, and deep-learning is an effective tool, for discovery of peripheral biomarkers of neurobehavioral deficits in children of diverse adverse pregnancies.


Nutrient intake, nutritional status, and cognitive function with aging.
With the demographic aging of populations worldwide, diseases associated with aging are becoming more prevalent and costly to individuals, families, and healthcare systems. Among aging-related impairments, a decline in cognitive function is of particular concern, as it erodes memory and processing abilities and eventually leads to the need for institutionalized care. Accumulating evidence suggests that nutritional status is a key factor in the loss of cognitive abilities with aging. This is of tremendous importance, as dietary intake is a modifiable risk factor that can be improved to help reduce the burden of cognitive impairment. With respect to nutrients, there is evidence to support the critical role of several B vitamins in particular, but also of vitamin D, antioxidant vitamins (including vitamin E), and omega-3 fatty acids, which are preferentially taken up by brain tissue. On the other hand, high intakes of nutrients that contribute to hypertension, atherosclerosis, and poor glycemic control may have negative effects on cognition through these conditions. Collectively, the evidence suggests that considerable slowing and reduction of cognitive decline may be achieved by following a healthy dietary pattern, which limits intake of added sugars, while maximizing intakes of fish, fruits, vegetables, nuts, and seeds.


Pharyngeal movements during feeding sequences of Navanax inermis (Gastropoda: Opisthobranchia) in successive stages of dissection.
Feeding in Navanax inermis Cooper was filmed and analysed after various dissections. In preparations with a cut through the body wall exposing the pharynx and buccal ganglia, completely normal feeding was observed. In addition to seven motor acts previously described in intact animals, an eighth act, peristalsis, was observed. In preparations with the pharynx excised from the animal but attached to the buccal ganglia, four motor acts were observed: flaring, expansion, contraction and peristalsis. In addition to increasing information about the nature of feeding movements in Navanax, these data indicate that preparations suitable for neurophysiological studies are capable of producing a variety of feeding acts.


A radiobiological model for the relative biological effectiveness of high-dose-rate 252Cf brachytherapy.
While there is significant clinical experience using both low- and high-dose-rate 252Cf brachytherapy, there are minimal data regarding values for the neutron relative biological effectiveness (RBE) with both modalities. The aim of this research was to derive a radiobiological model for 252Cf neutron RBE and to compare these results with neutron RBE values used clinically in Russia. The linear-quadratic (LQ) model was used as the basis to characterize cell survival after irradiation, with identical cell killing rates (S(N) = S(gamma)) between 252Cf neutrons and photons used for derivation of RBE. Using this equality, a relationship among neutron dose and LQ radiobiological parameter (i.e., alpha(N), beta(N), alpha(gamma), beta(gamma)) was obtained without the need to specify the photon dose. These results were used to derive the 252Cf neutron RBE, which was then compared with Russian neutron RBE values. The 252Cf neutron RBE was determined after incorporating the LQ radiobiological parameters obtained from cell survival studies with fast neutrons and teletherapy photons. For single-fraction high-dose-rate neutron doses of 0.5, 1.0, 1.5 and 2.0 Gy, the total biologically equivalent doses were 1.8, 3.4, 4.7 and 6.0 RBE Gy with 252Cf neutron RBE values of 3.2, 2.9, 2.7 and 2.5, respectively. Using clinical data for late-responding reactions from 252Cf, Russian investigators created an empirical model that predicted high-dose-rate 252Cf neutron RBE values ranging from 3.6 to 2.9 for similar doses and fractionation schemes and observed that 252Cf neutron RBE increases with the number of treatment fractions. Using these relationships, our results were in general concordance with high-dose-rate 252Cf RBE values obtained from Russian clinical experience.


Knowledge, Attitude and Practice Regarding Pharmacovigilance and Consumer Pharmacovigilance among Consumers at Lalitpur District, Nepal.
Adverse drug reactions (ADRs) can be a big threat to the health of people in Nepal as a variety of medicines are consumed in the country. Involving consumers in pharmacovigilance can strengthen ADR reporting. The study aims to find out knowledge, attitude and practice regarding pharmacovigilance and consumer pharmacovigilance among consumers at Lalitpur district, Nepal Methods: It was carried out in outpatients visiting in KIST Medical College and Teaching Hospital, Lalitpur, Nepal. Participant's knowledge, attitude and practice were measured by noting their agreement with a set of 21 statements along with multiple choice and open ended questions. A total of 157 outpatients were surveyed. The knowledge scores for males (12) was better compared to the females (11), but the scores for attitude and practice were same for both groups. The maximum score for knowledge was 29, attitude was 6 and practice was 10. The overall KAP scores was 45. The total scores for knowledge, attitude and practice for males (24) were better compared to female (22) respondents. Seventy-one patients (68%) who participated in this study favoured establishing a consumer centre for obtaining information about ADRs. Knowledge scores among consumers regarding pharmacovigilance is low and require advocacy and improvement.


Urban-rural difference in the associations between living arrangements and the health-related quality of life (HRQOL) of the elderly in China-Evidence from Shaanxi province.
So far limited evidence exist comparing the difference between urban and rural elder residents in relation to how living arrangements correlates to health-related quality of life(HRQOL) of the elderly. This study aims to compare the HRQOL of the elderly with four living arrangements: living with spouse only (LS), living alone (LA), living with a spouse and adult children(LSC) and the single elderly living with adult children (SLC) in urban and rural areas of China. The data were drawn from the 2013 wave of Chinese National Health Service Survey in Shaanxi Province, which included 11,729 elderly people. The Chinese version of the EQ-5D-3L questionnaire was used to measure the HRQOL. Tobit regression model and logistic regression models were employed to estimate the associations between living arrangements and the HRQOL of the elderly. The EQ-5D utility scores of the urban elderly with four different living arrangements (LS, LA,LSC and SLC) were 0.9141, 0.8392, 0.8176 and 0.9080, which were almost all higher than their rural counterparts. After controlling other confounding variables, tobit regression estimates showed that the EQ-5D utility scores of the single elderly either living alone or living with adult children were lower than the elderly living with a spouse in urban areas. In rural areas only the single elderly living with adult children were more disadvantaged. Additionally the logistic regression results showed living-alone elderly had worse psychological health and the single elderly living with adult children had worse physical health. The findings suggest that the urban elderly have better HRQOL than the rural elderly and the elderly with different living arrangements in urban and rural area have different HRQOL. More attention should be given to the poor mental health of the elderly living alone and the worse physical health of the single elderly living with adult children.


Receipt of Warnings Regarding Potentially Impairing Prescription Medications and Associated Risk Perceptions in a National Sample of U.S. Drivers.
Reducing drug-involved driving is a national policy priority, but little is known about the extent to which drivers receive warnings about the impairment potential of their prescribed medications. We used data from the 2013-2014 National Roadside Survey (NRS) to quantify the proportion of drivers who received warnings regarding potentially impairing medications and the association with driving-related risk perceptions. Drivers randomly selected at 60 sites completed the self-administered survey, which contained questions on their use of prescription medications. Overall, 7,405 drivers completed the prescription drug portion of the NRS. Of these, 19.7% reported recent use (within the past 2 days) of a potentially impairing prescription drug, and 78.2% said the drug had been prescribed for their use. Users of prescribed sedatives (85.8%) and narcotics (85.1%) were most likely to report receiving information about potential impairment, compared with only 57.7% and 62.6% of users of prescribed stimulant and antidepressant medications, respectively. Receipt of warnings varied by sex, race/ethnicity, income, geographic region, and time of day. For a majority of drug categories, drivers who reported receiving warnings had significantly higher odds of perceived risk of impaired driving/crash and criminal justice involvement. Most users of prescription medications reported that the drug was prescribed for their use, but not all reported receiving warnings about driving impairment. Our study provides evidence of missed opportunities for information provision on impaired driving, identifies subgroups that may warrant enhanced interventions, and provides preliminary evidence that receipt of impairment warnings is associated with increased perceptions of driving-related risk.


Height prediction from ulna length.
Height is fundamental to assessing growth and nutrition, calculating body surface area, and predicting pulmonary function in childhood. Its measurement is hindered by muscle weakness, joint, or spinal deformity. Arm span has been used as a substitute, but is inaccurate. The objective of the study was to identify a limb measurement that precisely and reproducibly predicts height in childhood. Males (n=1144) and females (n=1199), aged 5 years 4 months to 19 years 7 months, without disability were recruited from Melbourne schools. Height, arm span, ulna, forearm, tibia, and lower leg lengths were measured with a Harpenden stadiometer and anthropometer. Prediction equations for height based on ulna length (U) and age in years (A) were developed using linear regression. Ulna centile charts were developed by the LMS method. For males, height (cm)=4.605U+1.308A+28.003 (R2=0.96); for females, height (cm)=4.459U+1.315A+31.485 (R2=0.94). Intra- and inter-observer variability was 0.41% and 0.61% relative to the mean, respectively. Height prediction equations from tibia, forearm, and lower leg length were calculated. We show that ulna measurement is reproducible and precisely predicts height in school-age children. It appears to be superior to arm span measurement when neuromuscular weakness, joint, or spinal deformity exists. Ulna growth charts should facilitate growth assessment.


Sensitivity assessment of denitrifying bacteria against typical antibiotics in groundwater.
The effects of antibiotics on nitrate denitrification in groundwater have acquired growing concern. Denitrification is a microbially mediated process. The effects of antibiotics on denitrification were mainly reflected in denitrifying bacteria. However, little is known about the relationship between antibiotics and denitrifying bacteria. Based on this, both direct antimicrobial susceptibility testing and microbial batch-culture experiments were conducted to assess the influences of typical antibiotics on denitrifying groundwater bacteria, mainly Pseudomonas (46.17%). Denitrifying bacteria, screened from a long-term groundwater denitrification environment, were tested for sensitivity to five typical antibiotics in groundwater: sulfamethoxazole (SMX), erythromycin (ERY), enrofloxacin (ENR), clindamycin (CLI), and tetracycline (TCY). The results showed that the sensitivity of denitrifying bacteria to antibiotics is mainly related to the type and concentration of antibiotics. For antibiotic types, the order of sensitivity by quantitative assessment is ENR > TCY > SMX > ERY > CLI. Fluoroquinolones (FQs) represented by ENR were selected to explore their concentration effects. The influences on denitrifying bacteria were divided into the high concentration effect (500 μg L-1 to 100 mg L-1) and the low concentration effect (100 ng L-1 to 10 μg L-1) with about 100 μg L-1 as a boundary. Exposure to high concentrations had significant inhibitory effects on bacterial growth and exhibited dose dependency, especially for ciprofloxacin (CIP). The low concentration effect was independent of concentration, which may be stimulation or inhibition. The stimulation mainly occurred due to ENR-exposure. For inhibitory effects, Lomefloxacin (LOM) was more effective than other FQs. Especially for inhibition at ng-level exposure, LOM and norfloxacin (NOR) exposures led to the highest and lowest inhibition rates, respectively.


Motivations, substance use and other correlates amongst property and violent offenders who regularly inject drugs.
To examine the prevalence, correlates and motivations for the commission of property and violent crime amongst a sample of people who inject drugs (PWID). Data were obtained from the 2013 Illicit Drug Reporting System (IDRS), which includes a cross-sectional sample of 887 PWID. Eighteen percent of PWID had committed a property offence and 3% had committed a violent offence in the month preceding interview. Opioid dependence (AOR 2.57, 95% CI 1.29-5.10) and age (AOR 0.96, 95% CI 0.93-0.99) were found to be the strongest correlates of property crime. The majority of property offenders (75%) attributed their offending to financial reasons, however those under the influence of benzodiazepines were proportionately more likely to nominate opportunistic reasons as the main motivation for their last offence. Stimulant dependence (AOR 5.34, 95% CI 1.91-14.93) was the only significant correlate of past month violent crime, and the largest proportion of violent offenders (47%) attributed their offending to opportunistic reasons. The majority of both property (71%) and violent offenders (73%) reported being under the influence of drugs the last time they committed an offence; the largest proportion of property offenders reported being under the influence of benzodiazepines (29%) and methamphetamine (24%), whilst violent offenders mostly reported being under the influence of heroin and alcohol (32% respectively). Criminal motivations, substance use and other correlates vary considerably across crime types. This suggests that crime prevention and intervention strategies need to be tailored according to individual crime types, and should take into account self-reported criminal motivations, as well as specific risk factors that have been shown to increase the likelihood of offending.


The role for hip surveillance in children with cerebral palsy.
Spastic hip displacement is the second most common deformity seen in children with cerebral palsy (CP), and the long-term effects can be debilitating. Progressive hip displacement leading to dislocation can result in severe pain as well as impaired function and quality of life. Recent population-based studies have demonstrated that a child's Gross Motor Functional Classification System (GMFCS) level is most predictive for identifying hips "at-risk" for progressive lateral displacement. As a result, in many developed countries, hip surveillance has now been adopted as an integral piece of the comprehensive care puzzle for the management of children with spastic hip displacement. This paper reviews the spectrum of treatments available for progressive hip displacement, examines the current literature on the success of hip surveillance, and illustrates an example of a current hip surveillance program stratified by the GMFCS level.


Pneumatic nano-sieve for CRISPR-based detection of drug-resistant bacteria.
The increasing prevalence of antibiotic-resistant bacterial infections, particularly methicillin-resistant Staphylococcus aureus (MRSA), presents a significant public health concern. Timely detection of MRSA is crucial to enable prompt medical intervention, limit its spread, and reduce antimicrobial resistance. Here, we introduce a miniaturized nano-sieve device featuring a pneumatically-regulated chamber for highly efficient MRSA purification from human plasma samples. By using packed magnetic beads as a filter and leveraging the deformability of the nano-sieve channel, we achieved an on-chip concentration factor of ∼15-fold for MRSA. We integrated this device with recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas detection system, resulting in an on-chip limit of detection (LOD) of approximately 100 CFU mL-1. This developed approach provides a rapid, precise, and centrifuge-free solution suitable for point-of-care diagnostics, with the potential to significantly improve patient outcomes in resource-limited medical conditions.


Sex differences in Seoul virus infection are not related to adult sex steroid concentrations in Norway rats.
Field studies of hantavirus infection in rodents report that a higher percentage of infected individuals are males than females. To determine whether males were more susceptible to hantavirus infection than females, adult male and female Long Evans rats (Rattus norvegicus) were inoculated with doses of Seoul virus ranging from 10(-4) to 10(6) PFU. The 50% infective doses (ID(50)) were not significantly different for male and female rats (10(0.05) and 10(0.8) PFU, respectively). To determine whether sex differences in response to infection were related to circulating sex steroid hormones, sex steroid concentrations were manipulated and antibody responses and virus shedding were assessed following inoculation with the ID(90). Regardless of hormone treatment, males had higher anti-Seoul virus immunoglobulin G (IgG) and IgG2a (i.e., Th1) responses than females and IgG1 (i.e., Th2) responses similar to those of females. Males also shed virus in saliva and feces longer than females. Manipulation of sex steroids in adulthood did not alter immune responses or virus shedding, suggesting that sex steroids may organize adult responses to hantavirus earlier during ontogeny.


Occurrence of Vibrio parahaemolyticus and Vibrio alginolyticus in the German Bight over a seasonal cycle.
Bacteria of the genus Vibrio are an important component of marine ecosystems worldwide. The genus harbors several human pathogens, for instance the species Vibrio parahaemolyticus, a main cause for foodborne gastroenteritis in Asia and the USA. Pathogenic V. parahaemolyticus strains emerged also in Europe, but little is known about the abundance, pathogenicity and ecology of V. parahaemolyticus especially in Northern European waters. This study focuses on V. parahaemolyticus and its close relative Vibrio alginolyticus in the North Sea (Helgoland Roads, Germany). Free-living, plankton-attached and shellfish-associated Vibrio spp. were quantified between May 2008 and January 2010. CFUs up to 4.3 × 10(3) N l(-1) and MPNs up to 240 N g(-1) were determined. Phylogenetic classification based on rpoB gene sequencing revealed V. alginolyticus as the dominant Vibrio species at Helgoland Roads, followed by V. parahaemolyticus. We investigated the intraspecific diversity of V. parahaemolyticus and V. alginolyticus using ERIC-PCR. The fingerprinting disclosed three distinct groups at Helgoland Roads, representing V. parahaemolyticus, V. alginolyticus and one group in between. The species V. parahaemolyticus occurred mainly in summer months. None of the strains carried the virulence-associated genes tdh or trh. We further analyzed the influence of nutrients, secchi depth, temperature, salinity, chlorophyll a and phytoplankton on the abundance of Vibrio spp. and the population structure of V. parahaemolyticus. Spearman Rank analysis revealed that particularly temperature correlated significantly with Vibrio spp. numbers. Based on multivariate statistical analyses we report that the V. parahaemolyticus population was structured by a complex combination of environmental parameters. To further investigate these influences is the key to understanding the dynamics of Vibrio spp. in temperate European waters, where this microbial group and especially the pathogenic species, are likely to gain in importance.


Phosphonate analogues of pyruvate. Probes of substrate binding to pyruvate oxidase and other thiamin pyrophosphate-dependent decarboxylases.
A number of enzymes catalyze the removal of carbon dioxide from pyruvate through covalent participation of the coenzyme thiamin pyrophosphate. The conversions of the decarboxylated adduct, hydroxyethyl thiamin pyrophosphate, to subsequent products distinguishes the function of these enzymes. Acetaldehyde is produced by pyruvate decarboxylase, acetic acid by pyruvate oxidase and acetyl coenzyme A by pyruvate dehydrogenase. Differences and details of steps prior to decomposition of hydroxyethyl thiamin pyrophosphate can be evaluated through the use of two substrate analogues, methyl acetylphosphonate and acetylphosphonate. Methyl acetylphosphonate and acetylphosphonate are competitive inhibitors toward pyruvate with Escherichia coli pyruvate oxidase and E. coli pyruvate dehydrogenase but the value of the Ki for the oxidase is more than three orders of magnitude higher than for the dehydrogenase. Yeast pyruvate decarboxylase is not inhibited at all under the same conditions. The binding of methyl acetylphosphonate results in ligand-induced changes in the near ultraviolet circular dichorism spectrum of the oxidase. This spectral perturbation is only seen in the presence of the cofactor, thiamin pyrophosphate, strongly suggesting that the inhibitor is binding at the same site as the substrate, pyruvate, on the enzyme. Kinetic data suggest that lipid activators of pyruvate oxidase increase the affinity of the enzyme for pyruvate and its analogues.