Effect of job rotation on work demands, workload, and recovery of refuse truck drivers and collectors.
Job rotation is often advocated to reduce workload, but its efficacy has seldom been investigated. The aim of this study is to compare the work demands, workload, and recovery among truck driving, refuse collecting, and rotating between these two jobs, between days and during the day. Three teams of 3 employees each participated in this study. Work demands were assessed by systematic observation of tasks and activities. Workload was quantified by means of heart rate, oxygen uptake, subjective ratings, and urinary excretion rates of catecholamines. Recovery was quantified by excretion rates of catecholamines after work. Job rotation between driving and collecting is an effective measure to reduce physical workload as compared with collecting only and to decrease mental workload as compared with driving only. However, job rotation resulted in increased physical workload as compared with driving only. Job rotation did not increase mental workload as compared with collecting only. No effects were seen on recovery. No differences were found between rotating between days and during the day. Actual or potential applications of this research include the recommendation that before job rotation is introduced, its efficacy be determined in terms of well-chosen workload measures because a reduction in work demands does not directly imply a reduction in workload. Therefore, job rotation might be less effective than expected.


Alendronate/folic acid-decorated polymeric nanoparticles for hierarchically targetable chemotherapy against bone metastatic breast cancer.
To considerably enhance treatment efficacy for bone metastatic breast cancer via dual bone/tumor-targeted chemotherapy, a nanoparticle-based delivery system comprising poly(lactic-co-glycolic acid) (PLGA) as the hydrophobic core coated with alendronate-modified d-α-tocopheryl polyethylene glycol succinate (ALN-TPGS) and folic acid-conjugated TPGS (FA-TPGS) was developed as a vehicle for paclitaxel (PTX) in this work. The ALN/FA-decorated nanoparticles not only showed superior ALN-mediated binding affinity for hydroxyapatite abundant in bone tissue but also promoted uptake of payloads by folate receptor-overexpressing cancer cells to significantly augment PTX cytotoxicity. Notably, through dual-targetable delivery to the bone matrix and folate receptor-overexpressing 4T1 tumors, the PTX-loaded nanoparticles substantially accumulated in bone metastases in vivo and inhibited 4T1 tumor growth and lung metastasis, leading to significant improvement of the survival rate of treated mice. Upon treatment with the ALN/FA-decorated PTX-loaded nanoparticles, the bone destruction and bone loss of the tumor-bearing mice were appreciably retarded, and the adverse effects on normal tissues were alleviated. These results demonstrate that the ALN/FA-decorated PTX-loaded delivery system developed in this study shows great promise for the effective treatment of bone metastatic breast cancer.


Perceptibility curves for the Digora system.
To construct perceptibility curves (PCs) for given calibration settings in order to define psychophysical properties of the Digora storage phosphor system and to evaluate the effects of automatic exposure correction (AEC) on the PCs. The Digora system was calibrated at two exposures, 80 microC kg(-1) (high calibration) and 40 microC kg(-1) (low calibration). Since the grey levels displayed in the radiographs are adjusted by AEC, dose-response functions at high calibration were obtained using AEC on and off modes. The dose-response function at low calibration was obtained with AEC off. The PC at each experimental setting was calculated using known physical parameters of the system and the performance of the average observer used in a previous study. In addition, PCs were also constructed using transmitted radiation flux behind the test object calculated from the attenuation coefficient in order to study observer and system performance. PCs obtained under these conditions were compared. The PC using calculated transmitted radiation flux behind the test object showed a wide plateau at the peak owing to AEC, while the PC obtained by a modified approach showed a higher but narrower peak. There were no differences between the two PCs using AEC on and off modes when the PCs were constructed using a modified approach. There were no differences between the two PCs obtained at high and low calibration settings or between the three PCs obtained with AEC on except for the position along the exposure axis. Psychophysical properties of the Digora system may be determined if we employ registered exposures from a dose-response function with AEC off under a given calibration setting. Under these circumstances the shape and height of the PCs will be unchanged irrespective of the AEC mode.


Graphene quantum dots/L-cysteine coreactant electrochemiluminescence system and its application in sensing lead(II) ions.
A new coreactant electrochemiluminescence (ECL) system including single-layer graphene quantum dots (GQDs) and L-cysteine (L-Cys) was found to be able to produce strong cathodic ECL signal. The ECL signal of GQD/L-Cys coreactant system was revealed to be mainly dependent on some key factors, including the oxidation of L-Cys, the presence of dissolved oxygen and the reduction of GQDs. Then, a possible ECL mechanism was proposed for the coreactant ECL system. Furthermore, the ECL signal of the GQD/L-Cys system was observed to be quenched by lead(II) ions (Pb(2+)). After optimization of some important experimental conditions, including concentrations of GQDs and L-Cys, potential scan rate, response time, and pH value, an ECL sensor was developed for the detection of Pb(2+). The new methodology can offer a rapid, reliable, and selective detection of Pb(2+) with a detection limit of 70 nM and a dynamic range from 100 nM to 10 μM.


Modification of the existing maximum residue levels for copper compounds in other small fruits and berries.
In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Spiess-Urania Chemicals GmbH submitted a request to the competent national authority in Austria to modify the existing maximum residue levels (MRLs) for the active substance copper compounds in the whole group of other small fruits and berries. The data submitted in support of the request were found to be sufficient to derive MRL proposals for the whole subgroup of other small fruits and berries. Adequate analytical methods for enforcement of mineral copper independently from its chemical form are available for matrices under consideration at the validated limit of quantification (LOQ) of 5 mg/kg. Based on indicative risk assessment results, EFSA concluded that the long-term intake of copper residues resulting from the intended and existing uses, natural background levels and monitoring levels might present a risk to consumer health. Although residues in other small fruits and berries are minor contributors to the overall consumer exposure, a risk management decision has to be taken on whether it is appropriate to increase the existing MRLs for these crops, given that a potential consumer intake concern could not be excluded.


The Biology of Aging and Cancer: Frailty, Inflammation, and Immunity.
The majority of patients with common malignancies are older adults. Intrinsic complex biological changes of aging along with inflammation, immunosenescence, age-associated chronic diseases, and extrinsic environmental and psychosocial factors have significant impact on not only development and behavior of individual malignancies, but also physiologic reserve and vulnerability of older patients who suffer from them. As a result, clinical practice of geriatric oncology demands integration of careful geriatric assessment and management. This article provides an overview of basic biology of aging and its relationship with cancer. After a brief introduction about the definition and mechanisms of aging, as well as age-related biological and physiological changes, the discussion mainly focuses on recent development and insights into the relationship of frailty, inflammation, and immunity with cancer, highlighting how the new knowledge can help further improve assessment and treatment of older patients with malignancies and promote cancer research.


[Reconceptualising the meaning of scientific communication: open access].
The recent US law (H.R.2764) affecting NIH policy and the recent unanimous vote by the Arts and Science faculty of Harvard University in favour of a mandatory deposit of researchers' publications in a suitable repository have brought the Open Access movement into public light. After reviewing the historical background of Open Access, its evolution and extension in the United States, Great Britain, France and Canada are examined. Policies aiming at strengthening Open Access to scientific research are viewed as the direct consequence of treating scientific publishing as an integral part of the research cycle. It should, therefore, be wrapped into the financing of research. As the greater part of research is funded by public money, it appears legitimate to make its results as widely available as is possible. Open Access journals and repositories with strong deposit mandates form the backbone of the strategies to achieve the objective of Open Access. Despite the claims of some publishers, Open Access does not weaken or threaten the peer review process, and it does not conflict with copyright laws.


The efficacy of a percutaneous expandable titanium device in anatomical reduction of vertebral compression fractures of the thoracolumbar spine.
To evaluate the feasibility of a minimally invasive technique using a titanium expandable device to achieve anatomical restoration of vertebral compression fractures (VCF) of the thoracolumbar spine. This prospective study included 27 patients diagnosed with VCF (Magerl classification A.1.2, A.1.3, and A.3.1) of the thoracolumbar spine treated with percutaneous cement augmentation using the SpineJack® device. The study was conducted in Valladolid University Hospital, Valladolid, Spain from January to December 2012, with a minimum one-year follow up. Preoperative evaluation included visual analogue scale (VAS) for pain, and radiological assessment of the VCF using 3-dimensional computed tomography (3D-CT) scans for measurements of vertebral heights and angles. The patients were followed at 3, 6, and 12 months with clinical VAS and radiological assessments. The procedure was performed in 27 patients with a mean age of 55.9 ± 17.3 years, 55.6% females. All patients underwent surgery within 6 weeks from time of injury. No procedure related complications occurred. Pain measured by VAS score decreased from 7.0 preoperatively to 3.2 within 24 hours, and remained 2.2 at 3 months, 2.1 at 6 months, and 1.5 at 12-months follow-up (p<0.05). Mean height restorations for the anterior was 3.56 mm, central was 2.49, and posterior vertebral was 1.28 mm, and maintained at 12-months follow-up (p=0.001). This new percutaneous technique for VCF has shown good clinical results in pain control and the possibility to reduce both vertebral kyphosis angles and fractured endplates seen in 3D-CT scans assessment method. Further studies are needed to confirm those results on larger cohorts with long-term follow up.


Expression of membrane type 1 matrix metalloproteinase, matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 in human cartilaginous tumors with special emphasis on mesenchymal and dedifferentiated chondrosarcoma.
Membrane type 1 matrix metalloproteinase (MT1-MMP) has been identified as an activator of the proenzyme of matrix metalloproteinase 2 (MMP-2: gelatinase A), and has also been shown to play a crucial role in tumor invasion by activating proMMP2 in both lung and gastric carcinoma. The tissue inhibitor of metalloproteinase 2 (TIMP-2) plus the MT1-MMP complex also plays an important role in the activation of proMMP-2. In this study, the expressions of MT1-MMP, MMP-2 and TIMP-2 were evaluated in 10 enchondromas, 34 conventional chondrosarcomas, 5 clear-cell chondrosarcomas, 7 mesenchymal chondrosarcomas and 8 dedifferentiated chondrosarcomas. The expressions were immunohistochemically visualized on paraffin sections and the levels of expression were assessed semiquantitatively. The extent of staining was assessed by the extent score in order to determine the overall level of expression. The extent scores of MT1-MMP, MMP-2 and TIMP-2 in grade 2 chondrosarcoma were significantly higher than those in either enchondroma or grade 1 chondrosarcoma (P < 0.05). In conventional chondrosarcoma, significant correlations were found between the extent scores of MT1-MMP and MMP-2 (P < 0.001), MT1-MMP and TIMP-2 (P < 0.01), and MMP-2 and TIMP-2 (P < 0.01). The undifferentiated small round tumor cells of mesenchymal chondrosarcoma showed lower positive rates and extent scores for MT1-MMP (2/7, 0.7 +/- 0.5) and MMP-2 (3/7, 0.7 +/- 0.4) than for cartilaginous components of mesenchymal chondrosarcoma [MT1-MMP (4/7, 1.3 +/- 0.5) and MMP-2 (7/7, 1.9 +/- 0.3)] or conventional chondrosarcoma. In dedifferentiated chondrosarcoma, the extent scores of MT1-MMP, MMP-2 and TIMP-2 in low-grade cartilaginous components were not significantly different from those in conventional chondrosarcoma; however, the high-grade anaplastic components showed high extent scores for MT1-MMP, MMP-2 and TIMP-2, compared with the low-grade cartilaginous components of dedifferentiated chondrosarcoma or conventional chondrosarcoma. According to our results, the expression of MT1-MMP as well as that of MMP-2 or TIMP-2 demonstrated a significant correlation with the tumor grade in human cartilaginous tumors. Furthermore, the expressions of MT1-MMP, MMP-2 and TIMP-2 were also found to play a crucial role in invasion in the high-grade components of dedifferentiated chondrosarcoma.


Food allergy: which tests are worth doing and which are not?
Adverse reactions to foods may arise by a variety of mechanisms, both immune (IgE and non-IgE) and non-immune mediated. This article considers those assays useful in the diagnosis of Type 1 hypersensitivity to foods (IgE-based) and, importantly, discusses those assays where evidence is lacking for their use. In all cases of suspected food allergy, a full clinical history is indispensable in facilitating diagnosis. Total serum IgE is not a suitable screen for food allergy. Suspect allergens may be confirmed by either skin prick testing or serological assays for specific IgE. Several studies suggest concentrations of food-specific IgE at which there is a high probability of reaction on food challenge. These cut-off levels are now being used by physicians to direct clinical advice. However, it is important to note that not all studies agree on these limits and the chosen cut-off is dependent on the population studied and the assay used.


Effect of dietary sodium zeolite A and graded levels of calcium on growth, plasma, and tibia characteristics of chicks.
Sodium zeolite A (SZA), a synthetic sodium aluminosilicate having high ion-exchange capacity, has been shown to increase eggshell specific gravity in laying hens and to improve Ca utilization in chickens. A 4 x 2 factorial arrangement of treatments was used to investigate the effect of dietary Ca (.6, .8, 1.0, and 1.2%) and SZA (0 and .75%) on growth, plasma, and tibia characteristics of chicks from 5 to 15 days of age. Increasing dietary Ca linearly increased (P less than .05) Ca and alkaline phosphatase (AP) in plasma and increased tibia shearing force and percentage ash, Ca, and P in tibiae. However, dietary Ca linearly decreased (P less than .05) inorganic P and Mg in plasma and Mg and Mn in tibiae. Sodium zeolite A decreased (P less than .05) plasma P and AP and tibia Mg but increased (P less than .05) tibia Ca, Zn, Al, and Mn concentrations. Tibia ash and shearing force were increased in chicks fed SZA receiving inadequate dietary Ca, but they were decreased in chicks fed SZA and excess Ca (Ca by SZA interaction, P less than .05). Tibia density showed a similar trend, but the effect was not significant (Ca by SZA interaction, P less than .12). The addition of SZA enhanced tibia ash, density, and shearing force when dietary Ca was low; however, when added to diets containing 1.2% Ca, SZA reduced many bone mineralization indices with the exception of tibia Ca.


Should Canadian health promoters support a food stamp-style program to address food insecurity?
Food insecurity is an urgent public health problem in Canada, affecting 4 million Canadians in 2012, including 1.15 million children, and associated with significant health concerns. With little political will to address this significant policy issue, it has been suggested that perhaps it is time for Canada to try a food stamp-style program. Such a program could reduce rates of food insecurity and improve the nutritional health of low-income Canadians. In this article, we explore the history of the US food stamp program; the key impetus of which was to support farmers and agricultural interests, not to look after the needs of people living in poverty. Though the US program has moved away from its roots, its history has had a lasting legacy, cementing an understanding of the problem as one of lack of food, not lack of income. While the contemporary food stamp program, now called Supplemental Nutrition Assistance Program (SNAP), reduces rates of poverty and food insecurity, food insecurity rates in the USA are significantly higher than those in Canada, suggesting a food stamp-style program per se will not eliminate the problem of food insecurity. Moreover, a food stamp-style program is inherently paternalistic and would create harm by reducing the autonomy of participants and generating stigma, which in itself has adverse health effects. Consequently, it is ethically problematic for health promoters to advocate for such a program, even if it could improve diet quality.


Effect of avermectin B1a on chick neuronal gamma-aminobutyrate receptor channels expressed in Xenopus oocytes.
Chick brain mRNA was isolated and injected into Xenopus oocytes. This led to the expression of gamma-aminobutyrate (GABA) channels easily accessible for current measurements using the voltage clamp technique. The effect of the anthelmintic natural product avermectin B1a on the GABA current was studied quantitatively. In the presence of the drug, GABA-induced chloride currents were strongly enhanced in a dose-dependent manner. Half-maximal stimulation of the current evoked by 5 microM GABA was found with about 0.1 microM avermectin B1a. Avermectin B1a did not affect the reversal potential of the current or the maximal response elicited by GABA, and did not alter the membrane permeability in the absence of GABA. The major effects of avermectin B1a were a shift of the Ka for GABA from 21 microM to 2 microM, and a decrease of the apparent Hill coefficient for GABA from 1.7 to 1.1. Furthermore, in the presence of avermectin B1a, desensitization of the GABA current was strongly inhibited. The benzodiazepine-binding site ligand Ro 15-1788 did not affect the action of avermectin B1a if present at concentrations up to 1 microM. The stimulatory effects of the drug were additive to the ones by the barbiturate pentobarbital, if both agents were added at low concentrations. At higher concentrations each of these agents inhibited the stimulatory effects of the other.


From friendfunding to crowdfunding: Relevance of relationships, social media, and platform activities to crowdfunding performance.
Crowdfunding involves raising small amounts of money from a large number of people, typically via the Internet and social networks, to fund a project. Crowdfunding projects are mainly funded by the project creator's relatively small network of family and friends. We argue that mobilizing funders outside this close network positively contributes to the success of a crowdfunding success. To study how project creators seek to attract funding from more distant/potential resources (latent ties) in addition to existing networks (strong and weak ties), we examined usage of social media (Facebook and Twitter) and the crowdfunding platform (website). We analyzed 10 cultural projects hosted on the Dutch crowdfunding platform "Voordekunst." Our results contribute to theorizing on latent tie activation by demonstrating that social media messages and platform updates add economic value to the crowdfunding effort. Our study also explains the moderating effect of these messages on funders of various tie strengths.


Antimicrobial activity of extracts from in vivo and in vitro propagated Lamium album L. plants.
The antimicrobial activity of 18 different extracts from in vivo and in vitro grown L. album L. plants was evaluated against clinical bacteria and yeasts using the well diffusion method. All the used extracts demonstrated antibacterial activity, whereas only the water extracts from leaves (in vivo) possessed antifungal activity against Candida albicans NBIMCC 72 and Candida glabrata NBIMCC 8673 (14 and 20 mm diameter of inhibition zones and MIC 10 mg/ml, respectively). The methanol and ethanol extracts obtained from the in vitro propagated plants had a broader spectrum of antibacterial activity than those from in vivo plants, while the opposite tendency was observed for the chloroform extracts. All tested flower extracts possessed antimicrobial activity. The chloroform extract from in vivo flowers demonstrated the highest activity against E. faecalis NBIMCC 3915, S. aureus NBIMCC 3703, P. hauseri NBIMCC 1339 and P. aeruginosa NBIMCC 3700 (22 mm, 13 mm, 11 mm, 23 mm zone diameter of inhibition and MIC 0.313 mg/ml, respectively). The water extracts from leaves (both in vivo and in vitro) possessed higher antibacterial activity than extract from flowers. The obtained results showed that both in vivo and in vitro propagated L. album L. could be used as a source of antibacterial substances.


Validity of GNRB® arthrometer compared to Telos™ in the assessment of partial anterior cruciate ligament tears.
The main goal of this study was to compare the results of the GNRB(®) arthrometer to those of Telos™ in the diagnosis of partial thickness tears of the anterior cruciate ligament (ACL). A prospective study performed January-December 2011 included all patients presenting with a partial or full-thickness ACL tears without ACL reconstruction and with a healthy contralateral knee. Anterior laxity was measured in all patients by the Telos™ and GNRB(®) devices. This series included 139 patients, mean age 30.7 ± 9.3 years. Arthroscopic reconstruction was performed in 109 patients, 97 for complete tears and 12 single bundle reconstructions for partial thickness tears. Conservative treatment was proposed in 30 patients with a partial thickness tear. The correlation between the two devices was evaluated by the Spearman coefficient. The optimal laxity thresholds were determined with ROC curves, and the diagnostic value of the tests was assessed by the area under the curve (AUC). The differential laxities of full and partial thickness tears were significantly different with the two tests. The correlation between the results of laxity measurement with the two devices was fair, with the strongest correlation between Telos™ 250 N and GNRB(®) 250 N (r = 0.46, p = 0.00001). Evaluation of the AUC showed that the informative value of all tests was fair with the best results with the GNRB(®) 250 N: AUC = 0.89 [95 % CI 0.83-0.94]. The optimal differential laxity threshold with the GNRB(®) 250 N was 2.5 mm (Se = 84 %, Sp = 81 %). The diagnostic value of GNRB(®) was better than Telos™ for ACL partial thickness tears.


Refined sensory measures of neural repair in human spinal cord injury: bridging preclinical findings to clinical value.
Sensory input from the periphery to the brain can be severely compromised or completely abolished after an injury to the spinal cord. Evidence from animal models suggests that endogenous repair processes in the spinal cord mediate extensive sprouting and that this might be further attenuated by targeted therapeutic interventions. However, the extent to which sprouting can contribute to spontaneous recovery after human spinal cord injury (SCI) remains largely unknown, in part because few measurement tools are available in order to non-invasively detect subtle changes in neurophysiology. The proposed application of segmental sensory evoked potentials (e.g., dermatomal contact heat evoked potentials and somatosensory evoked potentials) to assess conduction in ascending pathways (i.e., spinothalamic and dorsal column, respectively) differs from conventional approaches in that individual spinal segments adjacent to the level of lesion are examined. The adoption of these approaches into clinical research might provide improved resolution for measuring changes in sensory impairments and might determine the extent by which spontaneous recovery after SCI is mediated by similar endogenous repair mechanisms in humans as in animal models.


PF15p is the chlamydomonas homologue of the Katanin p80 subunit and is required for assembly of flagellar central microtubules.
Numerous studies have indicated that the central apparatus plays a significant role in regulating flagellar motility, yet little is known about how the central pair of microtubules or their associated projections assemble. Several Chlamydomonas mutants are defective in central apparatus assembly. For example, mutant pf15 cells have paralyzed flagella that completely lack the central pair of microtubules. We have cloned the wild-type PF15 gene and confirmed its identity by rescuing the motility and ultrastructural defects in two pf15 alleles, the original pf15a mutant and a mutant generated by insertional mutagenesis. Database searches using the 798-amino-acid polypeptide predicted from the complete coding sequence indicate that the PF15 gene encodes the Chlamydomonas homologue of the katanin p80 subunit. Katanin was originally identified as a heterodimeric protein with a microtubule-severing activity. These results reveal a novel role for the katanin p80 subunit in the assembly and/or stability of the central pair of flagellar microtubules.


Machine-Learning Based Channel Quality and Stability Estimation for Stream-Based Multichannel Wireless Sensor Networks.
Wireless sensor networks (WSNs) have become more and more diversified and are today able to also support high data rate applications, such as multimedia. In this case, per-packet channel handshaking/switching may result in inducing additional overheads, such as energy consumption, delays and, therefore, data loss. One of the solutions is to perform stream-based channel allocation where channel handshaking is performed once before transmitting the whole data stream. Deciding stream-based channel allocation is more critical in case of multichannel WSNs where channels of different quality/stability are available and the wish for high performance requires sensor nodes to switch to the best among the available channels. In this work, we will focus on devising mechanisms that perform channel quality/stability estimation in order to improve the accommodation of stream-based communication in multichannel wireless sensor networks. For performing channel quality assessment, we have formulated a composite metric, which we call channel rank measurement (CRM), that can demarcate channels into good, intermediate and bad quality on the basis of the standard deviation of the received signal strength indicator (RSSI) and the average of the link quality indicator (LQI) of the received packets. CRM is then used to generate a data set for training a supervised machine learning-based algorithm (which we call Normal Equation based Channel quality prediction (NEC) algorithm) in such a way that it may perform instantaneous channel rank estimation of any channel. Subsequently, two robust extensions of the NEC algorithm are proposed (which we call Normal Equation based Weighted Moving Average Channel quality prediction (NEWMAC) algorithm and Normal Equation based Aggregate Maturity Criteria with Beta Tracking based Channel weight prediction (NEAMCBTC) algorithm), that can perform channel quality estimation on the basis of both current and past values of channel rank estimation. In the end, simulations are made using MATLAB, and the results show that the Extended version of NEAMCBTC algorithm (Ext-NEAMCBTC) outperforms the compared techniques in terms of channel quality and stability assessment. It also minimizes channel switching overheads (in terms of switching delays and energy consumption) for accommodating stream-based communication in multichannel WSNs.


Risky driving and recorded driving offences: a 24-year follow-up study.
Permanent individual differences in driver behavior and accident risk have long been under active debate. Cognitive and personality factors have correlated with risky driving indicators in cross-sectional studies, and prospective cohort studies are now increasingly revealing early antecedents of risky behavior and injury mortality in adult age, with connections to stable personality traits. However, long-term stability in driver behavior or accident involvement has not been documented in a general driver population.This study reports 24-year follow-up data from a study that compared the recorded offenses between 134 drivers stopped by the police because of sustained risky driving and 121 control drivers stopped at the same locations at the same time in 1987 (Rajalin, 1994. Accid. Anal. Prev., 26, 555-562). Data were compiled from national driver records and accident statistics for the same drivers again 24 years later, and their yearly mileage and speed behavior was requested in a mail survey. The results showed that the two groups of drivers sampled on one trip a quarter of a century ago still differ from each other. The offenders still have more entries in their driver record, also when adjusted for age and mileage (OR=1.59, CI=1.03-2.46), they still report in the survey that they drive faster and overtake other cars more often. The results show that individual differences in driver behavior persist for decades, perhaps for life. However, in this on-road sample, the effect seems to be moderated by occupation which also presumably explains the lower mortality among the offenders during this 24-year follow-up.


Karen and Lawa medicinal plant use: uniformity or ethnic divergence?
We here tease apart the ethnopharmacological knowledge of plants in two Thai villages to determine to which degree the uses are particular to individual ethnic groups and to which degree they are part of a generalized and uniform set of widespread medicinal plants used over a large geographic range. We compared Karen and Lawa knowledge of medicinal plants in the Mae Cheam watershed of northern Thailand, where both ethnic groups have settled and share ecological conditions for resource extraction. We were interested in documenting the degree to which these two ethnic groups use the same or different medicinal plant species. The use of the same plant species by the two groups was considered a sign of uniform and cross-cultural local knowledge, whereas the use of different medicinal plants by each group was considered a sign of culturally specific local knowledge that developed within each ethnic group. We inventoried the plant species in different habitats around one Karen village and one Lawa village using stratified vegetation plots and using semi-structured questionnaires we interviewed 67 key informants regarding their use of plants for medicine. We then calculated the Fidelity level FL (FL values near 100% for a species indicate that almost all use reports refer to the same way of using the species, whereas low FL values indicate that a species is used for many different purposes) and cultural importance index CI (the sum of the proportion of informants that mention each of the use categories for a given species) to estimate the variation in medicinal plant use. We used Jaccard's Index JI (This index relates the number of shared species to the total number of species) to analyze the similarity of medicinal plant use between the two villages. A total of 103 species of medicinal plant species in 87 genera and 41 families were identified and they were used to cure 35 ailments. The FL of the medicinal plant species varied from 10% to 100%, was different for each ailment, and differed between the two ethnic groups. The most important medicinal plant species, those with the highest CI value, were not the same in the two villages. Costus speciosus, which is used to treat urinary infections and wounds in animals, had the highest CI value in the Karen village, whereas Sambucus javanica, which is used to treat wounds, fractures, bloat, and edema in humans, had the highest CI value in the Lawa village. Only 17 medicinal species (16.5%) were shared between the two villages. Methods of preparation and application were significantly different between the two villages, whereas the plant parts used, habit, and route of administration were similar. Our study demonstrates that ethnic groups that live in the same geographic area can have significantly different traditional knowledge systems for medicinal plants, at least when it comes to the species used and their preparation and medicinal application. We assume that differences in cultural history and background in the two villages led to differences in medicinal plant use, preparation, and application.


Biological evaluation of dodecaborate-containing L-amino acids for boron neutron capture therapy.
To develop a boron carrier for practical purposes, new boron-containing amino acids with an undecahydro-closo-dodecaboranylthio ([(10)B(12)H(11)S](2-)-) unit in the side chain of the α-amino acid have already been designed and synthesized. In the present paper, cytotoxicity, the incorporation amounts into tumor cells, and the tumor cell killing effects of these compounds were elucidated to evaluate their usefulness as boron carriers. Furthermore, the microdistribution of the amino acids in tumor cells was established.


Cleavage site specificity and conformational selection in type I collagen degradation.
Excessive degradation of type I collagen is associated with a variety of human diseases such as arthritis, tumor metastasis, and atherosclerosis. Methods that further our understanding of collagenolysis may therefore provide insights into the mechanism of several important disorders. Prior experiments suggest that cleavage of collagen in vitro requires intact full-length collagenase, a multidomain protein containing both a catalytic and a hemopexin-like domain. In this work we demonstrate that type I collagen can be degraded at room temperature, a temperature well below the melting temperature of type I collagen, by collagenase deletion mutants that only contain the catalytic domain of the enzyme. Furthermore, these mutant enzymes hydrolyze the same peptide bond that is recognized by the corresponding full-length enzymes. Hence enzyme specificity at room temperature is achieved without the hemopexin-like domain. We demonstrate that these findings can be explained in light of a conformational selection mechanism that dictates that collagenases preferentially recognize and cleave preformed partially unfolded states of collagen.


Preconception optimization of glycaemic control in diabetes.
The prevalence of Diabetes Mellitus is increasing worldwide. In developing countries 25% of adult females with diabetes are in the reproductive age. Thus in developing countries increased number of pregnancies are complicated by diabetes. Uncontrolled diabetes in pregnancy is associated with increased risk for both mother and foetus. These risks can be minimized by good control of diabetes before and during pregnancy. Management in the preconception period is discussed in this review article. Detailed management involves general advice of lifestyle modification followed by specific details of screening for complications of diabetes. Changes in the drugs for both glycaemic control and other co-morbid conditions are discussed. The recommended insulin regimen in the preconception period and monitoring of glycaemic control by self-monitoring of blood glucose (SMBG) and HbA1C has also been highlighted.


Combined effects of red pepper and caffeine consumption on 24 h energy balance in subjects given free access to foods.
The effects of red pepper and caffeine ingestion on energy and macronutrient balances were examined in eight Caucasian male subjects. All subjects participated in two randomly assigned conditions: control and experimental (red pepper and caffeine). After ingesting a standardized breakfast, subjects ate three meals ad libitum (lunch, dinner and breakfast) and snacks which were served approximately 2 h after the lunch and dinner over a 24 h period. Two appetizers with or without 3 g red pepper) were given before lunch and dinner, and a drink (decaffeinated coffee with or without 200 mg caffeine) was served at all meals and snacks except for the after-dinner snack. It is also important to note that on the experimental day, 8.6 and 7.2 g red pepper were also added to lunch and dinner respectively. Red pepper and caffeine consumption significantly reduced the cumulative ad libitum energy intake and increased energy expenditure. The mean difference in energy balance between both conditions was 4000 kJ/d. Moreover, the power spectral analysis of heart rate suggested that this effect of red pepper was associated with an increase in sympathetic:parasympathetic nervous system activity ratio. These results indicate that the consumption of red pepper and caffeine can induce a considerable change in energy balance when individuals are given free access to foods.


Incidence and recurrence of acute otitis media in Taiwan's pediatric population.
To report the incidence and recurrence of acute otitis media (AOM) in Taiwan's pediatric population. Information from children (aged <= 12 years) with a diagnosis of AOM was retrieved from the 2006 National Healthcare Insurance claims database. We calculated the cumulative incidence rate and the incidence density rate of recurrent AOM within one year after the initial diagnosis in 2006. We used a multivariate logistic regression model to assess the predictors for recurrence of AOM. The annual incidence rate of AOM was estimated to be 64.5 cases per 1,000 children. The overall one-year cumulative incidence rate of recurrence was 33.1%, and the incidence density rate was 33.5 cases per 100 person-years, with the highest figure (41.2 cases per 100 person-years) noted for children aged 0-2 years. Recurrence was significantly associated with age, gender, place of treatment, and physician specialty. AOM remains a major threat to children's health in Taiwan. Male children and very young children require more aggressive preventive strategies to reduce the risk of recurrence.


Epidemiology of lower respiratory infection and pneumonia in South Africa (1997-2015): a systematic review protocol.
Lower respiratory infections (LRIs) and pneumonia are among the leading causes of death worldwide, especially in children aged under 5 years, and these patterns are reflected in the South African population. Local epidemiological data for LRIs and pneumonia are required to inform the Second National Burden of Disease Study underway in South Africa. The aim of this systematic review is to identify published studies reporting the prevalence, incidence, case fatality, duration or severity of LRI and pneumonia in adults and children in South Africa. Electronic database searches will be conducted to obtain studies reporting on the prevalence, incidence, case fatality, duration and severity of LRI and pneumonia in South Africa between January 1997 and December 2015. Studies that are assessed to have moderate or low risk of bias will be included in a meta-analysis, if appropriate. Where meta-analysis is not possible, the articles will be described narratively. Subgroup analysis (eg, age groups) will also be conducted where enough information is available. This systematic review will only include published data with no linked patient-level information; thus, no ethics approval is required. The findings will be used to calculate the burden of disease attributed to LRI and pneumonia in South Africa and will highlight the type of epidemiological data available in the country. The article will be disseminated in a peer-reviewed publication. CRD42016036520.


Interrater Reliability and Age-Based Normative Values for Radiographic Indices of the Ankle Syndesmosis in Children.
While recent research has investigated the normative values, discriminative capacity, and interrater reliability of radiographic indices for the evaluation of the syndesmosis in adults, no such data exist for children. The purposes of the present study were (1) to determine the interrater reliability of common radiographic measures of syndesmosis and deltoid ligament competency in children and (2) to establish age-based normative values. A consecutive series of patient radiographs from a Level-I pediatric trauma center were identified and were used to create an age and sex-balanced cohort of 282 patients. Subjects between 2 and 17 years of age were randomly selected from a pool of patients who had a complete 3-view (anteroposterior, lateral, and mortise) radiographic ankle series and a final diagnosis without osseous or ligamentous injury. Eight age and sex-balanced groups were created for analysis. Three independent raters evaluated all radiographs and recorded radiographic indices that are commonly used for the evaluation of ankle trauma: width of medial clear space, width of superior clear space, tibiofibular clear space, tibiofibular overlap, and medial clear space/superior clear space ratio. Interrater reliability was calculated with use of the intraclass correlation coefficient (ICC); means and standard deviations were used to report age-group normative values. Two hundred and eighty-two patients (mean age [and standard deviation], 9.6 ± 4.6 years) were analyzed. The superior clear space and tibiofibular overlap demonstrated excellent interrater reliability (ICC = 0.915 and 0.964, respectively), the medial clear space and tibiofibular clear space demonstrated substantial agreement (ICC = 0.656 and 0.635, respectively), and the medial clear space/superior clear space ratio demonstrated moderate agreement (ICC = 0.418). The medial clear space could not be reliably measured until the age of 8 years because of insufficient ossification of the medial malleolus. Tibiofibular overlap demonstrated a linear increase over time, ranging from -1.4 mm in 2 and 3-year-old patients to 6.7 mm in 16 and 17-year-old patients (R2 = 0.995). Normative values varied by age and sex. The medial clear space and medial clear space/superior clear space ratio could not be reliably assessed for children under 8 years of age and were thus characterized by suboptimal interrater reliability. Tibiofibular overlap had excellent interrater agreement, changed predictably with skeletal growth, and may be useful for future research as well as the clinical assessment of pediatric ankle injuries to guide clinical decision-making. Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.


The impact of physiological noise on hemodynamic-derived estimates of directed functional connectivity.
Measuring the strength of directed functional interactions between brain regions is fundamental to understand neural networks. Functional near-infrared spectroscopy (fNIRS) is a suitable method to map directed interactions between brain regions but is based on the neurovascular coupling. It, thus, relies on vasomotor reactivity and is potentially biased by non-neural physiological noise. To investigate the impact of physiological noise on fNIRS-based estimates of directed functional connectivity within the rostro-caudal hierarchical organization of the prefrontal cortex (PFC), we systematically assessed the effects of pathological perturbations of vasomotor reactivity and of externally triggered arterial blood pressure (aBP) fluctuations. Fifteen patients with unilateral stenosis of the internal carotid artery (ICA) underwent multi-channel fNIRS during rest and during metronomic breathing, inducing aBP oscillations at 0.1 Hz. Comparisons between the healthy and pathological hemispheres served as quasi-experimental manipulation of the neurovascular system's capability for vasomotor reactivity. Comparisons between rest and breathing served as experimental manipulation of two different levels of physiological noise that were expected to differ between healthy and pathological hemispheres. In the hemisphere affected by ICA stenosis, the rostro-caudal hierarchical organization of the PFC was compromised reflecting the pathological effect on the vascular and neural level. Breathing-induced aBP oscillations biased the magnitude of directed interactions in the PFC, but could be adjusted using either the aBP time series (intra-individual approach) or the aBP-induced fNIRS signal variance (inter-individual approach). Multi-channel fNIRS, hence, provides a sound basis for analyses of directed functional connectivity as potential bias due to physiological noise can be effectively controlled for.


LRRK2 kinase plays a critical role in manganese-induced inflammation and apoptosis in microglia.
Long-term exposure to elevated levels of manganese (Mn) causes manganism, a neurodegenerative disorder with Parkinson's disease (PD)-like symptoms. Increasing evidence suggests that leucine-rich repeat kinase 2 (LRRK2), which is highly expressed in microglia and macrophages, contributes to the inflammation and neurotoxicity seen in autosomal dominant and sporadic PD. As gene-environment interactions have emerged as important modulators of PD-associated toxicity, LRRK2 may also mediate Mn-induced inflammation and pathogenesis. In this study, we investigated the role of LRRK2 in Mn-induced toxicity using human microglial cells (HMC3), LRRK2-wild-type (WT) and LRRK2-knockout (KO) RAW264.7 macrophage cells. Results showed that Mn activated LRRK2 kinase by phosphorylation of its serine residue at the 1292 position (S1292) as a marker of its kinase activity in macrophage and microglia, while inhibition with GSK2578215A (GSK) and MLi-2 abolished Mn-induced LRRK2 activation. LRRK2 deletion and its pharmacological inhibition attenuated Mn-induced apoptosis in macrophages and microglia, along with concomitant decreases in the pro-apoptotic Bcl-2-associated X (Bax) protein. LRRK2 deletion also attenuated Mn-induced production of reactive oxygen species (ROS) and the pro-inflammatory cytokine TNF-α. Mn-induced phosphorylation of mitogen-activated protein kinase (MAPK) p38 and ERK signaling proteins was significantly attenuated in LRRK2 KO cells and GSK-treated cells. Moreover, inhibition of MAPK p38 and ERK as well as LRRK2 attenuated Mn-induced oxidative stress and cytotoxicity. These findings suggest that LRRK2 kinase activity plays a critical role in Mn-induced toxicity via downstream activation of MAPK signaling in macrophage and microglia. Collectively, these results suggest that LRRK2 could be a potential molecular target for developing therapeutics to treat Mn-related neurodegenerative disorders.


Brain Activity in Response to Trauma-specific, Negative, and Neutral Stimuli. A fMRI Study of Recent Road Traffic Accident Survivors.
Most studies of neuro-functional patterns in trauma-exposed individuals have been conducted considerable time after the traumatic event. Hence little is known about neuro-functional processing shortly after trauma-exposure. We investigated brain activity patterns in response to trauma reminders as well as neutral and negative stimuli in individuals who had recently (within 3 weeks) been involved in a road traffic accident (RTA). Twenty-three RTA survivors and 17 non-trauma-exposed healthy controls (HCs) underwent functional MRI while viewing Trauma-specific, Negative, and Neutral pictures. Data were analyzed from four a priori regions of interest, including bilateral amygdala, subcallosal cortex, and medial prefrontal cortex. In addition, we performed a whole brain analysis and functional connectivity analysis during stimulus presentation. For both groups, Negative stimuli elicited more activity in the amygdala bilaterally than did Neutral and Trauma-specific stimuli. The whole brain analysis revealed higher activation in sensory processing related areas (bilateral occipital and temporal cortices and thalamus) as well as frontal and superior parietal areas, for the RTA group compared to HC, for Trauma-specific stimuli contrasted with Neutral stimuli. We also observed higher functional connectivity for Trauma-specific stimuli, between bilateral amygdala and somatosensory areas, for the RTA group compared to controls, when contrasted with Neutral stimuli. We argue that these results might indicate an attentional sensory processing bias toward Trauma-specific stimuli for trauma exposed individuals, a result in line with findings from the post-traumatic stress disorder literature.


Emotional distress and posttraumatic growth during the COVID-19 pandemic: The case of the ultra-Orthodox Jewish society in Israel.
The COVID-19 pandemic has been associated with a range of negative responses, including emotional distress, as well as with positive changes, such as posttraumatic growth (PTG). Among the vulnerability factors the literature lists SES and being part of a minority group. The aim of this study is to identify patterns of responses among the ultra-Orthodox Jewish society in Israel, in terms of both emotional distress (anxiety and depression) and multiple dimensions of PTG. The data were collected during the second wave of COVID-19 in Israel, between May and November 2020. The sample included 369 participants, all belonging to the ultra-Orthodox society. Latent class analysis was used to establish heterogeneous classes of participants displaying similar response patterns, using the Patient Health Questionnaire-9 (PHQ-9) for depression, the Generalized Anxiety Disorder-7 index (JAD-7), and the 10-item version of the Posttraumatic Growth Inventory (PTGI-10). Multinomial regression examined which of the predictors best distinguished between the classes. Three classes were identified, termed here Resilience, Growth, and Distress. As differential predictors of class membership, the study identified age; gender; self-rated health; and COVID-19-related potential negative experiences: economic decline, concerns, and microaggression. The Resilience and Growth patterns were the most prominent. A small number of participants formed a class characterized by high levels of distress. The findings contribute to understanding the psychological response patterns of a minority group to COVID-19. The characteristics of the three classes highlight the important role of potentially negative experiences related to COVID-19 in the response patterns. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Neural substrates of cognitive switching and inhibition in a face processing task.
We frequently need to change our current occupation, an operation requiring additional effortful cognitive demands. Switching from one task to another may involve two distinct processes: inhibition of the previously relevant task-set, and initiation of a new one. Here we tested whether these two processes are underpinned by separate neural substrates, and whether they differ depending on the nature of the task and the emotional content of stimuli. We used functional magnetic resonance imaging in healthy human volunteers who categorize emotional faces according to three different judgment rules (color, gender, or emotional expression). Our paradigm allowed us to separate neural activity associated with inhibition and switching based on the sequence of the tasks required on successive trials. We found that the bilateral medial superior parietal lobule and left intraparietal sulcus showed consistent activation during switching regardless of the task. On the other hand, no common region was activated (or suppressed) as a consequence of inhibition across all tasks. Rather, task-specific effects were observed in brain regions that were more activated when switching to a particular task but less activated after inhibition of the same task. In addition, compared to other conditions, the emotional task elicited a similar switching cost but lower inhibition cost, accompanied by selective decrease in the anterior cingulate cortex when returning to this task shortly after inhibiting it. These results demonstrate that switching relies on domain-general processes mediated by postero-medial parietal areas, engaged across all tasks, but also provide novel evidence that task inhibition produces domain-specific decreases as a function of particular task demands, with only the latter inhibition component being modulated by emotional information.


In vitro and in vivo characterization of a novel H1N1/2009 influenza virus reassortant with an NS gene from a highly pathogenic H5N1 virus, isolated from a human.
The triple-reassortant H1N1/2009 influenza A virus, which caused the first influenza pandemic of the 21st century, is generally associated with mild disease and a relatively low mortality rate comparable to that of seasonal influenza virus outbreaks. There is a growing concern about the potential for reassortment between the low-mortality H1N1/2009 and other high-mortality influenza viruses. Here, we describe and characterize a novel reassortant H1N1/2009 influenza virus, isolated from a human sample, that contained an NS gene from a highly pathogenic H5N1 virus. We evaluated the effect of the acquired NS gene on viral virulence both in vitro and in vivo and found that the novel NS-reassorted influenza virus replicated well in different cell lines and several organs of BALB/c mice without prior adaption and induced a cytokine imbalance. Therefore, there is a continued risk for further reassortment of the H1N1/2009 virus, and therefore, systematic surveillance should be enhanced to prepare for the next possible pandemic.


Partnership duration, concurrency, and HIV in sub-Saharan Africa.
A widely accepted explanation for the exceptionally high HIV prevalence in sub-Saharan Africa is the practice of long-term overlapping heterosexual partnering. This article shows that long-duration concurrent partnering can be protective against HIV transmission rather than promoting it. Monogamous partnering prevents sexual transmission to anyone outside the partnership and, in an initially concordant-seronegative partnership, prevents sexual acquisition of HIV by either partner. Those protections against transmission and acquisition last as long as the partnership persists without new outside partnerships. Correspondingly, these two protective effects characterise polygynous partnerships, whether or not the polygyny is formal or informal, until a partner initiates a new partnership. Stable and exclusive unions of any size protect against HIV transmission, and more durable unions provide a longer protective effect. Survey research provides little information on partnership duration in sub-Saharan Africa and sheds no light on the interaction of duration, concurrency, and HIV. This article shows how assumptions about partnership duration in individual-based sexual-network models affect the contours of simulated HIV epidemics. Longer mean partnership duration slows the pace at which simulated epidemics grow. With plausible assumptions about partnership duration and at levels of concurrency found in the region, simulated HIV epidemics grow slowly or not at all. Those results are consistent with the hypothesis that long-duration partnering is protective against HIV and inconsistent with the hypothesis that long-term concurrency drives the HIV epidemics in sub-Saharan Africa.


Selective two-photon absorption in carbon dots: a piece of the photoluminescence emission puzzle.
Carbon nanodots (Cdots) are now emerging as promising nonlinear fluorophores for applications in biological environments. A thorough and systematic approach to the two-photon induced emission of Cdots that could provide design guidelines to control their nonlinear emission properties is still missing. In this work, we address the nonlinear optical spectroscopy of Cdots prepared by controlled chemical cutting of graphene oxide (GO). The two-photon absorption in the 700-1000 nm region and the corresponding emission spectrum are carefully investigated. The highest two-photon absorption cross-section estimated was 130 GM at 720 nm. This value is comparable with the one reported for graphene nanoribbons with push-pull architecture. The emission spectrum depends on the excitation mode. At the same excitation energy, nonlinear excitation results in excitation-wavelength independent emission, while upon linear excitation the emission is excitation-wavelength dependent. The biphotonic interaction seems to be selective towards sp2 clusters bearing electron donor and acceptor groups found in push-pull architectures. Both linear and nonlinear emission can be understood based on the existence of isolated sp2 clusters involved in π-π stacking interactions with clusters in adjacent layers.


Protein kinase C-epsilon is the likely mediator of mucin exocytosis in human colonic cell lines.
The phorbol ester, phorbol 12-myristate 13-acetate (PMA), induces mucin secretion in the colonic tumor cell line T84 in a Ca(2+)-independent manner. To determine whether a specific protein kinase C (PKC) isoform is involved in colonic cells, we compared PMA-dependent mucin secretion by three human colonic tumor cell lines (T84, HT-29/A1, and LS 180) with the expression of PKC isoforms alpha, beta, delta, epsilon, and zeta, previously identified in human colon (L. A. Davidson, Y. H. Jiang, J. D. Derr, H. Aukema, J. R. Lupton, and R. S. Chapkin. Arch. Biochem. Biophys. 312:547-553, 1994). In each cell line PMA (10(-7) M) caused mucin secretion within 30 min. PMA-dependent mucin secretion was three to four times greater from HT-29/A1 and T84 cells than from LS 180 cells. All three-cell lines contained mRNA for PKC-alpha, PKC-epsilon, and PKC-zeta but not PKC-beta or -delta. Each cell line also expressed PKC-alpha, -epsilon, and -zeta protein. PKC-epsilon expression (mRNA and protein) was three to four times greater in HT-29/A1 and T84 cells than in LS 180 cells, correlating with PMA-responsive mucin secretion, whereas all cell lines contained similar levels of PKC-alpha mRNA and protein. When cells were stimulated by PMA, only PKC-epsilon was translocated from cytosol to membrane fractions early enough to stimulate mucin secretion. Because PKC-epsilon is also a Ca(2+)-independent isoform, it is likely to mediate mucin exocytosis in colonic cells.


Optimal function and health.
Regular physical activity is essential for the optimal function of many vital organs and tissues, and for general function. I am less sure about its direct and significant effects in the area of preventive medicine, but I can mention much indirect evidence to justify a whole-hearted promotion of physical exercise. Information about diet and exercise should be tied together. My present prescription for exercise is as follows: Daily -- at least 60 minutes of physical activity, not necessarily vigorous, nor all at the same time. During your daily routine, moving, walking, climbing stairs, etc., whether for one minute 60 times per day, 12 minutes 5 times a day, or any combination totalling 60 minutes, will burn up approximately 300 kcal (1.2MJ). Weekly -- at least two or three periods of 30 minutes of intermittent or sustained activity at submaximal rate of work (brisk walking, jogging, cycling, swimming, cross-country skiing, gymnastics etc.) are necessary for maintaining good cardiovascular fitness, and will consume an additional 750 kcal per week (3MJ).


Do Orthopaedic Virtual Clinic Visits Demonstrate Cost and Time Efficiencies Compared With In-person Visits?
There are numerous reasons for the increased use of telemedicine in orthopaedic surgery, one of which is the perception that virtual visits are more cost-effective than in-person visits. However, to our knowledge, no studies have compared the cost and time investment of virtual versus in-person visits using the time-driven activity-based costing (TDABC) method. Unlike methods that estimate cost based on charges for services rendered, TDABC provides a more precise measurement of costs, which is essential for assessing cost-effective innovations and moving to value-based healthcare. (1) Are virtual visits less costly than analogous in-person visits, as measured by TDABC? (2) Does TDABC yield cost estimates that are lower or higher than the ratio of costs to charges (RCC), which is a simple, frequently used costing method? (3) Do the total time commitments of healthcare personnel, and that of the surgeon specifically, vary between the virtual and in-person settings? Patients for this prospective, observational study were recruited from the practices of the highest-volume virtual-visit surgeons of three subspecialties (joints, hand, and sports) in a multihospital, tertiary-care academic institution in a metropolitan area in the Midwestern United States. Each surgeon had at least 10 years of clinical practice. Between June 2021 and September 2021, we analyzed both in-person and virtual return visits with patients who had an established relationship with the surgeon, because this represented the most frequent type of virtual visits and enabled a direct comparison between the two settings. New patients were not included in the study because of the limited availability of new-patient virtual visits; such patients often benefit from in-person physical examinations and on-site imaging. Additionally, patients seen for routine postoperative care were excluded because they were primarily seen in person by a physician assistant. Data were acquired during this period until 90 in-person and 90 virtual visits were collected according to selection criteria; no patients were lost to follow-up. Distinct process maps, which represent the steps involved in a clinic visit used to measure healthcare personnel time invested, were constructed for in-person and virtual clinic visits and used to compare total personnel and surgeon time spent. To calculate TDABC-derived costs, time allocated by personnel to complete each step was measured and used to calculate cost based on each personnel member's yearly salary. From the accounting department of our hospital, we acquired RCC cost data according to the level of service for a return visit. The total median cost, as measured by TDABC, was USD 127 (IQR USD 111 to 163) for an in-person visit and USD 140 (IQR USD 113 to 205) for a virtual visit (median difference USD 13; p = 0.16). RCC overestimated TDABC-calculated direct variable cost in five of six service levels (in-person levels 3, 4, and 5 and virtual levels 3 and 5) by a range of USD 25 to 88. Additionally, we found that virtual visits consumed 4 minutes less of total personnel time (in-person: 17 minutes [IQR 13.5 to 23.5 minutes], virtual: 13 minutes [IQR 11 to 19 minutes]; p < 0.001); however, this difference in personnel time did not equate to cost savings because surgeons spent 2 minutes longer on virtual visit activities than they did on in-person activities (in-person: 6 minutes [IQR 4.5 to 9.5 minutes], virtual: 8 minutes [IQR 5.5 to 13 minutes]; p = 0.003). Orthopaedic virtual visits did not deliver cost savings compared with in-person visits because surgeons spent more time on virtual visits and participated in virtual visits at the clinical site. Additionally, as anticipated, RCC overestimated costs as calculated by TDABC. These findings suggest that cost is not a primary advantage of transitioning to virtual visits, and that factors such as patient preference and satisfaction should be considered instead. Level II, economic and decision analysis.


Genetic variation in prostate-specific antigen-detected prostate cancer and the effect of control selection on genetic association studies.
Only a minority of the genetic components of prostate cancer risk have been explained. Some observed associations of SNPs with prostate cancer might arise from associations of these SNPs with circulating prostate-specific antigen (PSA) because PSA values are used to select controls. We undertook a genome-wide association study (GWAS) of screen-detected prostate cancer (ProtecT: 1,146 cases and 1,804 controls); meta-analyzed the results with those from the previously published UK Genetic Prostate Cancer Study (1,854 cases and 1,437 controls); investigated associations of SNPs with prostate cancer using either "low" (PSA < 0.5 ng/mL) or "high" (PSA ≥ 3 ng/mL, biopsy negative) PSA controls; and investigated associations of SNPs with PSA. The ProtecT GWAS confirmed previously reported associations of prostate cancer at three loci: 10q11.23, 17q24.3, and 19q13.33. The meta-analysis confirmed associations of prostate cancer with SNPs near four previously identified loci (8q24.21,10q11.23, 17q24.3, and 19q13.33). When comparing prostate cancer cases with low PSA controls, alleles at genetic markers rs1512268, rs445114, rs10788160, rs11199874, rs17632542, rs266849, and rs2735839 were associated with an increased risk of prostate cancer, but the effect-estimates were attenuated to the null when using high PSA controls (Pheterogeneity in effect-estimates < 0.04). We found a novel inverse association of rs9311171-T with circulating PSA. Differences in effect-estimates for prostate cancer observed when comparing low versus high PSA controls may be explained by associations of these SNPs with PSA. These findings highlight the need for inferences from genetic studies of prostate cancer risk to carefully consider the influence of control selection criteria.


Designing a Private and Secure Personal Health Records Access Management System: A Solution Based on IOTA Distributed Ledger Technology.
The privacy and security of patients' health records have been an ongoing issue, and researchers are in a race against technology to design a system that can help stop the compromising of patient data. Many researchers have proposed solutions; however, most solutions have not incorporated potential parameters that can ensure private and secure personal health records management, which is the focus of this study. To design and develop a solution, this research thoroughly investigated existing solutions and identified potential key contexts. These include IOTA Tangle, Distributed Ledger Technology (DLT), IPFS protocols, Application Programming Interface (API), Proxy Re-encryption (PRE), and access control, which are analysed and integrated to secure patient medical records, and Internet of Things (IoT) medical devices, to develop a patient-based access management system that gives patients full control of their health records. This research developed four prototype applications to demonstrate the proposed solution: the web appointment application, the patient application, the doctor application, and the remote medical IoT device application. The results indicate that the proposed framework can improve healthcare services by providing immutable, secure, scalable, trusted, self-managed, and traceable patient health records while giving patients full control of their own medical records.


Antifungal efficacy of F10SC veterinary disinfectant against Batrachochytrium dendrobatidis.
The Infectious disease chytridiomycosis, which is caused by the fungal pathogen Batrachochytrium dendrobatidis, has been identified as one of the most important drivers of amphibian declines and extinction. In vitro B. dendrobatidis is susceptible to a range of disinfectants, but not all have been tested on animals and some that have been proven effective have harmful side effects on the surrounding environment or the animals being treated. We tested the efficacy of F10SC veterinary disinfectant to treat B. dendrobatidis in experimentally infected tadpole and juvenile Sclerophrys gutturalis and tadpoles of Sclerophrys poweri and Amietia hymenopus. The minimum inhibitory concentration for F10SC on in vitro B. dendrobatidis ranged between 1:7000 for 5-min contact time and 1:10000 for 10-min contact time. Based on the survival data of test animals the no observed effect concentration for 15-min contact time was estimated to be 1:2000 dilution for juveniles, and 1:10000 for tadpoles. In S. gutturalis juveniles an 86% infection clearance rate was achieved after five 15-min doses of 1:3000 dilution. A 100% clearance was achieved in A. hymenopus tadpoles after seven 15-min doses of 1:10000 dilution, and after nine doses of the same treatment in S. poweri tadpoles. F10SC has the benefit of being a concentrated compound that provides a treatment protocol which is nontoxic to tadpoles and post-metamorphic individuals, has a short half-life and is effective against B. dendrobatidis during short contact times, but further testing on different species of amphibians is advised.


Bilateral infarction in the territory of the anterior cerebral arteries.
An elderly hypertensive man had extensive bilateral infarction in the distribution of the anterior cerebral arteries. The circle of Willis was fully formed, but occlusion of the dominant anterior cerebral artery, aggravated and perhaps caused by postlaparotomy hypotension, produced the dramatic lesions, causing akinetic mutism. This stroke pattern occurs in various settings and does not require an anomalous azygous unilateral supply to both anterior cerebral arteries.


Chromosomal inactivation of Bacillus subtilis exfusants: a prokaryotic model of epigenetic regulation.
Epigenetic mechanisms are not exclusively reserved to eukaryotic organisms. They are also observed in prokaryotes. As described first by Hotchkiss and Gabor, protoplast fusion between strains of Bacillus subtilis produces heterodiploid cells. Heterodiploidy is associated with the inactivation of one of the chromosomes. To study the physical structure of the fusion product and the molecular mechanisms of inactivation, we constructed heterodiploid clones containing two chromosomes labeled by a NotI restriction fragment length polymorphism. In the progeny, we identified haploid recombinant clones that contain a chromosome carrying large regions of inactivated DNA. Studies of both recombinants of the latter kind and heterodiploid cells indicated that chromosomal inactivation was not determined by alteration of the inactivated nucleotide sequence, but was probably due to a modification in the structure of the bacterial chromatin.


Fish soluble Toll-like receptor 5 (TLR5S) is an acute-phase protein with integral flagellin-recognition activity.
From an EST fragment of the rainbow trout that was predicted to contain leucine-rich repeats (LRR), we cloned the whole cDNA and identified a soluble form of TLR5 ortholog (rtTLR5S), which does not exist in the mouse and human. rtTLR5S was about 38% homologous to the extracellular domains of human (hu) and mouse (mo)TLR5, while rtTLR5S showed <25% homologous to those of other human or mouse TLRs. A chimera constructed of rtTLR5S and the intra-cellular TIR of huTLR5 expressed on HeLa cells signaled the presence of flagellin A and C from V. anguillarum, resulting in NF-kappaB activation. The mRNA of rtTLR5S was predominantly detected in the liver. The hepatoma cell line of the rainbow trout RTH149 that responded to flagellin, allowed to up-regulate rtTLR5S in response to V. anguillarum or its purified flagellin within 8 h. rtTLR5S, when co-expressed with membrane huTLR5 in HeLa cells, augmented huTLR5-mediated NF-kappaB activation in response to flagellin. These results, together with the genome information of the pufferfish Fugu (Fugu rubripes), suggest that in fish the soluble TLR5 is an acute-phase protein sensing bacterial infection via recognition of a variety of bacterial flagellins to augment NF-kappaB activation, and may be important for fish to survive from bacterial infection in the water.


Occupational health behaviors and habits of women on dairy farms in Pennsylvania.
The goal of this study was to determine what tasks women perform, behaviors that could result in exposure to zoonotic disease, and preventative measures practiced by women on dairy farms. A written survey was sent to a stratified, random sample of dairy farms in Pennsylvania (n = 3709) using a modified version of the Dillman method. The tasks most commonly performed by the respondents (n = 624) included milking (70.8%), feeding (60.6%), and cleaning stalls (42.6%). The use of personal protective equipment was infrequent. Gloves were always worn when milking by 32.7%. More respondents, 96.5%, changed their clothes at least sometimes before working in the barn as compared to when leaving the barn. Handwashing was always performed by 86.7% after assisting with delivering calves, whereas 71.1% always washed their hands after milking. Eating and drinking in the barn were practiced by 45.0% and 72.0%, respectively. Veterinary obstetric drugs were administered by 28.2% of the respondents. Most of the respondents, 89.7%, indicated that they felt they had minimal to no risk of contracting a disease from the animals with which they worked.


An analysis of the relationship between metabolism, developmental schedules, and longevity using phylogenetic independent contrasts.
Comparative studies of aging are often difficult to interpret because of the different factors that tend to correlate with longevity. We used the AnAge database to study these factors, particularly metabolism and developmental schedules, previously associated with longevity in vertebrate species. Our results show that, after correcting for body mass and phylogeny, basal metabolic rate does not correlate with longevity in eutherians or birds, although it negatively correlates with marsupial longevity and time to maturity. We confirm the idea that age at maturity is typically proportional to adult life span, and show that mammals that live longer for their body size, such as bats and primates, also tend to have a longer developmental time for their body size. Lastly, postnatal growth rates were negatively correlated with adult life span in mammals but not in birds. Our work provides a detailed view of factors related to species longevity with implications for how comparative studies of aging are interpreted.


Isolation of the gene for EILP, an elicitor-inducible LRR receptor-like protein, from tobacco by differential display.
We screened tobacco genes, which are differentially expressed in response to a fungal elicitor, and have isolated a gene which codes for a leucine-rich repeat (LRR) protein closely related to Cf genes in tomato. The EILP (elicitor inducible LRR protein) gene encodes 95 kDa protein, which consists of a putative membrane spanning region, 28 leucine-rich repeats and some N-linked glycosylation sites, and shows high homology to Cf-2/Cf-5 family genes. Southern blot analysis revealed the presence of some genes homologous to EILP in tobacco, like Cf genes in tomato. The expression of EILP was low at the basal level and increased by treatment with elicitor, implying that EILP is involved in both preexisting and inducible surveillance systems. The expression of EILP was activated by a non-pathogen, Pseudomonas syringae pv. glycinea, and in a delayed fashion by the tobacco pathogen P. syringae pv. tabaci, suggesting that the product of EILP may be involved in non-host disease resistance in tobacco.


Endoscopic versus open saphenous vein harvest for femoral to below the knee arterial bypass using saphenous vein graft.
Although the use of endoscopic vein harvest (EVH) in coronary artery bypass grafting is accepted, few studies have documented the implementation of EVH in peripheral vascular disease surgery. We hypothesized that EVH improves outcomes compared with open vein harvest (OVH) in patients undergoing femoral to below the knee arterial bypass surgery. The charts of 144 consecutive patients undergoing infrainguinal bypass surgery over the course of 27 months were reviewed. A femoral to below the knee arterial bypass with saphenous vein was done in 88 patients (29 had EVH, 59 had OVH). The preoperative characteristics evaluated were age, gender, renal function, history of diabetes, hypertension, tobacco use, and previous infrainguinal bypass surgery on the affected side. End points included wound complications, length of hospital stay, operative time, angiographic and operative interventions for graft occlusion, patency rates, limb salvage, acute renal failure, myocardial infarction, and death. Patient characteristics and demographics were similar in the EVH and OVH groups. No operative intervention for occlusion was required in the EVH group (0/29) compared with 13.4% in the OVH group (8/59) (P = .03). At the mean follow-up time of 21 months, primary patency rate was 92.8% in the EVH group and 80.6% in the OVH group (P = .12). No significant differences were found between the EVH and OVH groups in postoperative complications, length of hospital stay, operative time, patency rates, limb salvage, and death. Despite our initial concerns of damaging the venous conduit with a minimally invasive approach to saphenous vein harvest, EVH in our experience has resulted in a trend toward improved patency rates and decreased infectious wound complications while affording the benefit of improved cosmesis. An endoscopic approach results in smaller incisions, decreased interventions for occlusion, and improved outcomes compared with OVH. EVH is the procedure of choice for harvesting saphenous vein for femoral to below the knee arterial bypass surgery.


Alcohol and drowning in Australia.
To examine the contribution of alcohol to drowning deaths in Australia. Drowning deaths that occurred in Australia (excluding Queensland) from 1 July 2000 to 30 June 2001 were identified using the National Coroners Information System (NCIS). The current analysis was based on those deaths for which the Coronial process was completed by March 2003 ('Closed' cases). Comparison was made with the Australian Bureau of Statistics (ABS) national deaths data and with currently used values of attributable fractions for alcohol and drowning in Australia (these values are based on USA data on drownings from 1980 to 1984). 289 drowning deaths were identified, 5% less than comparable ABS data. Of these deaths, 240 were 'Closed' cases, and valid blood alcohol measurements were available for 137 (58%) of these. Alcohol appeared to contribute to approximately 19% of these fatal drowning incidents (25% for recreational aquatic activity; 16% for incidental falls into water; 12% for drowning due to suicide). Using > or = 0.10 g/100 ml as the cut-off, the estimated all-ages proportions of unintentional drowning attributed to alcohol was 17% in the current study, compared to the 34% currently used for Australia based on data from North America. A high level of alcohol appears to be present less frequently among recent drowning deaths in Australia than has been assumed to be the case to date. Nevertheless, many drowning victims have high levels of blood alcohol, and public health efforts to minimize the use of alcohol in association with activity on or near water should be continued. Despite some deficiencies, the NCIS appears to be a very useful source of information on public health issues, and to provide a better basis for assessing and monitoring alcohol-related drowning deaths in Australia than the published attributable fractions used to date.


Abdominal pain in HIV infection.
The causes of abdominal pain in patients with AIDS are different from those of the general population, and there are no guidelines as to which investigations are optimal. We reviewed our experience of 63 patients who presented with abdominal pain as the main reason for admission to the AIDS unit at St Stephen's and Westminster Hospital between January 1988 and January 1990. All patients were assessed within the same structured diagnostic programme. Thirty-five had upper abdominal pain, predominantly in the right upper quadrant in 27; seven had lower abdominal pain, which was concentrated in the right iliac fossa in three; 21 had diffuse abdominal pain. The causes of pain were determined satisfactorily in the majority of patients using routine gastroenterological investigations. The predominant site of pain had considerable predictive value in the diagnosis. The commonest cause of right upper quadrant pain was sclerosing cholangitis (17 of 27); endoscopic retrograde cholangio-pancreatography was necessary for a confident diagnosis. Diarrhoea was frequently associated (15 of 21) with diffuse abdominal pain; the commonest cause (six of 21) was cytomegalovirus colitis. Neoplasia was the cause of abdominal pain in eight patients. The other causes of abdominal pain and the utility of various investigations are discussed. An investigatory route which may provide maximum information has been suggested.


Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases.
Phospholipase A2 (PLA2) belongs to a family of enzymes that catalyze the cleavage of fatty acids from the sn-2 position of phospholipids. There are more than 19 different isoforms of PLA2 in the mammalian system, but recent studies have focused on three major groups, namely, the group IV cytosolic PLA2, the group II secretory PLA2 (sPLA2), and the group VI Ca(2+)-independent PLA2. These PLA2s are involved in a complex network of signaling pathways that link receptor agonists, oxidative agents, and proinflammatory cytokines to the release of arachidonic acid (AA) and the synthesis of eicosanoids. PLA2s acting on membrane phospholipids have been implicated in intracellular membrane trafficking, differentiation, proliferation, and apoptotic processes. All major groups of PLA2 are present in the central nervous system (CNS). Therefore, this review is focused on PLA2 and AA release in neural cells, especially in astrocytes and neurons. In addition, because many neurodegenerative diseases are associated with increased oxidative and inflammatory responses, an attempt was made to include studies on PLA2 in cerebral ischemia, Alzheimer's disease, and neuronal injury due to excitotoxic agents. Information from these studies has provided clear evidence for the important role of PLA2 in regulating physiological and pathological functions in the CNS.


Patterns of infection by lungworms, Rhabdias ranae and Haematoloechus spp., in northern leopard frogs: a relationship between sex and parasitism.
We examined a population of northern leopard frogs to determine whether sex biases in investment in immunity, previously reported for this host species under controlled exposures to lung nematodes, is predictive of patterns of parasitism in nature. We examined Rhabdias ranae and Haematoloechus spp. infections in 74 breeding adult, 28 non-breeding adult, and 53 juvenile frogs. Contrary to our predictions, R. ranae prevalence and mean abundance were higher in breeding female frogs (prevalence: 39.4%, abundance: 3.05 +/- 0.85) than on breeding males (prevalence: 26.0%, abundance: 1.17 +/- 0.52), although no sex bias was observed among non-breeding adults or juvenile frogs. Female frogs also carried larger R. ranae worms, on average, than did males (females: 6407.38 microm +/- 153.80; males: 5198 microm +/- 131.09), regardless of age or breeding condition. We observed no sex-linked patterns of parasitism by Haematoloechus spp. worms in either adult or juvenile frogs. Alternative hypotheses, such as differences among sexes in the selection of thermal clines for hibernation, may explain the observed female bias in parasitism by nematode lungworms in nature and, thus, need to be considered.


Identifying the relationships between water quality and land cover changes in the Tseng-Wen reservoir watershed of Taiwan.
The effects on water quality of land use and land cover changes, which are associated with human activities and natural factors, are poorly identified. Fine resolution satellite imagery provides opportunities for land cover monitoring and assessment. The multiple satellite images after typhoon events collected from 2001 to 2010 covering land areas and land cover conditions are evaluated by the Normalized Difference Vegetation Index (NDVI). The relationship between land cover and observed water quality, such as suspended solids (SS) and nitrate-nitrogens (NO(3)-N), are explored in the study area. Results show that the long-term variations in water quality are explained by NDVI data in the reservoir buffer zones. Suspended solid and nitrate concentrations are related to average NDVI values on multiple spatial scales. Annual NO(3)-N concentrations are positively correlated with an average NDVI with a 1 km reservoir buffer area, and the SS after typhoon events associated with landslides are negatively correlated with the average NDVI in the entire watershed. This study provides an approach for assessing the influences of land cover on variations in water quality.


[Solid-pseudopapillary tumor of the pancreas. Presentation of 3 clinical cases].
The solid-pseudopapillary tumors of the pancreas (TSPP) are a uncommon neoplasm (1- 2% of exocrine tumors). Are more frequent in young women and presents a low malignant potential (15% develop metastases). Its preoperative diagnosis is very difficult, because these tumors haven`t radiological features that makes distinguish from the other pancreatic cysts tumors. Usually are a histopathological finding. Surgical therapy provides good survival, even in the presence of metastases. We present 3 cases with clinical, imaging, treatment and histopathology to provide more information about this rare disease.


Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses.
There is a lack of synthesis of literature to determine hepatitis B vaccine (HepB) strategies for hepatitis B virus (HBV) supported by quality evidence. We aimed to explore the efficacy and safety of HepB strategies among people with different characteristics. PubMed, Cochrane Library, Embase, and Web of Science were searched for meta-analyses comparing the efficacy and safety of HepB up to July 2023. Twenty-one meta-analyses comparing 83 associations were included, with 16 high quality, 4 moderate, and 1 low quality assessed by AMSTAR 2. Highly suggestive evidence supports HepB booster and HepB with 1018 adjuvant (HBsAg-1018) for improved seroprotection, and targeted and universal HepB vaccination reduced HBV infection Suggestive evidence indicated that targeted vaccination decreased the rate of hepatitis B surface antibody positivity and booster doses increased seroprotection in people aged 10-20. Weak evidence suggests potential local/systemic reaction risk with nucleotide analogs or HBsAg-1018. Convincing evidence shows HLA-DPB1*04:01 and DPB1*04:02 increased, while DPB1*05:01 decreased, hepatitis B antibody response. Obesity may reduce HepB seroprotection, as highly suggested. Targeted vaccination could effectively reduce HBV infection, and adjuvant and booster vaccinations enhance seroprotection without significant reaction. Factors such as obesity and genetic polymorphisms may affect the efficacy.


Successional Dynamics in the Gut Microbiome Determine the Success of Clostridium difficile Infection in Adult Pig Models.
Clostridium difficile infections (CDI) are a major cause of antibiotic-associated diarrhea. It is hypothesized that CDI develops due to the antibiotic-induced disruption of the intestinal microbial community structure, which allows C. difficile to flourish. Here, we pre-treated weaned pigs with the antibiotics Clindamycin or Ciprofloxacin for 1 day, and subsequently inoculated them with a human and pig enteropathogenic C. difficile strain 078 spores. Body temperature, clinical signs of disease, and the fecal microbiome were monitored daily for 15 days. Clindamycin had a stronger effect on the pigs than Ciprofloxacin, resulting in drastic shifts in the fecal microbiome, decreases in microbial diversity and significant increases in body temperature, even in the absence of C. difficile. Fecal shedding of C. difficile was detectable for 3 and 9 days in Ciprofloxacin and Clindamycin treated pigs inoculated with C. difficile, respectively, and in both cases decreased cell proliferation rates were detected in colon tissue. The timing of C. difficile shedding coincided with the decrease in a large cluster of Firmicutes following Clindamycin treatment, a pattern which was also independent of C. difficile inoculation. The observed community patterns suggest that successional dynamics following antibiotic treatment facilitate C. difficile establishment. The similarities between the microbiome responses observed in our study and those previously reported in CDI-infected humans further support the utility of adult pigs as models for the study of CDI.


Osteoblast interactions with various hydroxyapatite based biomaterials consolidated using a spark plasma sintering technique.
This study investigated the osteoblast behaviors on various hydroxyapatite based biomaterials that were consolidated at 1100 degrees C for 3 min by a spark plasma sintering technique. The osteoblasts from human fetal osteoblast cell line were cultured in the medium on the various biomaterials surfaces (HA, RF21, 1SiHA, and 5SiHA) to assess the cell morphology and proliferation as well as cell differentiation (alkaline phosphatase activity). Moreover, the bone gamma-carboxyglutamic protein or osteocalcin in the medium were determined at different periods of culture. The present results indicated that the amount of osteocalcin in the medium decreased during the periods of culture. The highest osteocalcin production obtained from the biomaterial 5SiHA after cell culture for 2 days demonstrated that the presence of silica in the biomaterials enhanced the cell differentiation by the rapid release of silicate and calcium ions.


Hoxb7 inhibits transgenic HER-2/neu-induced mouse mammary tumor onset but promotes progression and lung metastasis.
Our previous studies have shown that HOXB7 mRNA is overexpressed in approximately 50% of invasive breast carcinomas and promotes tumor progression in breast cancer cells grown as xenografts in mice. In silico analysis of published microarray data showed that high levels of HOXB7 predict a poor outcome in HER-2-positive (P = 0.046), but not in HER-2-negative breast cancers (P = 0.94). To study the function of HOXB7 in vivo in the context of HER-2 overexpression, we generated mouse mammary tumor virus (MMTV)-Hoxb7 transgenic mice, and then crossed them with MMTV-HER-2/neu transgenic mice. In the mice carrying both Hoxb7 and HER-2/neu transgenes, Hoxb7 plays a dual role in mammary tumorigenesis. In double transgenic mice, overexpression of Hoxb7 delayed tumor onset and lowered tumor multiplicity. However, consistent with the clinical data, once the tumors appeared, their growth was faster and metastasis to the lungs occurred at a higher frequency. Our data show, for the first time, that deregulated expression of Hoxb7 in mammary tumor cells can significantly modulate HER-2/neu-oncogene induced tumorigenesis in vivo.


Dentists' treatment of underserved populations following participation in community-based clinical rotations as dental students.
The purpose of this study was to identify which underserved populations are being treated by dentists after participation in community-based clinical rotations as dental students and to determine which predictor variables are associated with dentists' treatment of these populations. A 25-item written survey was developed and mailed to University of Iowa College of Dentistry alumni (1992-2002; N = 745) to assess what percentage of their current total patient population was composed of each of the twelve identified populations. Separate statistical analyses (descriptive, bivariate, and generalized logistic regression) were performed for each underserved population. Three-hundred seventy-two dentists responded for an adjusted response rate of 50 percent. Respondents were most likely to treat "other ethnic groups" and low income populations. In contrast, 70 percent or more of all respondents said they never treat the homebound, homeless, and incarcerated. Additionally, over 40 percent of respondents said they never treat HIV+/AIDS patients and Medicaid patients. Logistic regression models showed that comfort in treating a population, treating more than seven populations, and having the total percentage of underserved populations treated within a practice total more than 50 percent were the most frequently associated (P < 0.05) and strongest predictors of treating the listed underserved populations. Although respondents reported treating most populations, community leaders and dentists should identify at-risk populations and develop protocols to help ensure that these populations are able to obtain, at a minimum, emergency care. Additionally, dental schools should develop educational curricula to help increase students' comfort in treating underserved populations.


Fluctuating selection models and McDonald-Kreitman type analyses.
It is likely that the strength of selection acting upon a mutation varies through time due to changes in the environment. However, most population genetic theory assumes that the strength of selection remains constant. Here we investigate the consequences of fluctuating selection pressures on the quantification of adaptive evolution using McDonald-Kreitman (MK) style approaches. In agreement with previous work, we show that fluctuating selection can generate evidence of adaptive evolution even when the expected strength of selection on a mutation is zero. However, we also find that the mutations, which contribute to both polymorphism and divergence tend, on average, to be positively selected during their lifetime, under fluctuating selection models. This is because mutations that fluctuate, by chance, to positive selected values, tend to reach higher frequencies in the population than those that fluctuate towards negative values. Hence the evidence of positive adaptive evolution detected under a fluctuating selection model by MK type approaches is genuine since fixed mutations tend to be advantageous on average during their lifetime. Never-the-less we show that methods tend to underestimate the rate of adaptive evolution when selection fluctuates.


Secreted phosphoprotein markers for neoplastic transformation of human epithelial and fibroblastic cells.
A wide variety of rodent tumor cells of both fibroblastic and epithelial origins secrete a major transformation-related phosphoprotein with a molecular weight of approximately 62,000. Tumorigenic cells, regardless of the transforming agent, secrete 10-fold or more of this 32P-labeled protein as compared with their nontumorigenic counterparts. In this study we have extended these previous findings to tumorigenic human cells of diverse origins (both sarcomas and carcinomas). Metabolic labeling of cells with [32P]orthophosphate and immunoprecipitation with antibody specifically directed against the rat transformation-dependent secreted phosphoprotein have been used to identify antigenically related human phosphoproteins (Mr 66,000-69,000). Of the 14 human cell lines examined, all 8 of the lethal tumorigenic cell populations secreted these phosphoproteins either in continuous culture or as fresh explants from nude mice while the six nonmalignant cell lines did not (tumorigenicity in all cases was assayed in nude mice). Included in our study were three tumorigenic human cell lines (two sarcomas, one carcinoma), each with a matched, nontumorigenic control. The very close correlation between secretion of these phosphoproteins and the tumor cell phenotype of both rodents and humans raises the possibility that they may be important for tumor growth in vivo.


[Problems in the radiologic diagnosis of osteogenic sarcoma].
Osteogenic sarcoma showing the signs of acute osteolytic process were hardest to diagnose. Since-reliable diagnosis depended on detection of neoplastic osteogenesis in involved bone, tomography proved to be of vital importance. Differential diagnosis was instrumental in dealing with osteolytic giant-cells and osteomyelitis. Diagnosis cannot be considered complete until histological examination is carried out. Whenever neoplastic osteogenesis is suspected, samples must be taken from relevant sites.


Purification, crystallization and preliminary X-ray diffraction studies to near-atomic resolution of dihydrodipicolinate synthase from methicillin-resistant Staphylococcus aureus.
In recent years, dihydrodipicolinate synthase (DHDPS; EC 188.8.131.52) has received considerable attention from both mechanistic and structural viewpoints. DHDPS is part of the diaminopimelate pathway leading to lysine, coupling (S)-aspartate-beta-semialdehyde with pyruvate via a Schiff base to a conserved active-site lysine. In this paper, the cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of DHDPS from methicillin-resistant Staphylococcus aureus, an important bacterial pathogen, are reported. The enzyme was crystallized in a number of forms, predominantly from PEG precipitants, with the best crystal diffracting to beyond 1.45 A resolution. The space group was P1 and the unit-cell parameters were a = 65.4, b = 67.6, c = 78.0 A, alpha = 90.1, beta = 68.9, gamma = 72.3 degrees . The crystal volume per protein weight (V(M)) was 2.34 A(3) Da(-1), with an estimated solvent content of 47% for four monomers per asymmetric unit. The structure of the enzyme will help to guide the design of novel therapeutics against the methicillin-resistant S. aureus pathogen.