The Role of Primary Care for the Oral Health of Rural and Urban Older Adults.
Rural populations often have restricted access to dental care and poor oral health. These problems may disproportionately affect older blacks in rural areas. Little is known about how access to primary health care may improve the oral health of rural seniors. This study examines whether the relationship between having a usual source of health care and oral health varies for white and black older adults in rural and urban areas in the United States. We draw on cross-sectional data of adults (50 years+) from the nationally representative Health and Retirement Study (n = 15,473). Multivariate logistic regression examined the role of a usual source of health care in conditioning racial differences in complete tooth loss and a dental visit in the past 2 years. A usual source of health care is a place, not including an emergency room, where a person goes when he or she is sick or needs health advice. In rural areas, blacks had high rates of tooth loss (28%) and low rates of dental visits (34%). Having a usual source of health care was associated with higher odds of a dental visit for all adults. In rural areas, the association between a usual source of health care and tooth loss varied by race (P < .001); blacks had more tooth loss than whites even with a usual source of health care. Access to primary health care was associated with improved oral health outcomes, but it did not close the gap between whites and blacks in rural areas.


Printed Drug-Delivery Systems for Improved Patient Treatment.
The use of various types of printing technologies offer potential solutions for personalized medicine and tailored dosage forms to meet the needs of individual treatments of the future. Many types of scenario for printed dosage form exist and the concepts include, on the simplest level, accurately deposited doses of drug substances. In addition, computer design allows endless opportunities to create suitable geometries with tailored functionality and different levels of complexity to control the release properties of one or multiple drug substances. It will take some time to convert these technological developments in printing to better treatments for patients, because challenges exist. However, printing technologies are developing fast and have the potential to allow the use of versatile materials to manufacture sophisticated drug-delivery systems and biofunctional constructs for personalized treatments.


Perceptual and Articulatory Changes in Speech Production Following PROMPT Treatment.
PROMPT (Prompts for Restructuring Oral Muscular Phonetic Targets) is a treatment approach that is widely used to improve sound production in children with speech impairments. This approach uses tactile cues to support and shape movements of the oral articulators in order to improve the production of individual sounds, syllables, words, and eventually connected speech. The underlying assumption is that tactile cuing will facilitate changes in articulator movements. This investigation examined articulator movement as well as the accuracy of speech production, before, during, and after a period of PROMPT treatment in a child with severe articulation impairment. A typically developing child was followed longitudinally as a control. The following research questions were addressed: (1) Does speech sound accuracy improve over an eight-week course of PROMPT treatment? (2) Does articulator movement (duration, displacement, velocity) change over an eight-week course of PROMPT treatment? The results revealed increased articulation accuracy and decreased movement duration, displacement, and velocity over the course of PROMPT treatment in the child with the articulation impairment. By the last treatment session, kinematic findings were most similar to those seen in the control. These results suggest that PROMPT facilitated changes in articulatory control in a single participant.


Schizosaccharomyces pombe ras1 and byr1 are functionally related genes of the ste family that affect starvation-induced transcription of mating-type genes.
We have further investigated the function of the ras1 and byr1 genes, which were previously shown to be critical for sexual differentiation in fission yeast cells. Several physiological similarities between strains containing null alleles of these genes supports the idea that ras1 and byr1 are functionally closely related. Furthermore, we have found that byr1 is allelic to ste1, one of at least 10 genes which when mutated can cause sterility. Since ras1 had previously been found to be allelic to ste5, both ras and byr genes are now clearly shown to be a part of the ste gene family, thus confirming their close functional relationship. The observation that the mating-type loci could overcome the sporulation block of ras1 and byr1 mutant strains prompted investigation of the role of the ras-byr pathway in the induction of the mating-type gene transcripts upon nitrogen starvation. By Northern analysis of RNA preparations from strains carrying wild-type or mutant ras1 alleles and grown to different stages of the growth cycle, we have shown that ras1 plays an important role in inducing the Pi transcript of the mating-type loci and the mei3 gene transcript. These observations provide a molecular basis for the role of the ste gene family, including ras1 and byr1, in meiosis and indicate that further characterization of other ste genes would be very useful for elucidating the mechanism of ras1 function in fission yeast cells.


Factors influencing decision-making around family presence during resuscitation: a grounded theory study.
The aim of this study was to examine factors impacting family presence during resuscitation practices in the acute care setting. Family presence during resuscitation was introduced in the 1980s, so family members/significant others could be with their loved ones during life-threatening events. Evidence demonstrates important benefits; yet despite growing support from the public and endorsement from professional groups, family presence is practiced inconsistently and rationales for poor uptake are unclear. Constructivist grounded theory design. Twenty-five health professionals, family members and patients informed the study. In-depth interviews were undertaken between October 2013-November 2014 to interpret and explain their meanings and actions when deciding whether to practice or participate in FPDR. The Social Construction of Conditional Permission explains the social processes at work when deciding to adopt or reject family presence during resuscitation. These processes included claiming ownership, prioritizing preferences and rights, assessing suitability, setting boundaries and protecting others/self. In the absence of formal policies, decision-making was influenced primarily by peoples' values, preferences and pre-existing expectations around societal roles and associated status between health professionals and consumers. As a result, practices were sporadic, inconsistent and often paternalistic rather than collaborative. An increased awareness of the important benefits of family presence and the implementation of clinical protocols are recommended as an important starting point to address current variations and inconsistencies in practice. These measures would ensure future practice is guided by evidence and standards for health consumer safety and welfare rather than personal values and preferences of the individuals 'in charge' of permissions.


Aspirin reduces experimental cerebral blood flow in vivo.
Aspirin therapy for stroke prophylaxis in low risk patients has paradoxically demonstrated an increased risk of ischemic stroke in several studies. Moreover, the MAST-Italy trial reported a near doubling of mortality with the addition of aspirin to thrombolytics while experimentally, we have noted that aspirin antagonizes t-PA-mediated clot lysis. The mechanisms responsible for these observations is unclear. Of interest, few studies have examined the effect of aspirin on cerebral blood flow (CBF). The objective of this study was to examine the acute effect of high dose aspirin on CBF in a rabbit model. Mean arterial pressure, arterial blood gases, and core and brain temperature were controlled throughout the protocol. CBF, measured by the technique of hydrogen clearance using Platinum-Iridium flow probes, was measured before and 20 min following aspirin administration (20 mg kg-1 i.v.) in a cohort of 50 rabbits and compared to rabbits receiving vehicle (n = 19). Following aspirin therapy, CBF (cc/100 g-1 min-1) was reduced from 80.8 +/- 27.4 to 65.1 +/- 31.7 (mean +/- SD), a reduction to 80.4 +/- 21.3% of baseline (p < 0.00001, t-test), whereas CBF in the control group remained unchanged (81.0 +/- 25.4 vs. 77.5 +/- 24.0, mean +/- SD). Thus aspirin acutely reduced CBF by approximately 20% in a rabbit model, perhaps related to inhibitory effects on prostacyclin and/or nitric oxide. This result may help explain the possible increase in ischemic stroke seen in low risk patients on aspirin therapy. A reduction in CBF by aspirin may also assist in understanding the antagonism of t-PA-mediated clot lysis by aspirin seen in our rabbit model of thromboembolic stroke, particularly since all agents which share the ability to reverse this antagonism (nitric oxide donors, beta blockers, hydralazine, prostacyclin) also increase CBF by approximately 20%. Future strategies for 'antiplatelet' therapy may benefit from using agents which do not adversely affect CBF.


A role for 5-HT in the action of antidepressant drugs.
Administration of antidepressant drugs to rodents appears to decrease 5-HT2 receptor function while transmission through postsynaptic 5-HT1 receptor synapses may be enhanced. Antidepressant drugs also alter 5-HT mechanisms in humans; some of these changes are congruent with effects noted in animal studies. Thus certain 5-HT-mediated neuroendocrine responses are enhanced by tricyclic antidepressants and monoamine oxidase inhibitors, and it seems likely that tricyclics may act as 5-HT2 receptor antagonists in the human brain. However, there is presently no firm evidence that any of these changes are necessary for the clinical efficacy of antidepressant drugs. The best evidence that 5-HT neurons may be involved in mediating antidepressant effects is the antidepressant activity of selective 5-HT uptake blockers.


Phase I active immunotherapy with combination of two chimeric, human epidermal growth factor receptor 2, B-cell epitopes fused to a promiscuous T-cell epitope in patients with metastatic and/or recurrent solid tumors.
PURPOSE To evaluate the maximum-tolerated dose (MTD), safety profile, and immunogenicity of two chimeric, B-cell epitopes derived from the human epidermal growth factor receptor (HER2) extracellular domain in a combination vaccine with a promiscuous T-cell epitope (ie, MVF) and nor-muramyl-dipeptide as adjuvant emulsified in SEPPIC ISA 720. PATIENTS AND METHODS Eligible patients with metastatic and/or recurrent solid tumors received three inoculations on days 1, 22, and 43 at doses of total peptide that ranged from 0.5 to 3.0 mg. Immunogenicity was evaluated by enzyme-linked immunosorbent assay, flow cytometry, and HER2 signaling assays. Results Twenty-four patients received three inoculations at the intended dose levels, which elicited antibodies able to recognize native HER2 receptor and inhibited both the proliferation of HER2-expressing cell lines and phosphorylation of the HER2 protein. The MTD was determined to be the highest dose level of 3.0 mg of the combination vaccine. There was a significant increase from dose level 1 (0.5 mg) to dose level 4 (3.0 mg) in HER2-specific antibodies. Four patients (one each with adrenal, colon, ovarian, and squamous cell carcinoma of unknown primary) were judged to have stable disease; two patients (one each with endometrial and ovarian cancer) had partial responses; and 11 patients had progressive disease. Patients with stable disease received 6-month boosts, and one patient received a 20-month boost. CONCLUSION The combination vaccines were safe and effective in eliciting antibody responses in a subset of patients (62.5%) and were associated with no serious adverse events, autoimmune disease, or cardiotoxicity. There was preliminary evidence of clinical activity in several patients.


Idiopathic ischemic necrosis of an accessory carpal bone in a dog.
A 6-year-old neutered female mixed-breed dog was evaluated because of a 6-week history of left forelimb lameness that varied in severity. Radiography revealed expansile and lytic changes of the left accessory carpal bone (ACB). Results of histologic evaluation of ACB core biopsy specimens indicated areas of bone necrosis. The entire left ACB was excised and submitted for histologic evaluation; results confirmed a diagnosis of idiopathic ischemic necrosis. Left pancarpal arthrodesis was performed to treat carpal hyperextension and persistent lameness. The dog had an excellent functional outcome with no other problems related to the carpus until its death 4 years later, further decreasing suspicion that the problem was attributable to an undetected neoplasm or bacterial or fungal osteomyelitis. The radiographic and histologic findings for the dog of this report were similar to previously reported findings for dogs with ischemic femoral head necrosis and humans with ischemic carpal (pisiform or lunate bone) necrosis. The etiology of the ischemic ACB necrosis in this dog was not determined. To the authors' knowledge, this is the first report of a dog with idiopathic ischemic ACB necrosis. Idiopathic ischemic necrosis should be included as a differential diagnosis for dogs with lameness and destructive and expansile ACB radiographic lesions. An excellent functional outcome may be attained by means of ACB excision and pancarpal arthrodesis.


Measuring Crowd Collectiveness.
Collective motions of crowds are common in nature and have attracted a great deal of attention in a variety of multidisciplinary fields. Collectiveness, which indicates the degree of individuals acting as a union, is a fundamental and universal measurement for various crowd systems. By quantifying the topological structures of collective manifolds of crowd, this paper proposes a descriptor of collectiveness and its efficient computation for the crowd and its constituent individuals. The Collective Merging algorithm is then proposed to detect collective motions from random motions. We validate the effectiveness and robustness of the proposed collectiveness on the system of self-driven particles as well as other real crowd systems such as pedestrian crowds and bacteria colony. We compare the collectiveness descriptor with human perception for collective motion and show their high consistency. As a universal descriptor, the proposed crowd collectiveness can be used to compare different crowd systems. It has a wide range of applications, such as detecting collective motions from crowd clutters, monitoring crowd dynamics, and generating maps of collectiveness for crowded scenes. A new Collective Motion Database, which consists of 413 video clips from 62 crowded scenes, is released to the public.


A double-blind, placebo-controlled study of the effects of policosanol in patients with intermittent claudication.
This study was undertaken to evaluate the efficacy and tolerability of policosanol, a new cholesterol-lowering drug with concomitant antiplatelet effects, in patients with intermittent claudication. After a baseline period of 6 weeks, 62 patients were randomized to receive, under double-blind conditions, either placebo (31 patients) or policosanol (31), 10 mg twice daily. Walking distances in a treadmill (constant speed 3.2 km/hr, slope 10 degrees) were assessed before and after 6 months of treatment. Both groups were similar at randomization. Policosanol increased significantly (p < 0.01) the initial claudication distance from 132.5+/-13.5 m (baseline) to 205.7+/-36.3 m (after therapy) and the absolute claudication distance (p<0.0001) from 229.5+/-22.0 m to 365.4+/-46.9 m; meanwhile both variables remained unchanged in the placebo group (p<0.05). The reduction of lower limb symptoms showed a greater benefit in the policosanol group. There was no significant change in either group in the ankle/arm pressure ratio. The treatment was well tolerated. There were 10 discontinuations (seven placebo, three policosanol) from the study. Six withdrawals occurred because of adverse events (AE); all were in placebo patients. There were five serious vascular AEs in the placebo group but none in the policosanol group (p<0.05). Overall, 12/31 (38.7%) placebo patients and 3/31 (9.7%) policosanol patients experienced AEs after randomization, which showed a lesser incidence of AEs in the policosanol group (p<0.01). The present study demonstrates a beneficial effect of policosanol in patients with intermittent claudication.


Spatially segregated feedforward and feedback neurons support differential odor processing in the lateral entorhinal cortex.
The lateral entorhinal cortex (LEC) computes and transfers olfactory information from the olfactory bulb to the hippocampus. Here we established LEC connectivity to upstream and downstream brain regions to understand how the LEC processes olfactory information. We report that, in layer II (LII), reelin- and calbindin-positive (RE(+) and CB(+)) neurons constitute two major excitatory cell types that are electrophysiologically distinct and differentially connected. RE(+) neurons convey information to the hippocampus, while CB(+) neurons project to the olfactory cortex and the olfactory bulb. In vivo calcium imaging revealed that RE(+) neurons responded with higher selectivity to specific odors than CB(+) neurons and GABAergic neurons. At the population level, odor discrimination was significantly better for RE(+) than CB(+) neurons, and was lowest for GABAergic neurons. Thus, we identified in LII of the LEC anatomically and functionally distinct neuronal subpopulations that engage differentially in feedforward and feedback signaling during odor processing.


Pollen tube attraction by the synergid cell.
In flowering plants, guidance of the pollen tube to the embryo sac (the haploid female gametophyte) is critical for successful fertilization. The target embryo sac may attract the pollen tube as the final step of guidance in the pistil. We show by laser cell ablation that two synergid cells adjacent to the egg cell attract the pollen tube. A single synergid cell was sufficient to generate an attraction signal, and two cells enhanced it. After fertilization, the embryo sac no longer attracts the pollen tube, despite the persistence of one synergid cell. This cessation of attraction might be involved in blocking polyspermy.


Clinical evaluation of the Hemi Wheelchair Cushion.
A foam cushion was designed for wheelchair users who propel their wheelchairs with the assistance of one lower extremity. It allows users to extend one hip to reach the ground without having to slide forward on the seat, thus maintaining a more erect posture. The cushion was evaluated to identify contraindications for its use. Eleven subjects (10 stroke patients and 1 patient with an above-the-knee amputation) were tested on the Hemi Wheelchair Cushion and on a second cushion chosen by their primary occupational therapists. Seat interface pressures, both before and after dynamic movement, sitting balance, and wheelchair mobility were measured for each cushion. An analysis of mean pressure values revealed no significant difference between the cushion (p = .80). Average pressures after dynamic movement showed a statistically significant difference from pressures before activity (p < .05). Subjective evaluation revealed that the Hemi Wheelchair Cushion did not adversely affect sitting balance or wheelchair mobility, and no contraindications for its use were identified. The results of this clinical evaluation indicate that the Hemi Wheelchair Cushion is an economical and appropriate option for wheelchair users who propel themselves with the assistance of one leg.


Use of Tracking and Reminder Systems for Colorectal Cancer Screening in Indian Health Service and Tribal Facilities.
Colorectal cancer (CRC) is a significant cause of morbidity and mortality among American Indian/Alaska Native (AI/AN) people. Screening at recommended intervals can detect CRC in its early, most treatable stages, or prevent CRC through removal of precancerous polyps. However, CRC screening percentages remain low among AI/AN people. Reminder and tracking systems can be used to improve CRC screening percentages. In this study we assessed the prevalence of CRC screening reminder and tracking systems in Indian Health Service (IHS), Tribal, or Urban (I/T/U) health facilities. A telephone survey of randomly selected small, medium and large I/T/U health facilities nationwide was conducted. Three health facilities from each of the 12 IHS areas nationwide were selected from a list of I/T/U healthcare facilities that provide CRC screening or refer patients to another facility for screening, with the goal of having one small, one medium, and one large I/T/U health facility from each IHS area. Thirty-four facilities (94%) participated in the telephone survey between April 1 and September 24, 2010. All facilities used the IHS Resource and Patient Management System to manage their patient care, and 82% used the Electronic Health Record (EHR) version. Over half of these facilities (55%) performed in-office fecal occult blood tests (FOBT) collected during a digital rectal exam, all of which reported that they also sent FOBT cards home with patients. Fifty-three percent of facilities used an opportunistic, visit-based approach to CRC screening. Nearly a third (32%) of facilities reported using a reminder system to notify patients that they were due for CRC screening. Almost two-thirds (65%) of facilities used a reminder system to notify health care providers that patients were due for CRC screening. While 73% of facilities used a system to track whether patients were due for CRC screening, only 61% used a system to track patient results for CRC screening, and 42% used a system to track patients with a personal history of polyps or CRC. A majority of facilities performed in-office FOBT tests using a digital rectal exam, which is a practice that is contrary to national CRC screening recommendations. Additionally, the majority of facilities reported not using an organized system for CRC screening. Use of patient reminders was suboptimal. However, facilities did report use of provider reminders, tracking when patients were due for CRC screening, and tracking CRC screening results. As the EHR system becomes more widely used and established, I/T/U facilities could be encouraged to increase their use of the EHR tools available to aid in systematically increasing CRC screening percentages.


Stability-based sorting: The forgotten process behind (not only) biological evolution.
Natural selection is considered to be the main process that drives biological evolution. It requires selected entities to originate dependent upon one another by the means of reproduction or copying, and for the progeny to inherit the qualities of their ancestors. However, natural selection is a manifestation of a more general persistence principle, whose temporal consequences we propose to name "stability-based sorting" (SBS). Sorting based on static stability, i.e., SBS in its strict sense and usual conception, favours characters that increase the persistence of their holders and act on all material and immaterial entities. Sorted entities could originate independently from each other, are not required to propagate and need not exhibit heredity. Natural selection is a specific form of SBS-sorting based on dynamic stability. It requires some form of heredity and is based on competition for the largest difference between the speed of generating its own copies and their expiration. SBS in its strict sense and selection thus have markedly different evolutionary consequences that are stressed in this paper. In contrast to selection, which is opportunistic, SBS is able to accumulate even momentarily detrimental characters that are advantageous for the long-term persistence of sorted entities. However, it lacks the amplification effect based on the preferential propagation of holders of advantageous characters. Thus, it works slower than selection and normally is unable to create complex adaptations. From a long-term perspective, SBS is a decisive force in evolution-especially macroevolution. SBS offers a new explanation for numerous evolutionary phenomena, including broad distribution and persistence of sexuality, altruistic behaviour, horizontal gene transfer, patterns of evolutionary stasis, planetary homeostasis, increasing ecosystem resistance to disturbances, and the universal decline of disparity in the evolution of metazoan lineages. SBS acts on all levels in all biotic and abiotic systems. It could be the only truly universal evolutionary process, and an explanatory framework based on SBS could provide new insight into the evolution of complex abiotic and biotic systems.


Training recruiters to randomized trials to facilitate recruitment and informed consent by exploring patients' treatment preferences.
Patients' treatment preferences are often cited as barriers to recruitment in randomized controlled trials (RCTs). We investigated how RCT recruiters reacted to patients' treatment preferences and identified key strategies to improve informed decision-making and trial recruitment. Audio-recordings of 103 RCT recruitment appointments with 96 participants in three UK multicenter pragmatic RCTs were analyzed using content and thematic analysis. Recruiters' responses to expressed treatment preferences were assessed in one RCT (ProtecT - Prostate testing for cancer and Treatment) in which training on exploring preferences had been given, and compared with two other RCTs where this specific training had not been given. Recruiters elicited treatment preferences similarly in all RCTs but responses to expressed preferences differed substantially. In the ProtecT RCT, patients' preferences were not accepted at face value but were explored and discussed at length in three key ways: eliciting and acknowledging the preference rationale, balancing treatment views, and emphasizing the need to keep an open mind and consider all treatments. By exploring preferences, recruiters enabled participants to become clearer about whether their views were robust enough to be sustained or were sufficiently weak that participation in the RCT became possible. Conversely, in the other RCTs, treatment preferences were often readily accepted without further discussion or understanding the reasoning behind them, suggesting that patients were not given the opportunity to fully consider all treatments and trial participation. Recruiters can be trained to elicit and address patients' treatment preferences, enabling those who may not have considered trial participation to do so. Without specific guidance, some RCT recruiters are likely to accept initial preferences at face value, missing opportunities to promote more informed decision-making. Training interventions for recruiters that incorporate key strategies to manage treatment preferences, as in the ProtecT study, are required to facilitate recruitment and informed consent. ProtecT RCT: Current Controlled Trials ISRCTN20141297. The other two trials are registered but have asked to be anonymized.


Biophotonic in situ sensor for plant leaves.
Knowledge of the water concentration of plants can be helpful in several environmental and agricultural domains. There are many methods for the determination of water content in plant leaves; however, most of them give a relative moisture level or an analytical measure after a previous calibration procedure. Even for other biochemical compounds such as dry matter or chlorophyll, the measurement techniques could be destructive. For this reason, a nondestructive method has been developed to measure the biochemical compounds of a plant leaf, using an infrared spectroscopy technique. One important advantage is the simplicity of the device (RAdiomètre portatif de Mesure In Situ, RAMIS) and its capability to perform measurements in situ. The prototype is a leaf-clip configuration and is made of LEDs at five wavelengths (656, 721, 843, 937, and 1550 nm), and a silicon/germanium photosensor. To compute the water content of vegetative leaves, the radiative transfer model PROSPECT was implemented. This model can accurately predict spectral transmittances in the 400 nm to 2500 nm spectral region as a function of the principal leaf biochemical contents: water, dry matter, and chlorophyll. Using the transmittance measured by RAMIS into an inversion procedure of A Model of Leaf Optical Properties Spectra, we are able to compute the values of water contents that show an agreement with the water contents measured directly using dry weight procedures. This method is presented as a possibility to estimate other leaf biochemical compounds using appropriate wavelengths.


Lobular neoplasia detected in MRI-guided core biopsy carries a high risk for upgrade: a study of 63 cases from four different institutions.
There are certain criteria to recommend surgical excision for lobular neoplasia diagnosed in mammographically detected core biopsy. The aims of this study are to explore the rate of upgrade of lobular neoplasia detected in magnetic resonance imaging (MRI)-guided biopsy and to investigate the clinicopathological and radiological features that could predict upgrade. We reviewed 1655 MRI-guided core biopsies yielding 63 (4%) cases of lobular neoplasia. Key clinical features were recorded. MRI findings including mass vs non-mass enhancement and the reason for biopsy were also recorded. An upgrade was defined as the presence of invasive carcinoma or ductal carcinoma in situ in subsequent surgical excision. The overall rate of lobular neoplasia in MRI-guided core biopsy ranged from 2 to 7%, with an average of 4%. A total of 15 (24%) cases had an upgrade, including 5 cases of invasive carcinoma and 10 cases of ductal carcinoma in situ. Pure lobular neoplasia was identified in 34 cases, 11 (32%) of which had upgrade. In this group, an ipsilateral concurrent or past history of breast cancer was found to be associated with a higher risk of upgrade (6/11, 55%) than contralateral breast cancer (1 of 12, 8%; P=0.03). To our knowledge, this is the largest series of lobular neoplasia diagnosed in MRI-guided core biopsy. The incidence of lobular neoplasia is relatively low. Lobular neoplasia detected in MRI-guided biopsy carries a high risk for upgrade warranting surgical excision. However, more cases from different types of institutions are needed to verify our results.


Helminthostachys zeylanica alleviates hepatic steatosis and insulin resistance in diet-induced obese mice.
Obesity and its associated health conditions, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are worldwide health problems. It has been shown that insulin resistance is associated with increased hepatic lipid and causes hepatic steatosis through a myriad of mechanisms, including inflammatory signaling. Helminthostachys zeylanica (HZ) is used widely as a common herbal medicine to relieve fever symptoms and inflammatory diseases in Asia. In the present study, we evaluated whether HZ has therapeutic effects on obesity, NAFLD and insulin resistance. The protective effects of HZ extract were examined using free fatty acid-induced steatosis in human HuS-E/2 cells and a high-fat diet-induced NAFLD in mice. The major components of the HZ extract are ugonins J and K, confirmed by HPLC. Incubation of human hepatocytes, HuS-E/2 cells, with palmitate markedly increased lipid accumulation and treatment with the HZ extract significantly decreased lipid deposition and facilitated AMPK and ACC activation. After 12 weeks of a high-fat diet with HZ extract treatment, the HFD mice were protected from hyperlipidemia and hyperglycemia. HZ extract prevented body weight gain, adipose tissue expansion and adipocyte hypertrophy in the HFD mice. In addition, fat accumulation was reduced in mice livers. Moreover, the insulin sensitivity-associated index, which evaluates insulin function, was also significantly restored. These results suggest that HZ has a promising pharmacological effect on high-fat diet-induced obesity, hepatic steatosis and insulin resistance, which may have the potential for clinical application.


Fatty liver is a good indicator of subclinical atherosclerosis risk in obese children and adolescents regardless of liver enzyme elevation.
To investigate the presence of association between nonalcoholic fatty liver disease (NAFLD) and subclinical atherosclerosis using carotid intima media thickness (c-IMT) in obese children and adolescents. Additionally, we wished to investigate the relationship between fatty liver and elevated liver enzymes. A total of 157 obese patients (78 boys and 79 girls, mean age: 11.3 ± 2.6 years, age range: 6-16 years) were enrolled in the study. Aminotransferase, fasting glucose and lipid levels were determined. An oral glucose tolerance test was performed. The c-IMT was measured. Infectious and metabolic causes of elevated liver enzymes were excluded. The diagnosis of NAFLD was based on ultrasound scan. Obese patients with NAFLD had markedly increased carotid IMT (mean: 0.48 mm, 95% CI: 0.47-0.49) than those without NAFLD (mean: 0.45 mm 95% CI: 0.44-0.45, p < 0.001). The presence of NAFLD significantly increased c-IMT whether the patient had elevated liver enzyme or not (ANOVA, p < 0.001). In a multiple-regression model, only the presence of NAFLD was associated with increased c-IMT (β = 0.031, SE (β) = 0.008, p < 0.001). Obese children and adolescents with NAFLD are at risk of early atherosclerotic changes. As liver function tests are not sufficient to identify patients with fatty liver, ultrasonographic evaluation of NAFLD might be considered in all obese children and adolescents.


Modulated thermal conductivity of 2D hexagonal boron arsenide: a strain engineering study.
On-going prediction and synthesis of two-dimensional materials attract remarkable attention to engineer high performance intended devices. Through this, comprehensive and detailed uncovering of the material properties could be accelerated to achieve this goal. Hexagonal boron arsenide (h-BAs), a graphene counterpart, is among the most attractive 2D semiconductors. In this work, our objective is to explore the mechanical, electronic, and thermal properties of h-BAs. We found that this novel 2D material can show a high elastic modulus of 260 GPa, which is independent of the loading direction. We also observed that this system shows a direct and narrow band-gap of 1.0 eV, which is highly desirable for electronic applications. The focus of our investigation is to gain an in-depth understanding of the thermal transport along the monolayer h-BAs and further tune the thermal conductivity by strain engineering. In this regard, the thermal conductivity of a stress-free and pristine monolayer was predicted to be 180.2 W m-1 K-1, which can be substantially enhanced to 375.0 W m-1 K-1 and 406.2 W m-1 K-1, with only 3% straining along the armchair and zigzag directions, respectively. The underlying mechanism for such a remarkable boosting of thermal conductivity in h-BAs was correlated to the fact that stretching makes the flexural out-of-plane mode the dominant heat carrier. Our results not only improve the understanding concerning the heat transfer in h-BAs nanosheets but also offer possible new routes to drastically improve the thermal conductivity, which can play critical roles in thermal management systems.


Towards High Performance Metal-Organic Framework-Microporous Polymer Mixed Matrix Membranes: Addressing Compatibility and Limiting Aging by Polymer Doping.
Membrane separation for gas purification is an energy-efficient and environment-friendly technology. However, the development of high performance membranes is still a great challenge. In principle, mixed matrix membranes (MMMs) have the potential to overcome current materials limitations, but in practice there is no straightforward method to match the properties of fillers and polymers (the main components of MMMs) in such a way that the final membrane performance reflects the high performance of the microporous filler and the processability of the continuous polymer phase. This issue is especially important when high flux polymers are utilized. In this work, we demonstrate that the use of small amounts of a glassy polymer in combination with high performance PIM-1 allow for the preparation of metal-organic framework (MOF)-based MMMs with superior separation properties and low aging rates under humid conditions, meeting the commercial target for post-combustion CO2 capture.


Incomplete punctal canalisation: the external and internal punctal membranes. Outcomes of membranotomy and adjunctive procedures.
To study the clinical and diagnostic profile of punctal dysgenesis with membranes, to classify and correlate the membranes clinicopathologically and study the outcomes of membranotomy. A prospective interventional study involving 55 dysgenetic puncta of 22 consecutive patients seen between July 2008 ansd December 2011. Data collected include demographics, clinical presentation, laterality, age at presentation, duration of symptoms, slit lamp examination, punctal profiles, types of membranes, associated lacrimal anomalies, management and outcomes. All the patients underwent membranotomy, after which the puncta were assessed for adequacy of the opening, the canaliculi were assessed with probes and irrigation was done to assess the patency of the lacrimal system. A minimal follow-up of 6 months was taken for final analysis. Primary outcome measures included were anatomical patency on irrigation and relief from epiphora assessed subjectively and also objectively by a dye disappearance test. The patients included 11 males and 11 females, with a mean age of 82.4 months (range 5-264 months) at presentation. Bilateral punctal involvement was seen in 59% (13/22) and all the four puncta were affected in 31.8% (7/22) of the patients. Epiphora was the most common complaint noted in 95% (21/22), and the symptoms were noticed since birth in 68.1% (15/22). External membranes over the puncta were noted in 86.4% (19/22) and internal punctal membranes in 13.6% (3/22) of patients. All the patients underwent membranotomy, however additional procedures like probing was done in 13.6% (3/22), mini-monoka intubation in 9.1% (2/22), Crawford's bicanalicular intubation in 9.1% (2/22) and dacryocystorhinostomy in 4.5% (1/22). Uniformly, the punctal membranes on histopathological examination were fibrovascular membranes. The anatomical patency was 100% and relief from symptoms was seen in 91% (20/22) of the patients. This study presents the largest series to date (n=55 puncta) exclusively on punctal dysgenesis with membranes and, for the first time, has shown the clinicopathological correlation of these membranes. Incomplete punctal canalisation is probably a better term and this study could be the starting point for further exploration into the etiopathogenesis and genetics of this intriguing congenital disorder.


Structure-Function Analysis of the ϕX174 DNA-Piloting Protein Using Length-Altering Mutations.
Although the ϕX174 H protein is monomeric during procapsid morphogenesis, 10 proteins oligomerize to form a DNA translocating conduit (H-tube) for penetration. However, the timing and location of H-tube formation are unknown. The H-tube's highly repetitive primary and quaternary structures made it amenable to a genetic analysis using in-frame insertions and deletions. Length-altered proteins were characterized for the ability to perform the protein's three known functions: participation in particle assembly, genome translocation, and stimulation of viral protein synthesis. Insertion mutants were viable. Theoretically, these proteins would produce an assembled tube exceeding the capsid's internal diameter, suggesting that virions do not contain a fully assembled tube. Lengthened proteins were also used to test the biological significance of the crystal structure. Particles containing H proteins of two different lengths were significantly less infectious than both parents, indicating an inability to pilot DNA. Shortened H proteins were not fully functional. Although they could still stimulate viral protein synthesis, they either were not incorporated into virions or, if incorporated, failed to pilot the genome. Mutant proteins that failed to incorporate contained deletions within an 85-amino-acid segment, suggesting the existence of an incorporation domain. The revertants of shortened H protein mutants fell into two classes. The first class duplicated sequences neighboring the deletion, restoring wild-type length but not wild-type sequence. The second class suppressed an incorporation defect, allowing the use of the shortened protein. The H-tube crystal structure represents the first high-resolution structure of a virally encoded DNA-translocating conduit. It has similarities with other viral proteins through which DNA must travel, such as the α-helical barrel domains of P22 portal proteins and T7 proteins that form tail tube extensions during infection. Thus, the H protein serves as a paradigm for the assembly and function of long α-helical supramolecular structures and nanotubes. Highly repetitive in primary and quaternary structure, they are amenable to structure-function analyses using in-frame insertions and deletions as presented herein.


Linear No-Threshold Model VS. Radiation Hormesis.
The atomic bomb survivor cancer mortality data have been used in the past to justify the use of the linear no-threshold (LNT) model for estimating the carcinogenic effects of low dose radiation. An analysis of the recently updated atomic bomb survivor cancer mortality dose-response data shows that the data no longer support the LNT model but are consistent with a radiation hormesis model when a correction is applied for a likely bias in the baseline cancer mortality rate. If the validity of the phenomenon of radiation hormesis is confirmed in prospective human pilot studies, and is applied to the wider population, it could result in a considerable reduction in cancers. The idea of using radiation hormesis to prevent cancers was proposed more than three decades ago, but was never investigated in humans to determine its validity because of the dominance of the LNT model and the consequent carcinogenic concerns regarding low dose radiation. Since cancer continues to be a major health problem and the age-adjusted cancer mortality rates have declined by only ∼10% in the past 45 years, it may be prudent to investigate radiation hormesis as an alternative approach to reduce cancers. Prompt action is urged.


Structural basis of ligand recognition in 5-HT3 receptors.
The 5-HT(3) receptor is a pentameric serotonin-gated ion channel, which mediates rapid excitatory neurotransmission and is the target of a therapeutically important class of anti-emetic drugs, such as granisetron. We report crystal structures of a binding protein engineered to recognize the agonist serotonin and the antagonist granisetron with affinities comparable to the 5-HT(3) receptor. In the serotonin-bound structure, we observe hydrophilic interactions with loop E-binding site residues, which might enable transitions to channel opening. In the granisetron-bound structure, we observe a critical cation-π interaction between the indazole moiety of the ligand and a cationic centre in loop D, which is uniquely present in the 5-HT(3) receptor. We use a series of chemically tuned granisetron analogues to demonstrate the energetic contribution of this electrostatic interaction to high-affinity ligand binding in the human 5-HT(3) receptor. Our study offers the first structural perspective on recognition of serotonin and antagonism by anti-emetics in the 5-HT(3) receptor.


The neonatal ilium-metaphyseal drivers and vascular passengers.
At birth the newborn is equipped with a developing locomotor apparatus, which will ultimately become involved in load transfer from the period when the child adopts a sitting posture through to the attainment of a bipedal gait. This load transfer has been considered to influence trabecular bone structural organization by setting up forces, which remodel the internal architecture into a functionally optimized form. However, during the neonatal developmental period the locomotor apparatus is nonweight bearing and instead only supports reflexive movements. Surprisingly, a structural organization has been identified within the internal trabecular architecture and external cortical morphology of the neonatal ilium, which appears to mimic the structural composition of the more mature bone. This study aims to build upon previous qualitative and quantitative investigation of this apparently precocious patterning by further examining structural data obtained from selected volumes of interest within the ilium. Analysis has revealed statistically significant differences in regional trabecular and cortical bone characteristics, which have formed the basis of a possible growth model for the ilium. Volumetric comparison has demonstrated the presence of three progressive "growth regions" and three "restricted growth regions," which appear to relate to metaphyseal and nonmetaphyseal borders of the ilium. Therefore, the structural data and statistical analysis presented in this study challenge the current concept of implied centrifugal ossification within the human ilium and present evidence of an alternative pattern of ossification that is largely dictated and controlled by vascular distribution and growth plate position.


Diversity and phylogeny of basidiomycetous yeasts from plant leaves and soil: Proposal of two new orders, three new families, eight new genera and one hundred and seven new species.
Nearly 500 basidiomycetous yeast species were accepted in the latest edition of The Yeasts: A Taxonomic Study published in 2011. However, this number presents only the tip of the iceberg of yeast species diversity in nature. Possibly more than 99 % of yeast species, as is true for many groups of fungi, are yet unknown and await discovery. Over the past two decades nearly 200 unidentified isolates were obtained during a series of environmental surveys of yeasts in phyllosphere and soils, mainly from China. Among these isolates, 107 new species were identified based on the phylogenetic analyses of nuclear ribosomal DNA (rDNA) [D1/D2 domains of the large subunit (LSU), the small subunit (SSU), and the internal transcribed spacer region including the 5.8S rDNA (ITS)] and protein-coding genes [both subunits of DNA polymerase II (RPB1 and RPB2), the translation elongation factor 1-α (TEF1) and the mitochondrial gene cytochrome b (CYTB)], and physiological comparisons. Forty-six of these belong to 16 genera in the Tremellomycetes (Agaricomycotina). The other 61 are distributed in 26 genera in the Pucciniomycotina. Here we circumscribe eight new genera, three new families and two new orders based on the multi-locus phylogenetic analyses combined with the clustering optimisation analysis and the predicted similarity thresholds for yeasts and filamentous fungal delimitation at genus and higher ranks. Additionally, as a result of these analyses, three new combinations are proposed and 66 taxa are validated.


Physical exercise, neuroplasticity, spatial learning and memory.
There has long been discussion regarding the positive effects of physical exercise on brain activity. However, physical exercise has only recently begun to receive the attention of the scientific community, with major interest in its effects on the cognitive functions, spatial learning and memory, as a non-drug method of maintaining brain health and treating neurodegenerative and/or psychiatric conditions. In humans, several studies have shown the beneficial effects of aerobic and resistance exercises in adult and geriatric populations. More recently, studies employing animal models have attempted to elucidate the mechanisms underlying neuroplasticity related to physical exercise-induced spatial learning and memory improvement, even under neurodegenerative conditions. In an attempt to clarify these issues, the present review aims to discuss the role of physical exercise in the improvement of spatial learning and memory and the cellular and molecular mechanisms involved in neuroplasticity.


Harmonization of malaria rapid diagnostic tests: best practices in labelling including instructions for use.
Rapid diagnostic tests (RDTs) largely account for the scale-up of malaria diagnosis in endemic settings. However, diversity in labelling including the instructions for use (IFU) limits their interchangeability and user-friendliness. Uniform, easy to follow and consistent labelling, aligned with international standards and appropriate for the level of the end user's education and training, is crucial but a consolidated resource of information regarding best practices for IFU and labelling of RDT devices, packaging and accessories is not available. The Roll Back Malaria Partnership (RBM) commissioned the compilation of international standards and regulatory documents and published literature containing specifications and/or recommendations for RDT design, packaging and labelling of in vitro diagnostics (IVD) (which includes RDTs), complemented with a questionnaire based survey of RDT manufacturers and implementers. A summary of desirable RDT labelling characteristics was compiled, which was reviewed and discussed during a RBM Stakeholder consultation meeting and subsequently amended and refined by a dedicated task force consisting of country programme implementers, experts in RDT implementation, IVD regulatory experts and manufacturers. This process led to the development of consensus documents with a list of suggested terms and abbreviations as well as specifications for labelling of box, device packaging, cassettes, buffer bottle and accessories (lancets, alcohol swabs, transfer devices, desiccants). Emphasis was placed on durability (permanent printing or water-resistant labels), legibility (font size, letter type), comprehension (use of symbols) and ease of reference (e.g. place of labelling on the box or cassette packaging allowing quick oversight). A generic IFU template was developed, comprising background information, a template for procedure and reading/interpretation, a selection of appropriate references and a symbol key of internationally recognized symbols together with suggestions about appropriate lay-out, style and readability. The present document together with its additional files compiled proposes best practices in labelling and IFU for malaria RDTs. It is expected that compliance with these best practices will increase harmonization among the different malaria RDT products available on the market and improve their user-friendliness.


Partial gastrectomy for resection of a gastric leiomyoma in a guinea pig (Cavia porcellus).
CASE DESCRIPTION A 4-year-old sexually intact male pet guinea pig (Cavia porcellus) was evaluated for a routine wellness examination. CLINICAL FINDINGS During physical examination, a small mass was palpated in the cranial aspect of the abdomen. Abdominal radiographic and ultrasonographic findings were suggestive of a gastric mass. Cytologic evaluation of a fine-needle aspirate of the mass was indicative of spindle cell proliferation most consistent with a sarcoma. TREATMENT AND OUTCOME The patient was anesthetized, and an exploratory laparotomy and partial gastrectomy were performed to resect the gastric mass. Histologic and immunohistochemical examinations of the mass revealed that it was a gastric leiomyoma. The patient recovered from surgery without complications. No evidence of mass recurrence was observed during an abdominal ultrasonographic examination performed approximately 19 months after surgery. CLINICAL RELEVANCE To our knowledge, this was the first report of the clinical diagnosis and successful surgical treatment of a gastric neoplasm in a guinea pig. Gastric leiomyomas are not uncommon in guinea pigs, and although benign, they can cause clinical signs if they become large enough to impair gastric function. Gastrointestinal surgery should be considered as a treatment option for guinea pigs with similar gastric neoplasms.


Sex-specific associations between life-history traits and a novel reproductive polymorphism in the Pacific field cricket.
Associations between heritable polymorphisms and life-history traits, such as development time or reproductive investment, may play an underappreciated role in maintaining polymorphic systems. This is because selection acting on a particular morph could be bolstered or disrupted by correlated changes in life history or vice versa. In a Hawaiian population of the Pacific field cricket (Teleogryllus oceanicus), a novel mutation (flatwing) on the X-chromosome is responsible for a heritable polymorphism in male wing structure. We used laboratory cricket colonies fixed for male wing morph to investigate whether males and females bearing the flatwing or normal-wing (wild-type) allele differed in their life-history traits. We found that flatwing males developed faster and had heavier testes than normal-wings, whereas flatwing homozygous females developed slower and had lighter reproductive tissues than normal-wing homozygous females. Our results advance our understanding of the evolution of polymorphisms by demonstrating that the genetic change responsible for a reproductive polymorphism can also have consequences for fundamental life-history traits in both males and females.


How vague is vague? A simulation study of the impact of the use of vague prior distributions in MCMC using WinBUGS.
There has been a recent growth in the use of Bayesian methods in medical research. The main reasons for this are the development of computer intensive simulation based methods such as Markov chain Monte Carlo (MCMC), increases in computing power and the introduction of powerful software such as WinBUGS. This has enabled increasingly complex models to be fitted. The ability to fit these complex models has led to MCMC methods being used as a convenient tool by frequentists, who may have no desire to be fully Bayesian. Often researchers want 'the data to dominate' when there is no prior information and thus attempt to use vague prior distributions. However, with small amounts of data the use of vague priors can be problematic. The results are potentially sensitive to the choice of prior distribution. In general there are fewer problems with location parameters. The main problem is with scale parameters. With scale parameters, not only does one have to decide the distributional form of the prior distribution, but also whether to put the prior distribution on the variance, standard deviation or precision. We have conducted a simulation study comparing the effects of 13 different prior distributions for the scale parameter on simulated random effects meta-analysis data. We varied the number of studies (5, 10 and 30) and compared three different between-study variances to give nine different simulation scenarios. One thousand data sets were generated for each scenario and each data set was analysed using the 13 different prior distributions. The frequentist properties of bias and coverage were investigated for the between-study variance and the effect size. The choice of prior distribution was crucial when there were just five studies. There was a large variation in the estimates of the between-study variance for the 13 different prior distributions. With a large number of studies the choice of prior distribution was less important. The effect size estimated was not biased, but the precision with which it was estimated varied with the choice of prior distribution leading to varying coverage intervals and, potentially, to different statistical inferences. Again there was less of a problem with a larger number of studies. There is a particular problem if the between-study variance is close to the boundary at zero, as MCMC results tend to produce upwardly biased estimates of the between-study variance, particularly if inferences are based on the posterior mean. The choice of 'vague' prior distribution can lead to a marked variation in results, particularly in small studies. Sensitivity to the choice of prior distribution should always be assessed.


Cranial irradiation increases risk of stroke in pediatric brain tumor survivors.
The purposes of this study were to determine the incidence of neurovascular events as late complications in pediatric patients with brain tumor and to evaluate radiation as a risk factor. Patients were ascertained using the tumor database of a pediatric tertiary care center. Included patients had a primary brain tumor, age birth to 21 years, initial treatment January 1, 1993, to December 31, 2002, and at least 2 visits with neuro-oncology. Radiation exposure included: whole brain, whole brain plus a focal boost, or focal brain. The primary outcome was stroke or transient ischemic attack. Of 431 subjects, 14 had 19 events of stroke or transient ischemic attack over a median follow-up of 6.3 years. The incidence rate was 548/100 000 person-years. Overall, 61.5% of subjects received radiation, including 13 of 14 subjects with events. Median time from first radiation to first event was 4.9 years. The stroke/transient ischemic attack hazard ratio for any brain irradiation was 8.0 (95% CI, 1.05-62; P=0.045); for the circle of Willis, radiation was 9.0 (95% CI, 1.2-70; P=0.035); and for focal noncircle of Willis, radiation was 3.4 (95% CI, 0.21-55; P=0.38). The incidence of neurovascular events in this population is 100-fold higher than in the general pediatric population and cranial irradiation is an important risk factor. By defining the incidence of this late effect, physicians are better able to counsel parents regarding treatment, monitor patients at risk, and target a population for primary stroke prevention in future studies.


Access to health care in post-apartheid South Africa: availability, affordability, acceptability.
We use a reliable, intuitive and simple set of indicators to capture three dimensions of access - availability, affordability and acceptability. Data are from South Africa's 2009 and 2010 General Household Surveys (n=190,164). Affordability constraints were faced by 23% and are more concentrated amongst the poorest. However, 73% of affordability constraints are due to travel costs which are aligned with findings of the availability constraints dimension. Availability constraints, involving distances and transport costs, particularly in underdeveloped rural areas, and inconvenient opening times, were faced by 27%. Acceptability constraints were noted by only 10%. We approximate acceptability with an indicator measuring the share of community members bypassing the closest health care facility, as we argue that reported health care provider choice is more reliable than stated preferences. However, the indicator assumes a choice of available and affordable providers, which may often not be an accurate assumption in rural areas. We recommend further work on the measurement of acceptability in household surveys, especially considering this dimension's importance for health reform.


The relative influences of host plant genotype and yearly abiotic variability in determining herbivore abundance.
Both plant genotype and yearly abiotic variation affect herbivore population sizes, but long-term data have rarely been used to contrast the relative contributions of each. Using a hierarchical Bayesian model, we directly compare effects of these two factors on the population size of a common herbivore, Aceria parapopuli, on Populus angustifolia × fremontii F(1) hybrid trees growing in a common garden across 8 years. Several patterns emerged. First, the Bayesian posterior estimates of tree genotype effects on mite gall number ranged from 0.0043 to 229 on a linear scale. Second, year effect sizes across 8 years of study ranged from 0.133 to 1.895. Third, in comparing the magnitudes of genotypic versus yearly variation, we found that genotypic variation was over 130 times greater than variation among years. Fourth, precipitation in the previous year negatively affected gall abundances, but was minimal compared to tree genotype effects. These findings demonstrate the relative importance of tree genotypic variation in determining herbivore population size. However, given the demonstrated sensitivity of cottonwoods to drought, the loss of individual tree genotypes from an altered climate would have catastrophic impacts on mites that are dependent upon these genotypes for their survival.


Modelling the elimination of hepatitis C as a public health threat in Iceland: A goal attainable by 2020.
In Iceland a nationwide program has been launched offering direct-acting antiviral (DAA) treatment for everyone living with hepatitis C virus (HCV). We estimate (i) the time and treatment scale-up required to achieve the World Health Organization's HCV elimination target of an 80% reduction in incidence; and (ii) the ongoing frequency of HCV testing and harm reduction coverage among people who inject drugs (PWID) required to minimize the likelihood of future HCV outbreaks occurring. We used a dynamic compartmental model of HCV transmission, liver disease progression and the HCV cascade of care, calibrated to reproduce the epidemic of HCV in Iceland. The model was stratified according to injecting drug use status, age and stage of engagement. Four scenarios were considered for the projections. The model estimated that an 80% reduction in domestic HCV incidence was achievable by 2030, 2025 or 2020 if a minimum of 55/1,000, 75/1,000 and 188/1,000 PWID were treated per year, respectively (a total of 22, 30 and 75 of the estimated 400 PWID in Iceland per year, respectively). Regardless of time frame, this required an increased number of PWID to be diagnosed to generate enough treatment demand, or a 20% scale-up of harm reduction services to complement treatment-as-prevention incidence reductions. When DAA scale-up was combined with annual antibody testing of PWID, the incidence reduction target was reached by 2024. Treatment scale-up with no other changes to current testing and harm reduction services reduced the basic reproduction number of HCV from 1.08 to 0.59, indicating that future outbreaks would be unlikely. HCV elimination in Iceland is achievable by 2020 with some additional screening of PWID. Maintaining current monitoring and harm reduction services while providing ongoing access to DAA therapy for people diagnosed with HCV would ensure that outbreaks are unlikely to occur once elimination targets have been reached. In Iceland, a nationwide program has been launched offering treatment for the entire population living with hepatitis C virus (HCV). A mathematical model was used to estimate the additional health system requirements to achieve the HCV elimination targets of the World Health Organization (WHO), as well as the year that this could occur. With some additional screening of people who inject drugs, Iceland could reach the WHO targets by 2020, becoming one of the first countries to achieve HCV elimination. The model estimated that once elimination targets were reached, maintaining current monitoring and harm reduction services while providing ongoing access to DAA therapy for people diagnosed with HCV would ensure that future HCV outbreaks are unlikely to occur.


Inhibition of Bone Marrow-Derived Mesenchymal Stem Cells Homing Towards Triple-Negative Breast Cancer Microenvironment Using an Anti-PDGFRβ Aptamer.
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are shown to participate in tumor progression by establishing a favorable tumor microenvironment (TME) that promote metastasis through a cytokine networks. However, the mechanism of homing and recruitment of BM-MSCs into tumors and their potential role in malignant tissue progression is poorly understood and controversial. Here we show that BM-MSCs increase aggressiveness of triple-negative breast cancer (TNBC) cell lines evaluated as capability to migrate, invade and acquire stemness markers. Importantly, we demonstrate that the treatment of BM-MSCs with a nuclease-resistant RNA aptamer against platelet-derived growth factor receptor β (PDGFRβ) causes the inhibition of receptor-dependent signaling pathways thus drastically hampering BM-MSC recruitment towards TNBC cell lines and BM-MSCs trans-differentiation into carcinoma-associated fibroblast (CAF)-like cells. Moreover, in vivo molecular imaging analysis demonstrated the aptamer ability to prevent BM-MSCs homing to TNBC xenografts. Collectively, our results indicate the anti-PDGFRβ aptamer as a novel therapeutic tool to interfere with BM-MSCs attraction to TNBC providing the rationale to further explore the aptamer in more complex pre-clinical settings.


Massive global ozone loss predicted following regional nuclear conflict.
We use a chemistry-climate model and new estimates of smoke produced by fires in contemporary cities to calculate the impact on stratospheric ozone of a regional nuclear war between developing nuclear states involving 100 Hiroshima-size bombs exploded in cities in the northern subtropics. We find column ozone losses in excess of 20% globally, 25-45% at midlatitudes, and 50-70% at northern high latitudes persisting for 5 years, with substantial losses continuing for 5 additional years. Column ozone amounts remain near or <220 Dobson units at all latitudes even after three years, constituting an extratropical "ozone hole." The resulting increases in UV radiation could impact the biota significantly, including serious consequences for human health. The primary cause for the dramatic and persistent ozone depletion is heating of the stratosphere by smoke, which strongly absorbs solar radiation. The smoke-laden air rises to the upper stratosphere, where removal mechanisms are slow, so that much of the stratosphere is ultimately heated by the localized smoke injections. Higher stratospheric temperatures accelerate catalytic reaction cycles, particularly those of odd-nitrogen, which destroy ozone. In addition, the strong convection created by rising smoke plumes alters the stratospheric circulation, redistributing ozone and the sources of ozone-depleting gases, including N(2)O and chlorofluorocarbons. The ozone losses predicted here are significantly greater than previous "nuclear winter/UV spring" calculations, which did not adequately represent stratospheric plume rise. Our results point to previously unrecognized mechanisms for stratospheric ozone depletion.


High biodiversity in a benzene-degrading nitrate-reducing culture is sustained by a few primary consumers.
A key question in microbial ecology is what the driving forces behind the persistence of large biodiversity in natural environments are. We studied a microbial community with more than 100 different types of species which evolved in a 15-years old bioreactor with benzene as the main carbon and energy source and nitrate as the electron acceptor. Using genome-centric metagenomics plus metatranscriptomics, we demonstrate that most of the community members likely feed on metabolic left-overs or on necromass while only a few of them, from families Rhodocyclaceae and Peptococcaceae, are candidates to degrade benzene. We verify with an additional succession experiment using metabolomics and metabarcoding that these few community members are the actual drivers of benzene degradation. As such, we hypothesize that high species richness is maintained and the complexity of a natural community is stabilized in a controlled environment by the interdependencies between the few benzene degraders and the rest of the community members, ultimately resulting in a food web with different trophic levels.


Single-photon detection beyond 1 µm: performance of commercially available germanium photodiodes.
Germanium avalanche photodiodes (APD's) working biased above the breakdown voltage detect single optical photons in the near-infrared wavelength range. We give guidelines for the selection of devices suitable for photon-counting applications among the commercial samples, and we discuss in detail how the devices should be operated to achieve the best performance, both in terms of noise-equivalent power (NEP) and the timing-equivalent bandwidth. We introduce the driving electronics and we show that, in the measurements of fast optical signals, the adoption of single-photon techniques is very favorable, notwithstanding that presently available photodiodes are not designed for this purpose. On the contrary, in the detection of cw signals, the lower NEP values achieved in photon counting may not be sufficient to justify the replacement of conventional analog p-i-n germanium detectors, which offer comparable performance with a definitely larger sensitive area. Finally, we show that, by properly choosing theoperating conditions, some selected APD's achieve an 85-ps time resolution in the detection of optical photons at a 1.3-µm wavelength, which corresponds to a timing-equivalent bandwidth of 1.8 GHz. To the best of our knowledge, this time resolution is the lowest reported to date for single-photon detectors in the near infrared.


Malignant Otitis Externa is Associated with Diabetes: A Population-Based Case-Control Study.
Despite studies reporting a possible association between malignant otitis externa (MOE) and diabetes, there are no large-scale population-based empirical studies. This nationwide, population-based case-control study explored the association of MOE occurrence with previously diagnosed diabetes. Data were retrieved from Taiwan's National Health Insurance Research Database, 753 patients with MOE (cases) and 2 259 propensity score-matched patients without MOE (controls). Multiple logistic regressions were conducted to examine the association of MOE with previously diagnosed diabetes. In total, 728 (24.2%) out of 3 012 sample patients had diabetes prior to the index date. Chi-square test revealed a significant difference in diabetes prevalence among cases and controls (54.8% vs 13.9%, p < 0.001). Simple logistic regression showed the odds ratio for prior diabetes among cases versus controls was 7.50 (95% CI, 6.22~9.03). The adjusted odds ratio of prior diabetes for cases versus controls was 10.07 (95% CI, 8.15~12.44) after adjusting for patient demographics and medical co-morbidities. This study found an association between MOE and diabetes. One clinical practice implication of our study is that when a patient with diabetes complains of otalgia or otorrhea, and physical examination shows swelling of the ear canal or granulation growth, physicians should consider the possibility of MOE.


High relaxivity and stability of a hydroxyquinolinate-based tripodal monoaquagadolinium complex for use as a bimodal MRI/optical imaging agent.
An octadentate ligand based on triazacyclononane and 8-hydroxyquinolinate/phenolate binding units leads to very soluble, highly stable lanthanide complexes. The monoaquagadolinium complex shows a high relaxivity as a result of the unusually long rotational correlation time, fast water exchange rate, and slow electronic relaxation. The ligand also acts as sensitizer of the near-IR luminescence emission of the Yb and Nd ions. It appears as an excellent candidate for use as a bimodal imaging agent.


Cigarette smoke cadmium breakthrough from traditional filters: implications for exposure.
Cadmium, a carcinogenic metal, is highly toxic to renal, skeletal, nervous, respiratory and cardiovascular systems. Accurate and precise quantification of mainstream smoke cadmium levels in cigarette smoke is important because of exposure concerns. The two most common trapping techniques for collecting mainstream tobacco smoke particulate for analysis are glass fiber filters and electrostatic precipitators. We observed that a significant portion of total cadmium passed through standard glass fiber filters that are used to trap particulate matter. We therefore developed platinum traps to collect the cadmium that passed through the filters and tested a variety of cigarettes with different physical parameters for quantities of cadmium that passed though the filters. We found <1% cadmium passed through electrostatic precipitators. In contrast, cadmium that passed through 92 mm glass fiber filters on a rotary smoking machine was significantly higher, ranging from 3.5 to 22.9% of total smoke cadmium deliveries. Cadmium passed through 44 mm filters typically used on linear smoking machines to an even greater degree, ranging from 13.6 to 30.4% of the total smoke cadmium deliveries. Differences in the cadmium that passed through from the glass fiber filters and electrostatic precipitator could be explained in part if cadmium resides in the smaller mainstream smoke aerosol particle sizes. Differences in particle size distribution could have toxicological implications and could help explain the pulmonary and cardiovascular cadmium uptake in smokers.


Correlation of IgE/IgG4 milk epitopes and affinity of milk-specific IgE antibodies with different phenotypes of clinical milk allergy.
Results from large-scale epitope mapping with a peptide microarray have been shown to correlate with clinical features of milk allergy. We sought to assess IgE and IgG4 epitope diversity and IgE affinity in different clinical phenotypes of milk allergy and identify informative epitopes that might be predictive of clinical outcomes of milk allergy. Forty-one subjects were recruited from a larger study on the effects of ingesting heat-denatured milk proteins in subjects with milk allergy. Using food challenges, subjects were characterized as being clinically reactive to all forms of milk (n = 17), being tolerant to heated milk (HM) products (n = 16), or having outgrown their milk allergy (n = 8). Eleven healthy volunteers without milk allergy served as control subjects. A peptide microarray was performed by using the previously published protocol. Subjects with milk allergy had increased epitope diversity compared with those who outgrew their allergy. HM-tolerant subjects had IgE-binding patterns similar to those who had outgrown their allergy, but IgG4-binding patterns that were more similar to those of the allergic group. Binding to higher numbers of IgE peptides was associated with more severe allergic reactions during challenge. There was no association between IgG4 peptides and clinical features of milk allergy. Using a competitive peptide microarray assay, allergic patients demonstrated a combination of high- and low-affinity IgE binding, whereas HM-tolerant subjects and those who had outgrown their milk allergy had primarily low-affinity binding. Greater IgE epitope diversity and higher affinity, as determined by using the peptide microarray, were associated with clinical phenotypes and severity of milk allergy.


Adjunctive bright light treatment with gradual advance in unipolar major depressive disorder with evening chronotype - A randomized controlled trial.
Unipolar non-seasonal depressed patients with concomitant evening chronotype were associated with poor clinical outcomes and higher non-remission rate. This study aims to examine the efficacy of adjunctive bright light therapy with gradual timing advance in a randomized, assessor and prescriber-blinded controlled trial. Participants were randomly allocated to receive 5 weeks of either bright white light therapy (BLT) or dim red light (DRL) with the same advancement protocol. Participants were followed up till 5 months after treatment. Primary outcomes included (i) remission rate and (ii) the severity of depression. The analysis was conducted using Kaplan-Meier survival analysis, Cox proportional hazard analysis and linear mixed models. A total of 93 participants (46.4 ± 11.7 years old, 80% female) were randomized. The cumulative remission rate for the BLT and the DRL groups was 67.4% and 46.7%, respectively. Time to remission was shorter for the BLT group relative to the DRL group (log-rank test p = 0.024). Cox proportional hazard survival analysis showed that patients in the BLT group had a higher probability of achieving remission relative to patients in the DRL group [hazard ratio = 1.9 (95% CI = 1.1- 3.4), p = 0.026]. Further sensitivity analysis demonstrated greater improvement in 17-Hamilton Depression Score (group × time interaction, p = 0.04) in the BLT group for those who were adherent to light therapy. The use of bright light therapy with gradual advance protocol is an effective adjunctive treatment resulting in quicker and a higher rate of remission of depression in patients with non-seasonal unipolar depression and evening-chronotype.


Use of acupuncture in the control of chemotherapy-induced nausea and vomiting.
Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and feared side effects of chemotherapy. Despite recent advances in pharmacologic antiemetic therapy, additional treatment for breakthrough CINV is needed. Acupuncture is a safe medical procedure with minimal side effects; several randomized controlled clinical trials have suggested its efficacy in controlling this side effect. A recent meta-analysis of those trials demonstrated that acupuncture significantly reduced the proportion of patients experiencing acute chemotherapy-induced vomiting. Those trials, however, did not show that acupuncture significantly alleviated acute chemotherapy-induced nausea or delayed CINV. The clinical relevance of these results were limited by the fact that they predated the use of aprepitant and that only 1 or 2 acupuncture points were stimulated during acupuncture treatment. More clinical trials to study the effect of acupuncture with additional antiemetic acupuncture points in adjunct to modern pharmacologic antiemetic therapy are needed.


Isolation and identification of novel antibacterial peptides produced by Lactobacillus fermentum SHY10 in Chinese pickles.
The aim of this study was to isolate and identify antibacterial peptides (ABPs) produced by lactic acid bacteria (LAB) in Chinese pickles. The cell-free supernatant collected from the culture of LAB with antibacterial activity against Staphylococcus aureus was used to purify ABPs. A total of 14 strains of LAB were found to have antibacterial activity. Among them, Lactobacillus fermentum (L. fermentum) SHY10 exhibited the most effective antibacterial activity. The antibacterial activity of cell-free supernatant reached the highest level after 20 h of L. fermentum SHY10 culture. Three novel ABPs were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In particular, the NQGPLGNAHR peptide showed antibacterial activity with an IC50 value of 0.957 mg/mL. In addition, molecular docking analysis revealed that this peptide interacted with DNA gyrase and dihydrofolate reductase by salt bridge formation, hydrogen bond interactions, and metal contact.


Characterization of Root-Knot Nematode Resistance in Medicago truncatula.
Root knot (Meloidogyne spp.) and cyst (Heterodera and Globodera spp.) nematodes infect all important crop species, and the annual economic loss due to these pathogens exceeds $90 billion. We screened the worldwide accession collection with the root-knot nematodes Meloidogyne incognita, M. arenaria and M. hapla, soybean cyst nematode (SCN-Heterodera glycines), sugar beet cyst nematode (SBCN-Heterodera schachtii) and clover cyst nematode (CLCN-Heterodera trifolii), revealing resistant and susceptible accessions. In the over 100 accessions evaluated, we observed a range of responses to the root-knot nematode species, and a non-host response was observed for SCN and SBCN infection. However, variation was observed with respect to infection by CLCN. While many cultivars including Jemalong A17 were resistant to H. trifolii, cultivar Paraggio was highly susceptible. Identification of M. truncatula as a host for root-knot nematodes and H. trifolii and the differential host response to both RKN and CLCN provide the opportunity to genetically and molecularly characterize genes involved in plant-nematode interaction. Accession DZA045, obtained from an Algerian population, was resistant to all three root-knot nematode species and was used for further studies. The mechanism of resistance in DZA045 appears different from Mi-mediated root-knot nematode resistance in tomato. Temporal analysis of nematode infection showed that there is no difference in nematode penetration between the resistant and susceptible accessions, and no hypersensitive response was observed in the resistant accession even several days after infection. However, less than 5% of the nematode population completed the life cycle as females in the resistant accession. The remainder emigrated from the roots, developed as males, or died inside the roots as undeveloped larvae. Genetic analyses carried out by crossing DZA045 with a susceptible French accession, F83005, suggest that one gene controls resistance in DZA045.


Assessing transcription factor motif drift from noisy decoy sequences.
Genome scale identification of transcription factor binding sites (TFBS) is fundamental to understanding the complexities of mRNA expression at both the cell and organismal levels. While high-throughput experimental methods provide associations between transcription factors and the genes they regulate under a specified experimental condition, computational methods are still required to pinpoint the exact location of binding. Moreover, since the binding site is an intrinsic property of the promoter region, computational methods are in principle more general than condition dependent experimental methods. Computational identification of TFBSs is complicated in at least two different ways. First, transcription factors bind a heterogeneous distribution of sites and therefore have a distribution of affinities. Second, the set of sequences for which a common site is to be determined do not all have a site for the TF of interest. In this paper, we evaluate the robustness of TFBS identification with respect to both effects. We show addition of upstream regions that do not have the TFBS destroy the specificity of the predicted binding site. We also propose a method to calculate the distance between position weight matrices that can be used to measure "drift'' from the canonical binding site. The results presented here could be useful in developing future transcription factor binding site identification algorithms.


Evaluation of a rebound tonometer (Tonovet) in clinically normal cat eyes.
To determine the accuracy of and to establish reference values for a rebound tonometer (Tonovet) in normal feline eyes, to compare it with an applanation tonometer (Tonopen Vet) and to evaluate the effect of topical anesthesia on rebound tonometry. Six enucleated eyes were used to compare both tonometers with direct manometry. Intraocular pressure (IOP) was measured in 100 cats to establish reference values for rebound tonometry. Of these, 22 cats were used to compare rebound tonometry with and without topical anesthesia and 33 cats to compare the rebound and applanation tonometers. All evaluated eyes were free of ocular disease. Both tonometers correlated well with direct manometry. The best agreement with the rebound tonometer was achieved between 25-50 mmHg. The applanation tonometer was accurate at pressures between 0 and 30 mmHg. The mean IOP in clinically normal cats was 20.74 mmHg with the rebound tonometer and 18.4 mmHg with the applanation tonometer. Topical anesthesia did not significantly affect rebound tonometry. As the rebound tonometer correlated well with direct manometry in the clinically important pressure range and was well tolerated by cats, it appears suitable for glaucoma diagnosis. The mean IOP obtained with the rebound tonometer was 2-3 mmHg higher than that measured with the applanation tonometer. This difference is within clinically acceptable limits, but indicates that the same type of tonometer should be used in follow-up examinations in a given cat.


A prospective evaluation of ultrasonography for the diagnosis of penetrating torso injury.
Ultrasound (US) is commonly used for the diagnosis of hemoperitoneum after blunt abdominal trauma, but the value of US as an aid for identification of operative lesions after penetrating trauma is not well documented. The purpose of this investigation was to determine the accuracy of US for the evaluation of penetrating torso trauma and to assess the impact of this information on patient management. We conducted a prospective cohort observational study of consecutive penetrating torso patients at a Level I trauma center. During the 6-month trial period, 177 victims of penetrating torso trauma were assessed by our trauma teams. Ninety-two patients had stab wounds, 84 patients had gunshot wounds, and 1 patient had a puncture wound. All 28 patients with positive US examination had an exploratory laparotomy or thoracotomy (one patient had more than one procedure), resulting in 26 therapeutic operations. There were 149 negative US examinations, but in this group, 36 patients underwent laparotomy or thoracotomy, and 28 had therapeutic operations. The overall accuracy of the US examination was therefore 85%, the sensitivity was 48%, and the specificity was 98%. There were only three patients who had their initial management altered by a positive US examination. The US examination lacks sensitivity to be used alone in determining operative intervention after gunshot or stab wounds. Rarely does US information contribute to the management of patients with penetrating abdominal injuries.


Childhood household dysfunction, school performance and psychiatric care utilisation in young adults: a register study of 96 399 individuals in Stockholm County.
Exposure to childhood household dysfunction increases the risk of psychiatric morbidity. Although school performance also has been linked with psychiatric morbidity, limited research has considered school performance as a mediating factor. To address this gap in the literature, the current register study examined whether school performance mediates the association between childhood household dysfunction (experienced between birth and age 14 years) and psychiatric care utilisation in young adulthood. We used a Swedish cohort of 96 399 individuals born during 1987-1991. Indicators of childhood household dysfunction were familial death, parental substance abuse and psychiatric morbidity, parental somatic disease, parental criminality, parental separation/single-parent household, public assistance recipiency and residential instability. Final school grades from the 9th year of compulsory school were used to create five categories. Estimates of risk of psychiatric care utilisation (measured as inpatient, outpatient and primary care) after the age of 18 years were calculated as HRs with 95% CIs. Mediation was tested with the bootstrap approach. Cumulative exposure to childhood household dysfunction was positively associated with psychiatric care utilisation. Specifically, individuals exposed to three or more indicators with incomplete school grades had the highest risk (HR=3.7 (95% CI 3.3 to 4.1) after adjusting for demographics), compared to individuals exposed to no indicators with highest grades. School performance was found to mediate the relationship. Our findings suggest that future efforts to prevent or mitigate the negative effects of childhood household dysfunction on psychiatric morbidity may benefit from integration of strategies that improve school performance among vulnerable youth.


The cell biology and pathogenic role of pulmonary intravascular macrophages.
Pulmonary intravascular macrophages (PIMs) are an extensive population of mature phagocytic cells adherent to the pulmonary capillary endothelium in selected species. They are not prevalent in lungs of commonly studied laboratory animals, such as rodents, and thus have only been recently appreciated. However, their potential role in host defense and acute lung injury has attracted interest, since a number of studies have demonstrated pulmonary localization of circulating particles, microbes, and endotoxin by PIMs. Those animal species, such as ruminants, that provide useful models of pathogen (or endotoxin)-induced acute lung injury demonstrate rapid pulmonary uptake of bacteria by PIMs. Inflammatory mediators released by activated PIMs may initiate the process and provoke accumulation of neutrophils and platelets. This review summarizes the morphological characteristics of PIMs and their species distribution. The role of these members of the mononuclear phagocyte system, both beneficial and potentially pathogenic, is reviewed. The question of whether PIMs have a role in acute lung injury in humans is also discussed.


Classifying lower extremity muscle fatigue during walking using machine learning and inertial sensors.
Fatigue in lower extremity musculature is associated with decline in postural stability, motor performance and alters normal walking patterns in human subjects. Automated recognition of lower extremity muscle fatigue condition may be advantageous in early detection of fall and injury risks. Supervised machine learning methods such as support vector machines (SVMs) have been previously used for classifying healthy and pathological gait patterns and also for separating old and young gait patterns. In this study we explore the classification potential of SVM in recognition of gait patterns utilizing an inertial measurement unit associated with lower extremity muscular fatigue. Both kinematic and kinetic gait patterns of 17 participants (29 ± 11 years) were recorded and analyzed in normal and fatigued state of walking. Lower extremities were fatigued by performance of a squatting exercise until the participants reached 60% of their baseline maximal voluntary exertion level. Feature selection methods were used to classify fatigue and no-fatigue conditions based on temporal and frequency information of the signals. Additionally, influences of three different kernel schemes (i.e., linear, polynomial, and radial basis function) were investigated for SVM classification. The results indicated that lower extremity muscle fatigue condition influenced gait and loading responses. In terms of the SVM classification results, an accuracy of 96% was reached in distinguishing the two gait patterns (fatigue and no-fatigue) within the same subject using the kinematic, time and frequency domain features. It is also found that linear kernel and RBF kernel were equally good to identify intra-individual fatigue characteristics. These results suggest that intra-subject fatigue classification using gait patterns from an inertial sensor holds considerable potential in identifying "at-risk" gait due to muscle fatigue.


Risk factors for sleep bruxism in the general population.
Sleep bruxism can have a significant effect on the patient's quality of life. It may also be associated with a number of disorders. However, little is known about the epidemiology of sleep bruxism and its risk factors in the general population. Cross-sectional telephone survey using the Sleep-EVAL knowledge based system. Representative samples of three general populations (United Kingdom, Germany, and Italy) consisting of 158 million inhabitants. Thirteen thousand fifty-seven subjects aged > or = 15 years (United Kingdom, 4,972 subjects; Germany, 4,115 subjects; and Italy, 3,970 subjects). None. Clinical questionnaire on bruxism (using the International Classification of Sleep Disorders [ICSD] minimal set of criteria) with an investigation of associated pathologies (ie, sleep, breathing disorders, and psychiatric and neurologic pathologies). Grinding of teeth during sleep occurring at least weekly was reported by 8.2% of the subjects, and significant consequences from teeth grinding during sleep (ie, muscular discomfort on awakening, disturbing tooth grinding, or necessity of dental work) were found in half of these subjects. Moreover, 4.4% of the population fulfilled the criteria of ICSD sleep bruxism diagnosis. Finally, subjects with obstructive sleep apnea syndrome (odds ratio [OR], 1.8), loud snorers (OR, 1.4), subjects with moderate daytime sleepiness (OR, 1.3), heavy alcohol drinkers (OR, 1.8), caffeine drinkers (OR, 1.4), smokers (OR, 1.3), subjects with a highly stressful life (OR, 1.3), and those with anxiety (OR, 1.3) are at higher risk of reporting sleep bruxism. Sleep bruxism is common in the general population and represents the third most frequent parasomnia. It has numerous consequences, which are not limited to dental or muscular problems. Among the associated risk factors, patients with anxiety and sleep-disordered breathing have a higher number of risk factors for sleep bruxism, and this must raise concerns about the future of these individuals. An educational effort to raise the awareness of dentists and physicians about this pathology is necessary.


Epididymal ligaments: anatomy and function.
Three ligaments are described in relation to the epididymis: superior and inferior epididymal, and vasal ligaments. The study was conducted on 38 cadavers and included direct dissection and histologic examination. The superior and inferior epididymal ligaments are triangular folds of the visceral tunica vaginalis, and extend from epididymis to testicle. The superior ligament binds the epididymal head to the testicle, protecting the fine efferent ductules from damage. The inferior ligament fixes body and tail and mesoepididymis; further, it prevents epididymal convolutions from unraveling. The vasal ligament is a fibrous band, which binds the proximal end of the vas to the epididymal tail. It maintains an acute epididymovasal angle. In two cadavers, the inferior epididymal and vasal ligaments were absent. Convolutions of the lower body and tail of the epididymis were unraveled. The mesoepididymis was broad, and the epididymis was freely mobile from side to side; the epididymo-vasal angle was opened. The role of the epididymal and vasal ligaments in fixation of the epididymis, preservation of blood supply to both testicle and epididymis, and preventing unraveling of epididymal convolutions is stressed. Absent epididymal ligaments lead to "mobile epididymis," which may cause infertility.


Zingiber officinale Roscoe alone and in combination with alpha-tocopherol protect the kidney against cisplatin-induced acute renal failure.
Oxidative stress due to abnormal production of reactive oxygen molecules (ROM) is believed to be involved in the etiology of toxicities of many xenobiotics. Evidences suggested that ROM is involved in the nephrotoxicity of a widely used synthetic anticancer drug cisplatin. The nephroprotective effects of ethanol extract of Zingiber officinale alone and in combination with vitamin E (alpha-tocopherol) were evaluated using cisplatin (single dose of 10 mg/kg body wt, i.p) induced acute renal damage in mice. The results of the study indicated that Z. officinale significantly and dose dependently protected the nephrotoxicity induced by cisplatin. The serum urea and creatinine levels in the cisplatin alone treated group were significantly elevated (P<0.01) with respect to normal group of animals. The levels were reduced in the Z. officinale (250 and 500 mg/kg, p.o) plus cisplatin, vitamin E (250 mg/kg) plus cisplatin, and Z. officinale (250 mg/kg) with vitamin E plus vitamin E treated groups. The renal antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and level of reduced glutathione (GSH) were declined; level of malondialdehyde (MDA) was elevated in the cisplatin alone treated group. The activities of SOD, CAT GPx and level of GSH were elevated and level of MDA declined significantly (P<0.05) in the Z. officinale (250 and 500 mg/kg) plus cisplatin and Z. officinale (250 mg/kg) with vitamin E plus cisplatin treated groups. The protective effect of Z. officinale (250 mg/kg body wt) was found to be better than that of vitamin E (250 mg/kg body wt). The results also demonstrated that combination of Z. officinale (250 mg/kg) with vitamin E (250 mg/kg) showed a better protection compared to their 250 mg/kg alone treated groups. This study concluded that ethanol extract of Z. officinale alone and in combination with vitamin E partially ameliorated cisplatin-induced nephrotoxicity. This protection is mediated either by preventing the cisplatin-induced decline of renal antioxidant defense system or by their direct free radical scavenging activity.


Staged Models for Interdisciplinary Research.
Modellers of complex biological or social systems are often faced with an invidious choice: to use simple models with few mechanisms that can be fully analysed, or to construct complicated models that include all the features which are thought relevant. The former ensures rigour, the latter relevance. We discuss a method that combines these two approaches, beginning with a complex model and then modelling the complicated model with simpler models. The resulting "chain" of models ensures some rigour and relevance. We illustrate this process on a complex model of voting intentions, constructing a reduced model which agrees well with the predictions of the full model. Experiments with variations of the simpler model yield additional insights which are hidden by the complexity of the full model. This approach facilitated collaboration between social scientists and physicists-the complex model was specified based on the social science literature, and the simpler model constrained to agree (in core aspects) with the complicated model.