Ovarian reserve, female age and the chance for successful pregnancy.
Both quantitative and qualitative factors regarding egg production are strong influences on IVF outcome. Markers of ovarian reserve such as basal FSH, clomiphene citrate challenge test (CCCT), and antral follicle counts are good predictors of the quantity of eggs which can be induced to grow. However, the quality of those eggs seems better predicted by the age of the women. In women past age 40, current success rates are low overall, even in those who good ovarian reserve who make many eggs; at this age, quantity does not make up for quality. By contrast, young women with limited ovarian reserve can have good success rates despite their limited cohort of eggs, because the eggs themselves are of high potential; here quality matters more than quantity. The ramifications of these observations include the following: diminished ovarian reserve should not be used as an exclusionary criterion in young women, because overall they still have satisfactory pregnancy rates, though their risk of cancellation is increased. In women past age 40, normal ovarian reserve testing is not reassuring because even reduced egg quality is likely to limit the opportunity for successful pregnancy no matter how many eggs are available.


Minimizing the number of origins in batches of weaned calves to reduce their risks of developing bovine respiratory diseases.
Bovine respiratory diseases (BRD) are a major concern for the beef cattle industry, as beef calves overwhelmingly develop BRD symptoms during the first weeks after their arrival at fattening units. These cases occur after weaned calves from various cow-calf producers are grouped into batches to be sold to fatteners. Cross-contaminations between calves from different origins (potentially carrying different pathogens), together with increased stress because of the process of batch creation, can increase their risks of developing BRD symptoms. This study investigated whether reducing the number of different origins per batch is a strategy to reduce the risk of BRD cases. We developed an algorithm aimed at creating batches with as few origins as possible, while respecting constraints on the number and breed of the calves. We tested this algorithm on a dataset of 137,726 weaned calves grouped into 9701 batches by a French organization. We also computed an index assessing the risks of developing BRD because of the batch composition by considering four pathogens involved in the BRD system. While increasing the heterogeneity of batches in calf bodyweight, which is not expected to strongly impact the performance, our algorithm successfully decreased the average number of origins in the same batch and their risk index. Both this algorithm and the risk index can be used as part of decision tool to assess and possibly minimize BRD risk at batch creation, but they are generic enough to assess health risk for other production animals, and optimize the homogeneity of selected characteristics.


Genetic predictors of controlled ovarian hyperstimulation: where do we stand today?
Nowadays, the use of IVF has improved the prospects of infertility treatment. The expected outcome of IVF depends greatly on the effectiveness of controlled ovarian hyperstimulation (COH), where exogenous gonadotrophins are used to induce folliculogenesis. The response to stimulation varies substantially among women and is difficult to predict. Several predictive markers of COH outcome have been proposed (e.g. maternal age and ovarian reserve), but the search for optimal predictors is ongoing. Pharmacogenetic studies demonstrate the effects of individual genetic variability on COH outcome and the potential for customizing therapy based on the patient's genome. MEDLINE, EMBASE, DARE, CINAHL and the Cochrane Library, and references from relevant articles were investigated up to February 2011 regarding any common genetic variation and COH/IVF outcome. Several polymorphisms in genes involved in FSH signalling, estrogen biosynthesis, folliculogenesis, folate metabolism and other aspects influence the response to exogenous gonadotrophin administration, resulting in differences in COH and IVF outcomes. Nevertheless, the most studied polymorphism FSHR Asn680Ser is practically the only genetic marker, together with ESR1 PvuII T/C, that could be applied in clinical tests. Although data are accumulating with evidence suggesting that the ovarian response to COH is mediated by various polymorphisms, the optimal biomarkers and the efficacy of the tests still remain to be evaluated.


X-linked hereditary motor sensory neuropathy (type 1) presenting with a stroke-like episode.
X-linked hereditary motor sensory neuropathy type 1 (CMTX 1) is caused by mutation in the GJB1 gene that codes for the connexin 32 protein. Central nervous system involvement with or without white matter changes on magnetic resonance imaging (MRI) has rarely been reported in this condition. We report the case of a 7-year-old, previously well male who presented with a stroke-like episode that manifested as left hemiparesis and dysphasia. An initial brain MRI showed white matter signal changes affecting the corpus callosum and periventricular areas with a posterior predominance. Our patient made a complete clinical recovery in 36 hours. Clinical examination at this stage showed no evidence of a peripheral neuropathy. A repeat brain MRI 6 weeks later showed almost complete resolution of the changes seen initially. Subsequent investigations showed a Val177Ala mutation in the GJB1 gene. This mutation has so far not been described in the Caucasian population and has been only described once before. Electrophysiological studies showed a mixed demyelinating and axonal sensorimotor neuropathy in keeping with CMTX 1. Five months after the initial presentation our patient developed clinical evidence of a peripheral neuropathy in the form of absent ankle reflexes, weak dorsiflexors, and evertors of both feet.


Review: Placental derived biomarkers of pregnancy disorders.
Pregnancy is one of the greatest physiological challenges that a women can experience. The physiological adaptations that accompany pregnancy may increase the risk of developing a number of disorders that can lead to both acute and chronic physiological outcomes. In addition, fetal development may be impaired and, if the fetus survives, the child may be at an increased risk of disease throughout life. Pregnancy disorders are poorly predicted by traditional risk factors and maternal history alone. The identification of biomarkers that can predict incidence and severity of disease would allow for improved and targeted prophylactic therapies to prevent adverse maternal and fetal outcomes. Many of these pregnancy disorders, including preeclampsia, intrauterine growth restriction, gestational diabetes mellitus and preterm birth are known to be regulated at least in part by poor trophoblast invasion and/or dysregulated placental function. Cellular stress within the placenta increases the release of a number of factors into the maternal circulation. While many of these factors minimally impact maternal biology, others affect key physiological systems and contribute to disease. Importantly, these factors may be detected in physiological fluids and have predictive capacity making them ideal candidates as biomarkers of pregnancy disorders. This review will discuss what is known about these placental derived biomarkers of pregnancy disorders and highlight potential clinical opportunities for disease prediction and diagnosis.


ADF/Cofilin-Mediated Actin Turnover Promotes Axon Regeneration in the Adult CNS.
Injured axons fail to regenerate in the adult CNS, which contrasts with their vigorous growth during embryonic development. We explored the potential of re-initiating axon extension after injury by reactivating the molecular mechanisms that drive morphogenetic transformation of neurons during development. Genetic loss- and gain-of-function experiments followed by time-lapse microscopy, in vivo imaging, and whole-mount analysis show that axon regeneration is fueled by elevated actin turnover. Actin depolymerizing factor (ADF)/cofilin controls actin turnover to sustain axon regeneration after spinal cord injury through its actin-severing activity. This pinpoints ADF/cofilin as a key regulator of axon growth competence, irrespective of developmental stage. These findings reveal the central role of actin dynamics regulation in this process and elucidate a core mechanism underlying axon growth after CNS trauma. Thereby, neurons maintain the capacity to stimulate developmental programs during adult life, expanding their potential for plasticity. Thus, actin turnover is a key process for future regenerative interventions.


Metastasis-Entrained Eosinophils Enhance Lymphocyte-Mediated Antitumor Immunity.
The recognition of the immune system as a key component of the tumor microenvironment (TME) led to promising therapeutics. Because such therapies benefit only subsets of patients, understanding the activities of immune cells in the TME is required. Eosinophils are an integral part of the TME especially in mucosal tumors. Nonetheless, their role in the TME and the environmental cues that direct their activities are largely unknown. We report that breast cancer lung metastases are characterized by resident and recruited eosinophils. Eosinophil recruitment to the metastatic sites in the lung was regulated by G protein-coupled receptor signaling but independent of CCR3. Functionally, eosinophils promoted lymphocyte-mediated antitumor immunity. Transcriptome and proteomic analyses identified the TME rather than intrinsic differences between eosinophil subsets as a key instructing factor directing antitumorigenic eosinophil activities. Specifically, TNFα/IFNγ-activated eosinophils facilitated CD4+ and CD8+ T-cell infiltration and promoted antitumor immunity. Collectively, we identify a mechanism by which the TME trains eosinophils to adopt antitumorigenic properties, which may lead to the development of eosinophil-targeted therapeutics. SIGNIFICANCE: These findings demonstrate antitumor activities of eosinophils in the metastatic tumor microenvironment, suggesting that harnessing eosinophil activity may be a viable clinical strategy in patients with cancer.


Endoscopic endonasal suturing of dural reconstruction grafts: a novel application of the U-Clip technology. Technical note.
Cerebrospinal fluid (CSF) leakage following endoscopic endonasal skull base resection can be a significant problem. A method for securing tissue grafts is needed. In this paper the authors used an endonasal suturing device to secure the graft reconstruction following endonasal tumor resection. The U-Clip anastomotic device (Medtronic), developed for cardiovascular anastomoses, was used to secure the tissue graft to native dura. A specialized needle driver and hemoclip applier were used for the application and deployment of this device. No suture tying was necessary, facilitating its endonasal application. The graft was successfully secured in its desired position to native dura by using the U-Clip anastomotic device. The patient did not suffer a postoperative CSF leak, and postoperative imaging and endoscopy revealed that the graft was in a good position. There was no complication from the use of the device. The U-Clip anastomotic device can be used as a suture device during endonasal surgery. It may prevent tissue graft migration and help prevent CSF leakage.


Should I stay or should I go?: consistency and switching of delivery locations among new mothers in 39 Sub-Saharan African and South/Southeast Asian countries.
The objective of this article is to assess the extent and determinants of switching delivery location between women's first and second deliveries. We used Demographic and Health Survey data from 39 low- and middle-income countries on delivery locations from >30 000 women who had their first two deliveries in the 5-year survey recall period. Each delivery was characterized as occurring at home or in a health facility, facilities were classified as public- or private-sector. The extent of switching was estimated for each country, region and overall. Multivariable logistic regression models assessed determinants of switching (home to facility or facility to home), using four dimensions (perceived/biological need, socioeconomic characteristics, utilization of care and availability of care). Overall, 49.0% of first and 44.5% of second deliveries occurred in health facilities. Among women who had their first delivery at home, 11.8% used a facility for their second (7.0% public-sector and 4.8% private-sector). Among women who had their first delivery in a facility, 21.6% switched to a home location for their second. The extent of switching varied by country; but the overall net effect was either non-existent (n = 20) or away from facilities (n = 17) in all but two countries-Cambodia and Burkina Faso. Four factors were associated with switching to a facility after a home delivery: higher education, urban residence, non-poor household status and multiple gestation. Majority of women consistently used the same delivery location for their first two deliveries. We found some evidence that where switching occurred, women were being lost from facility care during this important transition, and that all four included dimensions were important determinants of women's pattern of delivery care use. The relative importance of these factors should be understood in each specific context to improve retention in and provision of quality intrapartum care for women and their newborns.


Temporal focusing by use of composite X waves.
It is shown that highly focused pulses can be shaped by exciting a finite aperture with a spread-out pulse train of X waves. The basis of the proposed scheme is that the peaks of X waves, characterized by different apex angles, travel at different velocities. This property allows one to vary the temporal starting points of the initial excitations of a sequence of X waves so that all their peaks meet at a chosen focusing point. It is demonstrated that this simple criterion can be effective in producing a highly focused, composite X-wave pulse that exhibits a slower decay behavior than the individual X-wave components used in synthesizing it.


Quantitative modeling of near-field interactions incorporating polaritonic and electrostatic effects.
As scattering-scanning near-field optical microscopy (s-SNOM) continues to grow in prominence, there has been great interest in modeling the near-field light-matter interaction to better predict experimental results. Both analytical and numerical models have been developed to describe the near-field response, but thus far models have not incorporated the full range of phenomena accessible. Here, we present a finite element model (FEM), capable of incorporating the complex physical and spatial phenomena that s-SNOM has proved able to probe. First, we use electromagnetic FEM to simulate the multipolar response of the tip and illustrate the impact of strong coupling on signal demodulation. We then leverage the multiphysics advantage of FEM to study the electrostatic effect of metallic tips on semiconductors, finding that THz s-SNOM studies are most impacted by this tip-induced band-bending. Our model is computationally inexpensive and can be tailored to specific nanostructured systems and geometries of interest.


[Perfluorine (perftoran) influence on lipid peroxidation and salivary antioxidant activity in patients with periodontal disease].
As it was shown in the clinical study local use of perftoran in patients with periodontal disease led to significant reduction of lipid peroxidation (LPO) and significant increase of antioxidant activity (AOA) in saliva. The most prominent effect was observed in patients with medium or severe degree of the disease. The data allowed to speak about perftorane influence upon tissue respiration processes, that was confirmed by the corresponding changes in LPO and AOA. The proved ability of perftorane to oxygen transportation increased oxygen delivery to the tissues around parodontal pockets, that improves local metabolism, normalizes breathing (respiration) cycle, has the influence upon anaerobic microflora. As the result of local perftorane use a decrease of active forms of oxygen was registered.


Thymoma-associated neuromyotonia with antibodies against voltage-gated potassium channels presenting as chronic intestinal pseudo-obstruction.
Chronic intestinal pseudo-obstruction can occur as a paraneoplastic disorder, and several cases have been reported in association with thymoma or small-cell lung cancer. Autoantibodies against voltage-gated potassium channels (VGKCs) are found in acquired neuromyotonia (Isaac's syndrome), and have been reported in one case of slow transit constipation without apparent neurological disease. We describe a patient with VGKC antibodies, acquired neuromyotonia and thymoma, who first presented with a severe slow-transit constipation and in whom the gastrointestinal symptoms responded well to plasmapheresis. We suggest that VGKC antibodies might be helpful in patients with possible paraneoplastic chronic intestinal pseudo-obstruction, and a positive result should stimulate the search for a thymoma or other tumour and raise the possibility of immunotherapy.


Evaluating the effect of a community-based lay health advisor training curriculum to address immigrant children's caries disparities.
Previous programs had not designed the culturally adequate Lay Health Advisor (LHA) oral health training curriculum for medically underserved population. We evaluated the effects of LHA training curriculum for addressing immigrant children's caries disparities in their access to dental care. We used a pre/post-test study design. Immigrant women were recruited from churches, schools, and immigrant centers in an urban area. Four training classes were held. Each training cycle lasted 15 consecutive weeks, consisting of 1 weekly 2-h training session for 12 weeks followed by a 3-week practicum. The curriculum included training in caries-related knowledge, oral hygiene demonstrations, teaching techniques, communication skills, and hands-on practice sessions. Thirty-seven LHA trainees completed the course and passed the post-training exam. The data were collected using self-report questionnaires. The level of oral health knowledge, self-efficacy and attitudes toward oral hygiene were significantly increased after LHA training. There was a significant and over twofold increase in trainees' oral hygiene behaviors. An increase of >20% in LHA and their children's dental checkup was observed following training. After training, LHAs were more likely to have 3+ times of brushing teeth [Odds Ratio (OR) = 13.14], brushing teeth 3+ minutes (OR = 3.47), modified bass method use (OR = 30.60), dental flossing (OR = 4.56), fluoride toothpaste use (OR = 5.63) and child's dental visit (OR = 3.57). The cross-cultural training curriculum designed for immigrant women serving as LHAs was effective in improvement of oral hygiene behaviors and access to dental care.


ApoE3 Anchored Liposomal Delivery of Rivastigmine for Brain Delivery: Formulation, Characterization, and In Vivo Pharmacokinetic Evaluation.
Rivastigmine hydrogen tartrate (RHT) is an acetylcholinesterase (AChE) inhibitor used in the management of Alzheimer's disease (AD). RHT is a BCS class-I drug that undergoes significant first-pass metabolism. Permeating a hydrophilic drug through the brain remains a major challenge in brain delivery. In this study, the RHT was incorporated inside the hydrophilic core of liposomes (LPS) and then coated with the ApoE3. ApoE3-coated RHT-loaded liposomes (ApoE3-RHT-LPS) were fabricated through the thin film hydration method using DSPE-PEG. The coating of LPS with ApoE3 enhances brain uptake and improves Aβ clearance. The results obtained from the physicochemical characterization demonstrated that ApoE3-RHT-LPS shows a particle size of 128.6 ± 2.16 nm and a zeta potential of 16.6 ± 1.19. The % entrapment efficiency and % drug loading were found to be 75% and 17.84%, respectively. The data obtained from TEM and SEM studies revealed that the particle size of the LPS was less than 200 nm. An in vitro AChE assay was performed, and the results demonstrated the AChE inhibitory potential of ApoE3-RHT-LPS. Through the intravenous route, an in vivo pharmacokinetic study of formulation displayed improved brain uptake of RHT by ~ 1.3-fold than pure RHT due to ApoE3 coating. In vivo, biodistribution studies in vital organs suggested that the biodistribution of RHT to the liver was significantly reduced (p < 0.001), signifying an increase in the drug's half-life and blood circulation time. All research findings suggested that ApoE3 coating and LPS strategy are proven effective for improving the brain uptake of RHT designed for the management of AD.


The tracrRNA in CRISPR Biology and Technologies.
CRISPR-Cas adaptive immune systems in bacteria and archaea utilize short CRISPR RNAs (crRNAs) to guide sequence-specific recognition and clearance of foreign genetic material. Multiple crRNAs are stored together in a compact format called a CRISPR array that is transcribed and processed into the individual crRNAs. While the exact processing mechanisms vary widely, some CRISPR-Cas systems, including those encoding the Cas9 nuclease, rely on a trans-activating crRNA (tracrRNA). The tracrRNA was discovered in 2011 and was quickly co-opted to create single-guide RNAs as core components of CRISPR-Cas9 technologies. Since then, further studies have uncovered processes extending beyond the traditional role of tracrRNA in crRNA biogenesis, revealed Cas nucleases besides Cas9 that are dependent on tracrRNAs, and established new applications based on tracrRNA engineering. In this review, we describe the biology of the tracrRNA and how its ongoing characterization has garnered new insights into prokaryotic immune defense and enabled key technological advances.


The placebo effect in the motor domain is differently modulated by the external and internal focus of attention.
Among the cognitive strategies that can facilitate motor performance in sport and physical practice, a prominent role is played by the direction of the focus of attention and the placebo effect. Consistent evidence converges in indicating that these two cognitive functions can influence the motor outcome, although no study up-to-now tried to study them together in the motor domain. In this explorative study, we combine for the first time these approaches, by applying a placebo procedure to increase force and by manipulating the focus of attention with explicit verbal instructions. Sixty healthy volunteers were asked to perform abduction movements with the index finger as strongly as possible against a piston and attention could be directed either toward the movements of the finger (internal focus, IF) or toward the movements of the piston (external focus, EF). Participants were randomized in 4 groups: two groups underwent a placebo procedure (Placebo-IF and Placebo-EF), in which an inert treatment was applied on the finger with verbal information on its positive effects on force; two groups underwent a control procedure (Control-IF and Control-EF), in which the same treatment was applied with overt information about its inefficacy. The placebo groups were conditioned about the effects of the treatment with a surreptitious amplification of a visual feedback signalling the level of force. During the whole procedure, we recorded actual force, subjective variables and electromyography from the hand muscles. The Placebo-IF group had higher force levels after the procedure than before, whereas the Placebo-EF group had a decrease of force. Electromyography showed that the Placebo-IF group increased the muscle units recruitment without changing the firing rate. These findings show for the first time that the placebo effect in motor performance can be influenced by the subject's attentional focus, being enhanced with the internal focus of attention.


Attitudes and avatars instrument: development and initial testing.
The purpose of the study was to develop and test the initial psychometric properties of the ATTitudes and Avatars INstrument (ATTAIN). The integrated behavior model guided instrument development to measure the young adolescent boys' attitudes, intentions and actions to change their bodies. An adolescent health expert panel and young adolescent boys were recruited to test for content validity. Fifty-nine boys 11 to 14 years of age were recruited at a middle school in the USA during physical education class to conduct a pilot study to test for internal consistency and test-retest reliability. The ATTAIN was found to have high content validity, slightly below recommended levels for internal consistency, and varied test-retest reliability. The long-term goal of the development and testing of the ATTAIN is to make it available to researchers and professionals to screen and focus on adolescents' perceptions of their bodies and using those perceptions to attain and maintain healthy bodies. The results of this study suggest preliminarily a theoretically derived instrument with appropriate content for young adolescent boys and variable reliability. The attitudes, intentions, and actions survey items and avatars as measured by the ATTAIN, were meaningful to the boys. The ATTAIN has potential to be used as a screening instrument for young adolescents boys and understanding their attitudes toward their bodies; however, it will require continued development and testing to establish construct and discriminant validity.


Antihistamine selection in patients with allergic rhinitis.
Seven hundred eighty-two patients diagnosed as having either seasonal allergic rhinitis or perennial allergic rhinitis in a solo allergy practice were given five different antihistamine products representing each of the five classes of antihistamines. The following products were evaluated for 2 weeks each: tripelennamine, diphenhydramine, chlorpheniramine, hydroxyzine, and trimeprazine. Symptoms and side effects were graded 0 to 4. The more troublesome side effects, graded 3 or 4, were tabulated. The antihistamine products in order of increasing frequency of significant side effects were: trimeprazine, chlorpheniramine, hydroxyzine, diphenhydramine, and tripelennamine. The order of antihistamine preference by the patients was chlorpheniramine (27%), diphenhydramine (22%), tripelennamine (20%), hydroxyzine (16%), and trimeprazine (14%). Only seven of 758 patients (less than 1%) were unable to find an acceptable antihistamine class. Patients remained on their antihistamine class of first choice 78% of the time after 1 year, 71% after 3 years and 51% after 5 years. The antihistamine pack provides a rational approach to antihistamine selection in patients with allergic rhinitis.


Observations on prostaglandins in normal and leukemic human lymphocytes.
Prostaglandins E (PGE) and F2 alpha (PGF2 alpha) were measured in lymphocytes of normal subjects, children with acute lymphocytic leukemia (ALL), and adults with chronic lymphocytic leukemia (CLL). In ALL lymphocytes PGE increased from a normal value of 25 pgrams to 270 pgrams/10(6) cells, and PGF 2 alpha increased from a normal value of 31 pgrams to 482 pgrams/10(6) cells. In CLL lymphocytes, levels of PGE and PGF2 alpha were normal or low. When normal lymphocytes were stimulated with phytohemagglutinin (PHA), the level of PGE and PGF2 alpha fluctuated, followed by corresponding changes in the level of cyclic nucleotides. In cultured ALL lymphocytes, the level of PGE remained high, while cyclic 3':5'-adenosine monophosphate (c-AMP) level was constantly low, and the initial level of PGF2 alpha fluctuated in relation to similar oscillations of cyclic 3':5'-guanosine monophosphate (c-GMP). These values were lower, although not significantly, when ALL lymphocytes were stimulated with PHA. When CLL lymphocytes were stimulated with PHA, the level of PGE remained low (20 pgrams), as did that of c-AMP. The level of PGF2 alpha, after a brief initial increase (130 pgrams), returned to and remained at a lower level (60 pgrams) while the level of c-GMP was persistently high. These results suggest: (1) prostaglandins may indirectly influence the cell cycle, possibly through modulation of cyclase activity and levels of cyclic nucleotides; and (2) some derangement of this regulatory mechanism may be present in leukemic lymphocytes.


Challenges and advances for transcriptome assembly in non-model species.
Analyses of high-throughput transcriptome sequences of non-model organisms are based on two main approaches: de novo assembly and genome-guided assembly using mapping to assign reads prior to assembly. Given the limits of mapping reads to a reference when it is highly divergent, as is frequently the case for non-model species, we evaluate whether using blastn would outperform mapping methods for read assignment in such situations (>15% divergence). We demonstrate its high performance by using simulated reads of lengths corresponding to those generated by the most common sequencing platforms, and over a realistic range of genetic divergence (0% to 30% divergence). Here we focus on gene identification and not on resolving the whole set of transcripts (i.e. the complete transcriptome). For simulated datasets, the transcriptome-guided assembly based on blastn recovers 94.8% of genes irrespective of read length at 0% divergence; however, assignment rate of reads is negatively correlated with both increasing divergence level and reducing read lengths. Nevertheless, we still observe 92.6% of recovered genes at 30% divergence irrespective of read length. This analysis also produces a categorization of genes relative to their assignment, and suggests guidelines for data processing prior to analyses of comparative transcriptomics and gene expression to minimize potential inferential bias associated with incorrect transcript assignment. We also compare the performances of de novo assembly alone vs in combination with a transcriptome-guided assembly based on blastn both via simulation and empirically, using data from a cyprinid fish species and from an oak species. For any simulated scenario, the transcriptome-guided assembly using blastn outperforms the de novo approach alone, including when the divergence level is beyond the reach of traditional mapping methods. Combining de novo assembly and a related reference transcriptome for read assignment also addresses the bias/error in contigs caused by the dependence on a related reference alone. Empirical data corroborate these findings when assembling transcriptomes from the two non-model organisms: Parachondrostoma toxostoma (fish) and Quercus pubescens (plant). For the fish species, out of the 31,944 genes known from D. rerio, the guided and de novo assemblies recover respectively 20,605 and 20,032 genes but the performance of the guided assembly approach is much higher for both the contiguity and completeness metrics. For the oak, out of the 29,971 genes known from Vitis vinifera, the transcriptome-guided and de novo assemblies display similar performance, but the new guided approach detects 16,326 genes where the de novo assembly only detects 9,385 genes.


Dynamic regulation of mitochondrial function by glucocorticoids.
Glucocorticoids play an important biphasic role in modulating neural plasticity; low doses enhance neural plasticity and spatial memory behavior, whereas chronic, higher doses produce inhibition. We found that 3 independent measures of mitochondrial function-mitochondrial oxidation, membrane potential, and mitochondrial calcium holding capacity-were regulated by long-term corticosterone (CORT) treatment in an inverted "U"-shape. This regulation of mitochondrial function by CORT correlated with neuroprotection; that is, treatment with low doses of CORT had a neuroprotective effect, whereas treatment with high doses of CORT enhanced kainic acid (KA)-induced toxicity of cortical neurons. We then undertook experiments to elucidate the mechanisms underlying these biphasic effects and found that glucocorticoid receptors (GRs) formed a complex with the anti-apoptotic protein Bcl-2 in response to CORT treatment and translocated with Bcl-2 into mitochondria after acute treatment with low or high doses of CORT in primary cortical neurons. However, after 3 days of treatment, high, but not low, doses of CORT resulted in decreased GR and Bcl-2 levels in mitochondria. As with the in vitro studies, Bcl-2 levels in the mitochondria of the prefrontal cortex were significantly decreased, along with GR levels, after long-term treatment with high-dose CORT in vivo. These findings have the potential to contribute to a more complete understanding of the mechanisms by which glucocorticoids and chronic stress regulate cellular plasticity and resilience and to inform the future development of improved therapeutics.


Efficacy of empirically prescribed amoxicillin and amoxicillin + clavulanic acid in children's reactive arthritis: a randomised trial.
To evaluate the efficacy of early empiric prescription of amoxicillin and amoxicillin + clavulanic acid in children with reactive arthritis (ReA) when the arthritis-triggering microorganism is not identified. 138 children, ranging in age from 2 to 16 years, with ReA of up to 3 months duration were randomly assigned to 3 groups and either prescribed antibacterial treatment with amoxicillin or amoxicillin + clavulanic acid (amoxicillin-potassium clavulanate combination) or were not given antibiotics (control group). Patients in all 3 groups were prescribed the usual treatment with nonsteroidal antiinflammatory drugs. Both groups of patients under antibacterial treatment were randomised into 2 subgroups: patients given a 10- to 14-day or a 28-day-duration antibacterial course. The results of the study were evaluated after 1 and 3 months of observation by determining the percentage of patients that had no clinical or laboratory signs of disease activity. After 1 month of observation no signs of disease activity were found in 48.0% of patients who were prescribed amoxicillin, in 58.5% of patients treated with amoxicillin + clavulanic acid, and only in 13.0% of patients from the control group (p < 0.001 for either antibacterial treatment in comparison with the control group). After 3 months of observation no disease activity was found in 92.0% of patients who used amoxicillin, in 95.1% of those treated with amoxicillin + clavulanic acid, and in 58.7% of children from the control group (p < 0.001 for either antibacterial treatment in comparison with the control group). There was no significant difference in the efficacy of amoxicillin and amoxicillin + clavulanic acid. The duration of the antibacterial course showed no influence on the results of treatment. Amoxicillin or amoxicillin + clavulanic acid in 10- to 14-day courses are advisable, in addition to the antirheumatic treatment, for children in the early stage of ReA when the arthritis-triggering microorganism is not identified.


Temperature alters food web body-size structure.
The increased temperature associated with climate change may have important effects on body size and predator-prey interactions. The consequences of these effects for food web structure are unclear because the relationships between temperature and aspects of food web structure such as predator-prey body-size relationships are unknown. Here, we use the largest reported dataset for marine predator-prey interactions to assess how temperature affects predator-prey body-size relationships among different habitats ranging from the tropics to the poles. We found that prey size selection depends on predator body size, temperature and the interaction between the two. Our results indicate that (i) predator-prey body-size ratios decrease with predator size at below-average temperatures and increase with predator size at above-average temperatures, and (ii) that the effect of temperature on predator-prey body-size structure will be stronger at small and large body sizes and relatively weak at intermediate sizes. This systematic interaction may help to simplify forecasting the potentially complex consequences of warming on interaction strengths and food web stability.


Length-Dependent Magnetic Evolution of Anthenes on Au(111).
Nanographenes with zigzag edges, for example, anthenes, exhibit a unique nonbonding π-electron state, which can be described as a spin-polarized edge state that yields specific magnetic ground state. However, prior researches on the magnetism of anthenes with varying lengths on a surface is lacking. This study systematically fabricated anthenes with inherent zigzag carbon atoms of different lengths ranging from bisanthene to hexanthene. Their magnetic evolution on the Au(111) surface was analyzed through bond-resolved scanning probe techniques and density functional theory calculations. The analyses revealed a transition in magnetic properties associated with the length of the anthenes, arising from the imbalance between hybridization energy and the Coulomb repulsion between valence electrons. With the increasing length of the anthenes, the ground state transforms gradually from a closed-shell to an antiferromagnetic open-shell singlet, exhibiting a weak exchange coupling of 4 meV and a charge transfer-induced doublet. Therefore, this study formulated a chemically tunable platform to explore size-dependent π magnetism at the atomic scale, providing a framework for research in organic spintronics.


Characterization of vir-activated TnphoA gene fusions in Bordetella pertussis.
The expression of many of the known virulence determinants of Bordetella pertussis is coordinately regulated by the vir regulatory locus and reduced in response to environmental signals called modulators. We have previously identified eight TnphoA gene fusions in B. pertussis in which the expression of alkaline phosphatase was maximal in the absence of the modulators nicotinic acid and MgSO4. We have termed the genes identified by these fusions vir-activated genes. Here we report the characterization of these TnphoA mutant strains. Four fusion strains were defective in known virulence determinants. For one of these, fusion strain SK39, Southern blot hybridization demonstrated that TnphoA was inserted in the S1 subunit gene of pertussis toxin. Hemagglutination assays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblots identified three fusions strains, SK16, SK75, and SK91, that were defective in filamentous hemagglutinin. Whereas all three filamentous hemagglutinin-defective mutants showed either normal or enhanced colonization, the pertussis toxin-defective mutant showed a marked defect in pulmonary persistence. Of the four other fusion strains, two were deficient in outer membrane proteins. One of these, strain SK8, was defective in a major outer membrane protein of 95 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This strain colonized mouse lungs less well and did not induce lymphocytosis after aerosol challenge. The other strain, SK34, was defective in four outer membrane proteins, three of which were detectable only on a Western blot with polyclonal sera against B. pertussis. Two of our gene fusion strains did not show any defect in identifiable vir-regulated proteins.


Mathematical modeling of intercalation batteries at the cell level and beyond.
Mathematical modeling of lithium ion batteries is a key feature for a profound understanding of the whole spectrum of phenomena occurring in such electrochemical systems. Due to their inherent multi-scale nature, batteries cannot be described with a single equation. It is necessary to couple the physical chemistry, reaction kinetics, ion flow, heat generation, et cetera, appropriately to obtain a coupled set of equations (a model) which has predictive efficiency. To adapt ideas and expertise obtained in the field of modeling to future type of batteries, new electrode or electrolyte materials or to improve the model reliability, a universal basis is desirable. In this sense, we carefully derive the commonly used set of equations based on the most general form of linear non-equilibrium thermodynamics. Due to chemical and physical assumptions the set of equations is reduced to facilitate numerical computations. Transport equations for a general electrolyte are derived and different electroneutrality assumptions are applied to obtain Poisson-Nernst-Planck-type equations or a generalized Ohmic law. Electrodes are described with single and many particle models, e.g. for phase separating materials, and the transition to porous electrode theory is given. A mathematical treatment of the intercalation reaction is finally presented, based on surface charge densities and electrode potentials.


Effective Interventions for Diabetes Patients by Community Pharmacists: A Meta-analysis of Pharmaceutical Care Components.
To evaluate randomized controlled trials (RCTs) that included interventions provided by community pharmacists for patients with type 1 and 2 diabetes, the analysis of each component of the intervention(s), and the description of the training that the pharmacists received. The literature research was conducted in PubMed and in the Cochrane Central Register of Controlled Trials (January 2000 to April 2016) for RCTs with interventions provided by community pharmacists for patients with diabetes. Corresponding authors were contacted about missing data and intervention and training design. RCTs published in English or German were included if pharmaceutical care or medication therapy management was conducted by community pharmacists with diabetes patients. Basic information, intervention and training design data were extracted. The literature research resulted in 11 eligible studies for further analysis. The corresponding authors of 6 studies responded to our request and sent their raw data. The calculated meta-analytical effect of 640 analyzed patients was a hemoglobin A1C (A1C) difference of -0.66%, with a 95% CI of -0.86% to -0.45%. The analysis revealed that most intervention elements had a significant positive meta-analytical effect on the A1C values. Our meta-analysis suggests that community pharmacist-led interventions can improve glycemic control in patients with type 1 and 2 diabetes. The most effective intervention components were patient centered and interdisciplinary. Pharmaceutical care interventions should, therefore, include the following components: sending feedback to the physician, setting individual goals, reviewing medication, and assessing patients' health beliefs and medication knowledge.


Sizable Suppression of Thermal Hall Effect upon Isotopic Substitution in SrTiO_{3}.
We report measurements of the thermal Hall effect in single crystals of both pristine and isotopically substituted strontium titanate. We discovered a 2 orders of magnitude difference in the thermal Hall conductivity between SrTi^{16}O_{3} and ^{18}O-enriched SrTi^{18}O_{3} samples. In most temperature ranges, the magnitude of thermal Hall conductivity (κ_{xy}) in SrTi^{18}O_{3} is proportional to the magnitude of the longitudinal thermal conductivity (κ_{xx}), which suggests a phonon-mediated thermal Hall effect. However, they deviate in the temperature of their maxima, and the thermal Hall angle ratio (|κ_{xy}/κ_{xx}|) shows anomalously decreasing behavior below the ferroelectric Curie temperature T_{c}∼25 K. This observation suggests a new underlying mechanism, as the conventional scenario cannot explain such differences within the slight change in phonon spectrum. Notably, the difference in magnitude of thermal Hall conductivity and rapidly decreasing thermal Hall angle ratio in SrTi^{18}O_{3} is correlated with the strength of quantum critical fluctuations in this displacive ferroelectric. This relation points to a link between the quantum critical physics of strontium titanate and its thermal Hall effect, a possible clue to explain this example of an exotic phenomenon in nonmagnetic insulating systems.


Rad50 c.687delT does not contribute significantly to familial breast cancer in a French population.
Mutations in DNA repair genes are known for their association with hereditary breast cancer. BRCA1 and BRCA2 are the major genes for high-penetrance familial breast and ovarian cancer, whereas mutations in ATM or Chek2 confer more modest cancer risk. Additional genes involved in DNA double-strand break repair have more recently been associated with breast cancer risk: heterozygosity for deleterious mutations in components of the Rad50-Mre11-Nbs1 complex seems to predispose to breast cancer. In particular, the c.687delT mutation in Rad50 conferred an odds ratio of 4.3 for the risk of breast cancer in a study of Finnish breast cancer families. To explore the contribution of this mutation to breast cancer in French families for which no BRCA mutation could be found, we analyzed the relevant exon in 618 familial breast cancer cases and 513 controls with no personal or familial history of breast cancer. Rad50 was analyzed in its entirety for 231 familial cases, with no clearly deleterious mutations detected. These data together suggest that although founder mutations may make Rad50 a significant breast cancer risk factor in certain populations, it is not a factor in others.


Supervised maintenance programmes following pulmonary rehabilitation compared to usual care for chronic obstructive pulmonary disease.
Pulmonary rehabilitation benefits patients with chronic obstructive pulmonary disease (COPD), but gains are not maintained over time. Maintenance pulmonary rehabilitation has been defined as ongoing supervised exercise at a lower frequency than the initial pulmonary rehabilitation programme. It is not yet known whether a maintenance programme can preserve the benefits of pulmonary rehabilitation over time. Studies of maintenance programmes following pulmonary rehabilitation are heterogeneous, especially regarding supervision frequency. Furthermore, new maintenance models (remote and home-based) are emerging. To determine whether supervised pulmonary rehabilitation maintenance programmes improve health-related quality of life (HRQoL), exercise performance, and health care utilisation in COPD patients compared with usual care. Secondly, to examine in subgroup analyses the impact of supervision frequency and model (remote or in-person) during the supervised maintenance programme. We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, PEDro, and two additional trial registries platforms up to 31 March 2020, without restriction by language or type of publication. We screened the reference lists of all primary studies for additional references. We also hand-searched conference abstracts and grey literature through the Cochrane Airways Trials Register and CENTRAL. We included only randomised trials comparing pulmonary rehabilitation maintenance for COPD with attention control or usual care. The primary outcomes were HRQoL, exercise capacity and hospitalisation; the secondary outcomes were exacerbation rate, mortality, direct costs of care, and adverse events. Two review authors independently screened titles and abstracts, extracted data, and assessed the risk of bias. Results data that were similar enough to be pooled were meta-analysed using a random-effects model, and those that could not be pooled were reported in narrative form. Subgroup analyses were undertaken for frequency of supervision (programmes offered monthly or less frequently, versus more frequently) and those using remote supervision (e.g. telerehabilitation versus face-to-face supervision). We used the GRADE approach to assess the certainty of evidence. We included 21 studies (39 reports) with 1799 COPD patients. Participants ranged in age from 52 years to 88 years. Disease severity ranged from 24% to 88% of the predicted forced expiratory volume in one second. Programme duration ranged from four weeks to 36 months. In-person supervision was provided in 12 studies, and remote supervision was provided in six studies (telephone or web platform). Four studies provided a combination of in-person and remote supervision. Most studies had a high risk of performance bias due to lack of blinding of participants, and high risk of detection, attrition, and reporting bias. Low- to moderate-certainty evidence showed that supervised maintenance programmes may improve health-related quality of life at six to 12 months following pulmonary rehabilitation compared to usual care (Chronic Respiratory Questionnaire total score mean difference (MD) 0.54 points, 95% confidence interval (CI) 0.04 to 1.03, 258 participants, four studies), with a mean difference that exceeded the minimal important difference of 0.5 points for this outcome. It is possible that supervised maintenance could improve six-minute walk distance, but this is uncertain (MD 26 metres (m), 95% CI -1.04 to 52.84, 639 participants, 10 studies). There was little to no difference between the maintenance programme and the usual care group in exacerbations or all-cause hospitalizations, or the chance of death (odds ratio (OR) for mortality 0.73, 95% CI 0.36 to 1.51, 755 participants, six studies). Insufficient data were available to understand the impact of the frequency of supervision, or of remote versus in-person supervision. No adverse events were reported. This review suggests that supervised maintenance programmes for COPD patients after pulmonary rehabilitation are not associated with increased adverse events, may improve health-related quality of life, and could possibly improve exercise capacity at six to 12 months. Effects on exacerbations, hospitalisation and mortality are similar to those of usual care. However, the strength of evidence was limited because most included studies had a high risk of bias and small sample size. The optimal supervision frequency and models for supervised maintenance programmes are still unclear.


Defects in mismatch repair occur after APC mutations in the pathogenesis of sporadic colorectal tumours.
The roles of the intrinsic mutation rate and genomic instability in tumorigenesis are currently controversial. In most colorectal tumours, it is generally supposed that the first mutations occur at the adenomatous polyposis coli (APC) locus; APC mutations are thought to provide cells with a selective advantage but have no known effect on the mutation rate. It has also been suggested that genomic instability is the initiating event in colorectal tumorigenesis and, if this is true, mutations of DNA mismatch repair (MMR) genes (or at similar loci) are the most likely candidates. If defective MMR precedes APC mutations, the APC mutations of colon tumours with defective MMR and hence replication errors (RER+) should differ from those of RER- tumours, in at least three specific ways: (1) a higher frequency of allele loss at APC in RER- tumours; (2) more frameshift than nonsense mutations in RER+ tumours; and (3) APC mutations in simple repeat sequences [(N)n, (N1N2)n, or (N1N2N3)n] in RER+ tumours. We found no evidence that sporadic RER+ and RER- colon cancers (including cell lines) differ in any of these three ways. Although it remains possible that MMR is abnormal in tumours from HNPCC families before APC mutations occur, it is likely that in sporadic colon tumours, APC mutations, rather than genomic instability, are the initiating events in tumorigenesis.


Improving the Stability of Halide Perovskite Solar Cells Using Nanoparticles of Tungsten Disulfide.
Halide perovskites-based solar cells are drawing significant attention due to their high efficiency, versatility, and affordable processing. Hence, halide perovskite solar cells have great potential to be commercialized. However, the halide perovskites (HPs) are not stable in an ambient environment. Thus, the instability of the perovskite is an essential issue that needs to be addressed to allow its rapid commercialization. In this work, WS2 nanoparticles (NPs) are successfully implemented on methylammonium lead iodide (MAPbI3) based halide perovskite solar cells. The main role of the WS2 NPs in the halide perovskite solar cells is as stabilizing agent. Here the WS2 NPs act as heat dissipater and charge transfer channels, thus allowing an effective charge separation. The electron extraction by the WS2 NPs from the adjacent MAPbI3 is efficient and results in a higher current density. In addition, the structural analysis of the MAPbI3 films indicates that the WS2 NPs act as nucleation sites, thus promoting the formation of larger grains of MAPbI3. Remarkably, the absorption and shelf life of the MAPbI3 layers have increased by 1.7 and 4.5-fold, respectively. Our results demonstrate a significant improvement in stability and solar cell characteristics. This paves the way for the long-term stabilization of HPs solar cells by the implementation of WS2 NPs.


The structure and structural effects of VA rehabilitation bedservice care for stroke.
The purpose of this study was to: 1) examine the variation in organizational structure within rehabilitation bed-service units (RBU) in the Veterans Health Administration (VHA), and 2) evaluate the effects of RBU and parent hospital structure on stroke rehabilitation outcomes. Two VHA-wide surveys of acute and rehabilitation services for stroke were linked with 2 y of VHA rehabilitation outcomes for stroke patients. A random effects mixed model was used to adjust for patient level covariates, control for unique site effects, and test for facility level structural effects. After adjusting for patient covariates, four structural variables were associated with length of stay or patient functional gain. These results indicate that rehabilitation structure is important to rehabilitation outcome. The individual variables identified in this study, namely, diverse multidisciplinary staff, expert physician leadership, staff participation in team care, and richer rehabilitation equipment resources, may represent the distinct aspects of a successful, comprehensive rehabilitation unit.


Ultra-clean high-mobility graphene on technologically relevant substrates.
Graphene grown via chemical vapour deposition (CVD) on copper foil has emerged as a high-quality, scalable material, that can be easily integrated on technologically relevant platforms to develop promising applications in the fields of optoelectronics and photonics. Most of these applications require low-contaminated high-mobility graphene (i.e., approaching 10 000 cm2 V-1 s-1 at room temperature) to reduce device losses and implement compact device design. To date, these mobility values are only obtained when suspending or encapsulating graphene. Here, we demonstrate a rapid, facile, and scalable cleaning process, that yields high-mobility graphene directly on the most common technologically relevant substrate: silicon dioxide on silicon (SiO2/Si). Atomic force microscopy (AFM) and spatially-resolved X-ray photoelectron spectroscopy (XPS) demonstrate that this approach is instrumental to rapidly eliminate most of the polymeric residues which remain on graphene after transfer and fabrication and that have adverse effects on its electrical properties. Raman measurements show a significant reduction of graphene doping and strain. Transport measurements of 50 Hall bars (HBs) yield hole mobility μh up to ∼9000 cm2 V-1 s-1 and electron mobility μe up to ∼8000 cm2 V-1 s-1, with average values μh ∼ 7500 cm2 V-1 s-1 and μe ∼ 6300 cm2 V-1 s-1. The carrier mobility of ultraclean graphene reaches values nearly double than those measured in graphene processed with acetone cleaning, which is the method widely adopted in the field. Notably, these mobility values are obtained over large-scale and without encapsulation, thus paving the way to the adoption of graphene in optoelectronics and photonics.


Involvement of the lysophosphatidic acid-generating enzyme autotaxin in lymphocyte-endothelial cell interactions.
Autotaxin (ATX) is a secreted protein with lysophospholipase D activity that generates lysophosphatidic acid (LPA) from lysophosphatidylcholine. Here we report that functional ATX is selectively expressed in high endothelial venules (HEVs) of both lymph nodes and Peyer's patches. ATX expression was developmentally regulated and coincided with lymphocyte recruitment to the lymph nodes. In adults, ATX expression was independent of HEV-expressed chemokines such as CCL21 and CXCL13, innate immunity signals including those via TLR4 or MyD88, and of the extent of lymphocyte trafficking across the HEVs. ATX expression was induced in venules at sites of chronic inflammation. Receptors for the ATX enzyme product LPA were constitutively expressed in HEV endothelial cells (ECs). In vitro, LPA induced strong morphological changes in HEV ECs. Forced ATX expression caused cultured ECs to respond to lysophosphatidylcholine, up-regulating lymphocyte binding to the ECs in a LPA receptor-dependent manner under both static and flow conditions. Although in vivo depletion of circulating ATX did not affect lymphocyte trafficking into the lymph nodes, we surmise, based on the above data, that ATX expressed by HEVs acts on HEVs in situ to facilitate lymphocyte binding to ECs and that ATX in the general circulation does not play a major role in this process. Tissue-specific inactivation of ATX will verify this hypothesis in future studies of its mechanism of action.


Detection of rock bridges by infrared thermal imaging and modeling.
Characterization of rock discontinuities and rock bridges is required to define stability conditions of fractured rock masses in both natural and engineered environments. Although remote sensing methods for mapping discontinuities have improved in recent years, remote detection of intact rock bridges on cliff faces remains challenging, with their existence typically confirmed only after failure. In steep exfoliating cliffs, such as El Capitan in Yosemite Valley (California, USA), rockfalls mainly occur along cliff-parallel exfoliation joints, with rock bridges playing a key role in the stability of partially detached exfoliation sheets. We employed infrared thermal imaging (i.e., thermography) as a new means of detecting intact rock bridges prior to failure. An infrared thermal panorama of El Capitan revealed cold thermal signatures for the surfaces of two granitic exfoliation sheets, consistent with the expectation that air circulation cools the back of the partially detached sheets. However, we also noted small areas of warm thermal anomalies on these same sheets, even during periods of nocturnal rock cooling. Rock attachment via rock bridges is the likely cause for the warm anomalies in the thermal data. 2-D model simulations of the thermal behavior of one of the monitored sheets reproduce the observed anomalies and explain the temperature differences detected in the rock bridge area. Based on combined thermal and ground-based lidar imaging, and using geometric and rock fracture mechanics analysis, we are able to quantify the stability of both sheets. Our analysis demonstrates that thermography can remotely detect intact rock bridges and thereby greatly improve rockfall hazard assessment.


Urinary excretion of 5-L-oxoproline (pyroglutamic acid) during early life in term and preterm infants.
Urinary 5-L-oxoproline was measured in term and preterm infants from shortly after birth until 6 weeks of postnatal age to determine their ability to synthesise glycine. In term infants the excretion was five to 10 times that seen in normal adults, increasing from 105 mumol/mmol creatinine in the first 72 hours after birth to 170 mumol/mmol creatinine at 6 weeks of age. There was a significant inverse linear correlation between the excretion of 5-L-oxoproline and length of gestation or birthweight. By 6 weeks of age there was no longer a significant difference in 5-L-oxoproline between term and preterm infants. There was no difference in the excretion of 5-L-oxoproline between boys and girls, or between infants fed on human milk or an artificial formula. If, in part, variability in the excretion of 5-L-oxoproline is determined by the extent to which the endogenous formation of glycine is adequate, then glycine formation may be marginal during early life, more so in preterm than in term infants, providing additional evidence that glycine is a conditionally essential amino acid in the neonate.


Adverse effects and cognitive function among primary care patients taking opioids for chronic nonmalignant pain.
Chronic opioid therapy is commonly prescribed for chronic nonmalignant pain. Few published data describe the adverse effects experienced by patients with chronic nonmalignant pain being treated by primary care physicians. A prevalence study was conducted on a sample of 1,009 patients (889 receiving chronic opioids) being treated by 235 primary care physicians. Standardized questionnaires and medical record reviews were used to assess rates of addiction, pain diagnosis and severity, opioid adverse effects, and mental health. The mean daily dose of opioids was 92 mg using a morphine-equivalent conversion. Side effects included constipation (40 percent), sleeping problems (25 percent), loss of appetite (23 percent), and sexual dysfunction (18 percent), with patients on daily opioids experiencing more side effects than subjects on intermittent medication. The Medical Outcomes Study Mental Health Inventory (MOS-MHI) cognitive functioning scale indicated poorer cognitive function in the overall sample of chronic pain patients as compared to a general clinical sample (delta x 95 percent CI = 9.28, 13.76). However, there were limited differences in MOS scores between chronic pain subjects on daily opioids vs. intermittent opioids vs. no prescription opioids. A regression model suggests that psychological measures and pain severity are more predictive of decrements in cognitive function than specific opioid preparations or daily opioid dose. Physicians should closely monitor patients for adverse effects and adequacy of pain control when using chronic opioid therapy for chronic pain treatment. Psychological health, an important predictor of cognitive dysfunction, is a particularly important measure to actively monitor and manage.


The projection of individual axons from the parabrachial region of the brain stem to the dorsal lateral geniculate nucleus in the cat.
In mammals, the retinogeniculocortical pathway is the primary afferent route to visual cortex. The flow of information along this pathway can be modulated at the thalamic level (i.e., at the lateral geniculate nucleus) as a function of arousal, attention, and phenomena such as eye movements. Physiological studies indicate that an important source of this state-dependent influence on geniculate neuronal responsiveness is the parabrachial region of the brain stem. We used the anterograde tracer Phaseolus vulgaris leucoagglutinin to study the anatomical connections between the parabrachial region and the lateral geniculate nucleus. Labeled parabrachial axons are found throughout the thalamus, including all laminae of the lateral geniculate nucleus, the lateral posterior-pulvinar complex, the ventral lateral geniculate nucleus, the perigeniculate nucleus, and the reticular nucleus of the thalamus. Within these nuclei, the axons exhibit sporadically branched terminal arbors with boutons mostly en passant. Serial reconstructions indicate that individual parabrachial axons that innervate the lateral geniculate nucleus may terminate in other visual thalamic nuclei as well, but not in thalamic nuclei that subserve other modalities. Finally, the labeled parabrachial axons are morphologically heterogeneous; they differ in their innervation targets, terminal arbor shape, and the size spectrum of their boutons. These data suggest that this portion of the ascending parabrachial pathway, which may be functionally diverse, coordinates the responsiveness of the varied thalamic nuclei involved with vision.


Influence of Intrinsic and Extrinsic Food Attributes on Consumers' Acceptance of Reformulated Food Products: a Systematic Review.
Reducing the salt, sugar and fat content of food is recognised worldwide as one of the strategies available for reducing the incidence of obesity and non-communicable diseases. The food industry has a major influence on achieving these goals by preserving intrinsic (chemical and sensory properties) and modifying extrinsic (food packaging and other external information) food attributes that can influence purchasing decisions. This article is a literature review of studies that analyse the influence of intrinsic and/or extrinsic attributes on consumer product preference and purchasing decisions. A keyword search for relevant studies was conducted using Web of Science, an interdisciplinary electronic resource. Articles from other sources were also included and systematically reviewed. The search string identified 266 results. Thirty-eight articles were included in the final analysis and coded according to intrinsic and extrinsic food attributes, reformulated nutrient, food category, condition, research methods, consumer response, study location and sample size. There are several authors investigating the effect of intrinsic rather than extrinsic product attributes. Most research deals with processed foods in the category of milk and dairy products, followed by sweetened fruit juices, meat products, sweets and bread. Salt content is the attribute most often reduced, followed by sugar and fat. Consumers find it hard to swap potential health benefits for hedonic attributes. When evaluating products in expected conditions, they usually rate the reformulated product more highly than the conventional one, while in informed conditions they usually choose the regular product. When products are labelled with a traffic light or nutritional warnings, consumers opt for a reformulated product, even in informed conditions. This review highlights the heterogeneity between food groups, and the fact that many factors influence consumers' product preferences and purchasing decisions. The product should be analysed as a whole and tested in blind, expected and informed conditions, as each individual factor represents a phase of the consumer purchasing decision. The extent of nutrient reduction should be determined by calculating the difference threshold, and the industry should reformulate products gradually based on how consumers detect the reduction.


A narrative inquiry into the Hong Kong Chinese adults' concepts of health through their cultural stories.
Abundant studies have investigated how health concepts held by individuals shape and are shaped by psychosocial and cultural factors, though many were limited to the conceptual level. The meaning and significance of health behaviours are better understood as an expression of something occurring over time. This narrative study explores how Hong Kong Chinese adults understand the meaning of health and the ways by which they construct and express these meanings in their lives. Additionally, by recognizing the central features of temporality, personal-social interactions within a place/culture in narrative thinking, this narrative inquiry may help health-care professionals to revisit the meaning of health promotion within the context of an individual's life situation. Five participants were recruited for the study. Data were collected through a series of audio-taped unstructured interviews and conversations with each participant. Findings underscore several features of participants' concepts and expressions of health: the significance of Confucian teachings on roles and responsibilities, Eastern view of self, Western biomedical orientation, and Hong Kong's unique work culture. Their responses not only express the attitudes and behaviours of individuals, but also the ways they engage in their constructed identity. Participants' concepts of health evolved over time according to the personal meanings attached to them at various life stages. While participants recognized the interconnectedness of the mind and body, the physical foci of traditional Western medicine remained salient in their health stories. Furthermore, there is a clear delineation of personal management of the psychological health and professional management of physical health.


Viscoelastic optical nonlocality of low-loss epsilon-near-zero nanofilms.
Optical nonlocalities are elusive and hardly observable in traditional plasmonic materials like noble and alkali metals. Here we report experimental observation of viscoelastic nonlocalities in the infrared optical response of epsilon-near-zero nanofilms made of low-loss doped cadmium-oxide. The nonlocality is detectable thanks to the low damping rate of conduction electrons and the virtual absence of interband transitions at infrared wavelengths. We describe the motion of conduction electrons using a hydrodynamic model for a viscoelastic fluid, and find excellent agreement with experimental results. The electrons' elasticity blue-shifts the infrared plasmonic resonance associated with the main epsilon-near-zero mode, and triggers the onset of higher-order resonances due to the excitation of electron-pressure modes above the bulk plasma frequency. We also provide evidence of the existence of nonlocal damping, i.e., viscosity, in the motion of optically-excited conduction electrons using a combination of spectroscopic ellipsometry data and predictions based on the viscoelastic hydrodynamic model.


Deep-dive into iron-based co-precipitation of arsenic: A review of mechanisms derived from synchrotron techniques and implications for groundwater treatment.
The co-precipitation of Fe(III) (oxyhydr)oxides with arsenic (As) is one of the most widespread approaches to treat As-contaminated groundwater in both low- and high-income settings. Fe-based co-precipitation of As occurs in a variety of conventional and decentralized treatment schemes, including aeration and sand filtration, ferric chloride addition and technologies based on controlled corrosion of Fe(0) (i.e., electrocoagulation). Despite its ease of deployment, Fe-based co-precipitation of As entails a complex series of chemical reactions that often occur simultaneously, including electron-transfer reactions, mineral nucleation, crystal growth, and As sorption. In recent years, the growing use of sophisticated synchrotron-based characterization techniques in water treatment research has generated new detailed and mechanistic insights into the reactions that govern As removal efficiency. The purpose of this critical review is to synthesize the current understanding of the molecular-scale reaction pathways of As co-precipitation with Fe(III), where the source of Fe(III) can be ferric chloride solutions or oxidized Fe(II) sourced from natural Fe(II) in groundwater, ferrous salts or controlled Fe(0) corrosion. We draw primarily on the mechanistic knowledge gained from spectroscopic and nano-scale investigations. We begin by describing the least complex reactions relevant in these conditions (Fe(II) oxidation, Fe(III) polymerization, As sorption in single-solute systems) and build to multi-solute systems containing common groundwater ions that can alter the pathways of As uptake during Fe(III) co-precipitation (Ca, Mg bivalent cations; P, Si oxyanions). We conclude the review by providing a perspective on critical knowledge gaps remaining in this field and new research directions that can further improve the understanding of As removal via Fe(III) co-precipitation.


Spastic disorders of the esophagus.
Spastic disorders of the esophagus are found in up to 50% of patients referred for manometry, therapy representing the most prevalent motility disorders in clinical practice. They share in common their manifestations of hypermotility, one of two principal types of esophageal motor dysfunction. Diffuse esophageal spasm is segregated from the nonspecific spastic disorders because of its demonstrated interference with bolus transit. However, the overlap among the spastic disorders in manifestation, course, and management is great; segregation of any disorder within this group is not of paramount importance. Spastic disorders, pain reproduction with provocative testing, and psychological abnormalities are coprevalent in patients with unexplained symptoms, but a cause-effect relationship of the motor abnormalities with the other findings is not established. The physician's charge in determining the relevance of a spastic disorder to the clinical presentation and for creating a treatment plan is to establish a direct relationship of motor dysfunction with symptoms-a task that may require correlation of transit abnormalities with symptoms using tests other than manometry. A variety of treatment options, invasive and noninvasive, are available today for patients who have spastic disorders, and each is effective in appropriately selected candidates.


Possible risk factors for primary adult onset dystonia: a case-control investigation by the Italian Movement Disorders Study Group.
Little is known about the aetiology of idiopathic adult onset dystonia. The Italian Movement Disorders Study Group promoted a case-control study on some hypothetical risk factors including past medical events, life events, life habits, occupational hazards, and family history of dystonia, parkinsonism, and tremor. Cases affected by idiopathic adult onset dystonia (age at symptom onset >20 years, duration of disease >one year and <five years) were selected among consecutive outpatients attending 14 Italian centres. Control outpatients matched for age (+/-5 years), sex, and referral centre were identified among diagnostic categories thought to be unassociated with study exposures. Information was obtained by a standardised questionnaire administered by medical interviewers. Conditional logistic univariate and multivariate regression analyses were performed by a standard statistical package. Multivariate analysis on 202 cases and 202 age and sex matched control outpatients indicated that head or facial trauma with loss of consciousness, family history of dystonia, and family history of postural tremor independently increased the risk of developing adult onset dystonia, whereas hypertension and cigarette smoking exerted a protective effect. The findings also suggested a positive association between local body injury-for example, previous ocular diseases and neck or trunk trauma-and dystonia of the same body part. The results support the idea that environmental and genetic factors may both be important in the aetiology of adult onset dystonia, and suggest aetiological clues worthy of further analytical investigation.


A new EC-PC threshold estimation method for in vivo neural spike detection.
This paper models in vivo neural signals and noise for extracellular spike detection. Although the recorded data approximately follow Gaussian distribution, they clearly deviate from white Gaussian noise due to neuronal synchronization and sparse distribution of spike energy. Our study predicts the coexistence of two components embedded in neural data dynamics, one in the exponential form (noise) and the other in the power form (neural spikes). The prediction of the two components has been confirmed in experiments of in vivo sequences recorded from the hippocampus, cortex surface, and spinal cord; both acute and long-term recordings; and sleep and awake states. These two components are further used as references for threshold estimation. Different from the conventional wisdom of setting a threshold at 3×RMS, the estimated threshold exhibits a significant variation. When our algorithm was tested on synthesized sequences with a different signal to noise ratio and on/off firing dynamics, inferred threshold statistics track the benchmarks well. We envision that this work may be applied to a wide range of experiments as a front-end data analysis tool.


Myeloperoxidase-deficient polymorphonuclear leucocytes. (II) Longitudinal study in acute myeloid leukaemia, untreated, in remission and in relapse.
Myeloperoxidase (MPO) activity of blood granulocytes was estimated in 96 cases of acute myeloid leukaemia (AML), in 35 patients obtaining complete remission and in 14 of these patients during later relapse. As the pretreatment value of MPO activity was the same in patients who died before obtaining remission as in patients obtaining complete remission, determination of MPO-deficient PMN has no prognostic value with respect to the probability of obtaining complete remission. While half of the untreated patients had increased numbers of MPO-deficient PMN in the blood, all patients in complete remission had normal MPO activity (P = 0.0002). A normalization of the MPO activity after induction therapy, therefore suggests remission. Positive correlations could be demonstrated between an initially abnormal MPO activity and abnormal activity at relapse as well as between an initially abnormal MPO activity and normal activity at relapse (P = 0.0004). It is concluded that determination of the % of MPO-deficient PMN in the blood, may be a useful indicator of complete remission in AML, and in serial determinations during the remission phase also an indicator of threatening relapse.


Methane Bubble Ascent within Fine-Grained Cohesive Aquatic Sediments: Dynamics and Controlling Factors.
Methane (CH4) is a potent greenhouse gas. Its release from aquatic sediments to the water column and potentially to the atmosphere, is a subject of great concern. A coupled macroscopic single-bubble mechanical/reaction-transport numerical model was used to explore the ascent of a mature CH4 bubble toward the seafloor in muddy aquatic sediment. Two bubble ascent scenarios were demonstrated: stable and dynamic. For small effective overburden loads (≤11 kPa), stable ascent is followed by dynamic ascent (which has not been previously demonstrated to the best of the our knowledge). This ultimately leads to the bubble being released to the water column. Higher effective overburden loads induce only stable bubble ascent, which stops at the gas horizon frequently observed below the seafloor. The depth of the gas horizon increases, while bubble rise velocity decreases with an increase in the overburden load. It is shown that the bubble migration scenario is managed predominantly by inner bubble pressure, which defines a bubble solute exchange with ambient porewaters. Predicting a bubble ascent scenario in muddy sediment will further allow estimation of CH4 emission to the atmosphere and evaluation of changes in the effective mechanical properties of aquatic sediment due to the ascending bubbles.


Mechanistic and genetic overlap of barley host and non-host resistance to Blumeria graminis.
SUMMARY Non-host resistance of barley to Blumeria graminis f.sp. tritici (Bgt), an inappropriate forma specialis of the grass powdery mildew fungus, is associated with formation of cell wall appositions (papillae) at sites of attempted fungal penetration and a hypersensitive cell death reaction (HR) of single attacked cells. Penetration resistance and HR are also typical features of race-non-specific and race-specific resistance of barley to the appropriate Blumeria graminis f.sp. hordei (Bgh), raising the question of whether genotypic differences in the cellular response of barley to Bgt are detectable. First, we analysed fungal penetration frequencies and HR in different barley accessions known to show altered non-host resistance. In genotypes with limited resistance to inappropriate cereal rust fungi, we concomitantly detected low penetration resistance to Bgt and significant differences of HR rates during attack from Bgt. Second, we tested barley mutants known to show altered host responses to Bgh. The rar1-mutation that suppresses many types of race-cultivar-specific resistances did not influence the non-host response of the Bgt-isolate used in this study. However, mutants of Ror1 and Ror2, two genes required for full race non-specific penetration resistance of mlo-barley to barley powdery mildew fungus, exhibited altered defence response to Bgt, including higher frequencies of fungal penetration. On these mutants, growth of the inappropriate fungus was arrested subsequent to penetration by HR. Together, the data show that barley defence response to the wheat powdery mildew fungus is determined by similar factors as race-specific and race-non-specific resistance to appropriate Bgh.


[The role of hemostasis system in the pathogenesis and course of multiple sclerosis].
The influence of anticoagulation components of hemostasis system and lupus anticoagulants (LA) upon the course of multiple sclerosis (MS) was studied. 57 patients with MS diagnosed according to McDonald's criteria (McDonald WI et al., 2001) were examined: 19 males and 38 females aged 16-62 (mean age 36.8 +/- 11.2 yrs) with 1-25 yrs history of MS (mean duration 8.1 +/- 5.7 yrs). 42 patients suffered from relapsing-remitting MS, 17 patients were affected by secondary progressive MS. The degree of neurological deficit was estimated in remission according to Expanded Disability Status Scale (EDSS), mean score was 3.8 +/- 1.7. The progression of MS was estimated as EDSS score per year ratio. In patients with relapsing-remitting MS the mean number of exacerbations per year was calculated. The following laboratory findings were evaluated: thrombin clotting time, antithrombin-III activity, plasminogen reserve by the level of streptokinase-induced euglobulin fibrinolysis, protein C activity, factor Va resistance to activated protein C, lupus anticoagulants (LA). It was revealed that LA could worsen relapsing-remitting MS: in LA-positive patients there were 1.41 +/- 0.69 exacerbations per year and progression score reached 0.82 +/- 0.30, whereas in LA-negative patients the figures were 0.74 +/- 0.58 (p < 0.001) and 0.48 +/- 0.33 (p < 0.01) respectively. All the patients showed decrease of protein C activity (p < 0.001) with no relation to LA activity or factor Va resistance to activated protein C. Normal level of plasminogen and antithrombin-III activity was supposed to be the marker of benign variant of MS. The course of MS was mild in patients with high antithrombin-III activity even if they were hypercoagulative--this suggests neuroprotective activity of antithrombin-III which may relate not only to its anticoagulation effect.


Idiopathic duct-centric pancreatitis: disease description and endoscopic ultrasonography-guided trucut biopsy diagnosis.
Recent data demonstrate the presence of two autoimmune pancreatitis (AIP) subtypes. All existing endoscopic ultrasonography-guided trucut biopsy (EUS-TCB) data pertain to type 1 disease. Our aim is to determine if EUS-TCB samples are sufficient for diagnosing type 2 AIP. This is a retrospective case series conducted in an academic tertiary care center. Patients included those with type 2 AIP (n = 5), retrospectively identified from a database of all patients with AIP, diagnosed by HISORt criteria (n = 125). The primary outcome measure was the diagnostic capability of EUS-TCB for type 2 AIP. 5 patients (4 male, 1 female; mean age 39.6 years) who underwent EUS-TCB were diagnosed with type 2 AIP. The serum IgG(4) level was elevated in 1 of the 4 patients tested. CT/MRI revealed diffuse pancreas enlargement (n = 3), a pancreas head mass (n = 1), and a normal pancreas (n = 1). Prior to EUS, AIP was not specifically suspected, but part of a broad differential (n = 3) or not suspected at all (n = 2). Fine-needle aspiration was negative for neoplasia and AIP. The TCB histology was definitive (n = 4) or suggestive (n = 1) for type 2 AIP. No complications developed. EUS-TCB may be safe and may provide sufficient material to definitively diagnose type 2 AIP. and IAP.


Malignant Triton Tumor (Malignant Peripheral Nerve Sheath Tumor With Rhabdomyoblastic Differentiation) Occurring in a Vascularized Free Flap Reconstruction Graft.
Malignant peripheral nerve sheath tumor (MPNST) is a rare form of sarcoma arising from Schwann cells or pluripotent cells of the neural crest. Malignant triton tumor (MTT) is a subtype of MPNST with a component of malignant rhabdomyoblasts in addition to malignant Schwann cells. MPNST and MTT are both aggressive malignancies that most commonly arise from large deep neurofibromas in patients with neurofibromatosis type 1 (NF-1). However, sporadic non-NF-1 cases of MTT have also been reported in the literature. We present a case of a 50-year-old African American male with no stigmata of NF-1 who developed a large mass in a free flap on the right calf. The free flap had been placed by plastic surgery 15 years previously following open right tibial and fibular fractures associated with a large soft tissue defect. Biopsy of the enlarging mass, followed by wide surgical excision, confirmed the pathology to be MTT. Although the development of a high-grade soft tissue sarcoma has been previously reported as a late complication of radiation therapy following free flap reconstructions, we believe this is the first reported case of sarcomatous transformation arising in a vascularized, free muscle transfer.


Simple epidemic models with segmentation can be better than complex ones.
Given a sequence of epidemic events, can a single epidemic model capture its dynamics during the entire period? How should we divide the sequence into segments to better capture the dynamics? Throughout human history, infectious diseases (e.g., the Black Death and COVID-19) have been serious threats. Consequently, understanding and forecasting the evolving patterns of epidemic events are critical for prevention and decision making. To this end, epidemic models based on ordinary differential equations (ODEs), which effectively describe dynamic systems in many fields, have been employed. However, a single epidemic model is not enough to capture long-term dynamics of epidemic events especially when the dynamics heavily depend on external factors (e.g., lockdown and the capability to perform tests). In this work, we demonstrate that properly dividing the event sequence regarding COVID-19 (specifically, the numbers of active cases, recoveries, and deaths) into multiple segments and fitting a simple epidemic model to each segment leads to a better fit with fewer parameters than fitting a complex model to the entire sequence. Moreover, we propose a methodology for balancing the number of segments and the complexity of epidemic models, based on the Minimum Description Length principle. Our methodology is (a) Automatic: not requiring any user-defined parameters, (b) Model-agnostic: applicable to any ODE-based epidemic models, and (c) Effective: effectively describing and forecasting the spread of COVID-19 in 70 countries.


Six cycles of doxorubicin and cyclophosphamide or Paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101.
The ideal duration of adjuvant chemotherapy for patients with lower risk primary breast cancer is not known. Cancer and Leukemia Group B trial 40101 was conducted using a phase III factorial design to define whether six cycles of a chemotherapy regimen are superior to four cycles. We also sought to determine whether paclitaxel (T) is as efficacious as doxorubicin/cyclophosphamide (AC), but with reduced toxicity. Between 2002 and 2008, the study enrolled women with operable breast cancer and zero to three positive nodes. Patients were randomly assigned to either four or six cycles of either AC or T. Study stratifiers were estrogen receptor/progesterone receptor (ER/PgR), human epidermal growth factor receptor 2 (HER2), and menopausal status. After 2003, all treatment was administered in dose-dense fashion. The primary efficacy end point was relapse-free survival (RFS). A total of 3,171 patients were enrolled; 94% were node-negative and 6% had one to three positive nodes. At a median follow-up of 5.3 years, the 4-year RFS was 90.9% and 91.8% for six and four cycles, respectively. The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95% CI, 0.84 to 1.28; P=.77). The 4-year OS was 95.3% and 96.3% for six and four cycles, respectively, with an HR of six to four cycles of 1.12 (95% CI, 0.84 to 1.49; P=.44). There was no interaction between treatment duration and chemotherapy regimen, ER/PgR, or HER2 status on RFS or OS. For women with resected primary breast cancer and zero to three positive nodes, we found no evidence that extending chemotherapy regimens of AC or single-agent T from four to six cycles improves clinical outcome.


Heregulin expression and prognosis in prostate adenocarcinoma.
Heregulins (HRG) are a family of growth factors acting as ligands to HER3, HER4 and HER family signalling. HRG has a concentration-dependent differential growth effect--low levels mitogenic, high levels inhibitory. HRG differentially affects hormone-naïve (inhibitory) and castrate-resistant (proliferative) prostate adenocarcinoma (CaP) cell lines. We postulate that differential HRG expression in CaP will be associated with alteration in tumour growth, development and prognosis. HRG expression was assessed in 2 cohorts: cohort 1 of 45 patients with paired hormone-naïve and castrate-resistant samples, and cohort 2 of 357 hormone-naïve samples. Correlations between HRG expression and biochemical relapse and survival were determined. In cohort 1, hormone-naïve samples' high membranous HRG expression was associated with increased time to relapse (p = 0.036), time to death from relapse (p = 0.002) and overall survival (p = 0.001). Membrane HRG fell significantly in post-relapse specimens. In cohort 2, high membranous HRG was associated with increased time to relapse (p = 0.004) and overall survival (p = 0.044) in patients treated with castration therapy but only with overall survival (p = 0.002) in the full cohort. High HRG expression is associated with improved prognosis in hormone-naïve CaP and a fall in expression occurs at castration escape indicating a protective role against castrate resistance.


Prevalence and severity of symptoms of asthma, allergic rhino-conjunctivitis and atopic eczema in secondary school children in Ibadan, Nigeria.
This study was part of the effort of the International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee to evaluate the epidemiology of asthma and allergic diseases around the world. Three thousand and fifty eight randomly selected children aged 13-14 years were studied, using a standard questionnaire developed and field tested by the ISAAC Steering Committee, to establish the prevalence and severity of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema. Of the 3,058 children, there were 1,659 (54.3%) females and 1,399 (45.7%) males (F:M ratio 1.2:1). The cumulative prevalence rates of wheezing, rhinitis other than common cold, and symptoms of eczema were 16.4%, 54.1% and 26.1%, respectively while within the immediate 12-month period, the rates were 10.7%, 45.2% and 22.4%, respectively. However, rhinitis associated with itchy eyes (allergic rhinoconjunctivitis) was reported by 39.2% of the school children. The prevalence of doctor-diagnosed asthma was 18.4%. Multiple logistic regression analysis showed that a higher prevalence of wheezing and rhinitis was associated with itchy eyes. The prevalence of severe symptoms of asthma, allergic rhinitis and eczema were higher when compared with a similar study in Kenya. However, the prevalence of symptoms of asthma was lower and that of allergic rhinoconjunctivitis higher in our series. There is a need for further studies to investigate the risk factors which might be responsible for the apparently different patterns in these two African countries.


Evidence for intramolecular processing of prosubtilisin sequestered on a solid support.
Subtilisin E is synthesized in Bacillus subtilis as a preprosubtilisin. The prepeptide is removed by a signal peptidase, and the propeptide is cleaved from the mature protein by the catalytic domain of subtilisin itself in an autocatalytic fashion. A six residue histidine-tag was attached to the C terminus of prosubtilisin and mature subtilisin to enable immobilization on a metal chelating resin. Guanidine-HC1 denatured histidine-tagged subtilisin and prosubtilisin were immobilized on Co2+ charged Talon resin, then renatured by dialysis of the resin against renaturation buffer. Refolding of the immobilized prosubtilisin resulted in its quantitative autoprocessing and the formation of active enzyme. Mature subtilisin on the other hand refolded into an active conformation with very low efficiency, and at the same concentration the steady-state rate attained was at least a 1000 times lower than that from prosubtilisin. The results give very strong support for an intramolecular autoprocessing pathway for prosubtilisin, in addition to an intermolecular one demonstrated before. The results also demonstrate rather convincingly the very much higher yield of active enzyme refolded from prosubtilisin than from mature protein under sequestered unimolecular conditions.


Advances in intraocular techniques in the treatment of retinal detachments arising from holes of the posterior pole.
Two groups of retinal detachments arising from macular holes were compared. The first group consisted of 27 consecutive cases operated upon during the years 1972-7 by various techniques (encircling and hemi-encircling procedures, scleral resection, scleral pocket, and silver clip). The second group consisted of 18 consecutive cases operated upon in the years 1978-81 by pars plana vitrectomy to release vitreous traction or make intraocular manoeuvres possible. In all cases of the second group an intraocular gas bubble was used to tamponade the macular hole, and the hole was coagulated only if necessary. There was not only a significantly better anatomical result in the second group, but the functional results were more favourable. Two-thirds of the eyes of the second group reached a visual acuity between 6/12 and 6/48, while in the first group none of the eyes gained a better vision than 6/60. The reading vision in 2/3 of the first group was negligible, while nearly half of the cases in the second group reached useful acuity between Jaeger 3 and 10.


A prospective study of obesity and risk of coronary heart disease among diabetic women.
To examine the relationship of obesity, measured as BMI, and weight change to incidence of coronary heart disease (CHD) among women with diabetes. We followed 5,897 women with type 2 diabetes in the Nurses' Health Study for < or = 20 years. Women were aged 40-74 years and had no history of cardiovascular disease or cancer at the beginning of the follow-up period. BMI values from three time points (age 18 years, year 1976, and current) were derived from the reported height (1976) and corresponding reported weight. Weight changes between age 18 years and 1976 and after diagnosis of diabetes were calculated. Women reported diagnoses of diabetes and CHD every 2 years. Incident CHD cases were confirmed by medical record review. During follow-up, we documented 418 incident cases of CHD (236 of nonfatal myocardial infarction and 182 of fatal CHD). After adjustment for age, smoking, and other coronary risk factors, current BMI was strongly associated with increased risk of CHD among diabetic women. The multivariate relative risks across increasing categories of BMI (<23.0, 23.0-24.9, 25.0-26.9, 27.0-29.9, 30.0-34.9, and > or = 35.0 kg/m(2)) were 1.0, 1.58, 1.85, 1.95, 2.80, and 3.21, respectively (P for trend <0.001). Increasing BMI values from age 18 years to 1976, before diagnosis of diabetes, were also positively associated with risk of CHD. Weight gain before the diagnosis of diabetes was related to increased risk of CHD. In contrast, weight change after diagnosis of diabetes was not associated with risk of CHD. These findings provide strong evidence that obesity and weight gain before diagnosis of diabetes are associated with future risk of CHD among women with type 2 diabetes.


What Black Women Know and Want to Know About Counseling and Testing for BRCA1/2.
Black women are just as likely to have hereditary breast cancer mutations as White women, yet their participation in genetic counseling and testing is substantially lower. This study sought to describe Black women's awareness and perceptions of BRCA1/2 testing and to identify barriers and motivators to seeking BRCA1/2 services. Fifty intercept interviews were conducted with Black women in public places (a professional women's basketball game, a grocery store, a faith-based community event, and the waiting area at a breast care clinic) in Washington, DC. More than half of the women (54%) were aware that genetic tests to determine risk for certain breast and ovarian cancers exist, but the majority (88%) had never heard of BRCA1/2, specifically. After hearing a description of BRCA1/2 genetic markers, 82% stated that they would agree to BRCA1/2 testing if it was offered to them. Perceived advantages of testing included cancer prevention and the ability to share information with family members. Perceived disadvantages included emotional distress associated with identification of the mutation and the potential misuse of results to deny healthcare or employment. Physician recommendation, self-care, and known family history were among the motivators for testing. Women listed possible media and venues for intervention. In spite of low rates of BRCA1/2 testing in the Black community, women in this sample were open to the idea. Interventions that address barriers and include cultural tailoring are necessary.