A randomised double-blind study comparing sodium feredetate with ferrous fumarate in anaemia in pregnancy.
Iron deficiency anaemia is a major health problem in India especially in women of reproductive age group. The World Health Organisation recommends that the haemoglobin concentration should not fall below 11.0 g/dl at any time during pregnancy. The aim of study was to compare the efficacy and safety of two doses of sodium feredetate with ferrous fumarate in improving haemoglobin profile in pregnant anaemic women. Pregnant women with gestation period between 12 and 26 weeks having serum haemoglobin < 10 g/dl, serum ferritin levels less than 12 microg/l were included in the study. Patients were divided into 3 groups and drugs administered accordingly. A total of 48 patients were available for analysis which included 37 patients who had completed all the visits up to 75 days follow-up and 11 patients who were treatment failures. In group A combination of sodium feredetate (containing 33 mg of elemental iron) along with vitamin B12 (15 microg) and folic acid (1.5 mg) was administered twice a day. In group B combination of sodium feredetate (containing 66 mg of elemental iron) along with vitamin B12 (15 microg) and folic acid (1.5 mg) was administered twice a day. In group C combination of ferrous fumarate (containing 100 mg of elemental iron) along with vitamin B12 (15 microg) and folic acid (1.5 mg) was administered twice a day. Patients were evaluated for Hb, RBC count, MCV, MCH and MCHC at day 0, 30, 45, 60 and 75. Serum ferritin, serum iron, TIBC and transferrin saturation were assessed at recruitment and end study. Mean rise of haemoglobin at the completion of study, over that of basal values was 1.79 g/dl (0.71 to 2.87, 95% CI, p < 0.05) in group A, 1.84 g/dl (0.82 to 2.86, 95% CI, p < 0.05) in group B and 1.63 g/dl (0.38 to 2.88, 95% CI, p < 0.05) in group C. Safety assessment was done by doing liver and kidney function test at the time of recruitment and end study. Low doses of sodium feredetate (33 mg and 66 mg of elemental iron given twice daily) produce comparable results as higher dose of ferrous fumarate (100 mg elemental iron given twice daily). As there were no adverse effects reported with sodium feredetate, it can be concluded from this study that this new formulation appears to be effective in improving haemoglobin profile in pregnant anaemic women and is tolerated well.


Collagen VI is a subepithelial adhesive target for human respiratory tract pathogens.
Bacterial engagement of specific host tissue structures can be a means of targeting a pathogen to a particular niche, establishing persistent infections and inducing invasion. In this context, primary adhesion is often the first crucial colonization step allowing pathogens to withstand the mechanical clearing mechanisms of the host. As a consequence, bacteria have evolved adhesins with the capacity to mediate interaction between microorganism and host. Here we describe collagen VI as a novel target for adherence of Streptococcus pyogenes and Streptococcus pneumoniae. In upper and lower airways this collagen was distributed in the lamina propria underneath the epithelial basement membrane. Both pathogens exhibited strong affinity to collagen VI as shown by light and electron microscopy in combination with immunodetection and in vitro binding assays. For S. pyogenes this interaction was mediated by M1 protein. The presented data provide evidence for a previously unrecognized role for collagen VI in host-pathogen interplay during respiratory tract infection.


The relationship between take-away methadone policies and methadone diversion.
The development of policies in relation to unsupervised doses of methadone (take-away doses) should be based upon the best available evidence. There are both risks and benefits associated with take-away doses. This study aimed to explore the relationship between take-away policies and one measure of harm: methadone injection rates. Six different states in Australia were compared in relation to their methadone take-away policy and rates of methadone injection within their population of injecting drug users. At a simplistic level, those states with restrictive and less flexible take-away policies tended to have the lowest reported prevalence of methadone injection. However, this does not fully explain variability in methadone injecting. There were also considerable differences between those states with similar take-away policies. Variables which appear to impact upon methadone injecting rates include: take-away policies, drug preference, drug availability, treatment availability and degree of treatment penetration. Consideration of the benefits, rather than merely the harms, of various take-away policy options may provide an evidence-based platform for take-away policy development.


[Asthma with aspirin intolerance].
We described asthma with sensitivity to aspirin and other nonsteroidal anti-inflammatory drugs (NSAID). It was presented clinical picture, diagnosis and pathomechanism of this syndrome. Specially was described the cyclooxygenase theory and genetic risk of aspirin induced asthma as well as tolerability of the new COX-2 inhibitors.


Regulation by muramyl dipeptide (MDP) of the lymphoproliferative responses and polyclonal activation of human peripheral blood mononuclear cells.
The ability of muramyl dipeptide (MDP), its adjuvant inactive stereoisomer, MDP(D-D), and the non-pyrogenic, adjuvant active analogue, MDP-butyl ester (MDP-BE), to induce in vitro proliferation and/or polyclonal activation (PA) of peripheral blood mononuclear cells (PBMNC) from normal volunteers, was studied. MDP, as well as its two analogues, were incapable of inducing 3H-thymidine uptake or immunoglobulin synthesis in PBMNC cultures from the majority of the individuals tested. However, these muramyl peptides were capable of regulating the in vitro proliferative responses of some individuals to concanavalin A and to soluble antigens of Candida albicans. At the same time, enhancement of the pokeweed mitogen-induced IgA and IgM but not IgG PA was observed with MDP, its adjuvant active analogue MDP-BE, but not with the adjuvant inactive stereoisomer MDP(D-D). Results are discussed with relation to a possible genetic restriction of the responsiveness to MDP.


Ultra-fast local-haplotype variant calling using paired-end DNA-sequencing data reveals somatic mosaicism in tumor and normal blood samples.
Somatic mosaicism refers to the existence of somatic mutations in a fraction of somatic cells in a single biological sample. Its importance has mainly been discussed in theory although experimental work has started to emerge linking somatic mosaicism to disease diagnosis. Through novel statistical modeling of paired-end DNA-sequencing data using blood-derived DNA from healthy donors as well as DNA from tumor samples, we present an ultra-fast computational pipeline, LocHap that searches for multiple single nucleotide variants (SNVs) that are scaffolded by the same reads. We refer to scaffolded SNVs as local haplotypes (LH). When an LH exhibits more than two genotypes, we call it a local haplotype variant (LHV). The presence of LHVs is considered evidence of somatic mosaicism because a genetically homogeneous cell population will not harbor LHVs. Applying LocHap to whole-genome and whole-exome sequence data in DNA from normal blood and tumor samples, we find wide-spread LHVs across the genome. Importantly, we find more LHVs in tumor samples than in normal samples, and more in older adults than in younger ones. We confirm the existence of LHVs and somatic mosaicism by validation studies in normal blood samples. LocHap is publicly available at http://www.compgenome.org/lochap.


Quantifying Photonic High-Dimensional Entanglement.
High-dimensional entanglement offers promising perspectives in quantum information science. In practice, however, the main challenge is to devise efficient methods to characterize high-dimensional entanglement, based on the available experimental data which is usually rather limited. Here we report the characterization and certification of high-dimensional entanglement in photon pairs, encoded in temporal modes. Building upon recently developed theoretical methods, we certify an entanglement of formation of 2.09(7) ebits in a time-bin implementation, and 4.1(1) ebits in an energy-time implementation. These results are based on very limited sets of local measurements, which illustrates the practical relevance of these methods.


Angle closure in younger patients.
Angle-closure glaucoma is rare in children and young adults; only scattered cases associated with specific clinical entities have been reported. We evaluated the findings in patients aged 40 or younger with angle closure in our database. Retrospective noncomparative case series. Our database was searched for patients aged 40 years or younger with angle closure. Data recorded included age at initial consultation, age at the time of diagnosis, gender, slit-lamp examination, gonioscopy, ultrasound biomicroscopy (from 1993 onward), clinical diagnosis, and therapy. Patients with prior incisional surgery were excluded, as were patients with anterior chamber proliferative mechanisms leading to angle closure. Sixty-seven patients (49 females, 18 males) met entry criteria. Mean age at the time of consultation was 34.4 +/- 9.4 (standard deviation) years (range, 3-68 years). Diagnoses included plateau iris syndrome (35 patients); iridociliary cysts (8 patients); retinopathy of prematurity (7 patients); uveitis (5 patients); isolated nanophthalmos (3 patients); relative pupillary block (2 patients); Weill-Marchesani syndrome (3 patients); and 1 patient each with Marfan syndrome, miotic-induced angle closure, persistent hyperplastic primary vitreous, and idiopathic lens subluxation. The etiology of angle closure in young individuals differs from the older population and is typically associated with structural/developmental ocular anomalies rather than relative pupillary block. After laser iridotomy, these eyes should be monitored for recurrent angle closure and the need for additional laser or incisional surgical intervention.


Natural Compounds as Inhibitors of Tyrosyl-tRNA Synthetase.
Tyrosyl-tRNA synthetases (TyrRSs) as essential enzymes for all living organisms are good candidates for therapeutic target in the prevention and therapy of microbial infection. We examined the effect of various polyphenols, alkaloids, and terpenes-secondary metabolites produced by higher plants showing many beneficial properties for the human organism, on bacterial aminoacylation reaction. The most potent inhibitors of Escherichia coli TyrRS are epigallocatechin gallate, acacetin, kaempferide, and chrysin, whereas the enzymes from Staphylococcus aureus and Pseudomonas aeruginosa are inhibited mainly by acacetin and chrysin. Most of them act as competitive inhibitors. Structure-activity relationship showed that the most potent flavonoid inhibitors contain hydroxyl group at position 5 and 7 of A ring and OCH3 group at position 4' of B ring.


Univariate associations between housing, management, and facility design factors and the prevalence of lameness lesions in fourteen small-scale dairy farms in Northeastern Algeria.
This cross-sectional study aimed to analyze the associations between different types of housing, management, and facilities on the prevalence of lame, causing lesions in smallholder dairy farms in Algeria. The on-site investigation took place between December 2012 and May 2015. All cows were locomotion scored on a four-point scale, and foot lesions causing lame were diagnosed and recorded. Factors related to the farm and the cows' conditions were also assessed. The association between the possible risk factors and lame lesions was assessed using univariate analysis. Of the 349 cows evaluated, 13% were lame (lameness score ≥2), with higher lameness values recorded for the hind feet than for the forefeet. Cows without lameness were classified as healthy. The two most frequent lesion diagnoses observed in lame cows were interdigital dermatitis/heel horn erosion (ID/HE; 39%) and interdigital phlegmon (IP; 35%), followed by traumatic lesions (T; 11%), digital dermatitis (DD; 8.7%), and laminitis-related diseases (L; 6.5%). The risk of being lame was increased in large herds with cows of the Holstein breed, and those in the third parity and above. Tie housing, concrete floor, concentrate feeding, zero-grazing, and the use of foot trimming occasionally were associated with increased risk for the presence of lame lesions. The region and footbathing frequency had no association with the prevalence of lame lesions (p≥0.05). These results have important implications; they indicate that several aspects of housing, management, and facility design are common protective factors for the prevalence of lame lesions. These factors should be maintained correctly to not only reduce the number of lame cows in these herds but also decrease the direct and indirect costs associated with cases of lameness.


Seamless Tube-Type Heater with Uniform Thickness and Temperature Distribution Based on Carbon Nanotubes Aligned by Circumferential Shearing.
The uniform temperature distribution, one of the requirements for long-term durability, is essential for composite heaters. An analytical model for temperature distribution of a tube-type heater was derived, and it revealed that thickness uniformity is one order more important than intrinsic material properties such as density, heat capacity, and electrical conductivity of the heating tube. We introduced a circumferential shearing process to fabricate a flexible, seamless tube-type heating layer of carbon nanotube/silicone rubber composite with outstanding uniform distribution of thickness and temperature, which may be attributed to a shorter characteristic dimension in the circumferential direction than in the axial direction. The temperature uniformity was experimentally verified at various temperatures under heating. The difference in measured thickness and temperature in circumferential direction was within ±1.3~3.0% (for tavg = 352.7 μm) and ±1.1% (for Tavg = 138.8 °C), respectively, all over the heating tube. Therefore, the circumferential shearing process can be effective for cylindrical heaters, like a heating layer of a laser printer, which fuse toners onto papers during printing.


The endocannabinoid/endovanilloid system and depression.
Depression is one of the most frequent causes of disability in the 21st century. Despite the many preclinical and clinical studies that have addressed this brain disorder, the pathophysiology of depression is not well understood and the available antidepressant drugs are therapeutically inadequate in many patients. In recent years, the potential role of lipid-derived molecules, particularly endocannabinoids (eCBs) and endovanilloids, has been highlighted in the pathogenesis of depression and in the action of antidepressants. There are many indications that the eCB/endovanilloid system is involved in the pathogenesis of depression, including the localization of receptors, modulation of monoaminergic transmission, inhibition of the stress axis and promotion of neuroplasticity in the brain. Preclinical pharmacological and genetic studies of eCBs in depression also suggest that facilitating the eCB system exerts antidepressant-like behavioral responses in rodents. In this article, we review the current knowledge of the role of the eCB/endovanilloid system in depression, as well as the effects of its ligands, models of depression and antidepressant drugs in preclinical and clinical settings.


Ultrahigh-Performance Optoelectronics Demonstrated in Ultrathin Perovskite-Based Vertical Semiconductor Heterostructures.
Two-dimensional (2D) atomic layered semiconductor (e.g., transition metal dichalcogenides, TMDCs) heterostructures display diverse novel interfacial carrier properties and have potential applications in constructing next generation highly compact electronics and optoelectronics devices. However, the optoelectronic performance of this kind of semiconductor heterostructures has difficulty reaching the expectations of practical applications, due to the intrinsic weak optical absorption of the atomic-thick component layers. Here, combining the extraordinary optoelectronic properties of quantum-confined organic-inorganic hybrid perovskite (PVK), we design an ultrathin PVK/TMDC vertical semiconductor heterostructure configuration and realize the controlled vapor-phase growth of highly crystalline few-nanometer-thick PVK layers on TMDCs monolayers. The achieved ultrathin PVKs show strong thickness-induced quantum confinement effect, and simultaneously form band alignment-engineered heterointerfaces with the underlying TMDCs, resulting in highly efficient interfacial charge separation and transport. Electrical devices constructed with the as-grown ultrathin PVK/WS2 heterostructures show ambipolar transport originating from p-type PVK and n-type WS2, and exhibit outstanding optoelectronic characteristics, with the optimized response time and photoresponsivity reaching 64 μs and 11174.2 A/W, respectively, both of which are 4 orders of magnitude better than the heterostructures with a thick PVK layer, and also represent the best among all previously reported 2D layered semiconductor heterostructures. This work provides opportunities for 2D vertical semiconductor heterostructures via incorporating ultrathin PVK layers in high-performance integrated optoelectronics.


Characteristics of drug-related hospital separations in Australia.
To examine (a) numbers of alcohol and drug-related hospital separations, 1999-2005; (b) demographics of these separations; (c) principal diagnoses co-occurring with drug-related problems; (d) length of hospital stay. Data from the National Hospital Morbidity Database (NHMD) were analysed. Hospital separations where alcohol, opioids, amphetamine, cannabis, cocaine, other drugs (such as sedatives and hypnotics) and pharmaceutical poisoning were mentioned were examined. Numbers per million persons were highest for alcohol, followed by other drugs, particularly sedatives and hypnotics. Alcohol and opioid-related problems were prominent among older age groups, whereas cannabis and pharmaceutical poisoning problems had greater proportions among 15-24 year olds. Opioid-related separations were relatively high in number within the context of prevalence of use, and often accompanied by principal diagnoses of physical or general health problems. Almost half of amphetamine and cannabis-related separations were accompanied by principal diagnoses of mental health problems. This research highlights the complexities of drug-related hospital presentations, indicating the need for thorough assessment of physical and mental problems, as well as a drug use history at the time of admission. Continued development of integrated models of care, targeting both mental health and drug use are essential. Consistent with the international literature, many of these separations are preventable, particularly those for pharmaceutical poisoning. Finally, ongoing efforts to reduce the significantly greater harms related to opioid use, as well as increasing treatment opportunities for opioid-dependent people in Australia is an important public health priority.


Multiple levels of mental attentional demand modulate peak saccade velocity and blink rate.
Every day we mentally process new information that needs to be attended, encoded and retrieved. Processing demands depend on the amount of information and the mental attentional capacity of the individual. Research shows that eye movement indices such as peak saccade velocity and blink rate are related to processes of attentional control, however it is still unclear how eye movements are affected by graded changes in task demand. We examine for the first time relations of eye movements to mental attentional tasks with six levels of task demand and two interference conditions. We report data on 57 adults who completed two versions of the color matching task and provided subjective self rating for each mental attentional demand level. Results show that peak saccade velocity and blink rate decrease as a function of mental attentional demand and correlate negatively with self rating of mental effort. Theoretically, new findings related to mental attentional demand and eye movements inform models of visual processing and cognition. Practically, results point to directions for further research to better understand complex relations among eye movements and mental attentional demand in pediatric populations and individuals with cognitive deficits.


Enhanced oral tolerance in transgenic mice with hepatocyte secretion of IL-10.
Several cytokines derived from Th3 and Tr1 cells, including IL-10, are believed to regulate oral tolerance, but direct evidence is lacking. We have explored the potential role of IL-10 by generating transgenic (TG) mice with sustained hepatocyte-specific expression of rat IL-10. TG mice expressed rat IL-10 downstream of a transthyretin promoter, which led to serum levels that were increased 10- to 100-fold compared with normal animals. Animals were orally administered 1 mg of whole OVA for 5 consecutive days, with control animals receiving PBS. There were six animal groups: Either OVA or PBS were fed orally to rat IL-10 TG mice, non-TG wild-type mice without IL-10 administration, and non-TG wild-type mice administered rat IL-10 systemically. On day 8, all mice were immunized with two injections of OVA, and then analyzed on day 18. T cell proliferation responses were reduced by 65.8 +/- 14.3% after feeding of OVA in rIL-10 TG animals, compared with 39.4 +/- 15.6% in the non-TG mice (p = 0.02). Anti-OVA titers were expressed as fold increase over naive non-TG mice. After feeding, titers decreased by approximately 33% (from 3- to 2-fold) in TG animals and, to a lesser extent, in non-TG animals. IFN-gamma secretion by cultured popliteal lymphocytes decreased in TG animals by 83% after feeding and by 69% in non-TG animals. IL-4 secretion increased 4-fold in TG-fed mice, but did not significantly change in non-TG OVA-fed animals. In contrast to hepatic TG expression of rIL-10, systemic administration of rIL-10 had only a modest effect on tolerance. IL-10, when transgenically expressed in the liver enhances mucosal tolerance to an oral Ag.


Capability of the two microorganisms Bifidobacterium breve B632 and Bifidobacterium breve BR03 to colonize the intestinal microbiota of children.
The total number of bacteria present in the gut microbiota of a newborn is consistently lower than the average found in adults, with the extent of this difference being directly related to body weight and age. It could be assumed that a lower number of viable probiotic cells is necessary to achieve significant gut colonization in infants and children. This study assessed the capability of Bifidobacterium breve B632 (DSM 24706) and Bifidobacterium breve BR03 (DSM 16604), 2 strains able to significantly inhibit some gram-negative bacteria in vitro, to integrate into the intestinal microbiota of children. Ten healthy children aged an average of 5.7±2.6 were given an oily suspension containing B. breve B632 and B. breve BR03 for 21 consecutive days. The daily dose was 100 million live cells of each strain. Fecal specimens were collected and analyzed at the beginning (d0) and at the end of the study (d21). Total fecal bifidobacteria and coliforms have been quantified by microbiological plate counts. A significant increase in total fecal bifidobacteria (from 8.99 to 9.47 log10 CFU/g, P=0.042) and a parallel decrease in total coliforms (from 8.60 to 7.93 log10 CFU/g, P=0.048) was recorded after 21 days of supplementation. An oily suspension has proved an effective way of providing probiotics to children. A lower viable cells concentration was sufficient to mediate this effect in the light of the fact that the intestinal microbiota of children harbors a considerably smaller amount of total bacteria compared with adults. In addition to gut colonization in healthy children, B. breve B632 and B. breve BR03 were able to decrease total fecal coliforms, therefore supporting their potential specific use in colicky infants.


Endogenous ROS production in early differentiation state suppresses endoderm differentiation via transient FOXC1 expression.
Oxidative stress plays a pivotal role in the differentiation and proliferation of cells and programmed cell death. However, studies on the role of oxidative stress in differentiation have mainly employed the detection of reactive oxygen species (ROS) during differentiation or generated by ROS inducers. Therefore, it is difficult to clarify the significance of endogenous ROS production in the differentiation of human cells. We developed a system to control the intracellular level of ROS in the initial stage of differentiation in human iPS cells. By introducing a specific substitution (I69E) into the SDHC protein, a component of the mitochondrial respiratory chain complex, the endogenous ROS level increased. This caused impaired endoderm differentiation of iPS cells, and this impairment was reversed by overproduction of mitochondrial-targeted catalase, an anti-oxidant enzyme. Expression of tumor-related FOXC1 transcription factor increased transiently as early as 4 h after ROS-overproduction in the initial stage of differentiation. Knockdown of FOXC1 markedly improved impaired endoderm differentiation, suggesting that endogenous ROS production in the early differentiation state suppresses endoderm differentiation via transient FOXC1 expression.


"Everyone sees you sitting there struggling with your food": experiences of adolescents and young adults with cerebral palsy.
Objective: The impact of difficulties with eating and drinking in adolescents and young adults with cerebral palsy is unknown. The purpose of this study is to find out which difficulties adolescents and young adults with cerebral palsy experience with eating and drinking in daily life and how they deal with these difficulties. The study also explores how they think about themselves with respect to eating and what does or does not help regarding social participation. Method: We collected the data from ten participants with spastic cerebral palsy (aged 15-23 years) living in the Netherlands. We used a qualitative study design with a conventional content analysis. Semi-structured in-depth interviews were used to identify meaningful factors related to eating and drinking difficulties. We coded relevant phrases from each interview and clustered and synthesized them into categories. Result: We derived four categories from the transcripts: (I) perceived eating and drinking difficulties (e.g., not managing to eat all food textures and/or choking); (II) challenges in physical and social context (e.g., accessibility of restaurants, menu supply, and/or needing assistance or not); (III) dealing with eating and drinking difficulties (e.g., adaptation, food avoidance, and/or giving up); (IV) Negative feelings about their eating and drinking (e.g., shame, frustration, fear for choking, and/or concerns about the future). One striking finding was that most participants had not recently received either monitoring or intervention for their feeding skills. Conclusion: This study shows that adolescents and young adults with cerebral palsy experience many restrictions in eating and drinking situations leading to negative feelings and lower participation levels, while little attention is directed towards these difficulties. Regular multidisciplinary rehabilitation programs should include evaluation, advice, and intervention regarding eating and drinking ability in order to increase social participation and self-management. Implications for Rehabilitation Adolescents and young adults with cerebral palsy experience difficulties with eating, drinking, and swallowing, and they encounter difficulties in participating in mealtimes with family and friends. Although adolescents and young adults with cerebral palsy rated their eating and drinking abilities as reasonable, they reported feelings of shame, frustration, fear, distress, and concerns for the future or unknown environments. Regular multidisciplinary involvement with eating and drinking is needed for purposes of evaluation, advice, and intervention throughout the life course, adjusted to living conditions and the latest evidence. Adolescents and young adults with cerebral palsy showed limited initiative in asking for personal assistance in eating and drinking activities.


Pott's Puffy Tumor.
Pott's puffy tumor is a potential complication of acute frontal sinusitis, characterized by subperiosteal abscess and osteomyelitis of the frontal bone. It can be managed with a combination of open and endoscopic sinus surgery and intravenous antibiotic therapy. In the current report, a 15-year-old male presented with a classic case of Pott's puffy tumor which was managed with bilateral ethmoidectomies, frontal sinusotomies, and frontal sinus trephination, resulting in discharge on intravenous antibiotic therapy and subsequent complete resolution of symptoms.


The role of tumor markers in gynecologic oncology.
Human chorionic gonadotropin is a highly sensitive and specific tumor marker for gestational trophoblastic neoplasia that accurately reflects tumor volume and the clinical course of disease. In women with endodermal sinus tumors and embryonal carcinomas, alpha-fetoprotein usually is a reliable marker, and it accurately predicts the presence of yolk sac elements in mixed germ cell tumors. CA 125 is the most widely utilized tumor marker presently available for use in patients with epithelial ovarian cancer. It has utility in monitoring therapy and differentiating benign from malignant pelvic masses. Measurement of serial CA 125 levels in postmenopausal women may facilitate screening for occult early stage disease. In the future, monoclonal antibodies that recognize tumor-associated antigens may prove useful for radionuclide imaging.


Endothelium: from whence to whither.
Today's perspective of the endothelial cell recognizes its real significance, heretofore neglected, and anticipates important future contributions to improved medical management. Like trustworthy posted guards of the vascular frontier, endothelial cells oversee and regulate not only fluid and solute traffic (between lumen and tissue) but also contribute valuable protective forces to act at each of its boundaries. Uniquely different from its guardian colleague, the nonnucleated platelet lacks ability to regenerate blocked metabolic functions (for example, thromboxane production), whereas the nucleated endothelial cell is metabolically complete and therefore able to regenerate blocked metabolic functions (for example, PGI2 production). The endothelial cell commands and modulates the circulation, regulating the contractility of its underlying smooth musculature and the rheologic properties of its overlying circulating fluid. Many overlooked contributions of the endothelial cells, from its luminal, abluminal, and abutting surfaces, modulate important, even critical, physiologic functions. Only very recently have management techniques begun to exploit these endothelial functions; but developing new techniques promise exciting therapeutic possibilities soon. As we look to that future, we must apply our knowledge to coronary artery disease, congestive heart failure, cerebrovascular disease, thromboembolism, diabetic degenerative disease, hemolytic uremic syndrome, shock lung, vasospastic disorders, and a great variety of other today's inadequately managed disorders of man and animals.


The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists for the Management of NAFLD.
The burden of cirrhosis from nonalcoholic fatty liver disease (NAFLD) is reaching epidemic proportions in the United States. This calls for greater awareness among endocrinologists, who often see but may miss the diagnosis in adults with obesity or type 2 diabetes mellitus (T2D) who are at the highest risk. At the same time, recent studies suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) are beneficial vs nonalcoholic steatohepatitis (NASH) in this population. This minireview aims to assist endocrinologists to recognize the condition and recent work on the role of GLP-1RAs in NAFLD/NASH. Evidence from observational studies, randomized controlled trials, and meta-analyses. Endocrinologists should lead multidisciplinary teams to implement recent consensus statements on NAFLD that call for screening and treatment of clinically significant fibrosis to prevent cirrhosis, especially in the high-risk groups (ie, people with obesity, prediabetes, or T2D). With no US Food and Drug Administration (FDA)-approved agents, weight loss is central to successful management, with pharmacological treatment options limited today to vitamin E (in people without T2D) and diabetes medications that reverse steatohepatitis, such as pioglitazone or GLP-1RA. Recently, the benefit of GLP-1RAs in NAFLD, suggested from earlier trials, has been confirmed in adults with biopsy-proven NASH. In 2021, the FDA also approved semaglutide for obesity management. A paradigm change is developing between the endocrinologist's greater awareness about their critical role to curve the epidemic of NAFLD and new clinical care pathways that include a broader use of GLP-1RAs in the management of these complex patients.


A study of the effect of renal pelvic and ureteric distention on the anorectal function with identification of the "reno-anal reflex".
Renal or ureteral diseases are often associated with gastrointestinal symptoms. In this communication, we studied the effect of renal pelvic or ureteric distension on the anorectal function in 12 healthy volunteers. A 3F balloon-tipped catheter was introduced into the renal pelvis. The balloon was filled with saline in increments of 2 ml up to 12 ml and the pressure response of the rectum and anal canal was recorded. Balloon filling was performed twice: rapidly (1 ml/sec) and slowly (1 ml/min). The test was repeated in the ureter with balloon fillings in increments of 0.25 ml up to 1 ml. The electromyographic (EMG) response of the external anal sphincter to distension of the renal pelvis or ureter was evaluated. The pressure response of the rectum, anal canal and external anal sphincter to distension of the anesthetised renal pelvis or ureter was then determined. The test was repeated after external anal sphincter anaesthetisation. Rapid renal pelvic or ureteric distension increased the anal canal pressure (p < 0.05) but did not change the rectal pressure (p > 0.05). With 10 and 12 ml rapid renal pelvis distension and with 0.75 and 1 ml rapid ureteric distension, the EMG activity of the external anal sphincter increased and was accompanied with loin and anal pain. Slow renal pelvic or ureteric distension caused no significant change in the anal or rectal pressures (p > 0.05) or in the EMG activity of the external anal sphincter and no anal pain was perceived. Distension of the anesthetised renal pelvis or ureter effected no changes in anal or rectal pressures (p > 0.05). The anesthetised external anal sphincter as well as the anal or rectal pressure did not respond to renal pelvis or ureteric distension. In conclusion, rapid renal pelvic or ureteric distension stimulates the mechanoreceptors in the renal pelvis or ureteric wall leading to reflex external anal sphincter contraction. This leads to elevation of the anal canal pressure. The findings suggest the possible involvement of a "reno-anal reflex" which is evoked on rapid renal pelvis or ureteric distension. Slow distension does not seem to trigger such a reflex.


Risk of cesarean section after induced versus spontaneous labor at term gestation.
To investigate whether the cesarean section (CS) rate is increased in women whose labor was induced compared to those who had spontaneous labor at term pregnancy. A retrospective study was performed in women whose labor was either induced (induction group, n=497) or spontaneous (spontaneous group, n=878) at 37+0 to 41+6 weeks of gestation from January 2008 to June 2009. Maternal age, parity, body mass index (BMI), Bishop scores, gestational age, hypertension, diabetes, delivery mode, indications for CS, neonatal outcome were compared between the two groups. Multiple logistic regression analysis was used to examine the association between the CS rate and labor induction after adjusting for potential confounding variables. CS (17.3% vs. 5.3%, P<0.001) and vacuum-assisted delivery (10.7% vs. 6.4%, P<0.001) rates were significantly higher in the induction group compared to the spontaneous group. The CS rate in the induction group was higher than the spontaneous group not only in nulliparous women (25.3% vs. 8.6%, P<0.001), but also in multiparous women (3.8% vs. 0.3%, P=0.002). However, after adjusting confounding factors, the higher CS rate was significantly associated with advanced maternal age, higher BMI, lower Bishop scores and nulliparity, with no demonstrable tie to labor induction. Neonatal outcome in the two groups were comparable. Although CS rate was higher in women whose labor was induced than those who had spontaneous labor, this higher rate was associated with maternal age, BMI, Bishop scores and parity, but was not impacted by labor induction per se.


High-Accuracy Semiempirical Quantum Models Based on a Minimal Training Set.
A great need exists for computationally efficient quantum simulation approaches that can achieve an accuracy similar to high-level theories at a fraction of the computational cost. In this regard, we have leveraged a machine-learned interaction potential based on Chebyshev polynomials to improve density functional tight binding (DFTB) models for organic materials. The benefit of our approach is two-fold: (1) many-body interactions can be corrected for in a systematic and rapidly tunable process, and (2) high-level quantum accuracy for a broad range of compounds can be achieved with ∼0.3% of data required for one advanced deep learning potential. Our model exhibits both transferability and extensibility through comparison to quantum chemical results for organic clusters, solid carbon phases, and molecular crystal phase stability rankings. Our efforts thus allow for high-throughput physical and chemical predictions with up to coupled-cluster accuracy for systems that are computationally intractable with standard approaches.


Preservation of Surface Conductivity and Dielectric Loss Tangent in Large-Scale, Encapsulated Epitaxial Graphene Measured by Noncontact Microwave Cavity Perturbations.
Regarding the improvement of current quantized Hall resistance (QHR) standards, one promising avenue is the growth of homogeneous monolayer epitaxial graphene (EG). A clean and simple process is used to produce large, precise areas of EG. Properties like the surface conductivity and dielectric loss tangent remain unstable when EG is exposed to air due to doping from molecular adsorption. Experimental results are reported on the extraction of the surface conductivity and dielectric loss tangent from data taken with a noncontact resonance microwave cavity, assembled with an air-filled, standard R100 rectangular waveguide configuration. By using amorphous boron nitride (a-BN) as an encapsulation layer, stability of EG's electrical properties under ambient laboratory conditions is greatly improved. Moreover, samples are exposed to a variety of environmental and chemical conditions. Both thicknesses of a-BN encapsulation are sufficient to preserve surface conductivity and dielectric loss tangent to within 10% of its previously measured value, a result which has essential importance in the mass production of millimeter-scale graphene devices demonstrating electrical stability.


Ethmoidal sarcoidosis.
Sarcoidosis is a multisystem granulomatous disease of unknown aetiology. Nasal sarcoidosis commonly affects the mucosa of the septum and the inferior turbinates. These patients may present with nasal discharge, crusting, obstruction, epistaxis or anosmia. We present an unusual case of nasal sarcoidosis involving the ethmoid sinus causing recurrent eyelid swelling and discuss its management.


Environment critical to teenagers' recovery.
The Teenage Cancer Trust (TCT), the charity devoted to improving the lives of teenager cancer sufferers, has released the initial results of an independent study which it says prove that a high quality built environment, of the calibre seen in its 13 existing U.K. teenage cancer units, not only boosts patient morale by giving sick youngsters a feeling of control, but also encourages young cancer sufferers to complete their treatment, significantly impacting the number of positive outcomes. Jonathan Baillie reports on the study's London launch.


Relationship among repeated sprint tests, aerobic fitness, and anaerobic fitness in elite adolescent soccer players.
The purpose of the study was to examine the relationships among aerobic fitness, anaerobic capacity, and performance indices of 2 different repeated sprint test (RST) protocols in a group of 33 elite adolescent soccer players (age range 16-18 years). All participants performed 4 tests: an aerobic power test (20-m shuttle run), the Wingate Anaerobic Test (WAnT), and 2 different RST protocols (12 x 20 and 6 x 40 m). Significant correlations (p < 0.05) were found between the fastest sprint (r = 0.618), total sprint time (r = 0.709), and performance decrement (PD; r = 0.411) of the 2 RST protocols. A significant negative correlation was found between the PD in the 12 x 20-m RST and calculated peak VO2(r = -0.60, p < 0.05). There was no significant correlation between PD of the 6 x 40-m RST and calculated peak VO2(r = -0.32, p = 0.09). The mean power in the WAnT was significantly correlated with the fastest sprint and the total sprint time of the 6 x 40-m protocol (r = -0.42 and -0.45, respectively) and with the total sprint time of the 12 x 20-m protocol (r = -0.47). There were no correlations between other indices of the WAnT and the 2 RSTs. Despite identical total work, different RST protocols represent different physiological implications. The aerobic system plays a significant role in the maintenance of intensity level during a soccer game, which is characterized by short bursts of activities. Anaerobic performance of repeated brief efforts imposes different physiological stress than a single prolonged activity and, thus, may reflect different physiological capabilities. Therefore, anaerobic testing procedures should consist of specific protocols that mimic the athlete's specific sports activity pattern.


Simultaneous Dual-Wavelength Source Raman Spectroscopy with a Handheld Confocal Probe for Analysis of the Chemical Composition of In Vivo Human Skin.
Confocal Raman spectroscopy (CRS) is a powerful tool that has been widely used for biological tissue analysis because of its noninvasive nature, high specificity, and rich biochemical information. However, current commercial CRS systems suffer from limited detection regions (450-1750 cm-1), bulky sizes, nonflexibilities, slow acquisitions by consecutive excitations, and high costs if using a Fourier transform (FT) Raman spectroscopy with an InGaAs detector, which impede their adoption in clinics. In this study, we developed a portable CRS system with a simultaneous dual-wavelength source and a miniaturized handheld probe (120 mm × 60 mm × 50 mm) that can acquire spectra in both fingerprint (FP, 450-1750 cm-1) and high wavenumber (HW, 2800-3800 cm-1) regions simultaneously. An innovative design combining 671 and 785 nm lasers for simultaneous excitation through a compact and high-efficiency (>90%) wavelength combiner was implemented. Moreover, to decouple the fused FP and HW spectra, a first-of-its-kind precise Raman spectra separation algorithm (PRSSA) was developed based on the maximum a posteriori probability (MAP) estimate. The accuracy of spectra separation was greater than 99%, demonstrated in both phantom experiments and in vivo human skin measurements. The total data acquisition time was reduced by greater than 50% compared to other CRS systems. The results proved our proposed CRS system and PRSSA's superior capability in fast and ultrawideband spectra acquisition will significantly improve the integration of CRS in the clinical workflow.


Ganglion cell tumours in the sella turcica in close morphological connection with pituitary adenomas.
Ganglion cell tumours in the sellar region are uncommon. They are usually associated with pituitary adenomas, while isolated ganglion cell neoplasms are extremely rare. We report the clinicopathological studies of five cases diagnosed as ganglion cell tumours located in the intrasellar region: four mixed/collision tumours composed of gangliocytoma and pituitary adenoma, and one isolated ganglioglioma unrelated to adenoma. Clinically, two patients presented with acromegaly, while three others were initially diagnosed as non-functioning adenomas. In four cases, the histopathological examination of surgical specimens revealed intermixed lesions composed of pituitary adenoma and ganglion cell elements. The adenomas appeared to secrete growth hormone. Electron microscopy enabled identification of the sparsely granulated somatotroph cells. Neoplastic neuronal lesions were composed of mature ganglion cells, including binucleate or multinucleate cells. In all cases, boundaries between adenomatous and gangliocytic components were not clearly demarcated, and numerous gangliocytic cells were closely intermingled with adenomatous tissue. One case lacked endocrine symptoms, and no pituitary adenoma was identified in the surgically excised material; it was finally diagnosed as low-grade ganglioglioma. The etiopathogenesis of ganglion cell neoplasms in the sellar region is not clearly defined. Our study revealed that if ganglion cell neoplasms were combined with adenoma, both neoplastic components were closely related to each other, and numerous neuronal elements were strictly intermingled with adenoma cells. Such a tissue pattern indicates that these neoplastic changes, including their common respective etiopathogeneses, are closely related. The identification of both components in sellar regions may have some nosological implications.


Effect of the Holiday Season on Weight Gain: A Narrative Review.
Several studies suggest that the holiday season, starting from the last week of November to the first or second week of January, could be critical to gaining weight. This study aims to review the literature to determine the effects of the holidays on body weight. In studies of adults, a significant weight gain was consistently observed during this period (0.4 to 0.9 kg, p < 0.05). The only study in college students found an effect on body fat but not on weight (0.1 kg, p = 0.71). The only study found in children did not show an effect on BMI percentile (-0.4%, p > 0.05) during this period. Among individuals with obesity who attempt to lose weight, an increase in weight was observed (0.3 to 0.9 kg, significant in some but not in all studies), as well as increase in weight in motivated self-monitoring people (0.4 to 0.6%, p < 0.001). Programs focused on self-monitoring during the holidays (phone calls and daily mailing) appeared to prevent weight gain, but information is limited. The holiday season seems to increase body weight in adults, even in participants seeking to lose weight and in motivated self-monitoring people, whereas in children, adolescents, and college students, very few studies were found to make accurate conclusions.


Role of magnesium and other divalent cations in ATP-utilizing enzymes.
While free MgATP shows tridentate coordination of Mg2+ by each of the three phosphates, enzyme-bound ATP generally coordinates metals at the beta- and gamma-phosphates and only occasionally at the alpha-phosphate. Enzyme-catalyzed reactions of ATP are in-line nucleophilic displacements at either the alpha-, beta-, or gamma-phosphorus atom, as dictated by the relative positions of the enzyme-bound substrates. The divalent cation activates the attacked phosphoryl group and/or the leaving group of ATP by charge neutralization, electron withdrawal, and by adjustment of the conformation of the polyphosphate chain. Some ATP reactions require an additional divalent cation at the active site to adjust the protein conformation and/or to interact with the other substrate.


Analysis of BCL6-interacting proteins by tandem mass spectrometry.
B-cell lymphoma 6 (BCL6) is a 95-kDa nuclear phosphoprotein and member of the Pox virus zinc finger/bric-a-brac, tramtrack, broad complex (POZ/BTB) family of transcription factors. BCL6 is a transcriptional repressor required for germinal center formation, and the gene encoding it is frequently altered in diffuse large B-cell and follicular lymphomas. The dysregulation of BCL6 has therefore been implicated in lymphomagenesis. A limited number of proteins is known to interact with BCL6 and modulate its activity or participate in its role in transcriptional regulation. Identification of additional BCL6-binding proteins could reveal potential signaling targets and previously undescribed functional roles for BCL6. We used a functional proteomic approach to determine the identity of proteins that interact with BCL6. Proteins were isolated by co-immunoprecipitation with an anti-BCL6 antibody and identified using MS/MS. We identified 61 proteins in the BCL6 immunocomplex from the following Gene Ontology categories: transcription regulator activity (n = 18), binding activity (n = 11), signal transducer activity (n = 10), catalytic activity (n = 8), structural molecule activity (n = 3), enzyme regulator activity (n = 3), transporter activity (n = 2), motor activity (n = 2), chaperone activity (n = 1), and unknown function (n = 3). Importantly we identified BCL6 and several previously reported BCL6-interacting proteins in the BCL6 immunocomplex. The remaining proteins have not been shown previously to be associated with BCL6. MS/MS results were validated on four proteins using immunoprecipitation and Western blotting. Two of these protein interactions were further confirmed by reciprocal immunoprecipitation. This study demonstrates the utility of antibody immunoprecipitation and subsequent peptide identification by MS/MS for the elucidation of BCL6-binding proteins. Many of the novel proteins identified in this study suggest additional functional roles for BCL6 beyond transcriptional repression.


Mental health survey among front-line medical workers after 2 years of supporting COVID-19 efforts in Hubei Province.
During the outbreak of COVID-19 in China, many health care workers have been involved in the front-line fight against the epidemic and have experienced major psychological challenges. This study was aimed at assessing the mental health of front-line health workers after 2 years of COVID-19 efforts. We recruited front-line health workers from Liaoning province who supported Hubei, the epicenter of the COVID-19 outbreak. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder scale (GAD-7), and Insomnia Severity Index (ISI) were used to assess psychological status. A total of 1101 of 1354 contacted individuals completed the survey (participation rate of 81.31%): 963 (87.5%) were 20-45 years of age, 919 (83.47%) were women, 845 (76.7%) were nurses, and 245 (22.3%) were physicians. After 2 years, the mental health symptoms among survey respondents were as follows: 46.6% had depression, 35.5% had anxiety, and 38.1% had insomnia. Thus, 2 years after the COVID-19 pandemic, the front-line health workers who had assisted Hubei province during the COVID‑19 pandemic in China still had high levels of depression, anxiety, and insomnia. Our findings suggest that the pandemic has had significant long-term effects on the mental health of front-line health workers. Therefore, mental health policies should offer long-term rather than short-term services.


[Isotope nephrography in the 2d half of pregnancy].
166 Women were investigated after 26 weeks of pregnancy, divided into 4 groups (normal pregnancy, after urinary tract infection, with cystopyelitis and with toxemia). Renography is a very sensitive method. Only 6,6% women had bilateraly normal function. Unilateral pathology was detected more often on the right side (17,6% versus 2,9%) and the damage was on the right side also more intensive (30% versus 8%), and present as early as in the 7. to 8. month of pregnancy. The damage of the secretion phase of the renogram in pregnancy is mostly sequal of the disturbed drainage following compression of the ureter trough varicosal veins and the pregnant uterus.


Complement activation in patients with Gambian sleeping sickness.
Low levels of complement components C3, C4 and factor B were found in the sera of most patients with early and advanced Gambian trypanosomiasis. C3 levels increased after treatment with melarsoprol (Mel B). Nearly all patients had high serum IgM levels and a significants correlation was found betwen high serum IgM levels and low serum C3 levels. High concentrations of cryglobulins, which contained IgM and C3, were found in most of sera tested. Formation of large molecular weight IgM complexes may play an important part in producing the low C3 levels found in patients with Gambian sleeping sickness.


Psychometric Properties of the Spanish version of the Family Adaptability and Cohesion Evaluation Scale IV.
Building on the expanding cross cultural interest in FACES, the Spanish version of the Family Adaptability and Cohesion Evaluation Scale (FACES IV), aimed at the assessment of the dimensions of cohesion and flexibility of the Circumplex Model, was validated following the author´s guidelines. The sample was composed by 665 college students. Besides, FACES II was also used and family communication, satisfaction, stress and strengths were also measured. The results supported its psychometric adequacy. Construct validity, concurrent and discriminant validity of all the scales were confirmed, maintaining the original structure of the instrument, with 6 scales, 4 Unbalanced scales (Disengaged, Enmeshed, Rigid, and Chaotic), and two Balanced scales (Cohesion and Flexibility). Additionally, the ratio scores confirmed the curvilinearity of the model. All the results supported the adequacy of the Spanish version, which is also promising for use in educational settings, in counseling and in research. Findings with the Spanish version of FACES IV are similar to findings in the United States and other countries.


Synthesis of robust hierarchical silica monoliths by surface-mediated solution/precipitation reactions over different scales: designing capillary microreactors for environmental applications.
A synthetic procedure to prepare novel materials (surface-mediated fillings) based on robust hierarchical monoliths is reported. The methodology includes the deposition of a (micro- or mesoporous) silica thin film on the support followed by growth of a porous monolithic SiO2 structure. It has been demonstrated that this synthesis is viable for supports of different chemical nature with different inner diameters without shrinkage of the silica filling. The formation mechanism of the surface-mediated fillings is based on a solution/precipitation process and the anchoring of the silica filling to the deposited thin film. The interaction between the two SiO2 structures (monolith and thin film) depends on the porosity of the thin film and yields composite materials with different mechanical stability. By this procedure, capillary microreactors have been prepared and have been proved to be highly active and selective in the total and preferential oxidation of carbon monoxide (TOxCO and PrOxCO).


Perioperative cardiovascular medicine: an update of the literature 2013-2014.
Perioperative medicine is an important and rapidly expanding area of interest across multiple specialties, including internal medicine, anesthesiology, surgery, cardiology, and hospital medicine. A multispecialty team approach that ensures the best possible patient outcomes has fostered collaborative strategies across the continuum of patient care. Staying current in this multidisciplinary field is difficult, because physicians interested in perioperative medicine would need to review multiple specialty journals on a regular basis. To facilitate this process, the authors performed a focused review of this literature published in 2013 and early 2014. In this update, key articles are reviewed that potentially impact clinical practice in perioperative cardiovascular risk prediction and risk management.


Model Reduction Through Progressive Latent Space Pruning in Deep Active Inference.
Although still not fully understood, sleep is known to play an important role in learning and in pruning synaptic connections. From the active inference perspective, this can be cast as learning parameters of a generative model and Bayesian model reduction, respectively. In this article, we show how to reduce dimensionality of the latent space of such a generative model, and hence model complexity, in deep active inference during training through a similar process. While deep active inference uses deep neural networks for state space construction, an issue remains in that the dimensionality of the latent space must be specified beforehand. We investigate two methods that are able to prune the latent space of deep active inference models. The first approach functions similar to sleep and performs model reduction post hoc. The second approach is a novel method which is more similar to reflection, operates during training and displays "aha" moments when the model is able to reduce latent space dimensionality. We show for two well-known simulated environments that model performance is retained in the first approach and only diminishes slightly in the second approach. We also show that reconstructions from a real world example are indistinguishable before and after reduction. We conclude that the most important difference constitutes a trade-off between training time and model performance in terms of accuracy and the ability to generalize, via minimization of model complexity.


Identification of tdh-positive Vibrio parahaemolyticus from an outbreak associated with raw oyster consumption in Spain.
Between August and September 1999, a total of 64 cases of illness were identified in three episodes of acute gastroenteritis associated with the consumption of live oysters from a typical outdoor street market in Galicia (northwest Spain). Nine case patients were hospitalized and analysis of their stool samples revealed the presence of Vibrio parahaemolyticus. The strains isolated from two stool samples were studied for antibiotic susceptibility, biochemical characteristics and presence of virulence factors. Both isolates were Kanagawa phenomenon positive and produced thermostable direct hemolysin, which is related to pathogenicity in humans. These results show the presence of pathogenic V. parahaemolyticus in mollusks harvested in Europe and reveal the risk of illness associated with their consumption, suggesting the revision of V. parahaemolyticus risk assessment associated with consumption of raw live shellfish.


Is decision-making influenced by interactions between extended wakefulness and weak emotional stressors? An experimental study.
In this study, we aimed to determine whether 21-hour continuous wakefulness decreases performance in the Iowa Gambling Task and examine the effect of the interaction between a weak emotional stressor and prolonged continuous wakefulness on the decision-making process, as measured by the Iowa Gambling Task. Approximately half of 38 healthy college students were in the sleep deprivation condition (they performed the task at 4:30 a.m.); the remainder were in the daytime condition (they performed the task during the day). The participants in each sleep condition were further divided into non-exposed and exposed to an emotional stressor via a social exclusion procedure before the task, with the Iowa Gambling Task score as the dependent variable. In the sleep deprivation condition, performance in the final block of the task was significantly worse in the group with an emotional stressor than the group without. There was no main effect of sleep conditions or emotional stressors on the task performance in either block. The results of this study suggest that even 21 hours of continuous wakefulness, which can occur in daily work life, may prevent appropriate learning in people exposed to an emotional stressor, even if the stress caused due to it is low.


Universal interrelation between measures of particle and polymer size.
The characterization of many objects involves the determination of a basic set of particle size measures derived mainly from scattering and transport property measurements. For polymers, these basic properties include the radius of gyration Rg, hydrodynamic radius Rh, intrinsic viscosity [η], and sedimentation coefficient S, and for conductive particles, the electric polarizability tensor αE and self-capacity C. It is often found that hydrodynamic measurements of size deviate from each other and from geometric estimates of particle size when the particle or polymer shape is complex, a phenomenon that greatly complicates both nanoparticle and polymer characterizations. The present work explores a general quantitative relation between αE, C, and Rg for nanoparticles and polymers of general shape and the corresponding properties η, Rh, and Rg using a hydrodynamic-electrostatic property interrelation.


Factors influencing the bond strength between glass polyalkenoate (ionomer) cements and dentine.
A series of investigations have been performed to study some factors influencing the tensile bond strength of glass polyalkenoate cements to dentine. The measured bond strength was affected by the method of storage of the teeth prior to testing, the nature of the dentine and the type of cement used for the tests. The most consistent results for bond strength measurements were obtained with teeth stored in neutral buffered formalin for more than 1 month after extraction, and then stored in distilled water for 4 weeks prior to bond strength determinations. The mean value obtained with this storage regime (1.62 MPa) was not different from that obtained using freshly extracted teeth (1.74 MPa). The bond strength to deciduous dentine (0.72 MPa) was significantly less than that to permanent dentine (1.62 MPa). There were significant differences between the measured bond strengths of the three materials tested, with Ketac-Fil giving the lowest result (1.62 MPa), then Ketac-Silver (2.41 MPa), ChemFil II formed the strongest bonds (4.65 MPa).


Antioxidative activities of 62 wild mushrooms from Nepal and the phenolic profile of some selected species.
Mushrooms have garnered immense popularity for their nutritional as well as medicinal values. The therapeutic potential of mushrooms in Nepal, a country well known for its biodiversity and natural medicinal resources, remains largely unstudied. Therefore, this study attempts to unveil the antioxidative properties of Nepalese wild mushrooms. Sixty-two wild mushroom samples were collected from several forests in different parts of Nepal. Ethanol and water extracts of the dried samples were tested for their antioxidative activities using total phenolic content (TPC), oxygen radical absorbance capacity (ORAC) assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing power (RP) assays. Ethanol extracts of samples belonging to the order Hymenochaetales showed significantly high activity in all the assays. Inonotus clemensiae had an exceptionally high TPC of 643.2 mg gallic acid equivalent (GAE)/g extract and also exhibited the lowest EC50 values in DPPH (0.081 mg/mL), ABTS (0.409 mg/mL), and EC0.5 value in reducing power (RP; 0.031 mg/mL) assays. High-performance liquid chromatography (HPLC) analysis of the top ten samples with the highest TPC was done to identify the phenolic compounds in the extracts, followed by liquid chromatography-mass spectrometry (LC-MS) analysis for some unknown compounds. These findings highlight the very strong antioxidative activity of Nepalese mushrooms, and paves the way for further research to explore their economic potential.


Using one halogen bond to change the nature of a second bond in ternary complexes with PCl and FCl halogen bonds.
Ab initio MP2/aug'-cc-pVTZ calculations have been carried out to determine the effect of the presence of one halogen bond on the nature of the other in ternary complexes H2XP:ClF:ClH and H2XP:ClF:ClF, for X = F, Cl, H, NC, and CN. The PCl bonds remain chlorine-shared halogen bonds in the ternary complexes H2XP:ClF:ClH, although the degree of chlorine sharing increases relative to the corresponding binary complexes. The FCl bonds in the ternary complexes remain traditional halogen bonds. The binding energies of the complexes H2XP:ClF:ClH increase relative to the corresponding binary complexes, and nonadditivities of binding energies are synergistic. In contrast, the presence of two halogen bonds in the ternary complexes H2XP:ClF:ClF has a dramatic effect on the nature of these bonds in the four most strongly bound complexes. In these, chlorine transfer occurs across the PCl halogen bond to produce complexes represented as (H2XP-Cl)+:-(F:ClF). In the ion-pair, the cation is also halogen bonded to the anion by a ClF- halogen bond, while the anion is stabilized by an -FCl halogen bond. The central ClF molecule no longer exists as a molecule. The binding energies of the ternary H2XP:ClF:ClF complexes are significantly greater than the binding energies of the H2XP:ClF:ClH complexes, and nonadditivities exhibit large synergistic effects. The Wiberg bond indexes for the complexes H2XP:ClF, H2XP:ClF:ClH, and H2XP:ClF:ClF, and the cations (H2XP-Cl)+ reflect the changes in the P-Cl and Cl-F bonds. Similarly, EOM-CCSD spin-spin coupling constants are also consistent with the changes in these same bonds. In particular, 1xJ(P-Cl) in H2XP:ClF complexes becomes 1J(P-Cl) in the ternary complexes with chlorine-transferred halogen bonds. A plot of these coupling constants shows a change in the curvature of the trendline as chlorine-shared halogen bonds in H2XP:ClF:ClH become chlorine-transferred halogen bonds in H2XP:ClF:ClF. 1xJ(F-Cl) coupling constants also reflect changes in the nature of FCl halogen bonds.


Improving Exercise-Based Interventions for People Living with Both COPD and Frailty: A Realist Review.
People living with both chronic obstructive pulmonary disease (COPD) and frailty have high potential to benefit from exercise-based interventions, including pulmonary rehabilitation, but face challenges completing them. Research to understand ways to optimise exercise-based interventions in this group is lacking. We aimed to understand how exercise-based interventions might improve outcomes for people living with both COPD and frailty. This realist review used database searches and handsearching until October 2019 to identify articles of relevance to exercise-based interventions for people living with COPD and frailty. A scoping search explored what is important about the context of living with COPD and frailty, and what mechanisms might be important in how exercise-based interventions result in their intended outcomes. Through discussion with stakeholders, the review scope was refined to areas deemed pertinent to improving care. We retained articles within this refined scope and identified additional articles through targeted handsearching. Data were extracted and synthesised in a narrative, prioritised by relevance and rigour. Of 344 records identified, 35 were included in the review and 20 informed the final synthesis. Important contextual factors to consider included: negative beliefs about themselves and exercise-based interventions; heterogenous presentation and comorbidities; decreased reserves and multidimensional loss; and experiencing unpredictable health and disruptions. In these circumstances, mechanisms that may help maximise outcomes from exercise-based interventions included: trusting relationships; creating a shared understanding of needs; having the capacity to address multidimensional concerns; being able to individualise approaches to needs and priorities; and flexible approaches to intervention delivery. Mixed-methods research and explicit theorising were often absent. Building trusting relationships, understanding priorities, using individualised and multidisciplinary approaches, and flexible service delivery can improve the value of exercise-based interventions for people living with both COPD and frailty. Development and evaluation of new and adapted interventions should consider these principles.


Hearing, speech, language, and vestibular disorders in the fetal alcohol syndrome: a literature review.
Fetal alcohol syndrome (FAS) is characterized in part by mental impairment, as well as craniofacial and ocular anomalies. These conditions are traditionally associated with childhood hearing disorders, because they all have a common embryonic origin in malformations of the first and second branchial arches, and have similar critical periods of vulnerability to toxic insult. A review of human and animal research indicates that there are four types of hearing disorders associated with FAS. These are: (1) a developmental delay in auditory maturation, (2) sensorineural hearing loss, (3) intermittent conductive hearing loss due to recurrent serous otitis media, and (4) central hearing loss. The auditory and vestibular systems share the same peripheral apparatuses (the inner ear and eighth cranial nerve) and are embryologically and structurally similar. Consequently, vestibular disorders in FAS children might be expected. The evidence for vestibular dysfunction in FAS is ambiguous, however. Like other syndromes associated with craniofacial anomalies, hearing disorders, and mental impairment, FAS is also characterized by a high prevalence of speech and language pathology. Hearing disorders are a form of sensory deprivation. If present during early childhood, they can result in permanent hearing, language, and mental impairment. Early identification and intervention to treat hearing, language, and speech disorders could therefore result in improved outcome for the FAS child. Specific recommendations are made for intervention and future research.


Response Guided Interferon Therapy for Genotype 3 of Chronic Hepatitis C: Compliance and Outcome.
To determine compliance and improvement in sustained viral response (SVR) by following response guided therapy (RGT) plan of interferon and ribavirin, for genotype 3 in chronic hepatitis C. Patients with chronic hepatitis C genotype 3, who were eligible for interferon-ribavirin therapy and consented for RGT, were included. Those with no rapid viral response (RVR), having coarse echotexture of liver or undergoing re-treatment, were advised 48 week treatment whereas, rest had 24 week standard therapy. PCR for HCV RNA checked 6 months after discontinuing treatment, was the primary end point of study. Of 154 patients, included in the study with mean age of 39.9 (±10.84) and male to female ratio 1.4/1 (94/60), majority of patients, 136 (88.4%) were treatment naïve whereas, 18 (11.6%) were being retreated. On ultrasound, 63 (40.9%) patients had coarse liver and 33 (21.4%) had splenomegaly. RVR was achieved in 99 (64.3%) patients. Overall 66(42.8%) patients merited extended duration of therapy as per RGT plan but only 22 (33%) were compliant. Treatment related side effects were the dominant reason for declining RGT in 33 (75%) patients. SVR was noted in 111 (72.1%) patients. Those patients with extended therapy (RGT), had SVR 90.9% (20/22), although, better but statistically not significant than those who stopped therapy at 6 months 77.2% (34/44) (p value 0.11). Response guided therapy plan did not improve SVR to pegylatedinterferon and ribavirin therapy in patients with genotype 3 and it has low patient compliance due to treatment related side effects.


Chemoselective Copper-Catalyzed Ullmann-Type Coupling of Oxazolidinones with Bromoiodoarenes.
We describe the highly selective copper-catalyzed Ullmann-type coupling of bromoiodoarenes with oxazolidinones. 3,4,7,8-Tetramethyl-1,10-phenanthroline (Me4Phen) was identified as an optimal ligand promoting the desired C-N bond formation, while minimizing the competitive bromo-iodo exchange pathway that leads to formation of iodo-substituted and bis-coupled side products. The developed method is highly selective with a >98:2 ratio of the bromo- vs iodo-substituted compounds obtained in the isolated products.


Limbic encephalitis associated with anti-NH2-terminal of α-enolase antibodies: A clinical subtype of Hashimoto encephalopathy.
Several types of autoantibodies have been reported in autoimmune limbic encephalitis (LE), such as antibodies against the voltage-gated potassium channel (VGKC) complex including leucine-rich glioma inactivated 1 (LGI1). We recently reported a patient with autoimmune LE and serum anti-NH2-terminal of α-enolase (NAE) antibodies, a specific diagnostic marker for Hashimoto encephalopathy (HE), who was diagnosed with HE based on the presence of antithyroid antibodies and responsiveness to immunotherapy. This case suggests that LE patients with antibodies to both the thyroid and NAE could be diagnosed with HE and respond to immunotherapy. The aim of this study was to clarify the clinicoimmunological features and efficacy of immunotherapy in LE associated with anti-NAE antibodies to determine whether the LE is a clinical subtype of HE.We examined serum anti-NAE antibodies in 78 LE patients with limbic abnormality on magnetic resonance imaging and suspected HE based on positivity for antithyroid antibodies. Nineteen of the 78 patients had anti-NAE antibodies; however, 5 were excluded because they were double positive for antibodies to the VGKC complex including LGI1. No antibodies against the N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (Caspr2), γ-aminobutyric acid-B receptor (GABABR), or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) were detected in the 19 patients. Among the remaining 14 who were positive only for anti-NAE antibodies, the median age was 62.5 (20-83) years, 9 (64%) were women, and 8 (57%) showed acute onset, with less than 2 weeks between onset and admission. Consciousness disturbance (71%) and memory disturbance (64%) were frequently observed, followed by psychiatric symptoms (50%) and seizures (43%). The frequency of these symptoms significantly differed between the acute- and subacute-onset groups. Abnormalities in cerebrospinal fluid and electroencephalogram were commonly observed (92% for both). Tumors were not identified in any cases. All patients responded to immunotherapy or spontaneously remitted, thereby fulfilling the criteria of HE.This study demonstrated that LE associated with anti-NAE antibodies is a nonparaneoplastic LE and various limbic symptoms that depend on the onset type. Favorable therapeutic efficacy suggests that this LE can be considered a clinical subtype of HE and that anti-NAE antibodies may be a promising indicator of the need for immunotherapy.


Ability evaluation by proxy: role of maximal performance and related attributes in social comparison.
Four experiments tested the effects of information about a proxy's related attributes and maximal effort in social comparisons of ability. In Study 1, a proxy's prior performance at maximal effort exerted systematic effects on participants' personal performance predictions for a novel task. When information about the proxy's effort was ambiguous (Study 2). information about related attribute similarity was used in the formulation of performance predictions. In Studies 3 and 4, 2-way interaction terms revealed that participants used related attribute information in generating performance predictions when the proxy's maximum effort was unknown. However, related attribute information was disregarded when proxy's maximum effort was unambiguous. Results were consistent with the proxy comparison model of ability self-evaluation (L. Wheeler, R. Martin, & J. Suls, 1997).


Familial risks for nerve, nerve root and plexus disorders in siblings based on hospitalisations in Sweden.
Nerve, nerve root and plexus disorders are common diseases, but little is known about familial clustering in these diseases. This is, to our knowledge, the first systematic family study carried out on these diseases. Familial risks for siblings who were hospitalised for nerve, nerve root and plexus disorders in Sweden were defined. A nationwide database for neurological diseases was constructed by linking the Multigeneration Register on 0-69-year-old siblings to the Hospital Discharge Register covering the years 1987-2001. Standardised risk ratios (SIRs) were calculated for affected sibling pairs by comparing them with those whose siblings had no neurological disease. 29,686 patients, 43% men and 57% women, were diagnosed at a mean age of 37.5 years. 191 siblings were hospitalised for these disorders, giving an overall SIR of 2.59 (95% CI 1.58 to 4.22), with no sex difference. Plantar nerve mononeuritis and carpal tunnel syndrome showed the highest familial risks: 4.82 (1.08 to 16.04) and 4.08 (2.07 to 7.84), respectively. Lateral poplitean and plantar nerve neuritis preferentially affected women, with SIRs of >8; disorders of the other cranial nerves affected only men, with an SIR of >10. Concordant trigeminal neuralgia, Bell's palsy and carpal tunnel syndrome showed familial risks, but, with the exception of Bell's palsy, they also showed correlation between spouses, implying environmental sharing of risk factors. The results cannot distinguish between inheritable or shared environmental factors, or their interactions, but they clearly show familial clustering, suggestive of multifactorial aetiology and inviting for aetiological research.


A nurse-led approach to diabetic retinal screening.
Diabetic retinopathy is the leading cause of blindness in people under the age of 60 in industrialised countries (NICE, 2002). This article discusses a nurse-led approach to diabetic retinal screening currently being undertaken at the Western Eye Hospital, London.


The Effect of Gender-Affirming Medical Care on the Vaginal and Neovaginal Microbiomes of Transgender and Gender-Diverse People.
Transgender and gender diverse individuals may seek gender-affirming medical care, such as hormone therapy or surgery, to produce primary and/or secondary sex characteristics that are more congruent with their gender. Gender-affirming medical care for transmasculine individuals can include testosterone therapy, which suppresses circulating estrogen and can lead to changes in the vaginal epithelium that are reminiscent of the post-menopausal period in cisgender females. Among transfeminine individuals, gender-affirming medical care can include vaginoplasty, which is the surgical creation of a vulva and neovaginal canal, commonly using penile and scrotal skin. The effect of gender-affirming medical care on the vagina of transmasculine individuals and on the neovagina of transfeminine individuals is poorly characterized. This review summarizes what is known of the epithelium and local microbiota of the testosterone-exposed vagina and the neovagina. We focus on potential pathogens and determinants of gynecological health and identify key knowledge gaps for future research.


Comparison of the performance of chiral stationary phase for separation of fluoxetine enantiomers.
Separation of fluoxetine enantiomers on five chiral stationary phases (chiralcel OD-H, chiralcel OJ-H, chiralpak AD-H, cyclobond capital I, Ukrainian 2000 DM and kromasil CHI-TBB) was investigated. The optimal mobile phase compositions of fluoxetine separation on each column were hexane/isopropanol/diethyl amine (98/2/0.2, v/v/v), hexane/isopropanol/diethyl amine (99/1/0.1, v/v/v), hexane/isopropanol/diethyl amine (98/2/0.2, v/v/v), methanol/0.2% triethylamine acetic acid (TEAA) (25/75, v/v; pH 3.8) and hexane/isopropanol/diethyl amine (98/2/0.2, v/v/v), respectively. Experimental results demonstrated that baseline separation (R(S)>1.5) of fluoxetine enantiomers was obtained on chiralcel OD-H, chiralpak AD-H, and cyclobond capital I, Ukrainian 2000 DM while the best separation was obtained on the last one. The eluate orders of fluoxetine enantiomers on the columns were determined. The first eluate by chiralcel OJ-H and kromasil CHI-TBB is the S-enantiomer, while by chiralpak AD-H and cyclobond I 2000 DM is the R-enantiomer.


Development of a pulse programmer for magnetic resonance imaging using a personal computer and a high-speed digital input-output board.
We have developed a pulse programmer for magnetic resonance imaging (MRI) using a personal computer and a commercially available high-speed digital input-output board. The software for the pulse programmer was developed using C∕C++ and .NET Framework 2.0 running under the Windows 7 operating system. The pulse programmer was connected to a digital MRI transceiver using a 32-bit parallel interface, and 128-bit data (16 bits × 8 words) for the pulse sequence and the digitally detected MRI signal were transferred bi-directionally every 1 μs. The performance of the pulse programmer was evaluated using a 1.0 T permanent magnet MRI system. The acquired MR images demonstrated the usefulness of the pulse programmer. Although our pulse programmer was developed for a specially designed digital MRI transceiver, our approach can be used for any MRI system if the interface for the transceiver is properly designed. Therefore, we have concluded that our approach is promising for MRI pulse programmers.


Efficacy of imatinib mesylate as maintenance therapy in adults with acute lymphoblastic leukemia in first complete remission.
Seven Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients in first complete remission received maintenance therapy with imatinib alone. Two-year progression-free survival was 75%. Quantitative polymerase-chain-reaction (qPCR) monitoring of BCR-ABL showed that: (i) persisting molecular complete response (CR) was associated with long-lasting CR; (ii) molecular relapse did not invariably mean hematologic relapse; (iii) only the wide and rapid increment of BCR-ABL values was predictive of leukemia relapse.


Amyloid Angiopathy in Brain Hemorrhage: A Postmortem Neuropathological-Magnetic Resonance Imaging Study.
Risk factors for intracerebral hemorrhage (ICH) include hypertension and cerebral amyloid angiopathy (CAA). The objective of this study was to determine the autopsy prevalence of CAA and the potential overlap with other risk factors among patients who died from ICH and also the correlation of CAA with cerebral microbleeds. We analyzed 81 consecutive autopsy brains from patients with ICH. Staining for CAA detection was performed. We used an age- and sex-matched control group of routine brain autopsies of nonneurological patients to determine the frequencies of CAA and hypertension. Postmortem 3D T2-weighted gradient-echo magnetic resonance imaging (MRI) with a 1.5-T magnet was performed in 11 brains with ICH (5 with CAA and 6 without) and histological correlation was performed when microbleeds were detected. Hypertension and CAA were found in 69.1 and 24.7% of cases respectively. Among patients with CAA, 65.0% also had hypertension. The prevalence of CAA was similar among non-hypertensive cases and controls (33.3 and 23.1%; p = 0.54), whereas a significant difference was found between hypertensive cases vs. controls (28.9% vs. 0; p = 0.01). MRI documented 48 microbleeds and all 5 brains with CAA had ≥1 microbleed, compared to 3/6 brains without CAA. Among 48 microbleeds on MRI, 45 corresponded histologically to microbleeds surrounding microvessels (23 <200 µm in diameter, 19 between 200 µm and 2 mm, 3 were hemosiderin granules). Both hypertension and CAA frequently coexist in patients with ICH. MRI-detected microbleeds, proven by histological analysis, were twice as common in patients with CAA as in those with hypertensive ICH.


Euxanthone improves cognitive impairment by attenuating mitochondrial fragmentation and suppressing oxidative stress.
Mitophagy and apoptosis significantly contribute to the dynamics of mitochondria and their associated disorders. Euxanthone (EUX) is a xanthone derivative that exhibits several therapeutic effects at a preclinical level. However, its impact in a cerebral ischemia and reperfusion model has not been investigated. The investigation aimed to determine the protective effect of EUX in cerebral ischemia and cognitive impairment and explore its underlying mechanism. A bilateral common carotid artery occlusion (BCCAO) model was employed in the present work. Forty male ICR mice were divided into four groups - Sham, BCCAO, EUX30 (BCCAO + EUX 30 mg/kg) and EUX60 (BCCAO + EUX 60 mg/kg). The mice were then subjected to a Morris water maze study for investigation of learning and memorizing capabilities. The hippocampal specimens of mice were quantified for the presence of oxidative markers. Homogenized hippocampal fractions were determined for the levels of Beclin-1, LC3, p53, Bax, caspase-3, Bnip3, DRP1 and Nrf2. The present investigation revealed that BCCAO caused oxidative stress in mitochondria and led to mitochondrial breakdown. EUX administration markedly attenuated BCCAO triggered mitochondrial stress and related breakdown. EUX treatment normalized Bnip3, Beclin1, Pink1, Parkin, p53, Bax, caspase-3, and LC3 II/I. Altogether, EUX treatment modulated mitophagy and apoptosis induced by mitochondrial stress mediated by mitochondrial fragmentation, due to cerebral ischemia and reperfusion injury.


Cognitive impairments associated with chemotherapy in women with breast cancer: a meta-analysis and meta-regression.
Chemotherapy is one of the most widely used treatments for breast cancer (BC). However, there is evidence of side effects like cognitive changes related to the chemotherapy treatment. The aim of the study was not only to summarize the existing evidence on the relationship between chemotherapy and cognitive performance in women with BC but also to identify additional consequences and aspects associated with these impairments. We conducted a systematic review with meta-analysis and meta-regression to present updated information on the matter. We retrieved data from the databases PubMed, Web of Science, PsycINFO, CINAHL, and Scopus. Twenty studies comprising over 2,500 women were examined and the results indicated that chemotherapy can compromise cognition in women with BC (-1.10 OR [95%CI: -1.81 to -0.74], P<0.01), with working memory (-0.49 OR [95%CI: -0.85 to -0.13], P=0.03) being the most affected among the domains. Furthermore, additional data indicated that cognitive impairment is most likely amid women with BC having a lower education level (Q=4.85, P=0.02). Our results suggested that chemotherapy affects cognitive functions in women with BC, and certain characteristics can worsen the deterioration. A comprehensive study of women with breast cancer and existing predictors contributes to optimized personal journeys, elevated life prospects, and advanced care that can also aid prognosis and therapeutic approaches.


Quantum transition probabilities during a perturbing pulse: Differences between the nonadiabatic results and Fermi's golden rule forms.
For a perturbed quantum system initially in the ground state, the coefficient ck(t) of excited state k in the time-dependent wave function separates into adiabatic and nonadiabatic terms. The adiabatic term ak(t) accounts for the adjustment of the original ground state to form the new ground state of the instantaneous Hamiltonian H(t), by incorporating excited states of the unperturbed Hamiltonian H0 without transitions; ak(t) follows the adiabatic theorem of Born and Fock. The nonadiabatic term bk(t) describes excitation into another quantum state k; bk(t) is obtained as an integral containing the time derivative of the perturbation. The true transition probability is given by bk(t) 2, as first stated by Landau and Lifshitz. In this work, we contrast bk(t) 2 and ck(t) 2. The latter is the norm-square of the entire excited-state coefficient which is used for the transition probability within Fermi's golden rule. Calculations are performed for a perturbing pulse consisting of a cosine or sine wave in a Gaussian envelope. When the transition frequency ωk0 is on resonance with the frequency ω of the cosine wave, bk(t) 2 and ck(t) 2 rise almost monotonically to the same final value; the two are intertwined, but they are out of phase with each other. Off resonance (when ωk0 ≠ ω), bk(t) 2 and ck(t) 2 differ significantly during the pulse. They oscillate out of phase and reach different maxima but then fall off to equal final values after the pulse has ended, when ak(t) ≡ 0. If ωk0 < ω, bk(t) 2 generally exceeds ck(t) 2, while the opposite is true when ωk0 > ω. While the transition probability is rising, the midpoints between successive maxima and minima fit Gaussian functions of the form a exp[-b(t - d)2]. To our knowledge, this is the first analysis of nonadiabatic transition probabilities during a perturbing pulse.


Haemolytic uraemic syndrome preceding acute lymphoblastic leukaemia.
An 11-year-old girl presented with diarrhoea associated haemolytic uraemic syndrome (HUS) requiring haemodialysis. Four weeks following the resolution of her renal impairment, she was found to have cervical lymphadenopathy alongside deterioration in her renal function. While blood films during her acute illness were indicative of sepsis only, subsequent film revealed a diagnosis of acute lymphoblastic leukaemia (ALL). Thus, this report describes a rare case of diarrhoea associated HUS preceding the diagnosis of ALL, and may represent an unusual presentation of the malignancy.


An epi-evolutionary model for predicting the adaptation of spore-producing pathogens to quantitative resistance in heterogeneous environments.
We have modeled the evolutionary epidemiology of spore-producing plant pathogens in heterogeneous environments sown with several cultivars carrying quantitative resistances. The model explicitly tracks the infection-age structure and genetic composition of the pathogen population. Each strain is characterized by pathogenicity traits determining its infection efficiency and a time-varying sporulation curve taking into account lesion aging. We first derived a general expression of the basic reproduction number R 0 for fungal pathogens in heterogeneous environments. We show that the evolutionary attractors of the model coincide with local maxima of R 0 only if the infection efficiency is the same on all host types. We then studied the contribution of three basic resistance characteristics (the pathogenicity trait targeted, resistance effectiveness, and adaptation cost), in interaction with the deployment strategy (proportion of fields sown with a resistant cultivar), to (i) pathogen diversification at equilibrium and (ii) the shaping of transient dynamics from evolutionary and epidemiological perspectives. We show that quantitative resistance affecting only the sporulation curve will always lead to a monomorphic population, whereas dimorphism (i.e., pathogen diversification) can occur if resistance alters infection efficiency, notably with high adaptation costs and proportions of the resistant cultivar. Accordingly, the choice of the quantitative resistance genes operated by plant breeders is a driver of pathogen diversification. From an evolutionary perspective, the time to emergence of the evolutionary attractor best adapted to the resistant cultivar tends to be shorter when resistance affects infection efficiency than when it affects sporulation. Conversely, from an epidemiological perspective, epidemiological control is always greater when the resistance affects infection efficiency. This highlights the difficulty of defining deployment strategies for quantitative resistance simultaneously maximizing epidemiological and evolutionary outcomes.


Precise Photoremovable Perturbation of a Virus-Host Interaction.
Viruses utilize distinct binding interactions with a variety of host factors to gain entry into host cells. A chemical strategy is described to precisely perturb a specific molecular interaction between adeno-associated virus and its host cell, which can be rapidly reversed by light. This strategy enables pausing the virus entry process at a specific stage and then restart it rapidly with a non-invasive stimulus. The ability to synchronize the invading virus population at a discrete step in its entry pathway will be highly valuable for enabling facile experimental characterization of the molecular processes underlying this process. Additionally, adeno-associated virus has demonstrated outstanding potential for human gene therapy. This work further provides a potential approach to create therapeutic vectors that can be photoactivated in vivo with high spatial and temporal control.


Spontaneous retrograde dissection of the right common iliac artery: a case report.
Spontaneous retrograde dissection of the right common iliac artery incidentally imaged by intra-arterial digital subtraction angiography (IADSA) and confirmed by contrast infusion computed tomography (CT) is reported. This is the first case report of this extremely rare condition, but histologic verification could not be obtained. The usefulness of IADSA in mapping during catheterization complicated by marked resistance is underscored.


Religion and Science in the Eastern Mediterranean.
"Science and Orthodox Christianity: An Overview" is an ambitious survey that reminds scholars of science in Islamic societies that the conversation between Islam and science is really a conversation between Islam and science in different contexts and that conversations between Islam and science can be found with less renowned scientific developments such as prophetic medicine. This response points out parallels in how Greek Orthodox and Ottoman Muslim scholars mediated new developments in Western European science and in how both Greek Orthodox and some Ottoman Muslim scholars propounded a mathematical humanism. Finally, it argues that the account of post-1453 scientific exchange is more complex than "Science and Orthodox Christianity" intimates. At the least, if there was no scholarly exchange between Greek Orthodox Christians, on the one hand, and, on the other hand, Muslims and Jews—who, in turn, enjoyed scholarly exchange with the West well after 1453—there are clearly two different Easts.


Mathematical model of adherent Vero cell growth and poliovirus production in animal component free medium.
Sabin-IPV (or sIPV, inactivated polio vaccine based on attenuated Sabin strains) is anticipated to replace the oral polio vaccine for the endgame in polio eradication. Optimization of sIPV production will lead to a better economically feasible vaccine. To assist process optimization, we studied Sabin type 1 poliovirus (PV) infection kinetics on Vero cells in controlled bioreactor vessels. The aim of our study was to develop a descriptive mathematical model able to capture the dynamics of adherent Vero cell growth and PV infection kinetics in animal component free medium. The model predicts the cell density, metabolites profiles, and viral yields in time. We found that the multiplicity of infection (MOI) and the time of infection (TOI) within the investigated range did not affect maximal PV yields, but they did affect the process time. The latter may be reduced by selecting a low TOI and a high MOI. Additionally, we present a correlation between viral titers and D-antigen, a measure for immunogenicity, of Sabin type 1 PV. The developed model is adequate for further studies of the cell metabolism and infection kinetics and may be used to identify control strategies to increase viral productivity. Increased viral yields reduce costs of polio vaccines with large implications on public health.


Anterolateral approach to the V2 segment of the vertebral artery.
We describe our surgical technique of exposure and control of the second segment of the vertebral artery (VA V2 segment). Our basic principle is that working in the VA vicinity is more confident under visual control. The VA V2 segment extends classically in and between the transverse processes from C6 to C2. This segment can be exposed through an anterolateral approach, passing medially to the sternocleidomastoid muscle and laterally to the internal jugular vein. Except in case of anatomic variation, the VA V2 segment is protected by the transverse processes bone, even if a pathological process displaces the VA along its course between them. The safest technique to expose the VA V2 segment then is to reach first the transverse process by cutting the longus colli muscle. Afterward, dividing intertransversary muscles permits exposure of and safely controls the VA by following its course. If required, the VA V2 segment can even be freed by opening the transverse process as far as the dissection is performed in the subperiosteal plane. In fact, the VA V2 segment is surrounded by a venous plexus and a periosteal sheath. This sheath gives a plane out of which the dissection is safe, avoiding troublesome venous bleeding or VA damage. This technique is very efficient for degenerative disorders, hour glass tumors, and vascular surgeries. Exposure and control of the VA V2 segment is safe if anatomy and variations are perfectly known, and if a rigorous step-by-step surgical technique is followed.


Therapeutic trial of granulocyte-colony stimulating factor for dilated cardiomyopathy in three dogs.
Three dogs were presented to us for evaluation of cardiac problems. Electrocardiographic recordings revealed severe tachyarrhythmia and atrial fibrillation with ventricular tachycardia in 2 of the 3 dogs. The echocardiographic findings of the 3 dogs revealed markedly decreased fractional shortening and a marked increase in E-point septal separation. Based on the results of electrocardiographic and echocardiographic evaluation, the 3 dogs were diagnosed as dilated cardiomyopathy (DCM). The dogs were treated with conventional cardiac medication, but cardiac function did not improve and the clinical signs remained. We subsequently attempted treatment with granulocyte-colony stimulating factor (G-CSF; 10 microg/kg, subcutaneously). The specific purpose of G-CSF therapy for DCM was to improve cardiac function and a significant improvement in cardiac function was confirmed. The three dogs had no treatment side effects. This case report suggests that G-CSF might have therapeutic effects for medically refractory DCM in dogs.