Euler-Poisson equations on Lie algebras and the N-dimensional heavy rigid body.
The classical Euler-Poisson equations describing the motion of a heavy rigid body about a fixed point are generalized to arbitrary Lie algebras as Hamiltonian systems on coad-joint orbits of a tangent bundle Lie group. the N-dimensional Lagrange and symmetric heavy top are thereby shown to be completely integrable.


Strain-sensitive electrical conductivity of carbon nanotube-graphene-filled rubber composites under cyclic loading.
Conductive rubber nanocomposites have been attracting interest for strain sensing applications owing to their large deformation and high sensitivity. In this paper, the strain sensing behavior of room temperature vulcanized (RTV) hybrid silicone rubber composites containing carbon nanotubes and graphene was systematically investigated. We studied the effects of the nanofiller content and strain amplitude on the strain sensing behavior of the nanocomposites, and found good stability and durability during cyclic loading. The shoulder peaks appeared in the cyclic loading curves owing to the competition between the reconstruction process of the conductive network during deformation and time-dependent features of the polymer material. Furthermore, our test results of different loading histories indicated that a sufficient recovery time could reduce or even eliminate the shoulder peak. Finally, the mechanical structure with a negative Poisson's ratio is designed to regulate the resistance response of the RTV nanocomposites, exhibiting a monotonic and more sensitive resistance response. Our research results explain the main factors contributing to the shoulder peak phenomenon of conductive nanocomposites and provide a regulation strategy for achieving a monotonic and highly sensitive resistance response.


Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis.
Assessment of long-term outcomes is essential in brain surgery for epilepsy, which is an irreversible intervention for a chronic condition. Excellent short-term results of resective epilepsy surgery have been established, but less is known about long-term outcomes. We performed a systematic review and meta-analysis of the evidence on this topic. To provide evidence-based estimates of long-term results of various types of epilepsy surgery and to identify sources of variation in results of published studies, we searched Medline, Index Medicus, the Cochrane database, bibliographies of reviews, original articles and book chapters to identify articles published since 1991 that contained > or =20 patients of any age, undergoing resective or non-resective epilepsy surgery, and followed for a mean/median of > or =5 years. Two reviewers independently assessed study eligibility and extracted data, resolving disagreements through discussion. Seventy-six articles fulfilled our eligibility criteria, of which 71 reported on resective surgery (93%) and five (7%) on non-resective surgery. There were no randomized trials and only six studies had a control group. Some articles contributed more than one study, yielding 83 studies of which 78 dealt with resective surgery and five with non-resective surgery. Forty studies (51%) of resective surgery referred to temporal lobe surgery, 25 (32%) to grouped temporal and extratemporal surgery, seven (9%) to frontal surgery, two (3%) to grouped extratemporal surgery, two (3%) to hemispherectomy, and one (1%) each to parietal and occipital surgery. In the non-resective category, three studies reported outcomes after callosotomy and two after multiple subpial transections. The median proportion of long-term seizure-free patients was 66% with temporal lobe resections, 46% with occipital and parietal resections, and 27% with frontal lobe resections. In the long term, only 35% of patients with callosotomy were free of most disabling seizures, and 16% with multiple subpial transections remained free of all seizures. The year of operation, duration of follow-up and outcome classification system were most strongly associated with outcomes. Almost all long-term outcome studies describe patient cohorts without controls. Although there is substantial variation in outcome definition and methodology among the studies, consistent patterns of results emerge for various surgical interventions after adjusting for sources of heterogeneity. The long-term (> or =5 years) seizure free rate following temporal lobe resective surgery was similar to that reported in short-term controlled studies. On the other hand, long-term seizure freedom was consistently lower after extratemporal surgery and palliative procedures.


In utero eye development documented by fetal MR imaging.
To date, very limited attention has been given to ocular abnormalities or growth parameters detected by fetal MR imaging. Our objective was to retrospectively determine the relationship between different parameters of eye development and estimated gestational age in the human fetus by use of fetal MR imaging. A retrospective study was performed to measure the transverse diameter, interocular distance, and lens diameter of the globes of 127 fetuses who had a morphologically normal central nervous system. Multiple single-shot T2 fast spin-echo images were obtained with a 1.5T magnet by use of contiguous 3-mm intervals in at least 2 orthogonal planes. Loess curves were fitted to explore the relationship between gestational age and each of the 3 measurements of interest. Different models were compared statistically to determine the model of best fit. For each variable of interest, the "best" model of eye growth was a quadratic function. Specifically, lens growth seems to plateau after 36 weeks of gestation, interocular distance plateaus after 36 weeks of gestation, and globe growth plateaus after 42 weeks of gestation. The lens, orbit, and interocular distance growth of the fetus can be demonstrated on fetal MR imaging. All 3 measurements suggest a quadratic model of growth, which indicates slowing of growth toward the end of gestation.


Golf buggy related head injuries.
Our department has recently managed three cases of serious head injuries resulting from falls from golf buggies. One of them sustained moderate head injury with a small cerebral contusion and skull fracture. Two of them sustained severe head injury with extensive cerebral contusions, extradural haematoma requiring craniotomy. Of the three patients, two made good recoveries whereas the third remained vegetative. We feel that instruction on the safe use of golf buggies is inadequate and should be intensified.


Erythrocyte survival in chronic renal failure. Role of secondary hyperparathyroidism.
The human erythrocyte (RBC) is a target organ for parathyroid hormone (PTH) and the hormone increases RBC osmotic fragility and induces their hemolysis. The present study was undertaken to examine whether elevated blood levels of PTH affect RBC survival, and therefore whether PTH, being an extracorpuscular factor, is responsible for the shortened RBC survival in chronic renal failure. 51Cr-labeled RBC survival was elevated in six normal dogs, in six animals with chronic renal failure and secondary hyperparathyroidism (NPX), and in six thyroparathyroidectomized dogs (NPX-TPTX) with comparable degree and duration of chronic renal failure. In the normal dogs, 51Cr-labeled RBC survival ranged between 22 and 35 (25.6 +/- 1.9) d. In the NPX dogs, 51Cr-labeled RBC survival was shortened and the values ranged between 16 and 20 (18.4 +/- 0.6) d, a value significantly (P less than 0.01) lower than normal dogs. In NPX-TPTX dogs, 51Cr-labeled RBC survival ranged between 20 and 33 (25.2 +/- 1.8) d, a value not different from that in normal dogs but significantly higher (P less than 0.01) than that in NPX animals. Our data demonstrate that excess blood levels of PTH and not other consequences of the uremic state are responsible for the shortened RBC survival in chronic renal failure.


Association of Previous Clinical Breast Examination With Reduced Delays and Earlier-Stage Breast Cancer Diagnosis Among Women in Peru.
Mammographic screening is impractical in most of the world where breast cancers are first identified based on clinical signs and symptoms. Clinical breast examination may improve early diagnosis directly by finding breast cancers at earlier stages or indirectly by heightening women's awareness of breast health concerns. To investigate factors that influence time to presentation and stage at diagnosis among patients with breast cancer to determine whether history of previous clinical breast examination is associated with earlier presentation and/or earlier cancer stage at diagnosis. In this cross-sectional analysis of individual patient interviews using a validated Breast Cancer Delay Questionnaire, 113 (71.1%) of 159 women with breast cancer treated at a federally funded tertiary care referral cancer center in Trujillo, Peru, from February 1 through May 31, 2015, were studied. Method of breast cancer detection and factors that influence time to and stage at diagnosis. Of 113 women with diagnosed cancer (mean [SD] age, 54 [10.8] years; age range, 32-82 years), 105 (92.9%) had self-detected disease. Of the 93 women for whom stage was documented, 45 (48.4%) were diagnosed with early-stage disease (American Joint Committee on Cancer [AJCC] stage 0, I, or II), and 48 (51.6%) were diagnosed with late-stage disease (AJCC stage III or IV). Mean (SD) total delay from symptom onset to initiation of treatment was 407 (665) days because of patient (mean [SD], 198 [449] days) and health care system (mean [SD], 241 [556] days) delay. Fifty-two women (46.0%) had a history of clinical breast examination, and 23 (20.4%) had undergone previous mammography. Women who underwent a previous clinical breast examination were more likely to have shorter delays from symptom development to presentation compared with women who had never undergone a previous clinical breast examination (odds ratio, 2.92; 95% CI, 1.30-6.60; P = .01). Women diagnosed with shorter patient delay were more likely to be diagnosed with early-stage disease (AJCC stage 0, I, or II) than those with longer patient delay (31 [58.5%] vs 11 [30.6%], P = .01). Women who underwent a previous clinical breast examination were more likely to be diagnosed with early-stage disease compared with women who had never undergone previous clinical breast examination; this relationship remained significant after controlling for insurance and household income (odds ratio, 2.44; 95% CI, 1.01-5.95; P = .048). In a population in which most breast cancers are self-detected, previous clinical breast examination was associated with shorter patient delay and earlier stage at breast cancer diagnosis. In regions of the world that lack mammographic screening, the routine use of clinical breast examination may provide a resource-appropriate strategy for improving breast cancer early diagnosis.


Estrous behavior in dairy cows: identification of underlying mechanisms and gene functions.
Selection in dairy cattle for a higher milk yield has coincided with declined fertility. One of the factors is reduced expression of estrous behavior. Changes in systems that regulate the estrous behavior could be manifested by altered gene expression. This literature review describes the current knowledge on mechanisms and genes involved in the regulation of estrous behavior. The endocrinological regulation of the estrous cycle in dairy cows is well described. Estradiol (E2) is assumed to be the key regulator that synchronizes endocrine and behavioral events. Other pivotal hormones are, for example, progesterone, gonadotropin releasing hormone and insulin-like growth factor-1. Interactions between the latter and E2 may play a role in the unfavorable effects of milk yield-related metabolic stress on fertility in high milk-producing dairy cows. However, a clear understanding of how endocrine mechanisms are tied to estrous behavior in cows is only starting to emerge. Recent studies on gene expression and signaling pathways in rodents and other animals contribute to our understanding of genes and mechanisms involved in estrous behavior. Studies in rodents, for example, show that estrogen-induced gene expression in specific brain areas such as the hypothalamus play an important role. Through these estrogen-induced gene expressions, E2 alters the functioning of neuronal networks that underlie estrous behavior, by affecting dendritic connections between cells, receptor populations and neurotransmitter releases. To improve the understanding of complex biological networks, like estrus regulation, and to deal with the increasing amount of genomic information that becomes available, mathematical models can be helpful. Systems biology combines physiological and genomic data with mathematical modeling. Possible applications of systems biology approaches in the field of female fertility and estrous behavior are discussed.


Ascending projections of nociceptive neurons from trigeminal subnucleus caudalis: A population approach.
Second-order neurons in trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1) are critical for craniofacial pain processing and project rostrally to terminate in: ventral posteromedial thalamic nucleus (VPM), medial thalamic nuclei (MTN) and parabrachial nuclei (PBN). The contribution of each region to trigeminal nociception was assessed by the number of phosphorylated extracellular signal-regulated kinase-immunoreactive (pERK-IR) neurons co-labeled with fluorogold (FG). The phenotype of pERK-IR neurons was further defined by the expression of neurokinin 1 receptor (NK1). The retrograde tracer FG was injected into VPM, MTN or PBN of the right hemisphere and after seven days, capsaicin was injected into the left upper lip in male rats. Nearly all pERK-IR neurons were found in superficial laminae of Vc-C1 ipsilateral to the capsaicin injection. Nearly all VPM and MTN FG-labeled neurons in Vc-C1 were found contralateral to the injection site, whereas FG-labeled neurons were found bilaterally after PBN injection. The percentage of FG-pERK-NK1-IR neurons was significantly greater (>10%) for PBN projection neurons than for VPM and MTN projection neurons (<3%). pERK-NK1-IR VPM projection neurons were found mainly in the middle-Vc, while pERK-NK1-immunoreactive MTN or PBN projection neurons were found in the middle-Vc and caudal Vc-C1. These results suggest that a significant percentage of capsaicin-responsive neurons in superficial laminae of Vc-C1 project directly to PBN, while neurons that project to VPM and MTN are subject to greater modulation by pERK-IR local interneurons. Furthermore, the rostrocaudal distribution differences of FG-pERK-NK1-IR neurons in Vc-C1 may reflect functional differences between these projection areas regarding craniofacial pain.


Biological features of core networks that result from a high-fat diet in hepatic and pulmonary tissues in mammary tumour-bearing, obesity-resistant mice.
We previously demonstrated that the chronic consumption of a high-fat diet (HFD) promotes lung and liver metastases of 4T1 mammary carcinoma cells in obesity-resistant BALB/c mice. To examine early transcriptional responses to tumour progression in the liver and lungs of HFD-fed mice, 4-week-old female BALB/c mice were divided into four groups: sham-injected, control diet (CD)-fed; sham-injected, HFD-fed (SH); 4T1 cell-injected, CD-fed (TC); 4T1 cell-injected, HFD-fed (TH). Following 16 weeks of either a CD or HFD, 4T1 cells were injected into the mammary fat pads of mice in the TC and TH groups and all mice were continuously fed identical diets. At 14 d post-injection, RNA was isolated from hepatic and pulmonary tissues for microarray analysis of mRNA expression. Functional annotation and core network analyses were conducted for the TH/SH Unique gene set. Inflammation in hepatic tissues and cell mitosis in pulmonary tissues were the most significant biological functions in the TH/SH Unique gene set. The biological core networks of the hepatic TH/SH Unique gene set were characterised as those genes involved in the activation of acute inflammatory responses (Orm1, Lbp, Hp and Cfb), disordered lipid metabolism and deregulated cell cycle progression. Networks of the pulmonary Unique gene set displayed the deregulation of cell cycle progression (Cdc20, Cdk1 and Bub1b). These HFD-influenced alterations may have led to favourable conditions for the formation of both pro-inflammatory and pro-mitotic microenvironments in the target organs that promote immune cell infiltration and differentiation, as well as the infiltration and proliferation of metastatic tumour cells.


Using functional electrical stimulation with stroke survivors: A survey of Victorian occupational therapists and physiotherapists.
Functional electrical stimulation (FES) improves active movement of the hemiplegic upper and lower limbs following stroke. The use of FES by Australian allied health clinicians in stroke rehabilitation is, however, unknown. The purpose of this study was to understand the use of FES in clinical practice. Reasons for the use of FES and potential variables that influence decision-making were also investigated. Cross-sectional study of Victorian allied health clinicians, using a snowball recruitment method. Ninety-seven eligible therapists completed the anonymous online survey. Data were analysed using frequency distributions. The majority of respondents were occupational therapists (n = 60; 62%). Approximately half of the respondents (n = 50; 52%) reported using FES in the past two years to improve a stroke survivor's ability to use their arm in daily activities. Respondents suggested that receiving workplace training from colleagues to learn how to use FES is the preferred method of education. Of those who received education (n = 80), 50 participants reported using FES in their practice. There is variable use of FES in stroke rehabilitation to increase active movement after stroke. While there was moderate agreement about when to use FES and useful education approaches for learning to use FES, further research is needed to better understand strategies which could be implemented to support increased FES use in stroke rehabilitation.


The study on telomere length for age estimation in a Thai population.
Age is one of the key parameters in establishing a physical characteristic profile of an individual. For biological evidence left in crime scenes such as blood, saliva, hair, etc, the evidence owner's age can be determined only by DNA extracted from these materials. Previous researches have found that there are certain DNA regions with specialized characteristic and function called telomere being able to predict age. The present study was to determine the correlation between telomere length and age as well as the effect of sex on the correlation and to create linear regression equation for age estimation in Thai population for forensic purposes. Blood samples obtained from unrelated healthy Thai fresh cadavers without anatomical organ abnormalities were used in this study. All cadaver subjects underwent the postmortem examination in jurisdiction of the Department of Forensic Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, and Institute of Forensic Medicine, Police General Hospital. Fifty blood samples from both sexes of all ages divided into 6 groups for equal age distribution (0-11, 12-23, 24-35, 36-47, 48-59, and 60 years old and older) were collected for a total of 100 samples. The extracted genomic DNA samples were then subjected to telomere length estimation by terminal restriction fragment (TRF) assay. The results showed that the mean TRF length was inversely correlated with age (r = -0.625), and sex did not have a statistically significant influence on the association between age and mean TRF length (P > 0.05). The obtained linear regression equation was y = 113.538 ± 9.604 - 0.012 × (R = 0.391; P < 0.001). However, the correlation was too low to be used for age estimation with high certainty and a possible reason for this in part would be the postmortem DNA degradation at some level, even using fresh cadaver blood, and other biological factors such as ethnicity and DNA sources. Roughly, those individuals who had a mean TRF length longer than 6.3 kilobase (kb), between 5.5 and 6.3 kb, and shorter than 5.5 kb aged younger than 28 years, 30 to 44 years, and older than 46 years, respectively (P < 0.01). As a preliminary study, this study highlighted that telomere length could act as a useful biomarker of aging in human population and might be used for rough age estimation in a Thai population. However, further studies with a larger sample size and/or in living human bloods as well as other cell types are recommended to support the results of this study.


Designing a nursing science curriculum for administrators in Austria.
Nursing education at the university level has been a goal of Austrian nurses for many years. To answer this need a nursing science curriculum for graduate nurses preparing for administrative and teaching roles in nursing was designed and developed for implementation at an Austrian university. Below, a report on its development.


Influence of yeast mannan on human neutrophil functions: inhibition of release of myeloperoxidase related to carbohydrate-binding property of the enzyme.
We investigated the possibility that dissolved mannan polysaccharide from Candida may have an inhibitory influence on the host defense mechanisms associated with neutrophils and thereby contribute to the pathogenesis of candidoses. We created a model for this hypothesis by using mannan derived from bakers' yeast (Saccharomyces cerevisiae) and mannan isolated from the serum of a patient with chronic mucocutaneous candidosis. We observed that these mannans inhibited the respiratory burst and release of myeloperoxidase stimulated by phagocytosis of serum-opsonized zymosan in vitro. Mannan did not inhibit release of three other lysosomal enzymes. The selective inhibition of release of myeloperoxidase was attributable to a carbohydrate-binding property of the enzyme, with the mannan causing co-sedimentation of the enzyme with the cellular fraction.


[The track of the clinical researcher].
In this issue, the students of the Maestría en Ciencias de la Salud Program, who are generally doctors, publish their work in the format of architectural design. The architectural design, allows to demonstrate in a schematic way, the objective, basal state, maneuver and outcome of their investigations. In this issue of the Revista Médica del IMSS, architectural design is used explicitly for the first time in a scientific publication. This innovation was achieved thanks to the collaboration of the editors and students of the Maestría en Ciencias de la Salud Program.


Ultrafast Photodoping and Plasmon Dynamics in Fluorine-Indium Codoped Cadmium Oxide Nanocrystals for All-Optical Signal Manipulation at Optical Communication Wavelengths.
We show the ultrafast photodoping and plasmon dynamics of the near-infrared (NIR) localized surface plasmon resonance (LSPR) of fluorine-indium codoped cadmium oxide (FICO) nanocrystals (NCs). The combination of high temporal resolution and broad spectral coverage allowed us to model the transient absorption (TA) spectra in terms of the Drude model, verifying the increase in carrier density upon ultrafast photodoping. Our analysis also suggests that a change in carrier effective mass takes place upon LSPR excitation as a result of the nonparabolic conduction band of the doped semiconductor with a consequently high signal response. Both findings are combined in this new type of plasmonic material. The combination of large transmission modulation with modest pump powers and ultrafast recombination times makes our results interesting for all-optical signal processing at optical communication wavelengths. At the same time, our results also give insights into the physical mechanisms of ultrafast photodoping and LSPR tuning of degenerately doped semiconductor NCs.


Overworked? Lighten your load.
Physician executives are suffering from creeping task migration--putting in too many hours for few appreciable results. Controlling this increasing workload has become one of the most important issues in health care, brought on by too few people trying to do too much. The only way to lessen the workload is to take charge, analyze, and act. Bosses won't care about the details. Several suggestions are presented to help physician executives downsize their workload while not reducing their output: (1) Compare your priorities with your boss's; (2) lighten up on the perfectionism; (3) change expectations; (4) look for "orphans" to cut--those projects that nobody is invested in; (5) don't target symbolic events; and (6) use logic to drive change. If you spend the next few months getting rid of the ineffective, inefficient, and redundant, you'll be ahead of the game. This is an ongoing task, and much easier done every three or four months than once a year.


Evidence for the existence of genetic variability in the tendency of Anopheles balabacensis to rest in houses and to bite man.
Mark-release-recapture experiments were carried out in Sabah, East Malaysia on the malaria and filariasis vector, Anopheles balabacensis. Samples of wild females were marked with different colours of fluorescent pigments, released in man-baited huts fitted with exit traps. Simultaneous collections and releases were also made in night-biting catches on a water buffalo and on four men. All subsequent recaptures were made in the same situation in which the mosquitoes were marked. The same individual mosquitoes were caught biting men and buffalo on different occasions and the numbers caught showed a strong preference for man over buffalo. The length of the oviposition cycle in the field was found to be 3.0 days. After blood-feeding on man in a hut, An. balabacensis were found to exit on the night or early morning. The same individual mosquitoes were found resting in the hut or exit trap on different occasions. The results indicate that there is strong evidence for the existence of genetic variability in the tendency of An. balabacensis to rest in houses and to bite man and buffalo. The obvious existence of this phenomenon is considered discouraging for the prospects of interruption of malaria transmitted by An. balabacensis in nature.


Vacuum-assisted breast biopsy in nonpalpable solid breast lesions without microcalcifications: the Greek experience.
To present the initial Greek experience with vacuumassisted breast biopsy (VABB) in the diagnosis of nonpalpable solid mammographic lesions without microcalcifications. We performed 83 VABB procedures (using a Fischer table and 11-guage Mammotome probes) in an 18- month period on women with nonpalpable solid breast tumors. We performed VABB procedures on women with breast imaging reporting and data system (BI-RADS) categories 3 and 4. VABB procedures excised more than 24 cores. Eighty-three women with nonpalpable lesions identified on mammography were evaluated; 42.2% were BI-RADS category 3, and 57.8% were BI-RADS 4. Of all solid tumors excised, 83.1% were benign, 3.6% were precursor lesions, and 13.3% of the lesions were malignant. No underestimation occurred. Clinically important hematoma developed in 4.8% of cases. VABB is an effective method for the diagnosis of nonpalpable solid lesions because of the lack of underestimation, although it is technically more difficult to focus on lesions without microcalcifications than those with microcalcifications on the Fischer table.


[Preservation of subvalvular mechanism at mitral valve replacement].
According to literature data there is no common approach to method of mitral valve replacement with preservation of subvalvular structures. Results of 175 operations of mitral valve replacement are analyzed. The preservation of fibrous-papillary contact must not be regarded as the goal itself, but it must improve the clinical effect of operation. Further study of left ventricle remodeling at mitral valve disease and repair of physiological function after surgery permits to predict and improve the functional results in early and long-term postoperative period.


Regulation of dietary choice by the decision-making circuitry.
To advance our understanding of how the brain makes food decisions, it is essential to combine knowledge from two fields that have not yet been well integrated: the neuro-computational basis of decision-making and the homeostatic regulators of feeding. This Review integrates these two literatures from a neuro-computational perspective, with an emphasis in describing the variables computed by different neural systems and how they affect dietary choice. We highlight what is unique about feeding decisions, the mechanisms through which metabolic and endocrine factors affect the decision-making circuitry, why making healthy food choices is difficult for many people, and key processes at work in the obesity epidemic.


A fast hemostatic and enhanced photodynamic 2-dimensional metal-organic framework loaded aerogel patch for wound management.
Achieving rapid hemostasis and highly effective antibacterial holds significant importance in the early-stage treatment of wounds. In this study, a hybrid aerogel patch comprising carbon quantum dots (CQDs) modified 2-dimensional (2D) porphyrinic metal-organic framework (MOF) nanosheets was designed by incorporating gelatin methacrylate (GelMA) and polyacrylamide (PAM) based matrix. On one hand, CQDs were stably doped onto the surface of the 2D MOF nanosheets, thereby enhancing the photodynamic activity through fluorescence resonance energy transfer (FRET) process. After the preparation of hybrid aerogel patch, the patch loaded with CQDs-doped 2D MOF exhibited excellent photodynamic bactericidal activity against Gram-positive Staphylococcus aureus (>99.99 %) and Gram-negative Escherichia coli (>99.99 %). On the other hand, the hybrid patch with highly porous and absorbent structure can rapidly absorb blood to aggregate clotting components and form a hydration barrier covering the wound to enhance hemostasis. Besides, the hemolysis and cytotoxicity assays demonstrated a good biocompatibility of this designed patch. In summary, this 2D MOF-loaded aerogel patch holds a potential to achieve rapid hemostasis and effective anti-infection in the early-stage treatment of traumatic wounds.


New species of Southeast Asian Dwarf Tarantula from Thailand: Phlogiellus Pocock, 1897 (Theraphosidae, Selenocosmiinae).
A new record of the tarantula genus Phlogiellus Pocock, 1897 from Thailand is described. Distributional data, natural history, morphological characters, and illustrations of male and female are provided. The Thai specimens belong to a new species, Phlogiellus longipalpussp. n. The diagnosis of the new species and related species are discussed.


Characteristics of an ideal rotavirus vaccine.
Rotavirus gastroenteritis primarily affects children younger than 5 years of age and is the leading cause of diarrhea-related hospitalizations worldwide. The substantial morbidity associated with this disease and the major burden on healthcare resources underscore the need for an effective vaccine. Two recently developed vaccines (RotaTeq [rotavirus vaccine, live, oral, pentavalent], and Rotarix [rotavirus vaccine, live]) share some characteristics of an ideal rotavirus vaccine. High efficacy, excellent tolerability, and no increased risk of intussusception were shown in separate clinical trials of more than 60,000 infants for each trial, as well as in smaller phase 3 clinical trials of each vaccine. Vaccination against rotavirus will substantially reduce rotavirus gastroenteritis-associated morbidity and mortality and, in so doing, bring about a significant reduction in rotavirus gastroenteritis-associated healthcare utilization.


Slow-tight-binding inhibition of enoyl-acyl carrier protein reductase from Plasmodium falciparum by triclosan.
Triclosan is a potent inhibitor of FabI (enoyl-ACP reductase, where ACP stands for acyl carrier protein), which catalyses the last step in a sequence of four reactions that is repeated many times with each elongation step in the type II fatty acid biosynthesis pathway. The malarial parasite Plasmodium falciparum also harbours the genes and is capable of synthesizing fatty acids by utilizing the enzymes of type II FAS (fatty acid synthase). The basic differences in the enzymes of type I FAS, present in humans, and type II FAS, present in Plasmodium, make the enzymes of this pathway a good target for antimalarials. The steady-state kinetics revealed time-dependent inhibition of FabI by triclosan, demonstrating that triclosan is a slow-tight-binding inhibitor of FabI. The inhibition followed a rapid equilibrium step to form a reversible enzyme-inhibitor complex (EI) that isomerizes to a second enzyme-inhibitor complex (EI*), which dissociates at a very slow rate. The rate constants for the isomerization of EI to EI* and the dissociation of EI* were 5.49x10(-2) and 1x10(-4) s(-1) respectively. The K(i) value for the formation of the EI complex was 53 nM and the overall inhibition constant K(i)* was 96 pM. The results match well with the rate constants derived independently from fluorescence analysis of the interaction of FabI and triclosan, as well as those obtained by surface plasmon resonance studies [Kapoor, Mukhi, N. Surolia, Sugunda and A. Surolia (2004) Biochem. J. 381, 725-733].


[Acquired remissions of insulin dependence in recent diabetes mellitus. Essential prognostic factors].
24 patients with recent diabetes mellitus (less than three years) were given an intravenous insulin infusion over a short period (84 to 252 hours) in an attempt to achieve a remission of their disease through rigorous normalization of blood glucose concentrations. After this treatment, strict control of diabetes mellitus was achieved with oral mediactions in 15 of the 24 patients. In 17 cases, onset of diabetes mellitus had been sudden and insulin was required immediately (acute cetosic diabetes: ACD); in 7 patients, signs of insulin deficiency had occurred only after seven months of hyperglycemia (secondary insulin-dependent diabetes mellitus: SIDDM). A strong probability of achieving an insulin-induced remission exists only during the first six months of ACD. The success of the insulin infusion is partly dependent upon the residual beta cell function. During the remission, which lasts for more than 12 months in 50% of cases, control of diabetes mellitus is optimal.


Boron neutron capture therapy for recurrent high-grade meningiomas.
Similar to glioblastomas, high-grade meningiomas are difficult pathologies to control. In this study, the authors used boron neutron capture therapy (BNCT), a tumor-selective intensive particle radiation modality, to treat high-grade meningioma. From June 2005 to September 2011, BNCT was applied 28 times in 20 cases of recurrent high-grade meningioma. All patients had previously undergone intensive treatments such as repetitive surgeries and multiple sessions of radiation therapy. Fluorine-18-labeled boronophenylalanine ((18)F-BPA) PET was performed before BNCT in 19 of the 20 cases; BPA is itself a therapeutic compound. Compound uptake, tumor shrinkage, long-term control rate including survival time, and failure pattern of the treated patients were all evaluated. Eighteen of 19 cases studied using (18)F-BPA PET showed good BPA uptake, with ratios of tumor to normal brain greater than 2.7. These ratios indicated the likely effects of BNCT prior to neutron irradiation. The original tumor sizes were between 4.3 cm(3) and 109 cm(3). A mean tumor volume reduction of 64.5% was obtained after BNCT within just 2 months. The median follow-up duration was 13 months. Six patients are still alive; at present, the median survival times after BNCT and diagnosis are 14.1 months (95% CI 8.6-40.4 months) and 45.7 months (95% CI 32.4-70.7 months), respectively. Clinical symptoms before BNCT, such as hemiparesis and facial pain, were improved after BNCT in symptomatic cases. Systemic metastasis, intracranial distant recurrence outside the radiation field, CSF dissemination, and local tumor progression were observed in 6, 7, 3, and 3 cases, respectively, during the clinical course. Apparent pseudoprogression was observed in at least 3 cases. Symptomatic radiation injuries occurred in 6 cases, and were controllable in all but 1 case. Boron neutron capture therapy may be especially effective in cases of high-grade meningioma.


[Temperature dependence of the acetylcholinesterase activity in synaptic membranes of the rat brain].
The temperature dependence (5-40 degrees C) of the acetylcholinesterase activity in synaptic membranes of the rat brain at different substrate concentrations was studied. At low substrate concentrations, the Arrhenius plot has two linear sections. At high concentration, there is one linear section throughout the temperature range. The addition of glycerol to incubation medium to final concentrations of 1 and 2% (w/v) increases the Michaelis constant, without affecting the maximal rate and the inhibition constant. The role of diffusion in the temperature dependence of the acetylcholinesterase activity is discussed.


The DefH9-iaaM-containing construct efficiently induces parthenocarpy in cucumber.
Parthenocarpy (seedless fruits) is a desirable trait that has been achieved in many plant cultivars. We generated parthenocarpic cucumber fruits by introducing the chimeric DefH9-iaaM construct into the cucumber genome using an Agrobacterium tumefaciens-mediated protocol. The construct consists of the DefH9 promoter from Antirrhinum majus and the iaaM coding sequence from Pseudomonas syringae. Transgenic plants were obtained from nine independent transformation events: half of these were tetraploid and did not produce seeds following self-pollination, while the remaining half were capable of displaying parthenocarpy in the subsequent reproductive generation. Of the fruits produced by the transgenic lines, 70-90% were parthenocarpic. The segregation of the marker gene in the transgenic T(1) progeny indicated single gene inheritance. The seed set in the transgenic lines and their F(1) hybrids was lower than in the non-transgenic control plants. Some of the methodological details and the practical significance of the results are discussed.


[Effect of ethacizin (diethylamine analog of ethmozine) on the efferent activity of the sympathetic and parasympathetic nerves of the heart].
This study examined the effects of the diethylamino analogue of ethmozin (ethacizin) (1 mg/kg, i.v.) on the spontaneous and reflex elicited efferent activity in thoracic cardiac sympathetic and parasympathetic nerves. Nitroglycerin and phenylephrine (4 and 8 micrograms/kg, i.v.) were administered to 15 anesthetized mongrel dogs while monitoring blood pressure and heart rate. In each dog, two cardiac nerves were isolated and efferent neurograms were simultaneously recorded and analyzed by microprocessor. Ethacizin significantly attenuated the spontaneous sympathetic efferent activity in both left and right, preganglionic (n-8) and postganglionic (n-14) sympathetic nerves to the heart. In contrast, reflex changes in sympathetic activity elicited by baroreceptor challenges, were not affected by ethacizin. Also, ethacizin did not significantly affect either spontaneous or baroreceptor reflex-induced parasympathetic efferent activities in 8 preganglionic nerves. Thus, this new phenothiazine derivative may exert part of its antiarrhythmic action through a reduction of the spontaneous sympathetic tonic discharges to the heart. The fact that ethacizin did neither reduce the reflex-induced changes in sympathetic or parasympathetic activities nor influence the tonic vagal discharges further suggests that the compound is not likely to interfere with reflexly mediated cardiovascular adaptive changes.


[Combination of photorefractive and phototherapeutic keratectomy in the treatment of keratoconus].
Twenty patients (28 eyes) with primary keratoconus of stages I-II (Amsler) were operated using photorefraction keratectomy (PRK) supplemented by phototherapeutic keratectomy (PRK). Mean UCVA before surgery was 0.04 +/- 0.004, BCVA 0.68 +/- 0.03. Eximer laser EC-5000(NIDEK) was used in the treatment. PRK included spherical, cylindrical ablations, or both. The diameter of ablation zone in PRK was 6 mm. in PTK the diameter of ablation zone was 8 mm, transition zone 9 mm. In PTK the ablation zone was decentered towards the cone apex (according to corneal computer topography). The method is patented in the Russian Federation. Visual acuity without correction notably improved in all 20 patients and its mean value after the operation was 0.73 +/- 0.03, 68% eye having visual acuity of 1.0. In one female patient keratoconus progressed 6 months after the operation. Haze was observed in 1 patient as a result of delayed reepithelialization. No progress of keratoconus was observed in other patients (period of observation 17.3 +/- 1.5 months). Hence, the new PRK-PTK method is an effective method for treating primary keratoconus of the first-second stage according to Amsler; the method arrests the progress of the condition in 96% cases.


[Evaluation of API 20 NE (version 6.0) in rare Gram-negative non-glucose-fermenting bacilli].
The ability of the API 20 NE method (6.0 version, bio-Mérieux, Marcy L'Etoile, France) to identify 188 strains of gram negative nonfermentative bacilli (NFB) was evaluated (Fenazinic pigment producing Pseudomonas aeruginosa and Acinetobacter spp. were excluded). These were isolated from patients treated at the Hospital de Clínicas José de San Martín of the University of Buenos Aires during the period 1996-2001. Strains were identified according to the Schreckenberger P testing method. Out of 188 NFB strains, 175 (93.09%) were correctly identified by the API 20 NE method at the genus and species level (IC95 = 88.47-96.27) while 61 (32.45%) required additional testing for correct identification. Thirteen strains (6.91%; IC95 3.73-11.53) could not be correctly identified and none of them were classified as "non identified". The API 20 NE method is a practical, easy to handle, fast and useful system for the identification of NFB since conventional manual methods take longer and require many biochemical, enzymatic and physiological tests which are sometimes not available depending on the size and capability of the laboratory. Although it is easy to handle, the API 20 NE identification system must be interpreted by an expert microbiologist who must compare the results obtained by this system with the information provided by the distinctive cultures and mobility patterns of these organisms.


An Evaluation of Two Different Broiler Catching Methods.
Catching is the first step in the pre-slaughter chain for broiler chickens. The process may be detrimental for animal welfare due to the associated handling. The aim of this pilot study was to compare two different methods to manually catch broilers: Catching the broilers by two legs and carrying them inverted (LEGS) or catching the broilers under the abdomen and carrying them in an upright position (UPRIGHT). Wing and leg fractures upon arrival at the abattoir, animal density in the drawers, birds on their back, broilers dead-on-arrival and time to fill the transport modules were investigated. The results showed that mean crating time was shorter in the UPRIGHT method (p = 0.007). There was a tendency for more wing fractures in broilers caught by the LEGS (p = 0.06). The animal density in the drawers was lower and with a smaller range in the UPRIGHT method (p = 0.022). The results indicate that catching the broilers under the abdomen in an upright position may improve broiler welfare in terms of fewer wing fractures, more consistent stocking density in drawers and potentially reduced loading time.


The American Shoulder and Elbow Surgeons Elbow Questionnaire: cross-cultural adaptation into German and evaluation of its psychometric properties.
The purpose of this clinical measurement (longitudinal) study was to cross-culturally adapt the American Shoulder and Elbow Surgeons standardized elbow assessment questionnaire (pASES-e) into German (pASES-eG) and evaluate its reliability and validity. Cross-cultural adaptation of the pASES-e was performed according to international guidelines. Seventy-five patients who had undergone elbow arthroplasty, on average of 11 years previously, were assessed using the pASES-eG, the German version of the Patient-Rated Elbow Evaluation (PREE-G), the Short Form-36 (SF-36), the Disabilities of Arm, Shoulder and Hand (DASH), and the clinical ASES-e to assess the construct validity of the pASES-eG. Its retest reliability was examined on 55-second assessments completed within two weeks. For reliability, the intraclass correlation coefficient was 0.93 for the pASES-eG total score. Its internal consistency was 0.90 (Cronbach's alpha). The pASES-eG total score correlated excellently with the PREE-G (0.92), well with the DASH (0.73), moderate with the physical component summary (0.62), and not with the mental component summary scores of the SF-36 (0.02). The pASES-eG correlated moderately with certain clinical findings (clinical ASES-e) (0.40-0.63). The pASES-eG represents a valid and reliable instrument for evaluating self-rated outcome in German-speaking patients with elbow pathology.


Photoinduced radical formation in hydrogen-bonded organic frameworks.
Hydrogen-bonded organic frameworks (HOFs) constructed from naphthalene-diimide bearing tectons undergo photochromic changes whilst forming radical bearing species within the framework structure.


Computational screening of single-atom doped In2O3 catalysts for the reverse water gas shift reaction.
The reverse water gas shift (RWGS) reaction is an important method for converting carbon dioxide (CO2) into valuable chemicals and fuels by hydrogenation. In this paper, the catalytic activity of single-atom metal-doped (M = Pt, Ir, Pd, Rh, Cu, Ni) indium oxide (c-In2O3) catalysts in the cubic phase for the RWGS reaction was investigated using density functional theory (DFT) calculations. This was achieved by identifying metal sites, screening oxygen vacancies, followed by further calculating the energy barriers for the direct and indirect dissociation pathways of the RWGS reaction. Our results show that the single-atom dopant in the indium oxide lattice promotes the creation of oxygen vacancies on the In2O3 surface, thereby facilitating the adsorption and activation of CO2 by the oxide surface and initiating the subsequent RWGS reaction. Furthermore, we find that the oxygen vacancy (OV) formation energy on the surface of the single-atom metal doped c-In2O3(111) surface can be used as a descriptor for CO2 adsorption, and the higher the OV formation energy, the more stable the CO2 adsorption structure is. The Cu/In2O3 structure has relatively high energy barriers for both direct (1.92 eV) and indirect dissociation (2.09 eV) in the RWGS reaction, indicating its low RWGS reactivity. In contrast, the Ir/In2O3 and Rh/In2O3 structures are more conducive to the direct dissociation of CO2 into CO, which may serve as more efficient RWGS catalysts. Furthermore, microkinetic simulations show that single atom metal doping to In2O3 enhances CO2 conversion, especially under high reaction temperatures, where the formation of oxygen vacancies is the limiting factor for CO2 reactivity on the M/In2O3 (M = Cu, Ir, Rh) models. Among these three single-atom catalysts, the Ir/In2O3 model was predicted to have the best CO2 reactivity at reaction temperatures above 573 K.


A new flow chamber for the study of shear stress and transmural pressure upon cells adhering to a porous biomaterial.
Biomaterials used in some biomedical devices are porous and exposed to normal and tangential flow of biofluids. To examine the influence of flow induced forces on the morphology and the biochemical responses of cells adhering to such biomaterials, a Hele-Shaw cell with a porous bottom wall was designed and characterized experimentally. Theoretical predictions for the flow in the chamber are provided and allow to quantify the shear stress and/or transmural pressure exerted on cells. It is thus possible to follow up continuously the shape changes of cells that are adherent on a permeable membrane used in bioreactors.


Complete Genome Sequence of Anoxybacillus flavithermus TNO-09.006, a Thermophilic Sporeformer Associated with a Dairy-Processing Environment.
Spores of thermophilic spore-forming bacteria are a common cause of contamination in dairy products. We isolated the thermophilic strain Anoxybacillus flavithermus TNO-09.006 from a milk-processing plant, and we report the complete genome of this isolate consisting of a single chromosome of 2.65 Mb.


Empowering the Water Oxidation Activity of the Bimetallic Metal-Organic Framework by Annexing Gold Nanoparticles over the Catalytic Surface.
Electrocatalytic water splitting to an anodic oxygen evolution reaction (OER) and a cathodic hydrogen evolution reaction (HER) is believed to be the most important application for sustainable hydrogen generation. Being a four-electron, four-proton transfer process, the OER plays the main obstacle for the same. Therefore, designing an effective electrocatalyst to minimize the activation energy barrier for the OER is a research topic of prime importance. The metal-organic framework (MOF) with a highly porous network is considered an appropriate candidate for the OER in alkaline conditions. Apart from several MOFs, the bimetallic one has an advantageous electrocatalytic performance due to the synergistic electronic interaction between two metal ions. However, most bimetallic MOFs have an obstacle to electrocatalytic application due to their low conductive nature, and therefore, they possess a barrier for charge transfer kinetics at the interface. Surface functionalization via various nanoparticles (NPs) is believed to be the most effective strategy for nullifying the conductive issue. In this work, we have designed a CoNi-based bimetallic MOF that was surface-functionalized by Au NPs (Au@CoNi-Bpy-BTC) for the OER under alkaline conditions. Au@CoNi-Bpy-BTC required an overpotential of just 330 mV, which is 56 mV lower as compared to the pristine MOF. Impedance analysis confirms an improved conductivity and charge transfer at the interface, where Au@CoNi-Bpy-BTC possesses a lower Rct value than CoNi-Bpy-BTC materials. Moreover, the Au-decorated MOF shows an 8.5 times increase in the TOF value compared to the pristine MOF. Therefore, this noble strategy toward the surface functionalization of MOFs via noble metal NPs is believed to be the most effective strategy for developing effective electrocatalysts for electrocatalytic application in energy-related fields. Overall, this report displays an exceptional correlation between the decorated NPs over the MOF surface, which can regulate the OER activity, as confirmed by experimental analysis.


Postnatal pediatric systemic antibiotic episodes during the first three years of life are not associated with mode of delivery.
Delivery by cesarean section (C-section) is associated with adverse short-term and long-term infant outcomes. Given that antibiotics during early life are prescribed for infant outcomes that are more likely among c-section deliveries, we hypothesized that postnatal antibiotic exposure will be greater among c-section infants compared to vaginally delivered infants. The aim of this paper was to evaluate if mode of infant delivery was associated with patterns of systemic antibiotic exposure in children during their first three years. Pediatric electronic health records from UFHealth, 2011 to 2017 were reviewed. We included singleton, term infants (37-42 weeks gestation) with a birth weight ≥ 2500 grams, with documented mode of delivery and well visits on record. Infants with a neonatal intensive care unit stay were excluded. Both oral and intravenous antibiotics for a 10-day duration were classified as a single episode. The primary outcome was antibiotic episodes in the first three years of life, and a sub-analysis was performed to compare broad-spectrum versus narrow-spectrum antibiotic exposures. The mean number of antibiotic episodes in 4,024 full-term infants was 0.34 (SD = 0.79) and 24.1% of infants had at least one antibiotic episode. Penicillins were the most prescribed antibiotic in children 0-1 years (66.9%) and cephalosporins were the most common antibiotic prescribed for children 1-3 years (56.2%). We did not detect a meaningful or significant rate ratio (RR) between mode of delivery and overall antibiotic episodes 1.14 (95% CI 0.99, 1.31), broad-spectrum episodes 1.19 (95% CI 0.93, 1.52, or narrow-spectrum episodes 1.14 (95% CI 0.97, 1.34). Our results do not support the hypothesis that postnatal antibiotic exposure was greater among infants delivered by cesarean section compare to infants delivered vaginally during the first three years of life.


Absence of CFAP69 Causes Male Infertility due to Multiple Morphological Abnormalities of the Flagella in Human and Mouse.
The multiple morphological abnormalities of the flagella (MMAF) phenotype is among the most severe forms of sperm defects responsible for male infertility. The phenotype is characterized by the presence in the ejaculate of immotile spermatozoa with severe flagellar abnormalities including flagella being short, coiled, absent, and of irregular caliber. Recent studies have demonstrated that MMAF is genetically heterogeneous, and genes thus far associated with MMAF account for only one-third of cases. Here we report the identification of homozygous truncating mutations (one stop-gain and one splicing variant) in CFAP69 of two unrelated individuals by whole-exome sequencing of a cohort of 78 infertile men with MMAF. CFAP69 encodes an evolutionarily conserved protein found at high levels in the testis. Immunostaining experiments in sperm from fertile control individuals showed that CFAP69 localized to the midpiece of the flagellum, and the absence of CFAP69 was confirmed in both individuals carrying CFPA69 mutations. Additionally, we found that sperm from a Cfap69 knockout mouse model recapitulated the MMAF phenotype. Ultrastructural analysis of testicular sperm from the knockout mice showed severe disruption of flagellum structure, but histological analysis of testes from these mice revealed the presence of all stages of the seminiferous epithelium, indicating that the overall progression of spermatogenesis is preserved and that the sperm defects likely arise during spermiogenesis. Together, our data indicate that CFAP69 is necessary for flagellum assembly/stability and that in both humans and mice, biallelic truncating mutations in CFAP69 cause autosomal-recessive MMAF and primary male infertility.


A retrospective notes-based review of patients lost to follow-up from anti-retroviral therapy at Mulanje Mission Hospital, Malawi.
To analyse patients with HIV who were lost to follow-up from anti-retroviral therapy (ART) at Mulanje Mission Hospital (MMH), Malawi. All patients on adult antiretroviral combinations at MMH, who were classified as lost to follow-up (LTFU) according to the national guidelines (patients missing a scheduled follow-up visit by more than two months) over a 12-month period, were included in the study and compared against a control group who had never been lost. Variables compared were gender, age, months on ART, time of year, WHO clinical stage, ART regimen, reported side effects, number of doses missed in the previous 12 months, whether the patient has been followed up in the community and if so, the length of time elapsed before follow-up. In all, 136 patients had been LTFU over the previous 12 months at MMH. Of these, 43 had incomplete or missing ART cards, resulting in 93 LTFU patient's data that could be analysed. Patients were more likely to get LTFU if they were men (p=0.03), who had been on anti-retroviral therapy for a short duration (p=0.06) and the proportion of patients who missed more than 4 doses in the previous 12 months was higher among LTFU patients (p=0.05). Only 34.4% of those LTFU had been traced in the community at the time of analysis. Of those traced, 27% had moved to another area, 5.5% had died, 5.5% had the wrong documentation and 62% gave no reason as to why they had missed appointments. This study in MMH has highlighted the importance and feasibility of comprehensive facility-level data-collection, both to identify local patient populations at risk of becoming lost to follow-up and to assess the follow-up measures in place to bring these lost to follow-up patients back into the programme. Even in the short time and with the small sample that was collected, there was evidence that patients most likely to get LTFU in MMH were young men, who had been on anti-retroviral therapy for a short duration and had missed over 4 doses in the last 12 months.


Prevalence and reasons for smoking in adolescent Swiss childhood cancer survivors.
Smoking harms health, particularly that of childhood cancer survivors, who face risk of pulmonary and cardiovascular diseases because of chemotherapy and radiotherapy to the chest. This nationwide study assessed smoking habits and reasons for smoking in adolescent survivors and healthy peers. As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to all Swiss resident survivors, who were aged 16-19 years. We compared smoking status and reasons for smoking between 511 survivors, 141 of their siblings, and 1,727 adolescents in a representative population-based study, the Tobacco Monitoring Switzerland (TMS). Current smoking was less prevalent in survivors (17%) and their siblings (17%) compared with TMS (32%). Survivors and TMS adolescents gave similar reasons for smoking. Stress control, smoking being a habit, and good taste were the reasons for smoking cited most often in both groups. Peer smoking was more important in survivors (49%) than in TMS (34%, P = 0.004). Most important reasons for not smoking in both groups were smoking being unhealthy and not wanting to be addicted. In Switzerland, survivors smoke as often as their siblings but less than the general population. Peer smoking was a more important reason for smoking in survivors than in the general population, suggesting that reducing smoking in peers could result in a reduction of smoking in survivors. Overall, reasons for smoking were very similar, thus interventions to reduce smoking in survivors could be the same as those used in the general population.


Measuring patterns of disability using the International Classification of Functioning, Disability and Health in the post-acute stroke rehabilitation setting.
To determine whether the International Classification of Functioning, Disability and Health (ICF) model is adequate for assessing disability patterns in stroke survivors in the sub-acute rehabilitation setting in terms of potential changes in functional profiles over time. Functional profiles of 197 stroke patients were assessed using the ICF Checklist and the Functional Independence Measure (FIMTM) at admission and discharge from rehabilitation hospital. The ICF Checklist was applied based on medical documentation and rehabilitation team meetings. Descriptive analyses were performed to identify changes in ICF categories and qualifiers from admission to discharge, and correlations between different improvement measures were calculated. Mean rehabilitation duration was 60 days; patients' mean age was 60 years, with mean FIM-score 75 at admission. Mean FIM-score improvement at discharge was 12.5. Within Body Functions, changes in at least 10% of patients were found regarding 13 categories; no categories within Body Structures, 24 within Activities and Participation, and 2 within Environmental Factors. Changes were mostly due to improvement in qualifiers, except for within Environmental Factors, where they were due to use of additional categories. Correlations between improvements in Body Functions and Activities and Participation (regarding capacity and performance), as well as between capacity and performance within Activities and Participation, were approximately 0.4. Rating ICF categories with qualifiers enables the detection of changes in functional profiles of stroke patients who underwent an inpatient rehabilitation programme. :


Fabrication of micro-axicons using direct-laser writing.
A novel direct-laser writing fabrication process for micro-axicons is demonstrated. A fiber-axicon-generated Bessel beam was utilized to write on UV-curable optical epoxy to form new axicons and axicon arrays, and geometrical parameters of the replicated epoxy axicons were analyzed in terms of both apex angle and proximity of the writing axicons. The shape of the fabricated axicons was demonstrated to be controllable through laser exposure, proximity, and apex angle of the source axicon, and the fabricated axicons are capable of generating a quality Bessel beam with an excellent focusing performance.


Magnetic resonance imaging of brain metastases: magnetisation transfer or triple dose gadolinium?
Magnetic resonance (MR) imaging of brain metastases relies on the neovascularity of metastases and the associated breach of blood-brain barrier manifesting as enhancement on T1-weighted images. There are 2 main strategies to improve the detection of brain metastases. One may increase the dose of gadolinium and increase the signal of the lesion. Alternatively, one may also lower the signal of the background (by magnetisation transfer suppression), in which case the enhancing lesion is rendered more conspicuous without increasing the dose of gadolinium. We aim to compare the efficacy of single-dose conventional spin-echo T1 scans with magnetisation transfer (MT) suppression with triple-dose conventional spin-echo T1 scans in the detection of brain metastases in 18 patients undergoing imaging for brain metastases. An incremental dose technique was employed. After administration of a single dose of gadolinium, MT suppressed T1-weighted scans were obtained, followed by a conventional T1 scan. Two doses of gadolinium were subsequently given, achieving a cumulative triple-dose, and a conventional T1-weighted scan was then performed. We found single-dose MT suppressed and triple-dose scans performed equally well and detected 26 metastatic lesions. They detected 5 (5/26, 19%) more lesions than the conventional single-dose T1 scans. Five (5/21, 24%) questionable lesions on single-dose conventional scans were confidently diagnosed on the single-dose MT suppressed and the triple-dose conventional scan. We conclude that single-dose MT suppressed scans are a cost-effective technique of detecting brain metastases.


[The use of histamine H2-receptor blockaders in the clinical picture of internal diseases].
The analysis of the literature, the material, and the results of the authors' own studies concerning the comprehensive investigation of blockers of histamine H2-receptors are presented. The attention is paid to the reparative action of drugs of this group, side effects, interaction with other drugs. The limitations and possibilities of their use in various diseases proceeding with gastric hypersecretion and hyperchlorhydria are determined.


Access to medicines through global health diplomacy.
The World Health Organisation (WHO) emphasizes that equitable access to safe and affordable medicines is vital to attaining the highest possible standard of health by all. Ensuring equitable access to medicines (ATM) is also a key narrative of the Sustainable Development Goals (SDGs), as SDG 3.8 specifies "access to safe, effective, quality and affordable essential medicines and vaccines for all" as a central component of universal health coverage (UHC). The SDG 3.b emphasizes the need to develop medicines to address persistent treatment gaps. However, around 2 billion people globally have no access to essential medicines, particularly in lower- and middle-income countries. The states' recognition of health as a human right obligates them to ensure access to timely, acceptable, affordable health care. While ATM is inherent in minimizing the treatment gaps, global health diplomacy (GHD) contributes to addressing these gaps and fulfilling the state's embracement of health as a human right.


Cinacalcet normalizes serum calcium in a double-blind randomized, placebo-controlled study in patients with primary hyperparathyroidism with contraindications to surgery.
Primary hyperparathyroidism (PHPT) is diagnosed by the presence of hypercalcemia and elevated or nonsuppressed parathyroid hormone (PTH) levels. Although surgery is usually curative, some individuals fail or are unable or unwilling to undergo parathyroidectomy. In such individuals, targeted medical therapy may be of value. Cinacalcet normalized calcium level and lowered PTH in patients with PHPT in several phase 2 and open-label studies. We compared cinacalcet and placebo in subjects with PHPT unable to undergo parathyroidectomy. Phase 3, double-blind, multi centere, randomized, placebo-controlled study. Sixty-seven subjects (78% women) with moderate PHPT were randomized (1:1) to cinacalcet or placebo for ≤28 weeks. Achievement of a normal mean corrected total serum calcium concentration of ≤10.3 mg/dl (2.575 mmol/l). Baseline median (quartile 1 (Q1), Q3) serum PTH was 164.0 (131.0, 211.0) pg/ml and mean (s.d.) serum Ca was 11.77 (0.46) mg/dl. Serum Ca normalized (≤10.3 mg/dl) in 75.8% of cinacalcet- vs 0% of placebo-treated subjects (P<0.001). Corrected serum Ca decreased by ≥1.0 mg/dl from baseline in 84.8% of cinacalcet- vs 5.9% of placebo-treated subjects (P<0.001). Least squares mean (s.e.m.) plasma PTH change from baseline was -23.80% (4.18%) (cinacalcet) vs -1.01% (4.05%) (placebo) (P<0.001). Similar numbers of subjects in the cinacalcet and placebo groups reported adverse events (AEs) (27 vs 20) and serious AEs (three vs four). Most commonly reported AEs were nausea and muscle spasms. These results demonstrate that cinacalcet normalizes serum calcium in this PHPT population and appears to be well tolerated.


Blood supply of the inferior turbinate and its clinical applications.
One of the most effective treatments of inferior turbinate (IT) hypertrophy is surgical reduction. Bleeding from the IT branch of the posterior lateral nasal artery (ITB) may interfere with the outcome of IT surgery. The aim of this study is to define the anatomic localization of the ITB and its variations and to investigate its clinical importance. Anatomic relations of the ITB were determined by microdissecting 20 adult, sagittally cross-sectioned head specimens. Branching characteristics of the ITB and its anatomical relations were evaluated. The most consistent two markers to define the ITB on the lateral nasal wall were the posterior attachment of the IT (PAIT) and the posterior attachment of the middle turbinate (PAMT). Mean horizontal distances of the ITB from the PAIT and the PAMT were 7.2 mm ± 2.8 mm (2.5-11.8 mm) and 8.2 mm ± 2.8 mm (4-14.6 mm), respectively. ITB was the only major artery that supplied the IT in 85% of the specimens, and, in 15%, there was more than one artery. ITB was located lateral to the IT in 95% and medial to the IT in 5%. The ITB coursed on the lateral nasal wall, vertically between the middle and ITs and always anterior to the PAIT. All the variations of blood supply to the IT were within a one square centimeter area, ∼1-cm anterior to the PAIT. Successful cauterization of this particular area may be an alternative cauterization site in IT surgery.


Contributions of higher-order proximal distribution functions to solvent structure around proteins.
The proximal distribution function (pDF) quantifies the probability of finding a solvent molecule in the vicinity of solutes. The approach constitutes a hierarchically organized theory for constructing approximate solvation structures around solutes. Given the assumption of universality of atom cluster-specific solvation, reconstruction of the solvent distribution around arbitrary molecules provides a computationally convenient route to solvation thermodynamics. Previously, such solvent reconstructions usually considered the contribution of the nearest-neighbor distribution only. We extend the pDF reconstruction algorithm to terms including next-nearest-neighbor contribution. As a test, small molecules (alanine and butane) are examined. The analysis is then extended to include the protein myoglobin in the P6 crystal unit cell. Molecular dynamics simulations are performed, and solvent density distributions around the solute molecules are compared with the results from different pDF reconstruction models. It is shown that the next-nearest-neighbor modification significantly improves the reconstruction of the solvent number density distribution in concave regions and between solute molecules. The probability densities are then used to calculate the solute-solvent non-bonded interaction energies including van der Waals and electrostatic, which are found to be in good agreement with the simulated values.


Massive invasion of organellar DNA drives nuclear genome evolution in Toxoplasma.
Toxoplasma gondii is a zoonotic protist pathogen that infects up to 1/3 of the human population. This apicomplexan parasite contains three genome sequences: nuclear (63 Mb); plastid organellar, ptDNA (35 kb); and mitochondrial organellar, mtDNA (5.9 kb of non-repetitive sequence). We find that the nuclear genome contains a significant amount of NUMTs (nuclear DNA of mitochondrial origin) and NUPTs (nuclear DNA of plastid origin) that are continuously acquired and represent a significant source of intraspecific genetic variation. NUOT (nuclear DNA of organellar origin) accretion has generated 1.6% of the extant T. gondii ME49 nuclear genome; the highest fraction ever reported in any organism. NUOTs are primarily found in organisms that retain the non-homologous end-joining repair pathway. Significant movement of organellar DNA was experimentally captured via amplicon sequencing of a CRISPR-induced double-strand break in non-homologous end-joining repair competent, but not ku80 mutant, Toxoplasma parasites. Comparisons with Neospora caninum, a species that diverged from Toxoplasma ~28 MY ago, revealed that the movement and fixation of 5 NUMTs predates the split of the two genera. This unexpected level of NUMT conservation suggests evolutionary constraint for cellular function. Most NUMT insertions reside within (60%) or nearby genes (23% within 1.5 kb) and reporter assays indicate that some NUMTs have the ability to function as cis-regulatory elements modulating gene expression. Together these findings portray a role for organellar sequence insertion in dynamically shaping the genomic architecture and likely contributing to adaptation and phenotypic changes in this important human pathogen.


Flightless birds are not neuroanatomical analogs of non-avian dinosaurs.
In comparative neurobiology, major transitions in behavior are thought to be associated with proportional size changes in brain regions. Bird-line theropod dinosaurs underwent a drastic locomotory shift from terrestrial to volant forms, accompanied by a suite of well-documented postcranial adaptations. To elucidate the potential impact of this locomotor shift on neuroanatomy, we first tested for a correlation between loss of flight in extant birds and whether the brain morphology of these birds resembles that of their flightless, non-avian dinosaurian ancestors. We constructed virtual endocasts of the braincase for 80 individuals of non-avian and avian theropods, including 25 flying and 19 flightless species of crown group birds. The endocasts were analyzed using a three-dimensional (3-D) geometric morphometric approach to assess changes in brain shape along the dinosaur-bird transition and secondary losses of flight in crown-group birds (Aves). While non-avian dinosaurs and crown-group birds are clearly distinct in endocranial shape, volant and flightless birds overlap considerably in brain morphology. Phylogenetically informed analyses show that locomotory mode does not significantly account for neuroanatomical variation in crown-group birds. Linear discriminant analysis (LDA) also indicates poor predictive power of neuroanatomical shape for inferring locomotory mode. Given current sampling, Archaeopteryx, typically considered the oldest known bird, is inferred to be terrestrial based on its endocranial morphology. The results demonstrate that loss of flight does not correlate with an appreciable amount of neuroanatomical changes across Aves, but rather is partially constrained due to phylogenetic inertia, evident from sister taxa having similarly shaped endocasts. Although the present study does not explicitly test whether endocranial changes along the dinosaur-bird transition are due to the acquisition of powered flight, the prominent relative expansion of the cerebrum, in areas associated with flight-related cognitive capacity, suggests that the acquisition of flight may have been an important initial driver of brain shape evolution in theropods.


Copper(II) and nickel(II) complexes of binucleating macrocyclic bis(disulfide)tetramine ligands.
Novel macrocyclic bis(disulfide)tetramine ligands and several Cu(II) and Ni(II) complexes of them with additional ligands have been synthesized by the oxidative coupling of linear tetradentate N2S2 tetramines with iodine. Facile demetalation of the Ni(II) oxidation products affords the free 20-membered macrocycles meso-9 and rac-9 and the 22-membered macrocycle 16, all of which are potentially octadentate N4S4 ligands. X-ray structure analyses reveal distinctly different conformations for the two isomers of 9; meso-9 shows a stepped conformation in profile with the disulfide groups corresponding to the rise of the step, whereas rac-9 exhibits a V conformation with the disulfide groups near the vertex of the V. No metal complexes of rac-9 have been isolated. Crystallographic studies of three Cu(II) complexes reveal that depending upon the size of the macrocyclic ligand and the nature of the additional ligands (I-, NCO-, and CH3CN), the Cu(II) coordination geometry shows considerable variation (plasticity), with substantial changes in the Cu(II)-disulfide bonding. Thus, a diiodide salt contains six-coordinate Cu(II) to which all four bridging disulfide sulfur atoms form strong equatorial bonds. In contrast, isocyanato complexes of the 20- and 22-membered macrocycles exhibit trigonal-bipyramidal Cu(II) and distorted cis-octahedral Cu(II) geometries, respectively, having only one and no short equatorially bound sulfur atoms. The coordination geometry of the latter complex can also be described as four-coordinate seesaw with two semicoordinated S(disulfide) ligands. Disulfide-->Cu(II) ligand-to-metal charge transfer absorptions of both isocyanato-containing Cu(II) species appear too weak to observe, probably because of poor overlap of the sulfur orbitals with the Cu(II) d-vacancy. The dual disulfide-bridged Ni(II) units of the crystallographically characterized octahedral Ni(II) complex of meso-9 with axial iodide and acetonitrile ligands promote substantial antiferromagnetic coupling (J = -13.0(2) cm-1).


Entrainment and resonance effects with a new mobile audio-visual stimulation device.
Entrainment and photic driving effects triggered by repetitive visual stimulation are long-established in clinical and therapeutic scenarios. Nonetheless, such stimulation patterns are typically bound to stationary clinical and laboratory applications. We investigated the effects of repetitive stimulation with a new dynamic auditory-visual stimulation pattern using a novel consumer-grade stimulation device for home application.Fourteen volunteers (study group) received 16 sessions of combined auditory-visual stimulation during four weeks. An additional control group (seven volunteers) received auditory-only stimulation for two sessions. From 64-channel electroencephalography recordings, we compared individual alpha peak frequencies (iAPF) between week one and week four as well as power values from the time-frequency analysis.The novel stimulation device yielded stable entrainment and resonance effects for all investigated stimulation frequencies. Both groups showed no differences in their iAPFs between weeks one and four. The power comparison suggests that there are similar entrainment and resonance effects in week one and week four within the study group.We conclude that the novel portable consumer-grade stimulation device is suitable for home-based auditory-visual stimulation leading to consistent entrainment and resonance effects over the course of 16 stimulation sessions over four weeks.


Improvement of Arabidopsis Biomass and Cold, Drought and Salinity Stress Tolerance by Modified Circadian Clock-Associated PSEUDO-RESPONSE REGULATORs.
Plant circadian clocks control the timing of a variety of genetic, metabolic and physiological processes. Recent studies revealed a possible molecular mechanism for circadian clock regulation. Arabidopsis thaliana (Arabidopsis) PSEUDO-RESPONSE REGULATOR (PRR) genes, including TIMING OF CAB EXPRESSION 1 (TOC1), encode clock-associated transcriptional repressors that act redundantly. Disruption of multiple PRR genes results in drastic phenotypes, including increased biomass and abiotic stress tolerance, whereas PRR single mutants show subtle phenotypic differences due to genetic redundancy. In this study, we demonstrate that constitutive expression of engineered PRR5 (PRR5-VP), which functions as a transcriptional activator, can increase biomass and abiotic stress tolerance, similar to prr multiple mutants. Concomitant analyses of relative growth rate, flowering time and photosynthetic activity suggested that increased biomass of PRR5-VP plants is mostly due to late flowering, rather than to alterations in photosynthetic activity or growth rate. In addition, genome-wide gene expression profiling revealed that genes related to cold stress and water deprivation responses were up-regulated in PRR5-VP plants. PRR5-VP plants were more resistant to cold, drought and salinity stress than the wild type, whereas ft tsf and gi, well-known late flowering and increased biomass mutants, were not. These findings suggest that attenuation of PRR function by a single transformation of PRR-VP is a valuable method for increasing biomass as well as abiotic stress tolerance in Arabidopsis. Because the PRR gene family is conserved in vascular plants, PRR-VP may regulate biomass and stress responses in many plants, but especially in long-day annual plants.


Epidemiological Markers for Interactions Among Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in Upper Respiratory Tract Carriage.
Cocolonization by Streptococcus pneumoniae and Haemophilus influenzae among children has been noted in numerous studies, as has an inverse relationship involving colonization with these species and Staphylococcus aureus. Interactions among these pathogens could mediate unanticipated outcomes of clinical interventions, including changes in H. influenzae and S. aureus disease incidence following pneumococcal vaccine introduction. However, it remains unclear whether cocolonization patterns represent true interspecies interactions or whether they result from confounding factors. We investigated polymicrobial carriage using longitudinal data from 369 Bedouin children and 400 Jewish children in Israel who were enrolled in a 7-valent pneumococcal conjugate vaccine (PCV7) trial. Children were swabbed 10 times between 2 and 30 months of age. The pathogens followed distinct age and seasonal distributions, but polymicrobial carriage associations persisted after controlling for these and other confounding factors. Receipt of PCV7 resulted in pneumococcal serotype replacement but did not influence total carriage of S. pneumoniae, H. influenzae, or S. aureus. The fact that S. pneumoniae, H. influenzae, and S. aureus polymicrobial carriage patterns do not result from confounding by age and season supports the idea of active interspecies interactions. However, pneumococcal serotype replacement may prevent changes in H. influenzae and S. aureus carriage among PCV7 recipients.


In situ dissecting the evolution of gene duplication with different histone modification patterns based on high-throughput data analysis in Arabidopsis thaliana.
Genetic regulation is known to contribute to the divergent expression of duplicate genes; however, little is known about how epigenetic modifications regulate the expression of duplicate genes in plants. The histone modification (HM) profile patterns of different modes of gene duplication, including the whole genome duplication, proximal duplication, tandem duplication and transposed duplication were characterized based on ChIP-chip or ChIP-seq datasets. In this study, 10 distinct HM marks including H2Bub, H3K4me1, H3K4me2, H3K4me3, H3K9ac, H3K9me2, H3K27me1, H3K27me3, H3K36me3 and H3K14ac were analyzed. Moreover, the features of gene duplication with different HM patterns were characterized based on 88 RNA-seq datasets of Arabidopsis thaliana. This study showed that duplicate genes in Arabidopsis have a more similar HM pattern than single-copy genes in both their promoters and protein-coding regions. The evolution of HM marks is found to be coupled with coding sequence divergence and expression divergence after gene duplication. We found that functionally selective constraints may impose on epigenetic evolution after gene duplication. Furthermore, duplicate genes with distinct functions have more divergence in histone modification compared with the ones with the same function, while higher expression divergence is found with mutations of chromatin modifiers. This study shows the role of epigenetic marks in regulating gene expression and functional divergence after gene duplication in plants based on sequencing data.


Spatial prediction of corn rootworm (Coleoptera: Chrysomelidae) adult emergence in Iowa cornfields.
The most common management options for corn rootworms are rotating corn with nonhost crops, planting genetically engineered corn resistant to corn rootworms (e.g., Bacillus thuringiensis [Bt] corn), and treating with a soil insecticide at planting time. Because these control tactics are preventive, the decision to apply controls has been made without any knowledge of rootworm density and spatial distribution. This study was conducted to predict the spatial distribution of adult emergence and to generate and test management zones for insecticides and Bt corn. To identify variables that correlated best with adult emergence the following year, plant height, plant stage, soil moisture, altitude, and corn rootworm adults were sampled spatially and temporally. Correlation and regression analyses showed that the best prediction for the adult emergence the following year was adult counts in the ear zone at peak population densities during the present year. Based on the prediction, geostatistics and the geographic information system were used to generate and test prescription maps with management zones for insecticides and Bt corn. Map-overlaying analysis showed that management zones for insecticides based on the economic injury level and Bt corn with 20% refuge had potential failure of 3-15% and 0-12% of field areas, respectively. This study demonstrated the spatial prediction of adult emergence the following year and generation of management zones, which has the potential of preventative, site-specific management of corn rootworms.


Effects of electron beam irradiation on dry matter degradation of wheat straw in the rumen.
The effect of electron beam irradiation at doses of 100, 200 and 300 kGy on ruminal dry matter degradation kinetics of wheat straw was investigated. Samples were irradiated by electron beam irradiator under identical conditions of temperature and humidity. Nylon bags of untreated or irradiated wheat straw were suspended in the rumen of three Taleshi steers for up to 96 h and resulting data were fitted to non-linear degradation model to calculate degradation parameters of dry matter. Results show that the washout fractions of dry matter increased linearly (p<0.001), but potentially degradable fraction and degradation rate decreased linearly (p<0.001) by electron beam irradiation. As a consequence, the effective degradability of dry matter increased linearly (p<0.001) with increasing irradiation dose. Electron beam irradiation at doses of 100, 200 and 300 kGy increased the effective degradability of dry matter at rumen outflow rate of 0.05/h by about 7, 15 and 18%, respectively. In the condition of this study, electron beam irradiation at dose of 200 kGy appeared to be a suitable dose for improving dry matter degradability of wheat straw in the rumen.


Rare Genome-Wide Copy Number Variation and Expression of Schizophrenia in 22q11.2 Deletion Syndrome.
Chromosome 22q11.2 deletion syndrome (22q11.2DS) is associated with a more than 20-fold increased risk for developing schizophrenia. The aim of this study was to identify additional genetic factors (i.e., "second hits") that may contribute to schizophrenia expression. Through an international consortium, the authors obtained DNA samples from 329 psychiatrically phenotyped subjects with 22q11.2DS. Using a high-resolution microarray platform and established methods to assess copy number variation (CNV), the authors compared the genome-wide burden of rare autosomal CNV, outside of the 22q11.2 deletion region, between two groups: a schizophrenia group and those with no psychotic disorder at age ≥25 years. The authors assessed whether genes overlapped by rare CNVs were overrepresented in functional pathways relevant to schizophrenia. Rare CNVs overlapping one or more protein-coding genes revealed significant between-group differences. For rare exonic duplications, six of 19 gene sets tested were enriched in the schizophrenia group; genes associated with abnormal nervous system phenotypes remained significant in a stepwise logistic regression model and showed significant interactions with 22q11.2 deletion region genes in a connectivity analysis. For rare exonic deletions, the schizophrenia group had, on average, more genes overlapped. The additional rare CNVs implicated known (e.g., GRM7, 15q13.3, 16p12.2) and novel schizophrenia risk genes and loci. The results suggest that additional rare CNVs overlapping genes outside of the 22q11.2 deletion region contribute to schizophrenia risk in 22q11.2DS, supporting a multigenic hypothesis for schizophrenia. The findings have implications for understanding expression of psychotic illness and herald the importance of whole-genome sequencing to appreciate the overall genomic architecture of schizophrenia.


Disordered recognition of facial identity and emotions in three Asperger type autists.
In this report we aim to explore severe deficits in facial affect recognition in three boys all of whom meet the criteria of Asperger's syndrome (AS), as well as overt prosopagnosia in one (B) and covert prosopagnosia in the remaining two (C and D). Subject B, with a familially-based talent of being highly gifted in physics and mathematics, showed no interest in people, a quasi complete lack of comprehension of emotions, and very poor emotional reactivity. The marked neuropsychological deficits were a moderate prosopagnosia and severely disordered recognition of facial emotions, gender and age. Expressive facial emotion, whole body psychomotor expression and speech prosody were quasi absent as well. In all three boys these facial processing deficits were more or less isolated, and general visuospatial functions, attention, formal language and scholastic performances were normal or even highly developed with the exception of deficient gestalt perception in B. We consider the deficient facial emotion perception as an important pathogenetic symptom for the autistic behaviour in the three boys. Prosopagnosia, the absent facial and bodily expression, and speech prosody were important but varying co-morbid disorders. The total clinical picture of non-verbal disordered communication is a complex of predominantly bilateral and/or right hemisphere cortical deficits. Moreover, in B, insensitivity to pain, smells, noises and internal bodily feelings suggested a more general emotional anaesthesia and/or a deficient means of expression. It is possible that a limbic component might be involved, thus making affective appreciation also deficient.


Pharmaceutical 3D printing: Design and qualification of a single step print and fill capsule.
Fused deposition modeling (FDM) 3D printing (3DP) has a potential to change how we envision manufacturing in the pharmaceutical industry. A more common utilization for FDM 3DP is to build upon existing hot melt extrusion (HME) technology where the drug is dispersed in the polymer matrix. However, reliable manufacturing of drug-containing filaments remains a challenge along with the limitation of active ingredients which can sustain the processing risks involved in the HME process. To circumvent this obstacle, a single step FDM 3DP process was developed to manufacture thin-walled drug-free capsules which can be filled with dry or liquid drug product formulations. Drug release from these systems is governed by the combined dissolution of the FDM capsule 'shell' and the dosage form encapsulated in these shells. To prepare the shells, the 3D printer files (extension '.gcode') were modified by creating discrete zones, so-called 'zoning process', with individual print parameters. Capsules printed without the zoning process resulted in macroscopic print defects and holes. X-ray computed tomography, finite element analysis and mechanical testing were used to guide the zoning process and printing parameters in order to manufacture consistent and robust capsule shell geometries. Additionally, dose consistencies of drug containing liquid formulations were investigated in this work.


Anti-idiotypic antibodies in autoimmune diseases.
The variable region (V region) of an antibody, the part of the molecule that binds to antigen, is itself antigenic and can elicit anti-V region antibodies when injected into animals of a different or even of the same species. The antigens of the V region constitute its idiotype, and they are defined by anti-idiotypic antibodies in polyclonal antisera or by monoclonal anti-idiotypic antibodies. An idiotype actually consists of multiple antigenic determinants, each of which is an idiotope. The antigenic determinants or idiotopes can reside in the heavy chain component of the V region, in its light chain component, or they may consist of a surface made up of parts of both chains. The idiotype of an antibody is, therefore, a way to describe by serological means the variable region of an antibody molecule. Originally, idiotypes were defined by heterologous antisera made, for example, by immunizing a rabbit with a monoclonal human myeloma protein. After extensive absorption with normal human immunoglobulins, such antisera were found to bind only to the V region of the immunizing myeloma immunoglobulin. Thus, idiotypes were originally thought to be unique markers of individual antibodies (hence their name). However, it is now known that different antibodies can share the same, or similar, idiotype. Even antibodies with different antigen-binding specificities can share the same idiotype if they use the same heavy or light chain in forming their V regions. Such antibodies constitute parallel sets. Thus, idiotypes can be: private (confined to a particular immunoglobulin molecule), public (shared by different antibodies), or cross-reactive (different idiotypes containing similar antigenic structures).(ABSTRACT TRUNCATED AT 250 WORDS)


In utero repair of rectal atresia after complete resection of a sacrococcygeal teratoma.
A case of a fetus with a prenatally diagnosed sacrococcygeal teratoma that produced high-output cardiac failure, hydrops, rectal atresia, and urinary tract obstruction is presented. The unique prenatal surgical management along with the embryogenesis of tumor-related rectal atresia is discussed. A large fetal sacrococcygeal teratoma with a significant intrapelvic component was detected at routine ultrasound in a 35-year-old gravida 3 para 2. Fetal hydrops developed rapidly due to high-output cardiac failure from the vascular 'steal' by the growing tumor. The urinary tract was obstructed due to the intrapelvic tumors mass. At 27 weeks' gestation, the female fetus underwent hysterotomy, resection of the entire mass and urinary diversion via bilateral flank ureterostomies. The rectum was found to be completely atretic due to apparent encasement by the tumor. Pull-through anorectoplasty was carried out concurrently. At 30 weeks' gestation, the mother developed preterm labor and a 1.8-kg was delivered by cesarean section. The baby did very well for 3 days but had a cardiac arrest and died due to an atrial perforation by a transfemoral venous catheter. To our knowledge this is the first report of a complete prenatal resection of a sacrococcygeal teratoma with concomitant pull-through anorectoplasty for rectal atresia.


Isomaltose production by modification of the fructose-binding site on the basis of the predicted structure of sucrose isomerase from "Protaminobacter rubrum".
"Protaminobacter rubrum" sucrose isomerase (SI) catalyzes the isomerization of sucrose to isomaltulose and trehalulose. SI catalyzes the hydrolysis of the glycosidic bond with retention of the anomeric configuration via a mechanism that involves a covalent glycosyl enzyme intermediate. It possesses a (325)RLDRD(329) motif, which is highly conserved and plays an important role in fructose binding. The predicted three-dimensional active-site structure of SI was superimposed on and compared with those of other alpha-glucosidases in family 13. We identified two Arg residues that may play important roles in SI-substrate binding with weak ionic strength. Mutations at Arg(325) and Arg(328) in the fructose-binding site reduced isomaltulose production and slightly increased trehalulose production. In addition, the perturbed interactions between the mutated residues and fructose at the fructose-binding site seemed to have altered the binding affinity of the site, where glucose could now bind and be utilized as a second substrate for isomaltose production. From eight mutant enzymes designed based on structural analysis, the R(325)Q mutant enzyme exhibiting high relative activity for isomaltose production was selected. We recorded 40.0% relative activity at 15% (wt/vol) additive glucose with no temperature shift; the maximum isomaltose concentration and production yield were 57.9 g liter(-1) and 0.55 g of isomaltose/g of sucrose, respectively. Furthermore, isomaltose production increased with temperature but decreased at a temperature of >35 degrees C. Maximum isomaltose production (75.7 g liter(-1)) was recorded at 35 degrees C, and its yield for the consumed sucrose was 0.61 g g(-1) with the addition of 15% (wt/vol) glucose. The relative activity for isomaltose production increased progressively with temperature and reached 45.9% under the same conditions.


Neighborhood walkability and sedentary time in Belgian adults.
Sedentary behavior (too much sitting) has deleterious health consequences that are distinct from lack of physical activity (too little exercise). This study aimed to examine the associations of neighborhood walkability and sociodemographic factors with adults' self-reported and objectively assessed sedentary time. This Belgian cross-sectional study was conducted between May 2007 and September 2008. Twenty-four neighborhoods were stratified on GIS-based walkability and neighborhood SES. In all, 1200 adults (aged 20-65 years; 50 per neighborhood; 42.7 [SD=12.6] years; 47.9% men) completed a sociodemographic survey and the International Physical Activity Questionnaire. They also wore an accelerometer for 7 days: Sedentary time was identified as accelerometer counts of less than 100 per minute. Statistical analyses were performed in 2009, using multilevel regression models, adjusted for physical activity levels and individual SES. Residents of high-walkable neighborhoods reported more sitting time than those of low-walkable neighborhoods (439.8 vs 403.4 minutes/day of daily sitting time, p<0.05). Living in high-walkable versus low-walkable neighborhoods was also associated with 2.9% more accelerometer-measured overall sedentary time (p<0.001). Being male, younger, unemployed, more highly educated, having a white-collar job (analysis for employed adults only), and living without children were all significantly associated with more sitting time. Contrary to expectations, living in a high-walkable neighborhood was associated with higher levels of sedentary time. If future studies in other contexts confirm these associations, environmental and policy innovations aiming to promote physical activity may need to address the potential negative health impact of sedentary behavior.


[A 38-year-old woman with an anovaginal fistula after consensual penile anal intercourse].
In this case report a 38-year-old woman was admitted to hospital with anal bleeding and perianal pain after a consensual vaginal intercourse followed by an anal intercourse during which she felt a sudden profound pain. Nine days later she was diagnosed with an anovaginal fistula. A diverting sigmoideostomy was performed, and spontaneous healing was awaited. Rectovaginal fistula without concomitant anal sphincter injury as a result of consensual penile anal intercourse is an extremely rare occurrence, described only once previously.