Mortality profiles in a country facing epidemiological transition: an analysis of registered data.
Sub-national analyses of causes of death and time-trends help to define public health policy priorities. They are particularly important in countries undergoing epidemiological transition like Peru. There are no studies exploring Peruvian national and regional characteristics of such epidemiological transition. We aimed to describe Peru's national and regional mortality profiles between 1996 and 2000. Registered mortality data for the study period were corrected for under-registration following standardized methods. Main causes of death by age group and by geographical region were determined. Departmental mortality profiles were constructed to evaluate mortality transition, using 1996 data as baseline. Annual cumulative slopes for the period 1996-2000 were estimated for each department and region. For the study period non-communicable diseases explained more than half of all causes of death, communicable diseases more than one third, and injuries 10.8% of all deaths. Lima accounted for 32% of total population and 20% of total deaths. The Andean region, with 38% of Peru's population, accounted for half of all country deaths. Departmental mortality predominance shifted from communicable diseases in 1996 towards non-communicable diseases and injuries in 2000. Maternal and perinatal conditions, and nutritional deficiencies and nutritional anaemia declined markedly in all departments and regions. Infectious diseases decreased in all regions except Lima. In all regions acute respiratory infections are a leading cause of death, but their proportion ranged from 9.3% in Lima and Callao to 15.3% in the Andean region. Tuberculosis and injuries ranked high in Lima and the Andean region. Peruvian mortality shows a double burden of communicable and non-communicable, with increasing importance of non-communicable diseases and injuries. This challenges national and sub-national health system performance and policy making.


Immunological identification of peripheral-blood lymphocytes from patients with lymphoproliferative disorders in Nigeria. I. Acute lymphocytic leukaemia (ALL).
The peripheral-blood lymphocytes of eight consecutively diagnosed cases of acute lymphocytic leukaemia (ALL) in Nigerians seen over a period of 2 years were classified as T, B and Null cells, using mainly sheep-rosetting (for T cells) and EAC-rosetting (for B cells) techniques. The patients' lymphocytes response to stimulation with phytohaemagglutinin (PHA) and basic haematological parameters were also determined. There were three male cases (37.5%), aged 10, 14 and 21 years who had T-cell ALL and one boy (12.5%) aged 10 years with B-cell ALL. The remaining four patients (50%) were two girls aged 6 and 6 1/2 years and two males aged 10 and 21 years who had lymphocytic leukaemia of the Null-cell class. These results from a tropical environment agree with previous findings among Caucasians with respect to the age and sex incidence and predominance of ALL with Null cells.


Fimbrial adhesions of Escherichia coli.
Fimbriae are long, threadlike protein polymers found on the surface of many strains of Escherichia coli. The presence of fimbriae has been found to be significantly correlated with pathogenicity, and specific fimbriae confer on pathogenic strains the ability to adhere to and colonize various specific host epithelia. A surprising variety of fimbrial adhesions have been found in E. coli; several unrelated groups of such proteins have been extensively characterized. Fimbriae of E. coli are strongly immunogenic. Their continuous interaction with host defenses has imposed heavy selective pressure on them, leading to a fine balance between functional necessity and maximal immunologic diversity. These important virulence factors may be exploited in various ways in the production of vaccination agents. Vaccines based on E. coli fimbriae have proved extremely successful in the veterinary sector, and several types of immunization are currently being tested in humans.


Mismatch Repair System Deficiency Is Associated With Response to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer.
Defective mismatch repair system (dMMR) has been shown to have a favorable impact on outcome in patients with colorectal cancer treated with surgery or immunotherapy, with adjuvant chemotherapy being discouraged unless there is nodal involvement. Its impact on radiosensitivity is unknown in patients with colorectal cancer. Patients treated for locally advanced rectal cancer between 2000 and 2016 were studied. Reported points included age, sex, clinical and radiologic tumor stages at diagnosis, modalities of neoadjuvant treatment, posttreatment pathologic staging, tumor regression score, and local, distant relapse-free, and overall survival. An inverse probability of treatment weighting propensity score analysis was performed to evaluate the association of mismatch repair proficiency with surgical and clinical outcomes. Among the 296 patients included, 23 (7.8%) had dMMR. Median follow-up was 43.0 months (interquartile range, 27.9-66.7). Patients with dMMR were significantly younger than the others. After inverse probability of treatment weighting propensity score matching, dMMR patients had higher pathologic downstaging rate (P < .0001), higher tumor regression grade (P = .024), and a longer recurrence-free survival (P < .0001). dMRR was associated with significant tumor downstaging after neoadjuvant chemoradiation and with increased recurrence-free survival. dMMR patients may have more radiosensitive tumors.


Latent typologies of posttraumatic stress disorder in World Trade Center responders.
Posttraumatic stress disorder (PTSD) is a debilitating and often chronic psychiatric disorder. Following the 9/11/2001 World Trade Center (WTC) attacks, thousands of individuals were involved in rescue, recovery and clean-up efforts. While a growing body of literature has documented the prevalence and correlates of PTSD in WTC responders, no study has evaluated predominant typologies of PTSD in this population. Participants were 4352 WTC responders with probable WTC-related DSM-IV PTSD. Latent class analyses were conducted to identify predominant typologies of PTSD symptoms and associated correlates. A 3-class solution provided the optimal representation of latent PTSD symptom typologies. The first class, labeled "High-Symptom (n = 1,973, 45.3%)," was characterized by high probabilities of all PTSD symptoms. The second class, "Dysphoric (n = 1,371, 31.5%)," exhibited relatively high probabilities of emotional numbing and dysphoric arousal (e.g., sleep disturbance). The third class, "Threat (n = 1,008, 23.2%)," was characterized by high probabilities of re-experiencing, avoidance and anxious arousal (e.g., hypervigilance). Compared to the Threat class, the Dysphoric class reported a greater number of life stressors after 9/11/2001 (OR = 1.06). The High-Symptom class was more likely than the Threat class to have a positive psychiatric history before 9/11/2001 (OR = 1.7) and reported a greater number of life stressors after 9/11/2001 (OR = 1.1). The High-Symptom class was more likely than the Dysphoric class, which was more likely than the Threat class, to screen positive for depression (83% > 74% > 53%, respectively), and to report greater functional impairment (High-Symptom > Dysphoric [Cohen d = 0.19], Dysphoric > Threat [Cohen d = 0.24]). These results may help inform assessment, risk stratification, and treatment approaches for PTSD in WTC and disaster responders.


High density lipoprotein subfractions during semistarvation in obese women.
The influence of a very low caloric diet (VLCD) on high density lipoproteins (HDL) is controversial. This study was designed to evaluate the influence of a VLCD on lipids and lipoproteins, especially on HDL subfractions (HDL2, HDL3) in obese women. After a 4-day period of isocaloric standard diet, 30 women at least 50% above ideal body weight were switched for 15 days on a protein-sparing modified diet providing 1.57 MJ per day. Mean body weight reduction was 5.6 +/- 0.7 kg. After the VLCD, total, very low density lipoproteins (VLDL), low density lipoproteins (LDL) and HDL cholesterol significantly decreased in all the subjects (p less than 0.01). Both HDL subfractions were depressed after the VLCD (p less than 0.01) but the reduction occurred predominantly in the HDL2 subfraction, thus inducing a decrease in the HDL2 to HDL3 cholesterol ratio (p less than 0.01). The VLCD was associated with a slight but not significant increase in the LDL to HDL cholesterol ratio. This increase was due mostly to the rise in the LDL to HDL2 cholesterol ratio (p less than 0.01). Further studies are needed to evaluate the long-term changes of HDL subfractions during weight-reducing regimens.


Variants in SNAP25 are targets of natural selection and influence verbal performances in women.
Descriptions of genes that are adaptively evolving in humans and that carry polymorphisms with an effect on cognitive performances have been virtually absent. SNAP25 encodes a presynaptic protein with a role in regulation of neurotransmitter release. We analysed the intra-specific diversity along SNAP25 and identified a region in intron 1 that shows signatures of balancing selection in humans. The estimated TMRCA (time to the most recent common ancestor) of the SNAP25 haplotype phylogeny amounted to 2.08 million years. The balancing selection signature is not secondary to demographic events or to biased gene conversion, and encompasses rs363039. This SNP has previously been associated to cognitive performances with contrasting results in different populations. We analysed this variant in two Italian cohorts in different age ranges and observed a significant genotype effect for rs363039 on verbal performances in females alone. Post hoc analysis revealed that the effect is driven by differences between heterozygotes and both homozygous genotypes. Thus, heterozygote females for rs363039 display higher verbal performances compared to both homozygotes. This finding was replicated in a cohort of Italian subjects suffering from neuromuscular diseases that do not affect cognition. Heterozygote advantage is one of the possible reasons underlying the maintenance of genetic diversity in natural populations. The observation that heterozygotes for rs363039 display higher verbal abilities compared to homozygotes perfectly fits the underlying balancing selection model. Although caution should be used in inferring selective pressures from observed signatures, SNAP25 might represent the first description of an adaptively evolving gene with a role in cognition.


ROSAT Detection of an X-ray Shadow in the 1/4-keV Diffuse Background in the Draco Nebula.
The detection by the Roentgen satellite (ROSAT) x-ray telescope of a shadow in the 1/4-kiloelectron volt (C band, 0.1 to 0.284 kiloelectron volt) cosmic diffuse background is reported. The location and morphology of the local minimum in x-rays are in clear agreement with a discrete H I cloud. The shadow is very deep with a minimum level at 50 percent of the surrounding emission; therefore, a minimum of 50 percent of the observed off-cloud flux must originate on the far side of the cloud. The analysis of H I velocity components links the cloud with the Draco nebula (distance approximately 600 parsecs); it then follows that there is significant 1/4-kiloelectron volt x-ray emission at a large distance (>400 parsecs) from the galactic plane along this line of sight. The extent of the distant emission region is uncertain, and, if it indicates the existence of a hot galactic corona, it must be patchy in nature.


Nickel-catalyzed regioselective hydrogen isotope exchange accelerated by 2-pyridones.
A nickel-catalyzed hydrogen isotope exchange has been developed with acetone-d6 as the deuterium source. The reaction showed an improved kinetic feature of H/D exchange under the assistance of 2-pyridones, efficiently affording regioselective labeled aryl and alkyl carboxamides.


Smoking is negatively associated with the presence of thyroglobulin autoantibody and to a lesser degree with thyroid peroxidase autoantibody in serum: a population study.
Autoimmune thyroid diseases are common and the prevalence of circulating thyroid antibodies (thyroid peroxidase antibody, TPO-Ab and thyroglobulin antibody, Tg-Ab) is high in the population. The knowledge of a possible association between lifestyle factors and circulating thyroid antibodies is limited. To evaluate the correlation between smoking habits and the presence of circulating TPO-Ab and Tg-Ab. In a cross-sectional comparative population study performed in two areas of Denmark with moderate and mild iodine deficiency, 4649 randomly selected subjects from the population in some predefined age groups between 18 and 65 years were examined. Blood tests were analysed for TPO-Ab and Tg-Ab using assays based on the RIA technique. The participants answered questionnaires, were clinically examined and blood and urine samples collected. Data were analysed in multivariate logistic regression models. There was a negative association between smoking and the presence of thyroid autoantibodies in serum. This association was observed for the presence of TPO-Ab and/or Tg-Ab, TPO-Ab (without respect to Tg-Ab status), Tg-Ab (without respect to TPO-Ab status) and both antibodies together. The association between smoking and thyroid autoantibodies was stronger for Tg-Ab than for TPO-Ab. There was no association between smoking and TPO-Ab measured alone or between smoking and TPO-Ab when Tg-Ab was included in the model as an explanatory variable. Smoking was negatively associated with the presence of thyroid autoantibodies with the strongest association between smoking and Tg-Ab. The study design precludes any conclusions as to the cause of the negative association between smoking thyroid autoantibodies.


Perioperative problems in elderly patients.
The number of elderly patients is increasing in all countries. It is estimated that about half of those over 65 will require an operation at some time, most commonly for cataract, prostatic hypertrophy, hernia, gallstones or fractured hip. Whilst overall morbidity and mortality is considerably increased in this age group, it does not appear to result from an increased liability to surgical complications, but rather to the complications of old age itself. The fundamental factor of ageing is a decreased capacity for adaptation, and this applies to virtually all organs and systems. Surgeons and anaesthetists must make allowances for these changes. Most important are cardio-respiratory limitations and altered pharmacokinetics and pharmacodynamics affecting drug action and elimination. These will be discussed in relation to the perioperative period. Once these are understood there should be no hesitation in accepting elderly patients for any form of surgery, provided the likely benefits outweigh the increased risk. Much discomfort in old age can be alleviated by a careful choice of surgery.


[Surgery of pulmonary metastasis from malignant melanoma. Results and criteria of surgical excision].
Lung metastases from malignant melanoma are frequent and they often inaugurate the metastatic stage. Exceptionally, they present as one or a few nodules, and in the absence of any other secondary lesion these cases raise the problem of surgical eradication. A retrospective multicentre study was carried out in a series of 38 patients and its results were compared to the data obtained from a review of 435 published cases in order to assess the value of surgery in terms of survival and to delimit its indications as closely as possible. Our series of 38 patients comprised 20 men and 18 women aged from 22 to 93 years (mean 51 years, median 55 years). The primary tumour was located in the trunk in 47 p. 100 of the cases; it was nodular in 33 p. 100 and superficial but extensive in 37.5 p. 100. The time elapsed before the metastases appeared varied from 0 to 108 months (median 40 months). Surgery had been radical in 70 p. 100 of the patients and usually limited, tumorectomies and segmentectomies accounting for 51 p. 100 of the operations. RESULTS. In this series the duration of survival varied between 2 and 144 months (mean 26 months, median close to 15 months), with a 20 p. 100 probability of survival at 5 years (fig. 1). Disease free survival varied from 0 to 144 months (mean 22.5 months, median 10.5 months) (fig. 2, curve 1). The parameters of response as regards patients, primary tumour, metastases and treatment were analysed. Response was uninfluenced by sex and slightly influenced by age, with a difference of borderline significance between subjects under and over 50. The primary tumour characteristics did not affect survival, and the features of metastases were of extremely varied importance. The number of operable metastases was not determinant. On the other hand, the presence of mediastinal lesions, either isolated or associated with lung lesions, worsened the prognosis of terms of survival and much more significantly so in terms of remission (fig. 3 and 4). The evaluation of evolutive characteristics, such as date of appearance and tumour doubling time, was inconclusive. Survival was of the same duration after wide and limited surgery, so that tumorectomy or segmentectomy should preferably be performed. The results of surgical treatment were determinant, with a highly significant difference in survival between radical and incomplete surgery (fig. 5 and fig. 2, curve 2). DISCUSSION. The median survival of patients operated upon for lung metastases is diversely evaluated in the literature as 8 to 29 months (table V), the mean figure of 16 months being virtually the same as that of our series. In this, as in most of the previously published series, the maximum duration of survival was beyond 8 to 10 years. The mean survival rate at 5 years is very close to the one we have recorded (20 p. 100) (table V). Compared with other treatments of lung metastases, surgery may be considered as capable of prolonging survival by 6 months; this is not much unless we add the possibility of a 5-year survival in 1 out of 5 operated patients and the possibility of a survival exceeding 8 or 10 years in 2 to 5 p. 100 of the cases. Some prognostic factors seem to constitute positive or negative criteria of operability. This is the case with mediastinal lesions which may consist of a metastasis of metastasis or of a lymph node invasion associated or not with the lung lesion, but in any case correspond to the involvement of more than one site. Mediastinal lesions must be systematically looked for and treated as contraindications of surgery, as shown by the differences in survival recorded in our series. Opinions differ as regards the value of evolutive parameters of the metastasis. For some authors, a more than 5 years interval before the metastasis appears is associated with a good chance of prolonged survival, whereas a less than 6 months or 1 year interval reflects a steadily high progressiveness and in practice precludes surgery. The value of the


The fate of hypoxic tissue on 18F-fluoromisonidazole positron emission tomography after ischemic stroke.
We studied 24 patients up to 51 hours after ischemic stroke using 18F-fluoromisonidazole positron emission tomography to determine the fate of hypoxic tissue likely to represent the ischemic penumbra. Areas of hypoxic tissue were detected on positron emission tomography in 15 patients, and computed tomography was available in 12 patients, allowing comparison with the infarct volume to determine the proportions of the hypoxic tissue volume that infarcted and survived. The proportion of patients with hypoxic tissue and the amount of hypoxic tissue detected declined with time. On average, 45% of the total hypoxic tissue volume survived and 55% infarcted. Up to 68% (mean, 17.5%) of the infarct volume was initially hypoxic. Most of the tissue "initially affected" proceeded to infarction. We correlated hypoxic tissue volumes with neurological and functional outcome assessed using the National Institutes of Health Stroke Scale, Barthel Index, and Rankin Score. Initial stroke severity correlated significantly with the "initially affected" volume, neurological deterioration during the first week after stroke with the proportion of the "initially affected" volume that infarcted, and functional outcome with the infarct volume. Significant reductions in the size of the infarct and improved clinical outcomes might be achieved if hypoxic tissue can be rescued.


Delayed nipple-sparing modified subcutaneous mastectomy: rationale and technique.
The problem of nipple-areola complex (NAC) preservation during mastectomy is a very intriguing and stimulating issue. In fact, in order to perform an oncologically safe operation, no mammary tissue (enclosed in the main galactophoric ducts) should remain; on the other hand, without the blood supply coming from the breast gland, NAC viability is greatly impaired because the surrounding vascular dermal network is not developed enough to support its metabolic requirements. We suggest therefore a two-step surgical procedure. The first step, on an outpatient basis with local tumescent anesthesia, is a mini-invasive cutting and coagulating procedure. It addresses the autonomization of the vascular supply to the NAC by detaching the galactophore stalk from the nipple and coagulating the deep vascular plexus. The second step, under general anesthesia and again with tumescent technique, removes the breast within its capsule, with careful checks of any remnant and adequate approach to the axilla. A subpectoralis prosthesis completes the procedure. In our view, this technique is electively suitable for prophylactic mastectomy, but also for stage I breast cancer, 2.5 cm from the NAC and 1.5 cm from the skin and pectoralis fascia, and it is very safe, simple, and effective.


Neuronal uptake and neuroprotective effect of curcumin-loaded PLGA nanoparticles on the human SK-N-SH cell line.
Curcumin, a natural polyphenolic pigment present in the spice turmeric (Curcuma longa), is known to possess a pleiotropic activity such as antioxidant, anti-inflammatory, and anti-amyloid-β activities. However, these benefits of curcumin are limited by its poor aqueous solubility and oral bioavailability. In the present study, a polymer-based nanoparticle approach has been utilized to deliver drugs to neuronal cells. Curcumin was encapsulated in biodegradable poly (lactide-co-glycolide) (PLGA) based-nanoparticulate formulation (Nps-Cur). Dynamic laser light scattering and transmission electronic microscopy analysis indicated a particle diameter ranging from 80 to 120 nm. The entrapment efficiency was 31% with 15% drug-loading. In vitro release kinetics of curcumin from Nps-Cur revealed a biphasic pattern with an initial exponential phase followed by a slow release phase. Cellular internalization of Nps-Cur was confirmed by fluorescence and confocal microscopy with a wide distribution of the fluorescence in the cytoplasm and within the nucleus. The prepared nanoformulation was characterized for cellular toxicity and biological activity. Cytotoxicity assays showed that void PLGA-nanoparticles (Nps) and curcumin-loaded PLGA nanoparticles (Nps-Cur) were nontoxic to human neuroblastoma SK-N-SH cells. Moreover, Nps-Cur was able to protect SK-N-SH cells against H2O2 and prevent the elevation of reactive oxygen species and the consumption of glutathione induced by H2O2. Interestingly, Nps-Cur was also able to prevent the induction of the redox-sensitive transcription factor Nrf2 in the presence of H2O2. Taken together, these results suggest that Nps-Cur could be a promising drug delivery strategy to protect neurons against oxidative damage as observed in Alzheimer's disease.


Genetic algorithm-based regularization parameter estimation for the inverse electrocardiography problem using multiple constraints.
In inverse electrocardiography, the goal is to estimate cardiac electrical sources from potential measurements on the body surface. It is by nature an ill-posed problem, and regularization must be employed to obtain reliable solutions. This paper employs the multiple constraint solution approach proposed in Brooks et al. (IEEE Trans Biomed Eng 46(1):3-18, 1999) and extends its practical applicability to include more than two constraints by finding appropriate values for the multiple regularization parameters. Here, we propose the use of real-valued genetic algorithms for the estimation of multiple regularization parameters. Theoretically, it is possible to include as many constraints as necessary and find the corresponding regularization parameters using this approach. We have shown the feasibility of our method using two and three constraints. The results indicate that GA could be a good approach for the estimation of multiple regularization parameters.


[Accuracy and practicability of the Prevical curette for the early diagnosis of endometrial carcinoma].
.he Prevical curette is a new instrument for an early diagnosis of carcinoma of the endometrium. The good acceptance of this method, which can be practised on an outpatient basis without anaesthesia, has been described by other groups of researchers. To check its reliability, we analysed endometrium specimens of 105 patients both cytologically and histologically. The collection of the material by the cytological method was successful in 99% of the cases, whereas clinical interpretation was possible in 94%. With nine carcinomas of the endometrium in the examined women, no false negative result was obtained. Hence, the use of this curette seems to be useful in patients with special risk factors and patients who cannot be anaesthetised. It should, always be kept in mind that the Prevical curette is conceived as a screening method which cannot replace histological clarification.


Association study of polymorphisms between the Radixin gene and rheumatoid arthritis in a Korean population.
Radixin (RDX) is part of the ezrin-radixin-moesin (ERM) protein family. It functions as a membrane-cytoskeletal linker in actin-rich cell surface structures and is thought to be essential for cortical cytoskeleton organization, cell motility, adhesion, and proliferation. An increase in phosphorylated ERM in fibroblast-like synoviocytes contributes to rheumatoid arthritis (RA) synovial hyperplasia. We examined the genetic association between the RDX gene and RA in a Korean population. To identify the relationship between RDX gene polymorphisms and RA, we genotyped 2 single nucleotide polymorphisms (SNPs; rs11213326 and rs12575162) of RDX using a direct sequencing method in 296 RA patients and 493 control subjects. In this study, the 2 SNPs showed no association with RA disease susceptibility. However, further analysis based on clinical information of the RA patient group showed that the SNPs were associated with the erythrocyte sedimentation rate (ESR) in RA patients. These data suggest an association between RDX polymorphisms and the clinical features of RA patients, particularly the ESR.


The cloak, dagger, and shield: proteases in plant-pathogen interactions.
Plants sense the presence of pathogens or pests through the recognition of evolutionarily conserved microbe- or herbivore-associated molecular patterns or specific pathogen effectors, as well as plant endogenous danger-associated molecular patterns. This sensory capacity is largely mediated through plasma membrane and cytosol-localized receptors which trigger complex downstream immune signaling cascades. As immune signaling outputs are often associated with a high fitness cost, precise regulation of this signaling is critical. Protease-mediated proteolysis represents an important form of pathway regulation in this context. Proteases have been widely implicated in plant-pathogen interactions, and their biochemical mechanisms and targets continue to be elucidated. During the plant and pathogen arms race, specific proteases are employed from both the plant and the pathogen sides to contribute to either defend or invade. Several pathogen effectors have been identified as proteases or protease inhibitors which act to functionally defend or camouflage the pathogens from plant proteases and immune receptors. In this review, we discuss known protease functions and protease-regulated signaling processes involved in both sides of plant-pathogen interactions.


On-line molecularly imprinted solid-phase extraction for the selective spectrophotometric determination of nicotine in the urine of smokers.
This work describes an on-line molecularly imprinted solid-phase extraction (MISPE) method for spectrophotometric determination of nicotine in urine samples of smokers. This method is based on manganese (VII) to manganese (VI) reduction in an alkaline medium, promoted by nicotine. Two wash solutions (1:4 (v/v) acetonitrile:sodium hydroxide--pH 11.4, and nitric acid--pH 2.5) were employed to circumvent interferences. Aqueous solutions containing nicotine plus different possible concomitants (cotinine, anabasine, norcotinine and caffeine) were tested individually. The analytical calibration curve was prepared in urine samples collected from non-smokers and spiked with nicotine standard from 1.1 to 60 micromol L(-1) (r(2)>0.998). The limit of quantification and the analytical frequency were 1.1 micromol L(-1) and 11 h(-1), respectively. The precision, evaluated using 3, 10 and 30 micromol L(-1) nicotine in urine, was 10, 10 and 4% (intra-day precision) and 12, 13 and 5% (inter-day precision), respectively. Accuracy was checked through high performance liquid chromatography and the results did not present significant differences at the 95% confidence level according to the Student's t-test.


A glucagon-like peptide-1 receptor antagonist reduces the insulin response to a glycaemic meal in ponies1.
High plasma concentrations of insulin can cause acute laminitis. Ponies and horses with insulin dysregulation (ID) exhibit marked hyperinsulinaemia in response to dietary hydrolysable carbohydrates. Glucagon-like peptide-1 (GLP-1), an incretin hormone released from the gastrointestinal tract, enhances insulin release, and is increased post-prandially in ponies with ID. The aim of this study was to determine whether blocking the GLP-1 receptor reduces the insulin response to a high glycaemic meal. Five adult ponies were adapted to a cereal meal then given two feed challenges 24 h apart of a meal containing 3 g/kg BW micronized maize. Using a randomised cross-over design all ponies received both treatments, where one of the feeds was preceded by the IV administration of a GLP-1 receptor blocking peptide, Exendin-3 (9-39) amide (80 µg/kg), and the other feed by a sham treatment of peptide diluent only. Blood samples were taken before feeding and peptide administration, and then at 30 min intervals via a jugular catheter for 6 hours for the measurement of insulin, glucose and active GLP-1. The peptide and meal challenge caused no adverse effects, and the change in plasma glucose in response to the meal was not affected (P = 0.36) by treatment: peak concentration 9.24 ± 1.22 and 9.14 ± 1.08 mmol/L without and with the antagonist, respectively. Similarly, there was no effect (P = 0.35) on plasma active GLP-1 concentrations: peak concentration 14.3 ± 1.36 pM and 13.7 ± 1.97 pM without and with the antagonist, respectively. However, the antagonist caused a significant decrease in the area under the curve for insulin (P = 0.04), and weak evidence (P = 0.06) of a reduction in peak insulin concentration (456 ± 147 μIU/mL and 370 ± 146 μIU/mL without and with the antagonist, respectively). The lower overall insulin response to the maize meal after treatment with the antagonist demonstrates that blocking the GLP-1 receptor partially reduced insulin production in response to a high starch, high glycaemic index, diet. Using a different methodological approach to published studies, this study also confirmed that GLP-1 does contribute to the excessive insulin production in ponies with ID.


Dual actions of S-nitrosylated derivative of vasoactive intestinal peptide as a vasoactive intestinal peptide-like mediator and a nitric oxide carrier.
Vasoactive intestinal peptide (VIP) has been postulated as a non-adrenergic non-cholinergic (NANC) transmitter in the relaxation of vascular and non-vascular systems. In order to synergize the vasoactivities of VIP with nitric oxide (NO), we synthesized a S-nitrosylated derivative of VIP, VIP-Gly-Cys-NO (VIPGC-NO). On aortic rings, VIPGC-NO exhibited a dose-dependent vasorelaxation similar to S-nitrosoglutathione (GSNO), and both induced complete vasorelaxation at 1 microM, whereas, VIP at 1 microM only produced 19% relaxation. The degree of vasorelaxation was proportional to the increases in cyclic GMP with no significant enhancement in cyclic AMP (cAMP) level. On precontracted tracheal rings, VIP, VIPGC-NO, VIPGC and GSNO produced relaxation with EC50 of 74+/-5, 32+/-6, 59+/-9, and 251+/-32 nM, respectively, which was consistent with increases in cyclic GMP (cGMP). A marked increase in cAMP was observed from the tracheal rings pretreated with VIP, VIPGC-NO and its parent VIP-Gly-Cys (VIPGC) as well as isoproterenol. Propranolol only blocked the airway relaxation induced by isoproterenol, but did not antagonize the relaxation induced by VIP, VIPGC and VIPGC-NO. On rabbit sphincter of Oddi, VIP, VIPGC-NO and VIPGC inhibited both basic and acetylcholine-induced contraction frequency and amplitude, whereas, GSNO was less potent than VIP and its derivatives over a range of 2 log units in this respect. On rat gastric fundus, these compounds inhibited contraction amplitude and frequency induced with 5-hydroxytryptamine (5-HT) in the order of inhibitory potency VIP > VIPGC-NO > VIPGC > isoproterenol > GSNO. Our data suggest that: (1) NO is selective in relaxing vascular smooth muscle via the cGMP pathway, whereas VIP is selective in relaxing non-vascular smooth muscles via the activation of both cGMP and cAMP pathways; (2) VIPGC-NO preserves the intrinsic function of VIP but acquires NO-like vasoactivities.


Improvement in the quality of black phosphorus by selecting a mineralizer.
The low-cost synthesis of high-quality black phosphorus (BP) has always been a challenge. Herein, we selected different mineralizers to synthesize high-crystallinity BP by the chemical vapor transport (CVT) method and demonstrated that the use of Pb instead of Sn can lead to higher purity BP. Residual Sn in Sn-BP was confirmed by X-ray photoelectron spectroscopy (XPS), but no mineralizer impurity was observed in Pb-BP. The performance of FET devices showed that the hole mobility of Pb-BP was significantly higher than that of Sn-BP. On the other hand, the Pb-BP devices exhibited good bipolarity with the highest hole mobility of 523 cm2 V-1 s-1 at room temperature and electron mobility of up to 28 cm2 V-1 s-1.


A single VHH-based toxin-neutralizing agent and an effector antibody protect mice against challenge with Shiga toxins 1 and 2.
Shiga toxin-producing Escherichia coli (STEC) is a major cause of severe food-borne disease worldwide, and two Shiga toxins, Stx1 and Stx2, are primarily responsible for the serious disease consequence, hemolytic-uremic syndrome (HUS). Here we report identification of a panel of heavy-chain-only antibody (Ab) V(H) (VHH) domains that neutralize Stx1 and/or Stx2 in cell-based assays. VHH heterodimer toxin-neutralizing agents containing two linked Stx1-neutralizing VHHs or two Stx2-neutralizing VHHs were generally much more potent at Stx neutralization than a pool of the two-component monomers tested in cell-based assays and in vivo mouse models. We recently reported that clearance of toxins can be promoted by coadministering a VHH-based toxin-neutralizing agent with an antitag monoclonal antibody (MAb), called the "effector Ab," that indirectly decorates each toxin molecule with four Ab molecules. Decoration occurs because the Ab binds to a common epitopic tag present at two sites on each of the two VHH heterodimer molecules that bind to each toxin molecule. Here we show that coadministration of effector Ab substantially improved the efficacy of Stx toxin-neutralizing agents to prevent death or kidney damage in mice following challenge with Stx1 or Stx2. A single toxin-neutralizing agent consisting of a double-tagged VHH heterotrimer--one Stx1-specific VHH, one Stx2-specific VHH, and one Stx1/Stx2 cross-specific VHH--was effective in preventing all symptoms of intoxication from Stx1 and Stx2 when coadministered with effector Ab. Overall, the availability of simple, defined, recombinant proteins that provide cost-effective protection against HUS opens up new therapeutic approaches to managing disease.


A Case of Sjögren's Syndrome That Presented with Alcohol-induced Purpura.
Sjögren syndrome (SS) is a systemic autoimmune disease that mainly affects the salivary and lacrimal glands. It may exist as a primary condition or in association with other systemic autoimmune diseases. Patients with SS usually complain of persistent dryness of the mouth and eyes and other features, including diverse general symptoms and cutaneous symptoms such as purpura. We report here on a case of 34-year-old woman who presented with purple non-blanching palpable purpura on both lower legs, and these lesions had developed soon after drinking alcohol 2 days previously. She had a 2 year history of repeatedly developing rashes in association with drinking alcohol. The physical examination showed dry eyes and dry mouth. The laboratory tests showed positivity for anti-Ro/SS-A antibody and RF and hyperimmunoglobulinemia. She was diagnosed as suffering with primary SS. Herein we report on a patient with primary SS and this patient initially presented with recurrent purpura in association with alcohol ingestion. Drinking alcohol had played a role as a possible aggravating factor for the cutaneous purpura of this patient with SS.


Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleus.
Diabetes is associated with an increased risk of deleterious changes in muscle mass and function or sarcopenia, leading to physical inactivity and worsening glycaemic control. Given the negative energy balance during sodium-glucose cotransporter-2 (SGLT2) inhibition, whether SGLT2 inhibitors affect skeletal muscle mass and function is a matter of concern. However, how SGLT2 inhibition affects the skeletal muscle function in patients with diabetes remains insufficiently explored. We aimed to explore the effects of canagliflozin (CANA), an SGLT2 inhibitor, on skeletal muscles in genetically diabetic db/db mice focusing on the differential responses of oxidative and glycolytic muscles. Db/db mice were treated with CANA for 4 weeks. We measured running distance and handgrip strength to assess skeletal muscle function during CANA treatment. At the end of the experiment, we performed a targeted metabolome analysis of the skeletal muscles. CANA treatment improved the reduced endurance capacity, as revealed by running distance in db/db mice (414.9 ± 52.8 vs. 88.7 ± 22.7 m, P < 0.05). Targeted metabolome analysis revealed that 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl 5'-monophosphate (AICARP), a naturally occurring AMP-activated protein kinase (AMPK) activator, increased in the oxidative soleus muscle (P < 0.05), but not in the glycolytic extensor digitorum longus muscle (P = 0.4376), with increased levels of AMPK phosphorylation (P < 0.01). This study highlights the potential role of the AICARP/AMPK pathway in oxidative rather than glycolytic skeletal muscles during SGLT2 inhibition, providing novel insights into the mechanism by which SGLT2 inhibitors improve endurance capacity in patients with type 2 diabetes.


Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.
The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression.


Exploration of the synthesis of three types of multicolor carbon dot originating from isomers.
Currently, the synthesis of carbon dots (CDs) exhibiting long-wavelength emission is still challenging. Herein, we have synthesized for the first time three types of CD with multicolor emission derived from isomers. Importantly, their particle size, nitrogen-doping amount and band gaps collectively regulate the fluorescence emission of the proposed CDs.


Production, purification, and characterization of recombinant hFSH glycoforms for functional studies.
Previously, our laboratory demonstrated the existence of a β-subunit glycosylation-deficient human FSH glycoform, hFSH(21). A third variant, hFSH(18), has recently been detected in FSH glycoforms isolated from purified pituitary hLH preparations. Human FSH(21) abundance in individual female pituitaries progressively decreased with increasing age. Hypo-glycosylated glycoform preparations are significantly more active than fully-glycosylated hFSH preparations. The purpose of this study was to produce, purify and chemically characterize both glycoform variants expressed by a mammalian cell line. Recombinant hFSH was expressed in a stable GH3 cell line and isolated from serum-free cell culture medium by sequential, hydrophobic and immunoaffinity chromatography. FSH glycoform fractions were separated by Superdex 75 gel-filtration. Western blot analysis revealed the presence of both hFSH(18) and hFSH(21) glycoforms in the low molecular weight fraction, however, their electrophoretic mobilities differed from those associated with the corresponding pituitary hFSH variants. Edman degradation of FSH(21/18)-derived β-subunit before and after peptide-N-glycanase F digestion confirmed that it possessed a mixture of both mono-glycosylated FSHβ subunits, as both Asn(7) and Asn(24) were partially glycosylated. FSH receptor-binding assays confirmed our previous observations that hFSH(21/18) exhibits greater receptor-binding affinity and occupies more FSH binding sites when compared to fully-glycosylated hFSH(24). Thus, the age-related reduction in hypo-glycosylated hFSH significantly reduces circulating levels of FSH biological activity that may further compromise reproductive function. Taken together, the ability to express and isolate recombinant hFSH glycoforms opens the way to study functional differences between them both in vivo and in vitro.


Directions in Music by Miles Davis: Using the Ecological Approach to Perception and Embodied Cognition to Analyze the Creative Use of Recording Technology in Bitches Brew.
In 1969 Miles Davis started to use the credit "Directions in Music by Miles Davis" on his record sleeves as a statement asserting his creative control of the recording process. This article develops the idea of using the ecological approach to perception and embodied cognition to provide a psychological/cognitive basis for an Actor Network Theory (and to a lesser extent Social Construction of Technology) analysis for the collaborative creative and technological network which came together for the making of Miles Davis' 1969 album, Bitches Brew. Using the notions of invariant properties and affordances from Gibson's work on the ecological approach to perception and of schemata from Lakoff's work in embodied cognition, the article seeks to provide a more nuanced approach to the process of translation in terms of the influence that agents exert upon each other.


FFAR1 activation attenuates histamine-induced myosin light chain phosphorylation and cortical tension development in human airway smooth muscle cells.
Activation of free fatty acid receptors (FFAR1 and FFAR4) which are G protein-coupled receptors (GPCRs) with established (patho)physiological roles in a variety of obesity-related disorders, induce human airway smooth muscle (HASM) cell proliferation and shortening. We reported amplified agonist-induced cell shortening in HASM cells obtained from obese lung donors. We hypothesized that FFAR1 modulate excitation-contraction (EC) coupling in HASM cells and play a role in obesity-associated airway hyperresponsiveness. In HASM cells pre-treated (30 min) with FFAR1 agonists TAK875 and GW9508, we measured histamine-induced Ca2+ mobilization, myosin light chain (MLC) phosphorylation, and cortical tension development with magnetic twisting cytometry (MTC). Phosphorylation of MLC phosphatase and Akt also were determined in the presence of the FFAR1 agonists or vehicle. In addition, the effects of TAK875 on MLC phosphorylation were measured in HASM cells desensitized to β2AR agonists by overnight salmeterol treatment. The inhibitory effect of TAK875 on MLC phosphorylation was compared between HASM cells from age and sex-matched non-obese and obese human lung donors. The mean measurements were compared using One-Way ANOVA with Dunnett's test for multiple group comparisons or Student's t-test two-group comparison. For cortical tension measurements by magnetic twisted cytometry, mixed effect model using SAS V.9.2 was applied. Means were considered significant when p ≤ 0.05. Unexpectedly, we found that TAK875, a synthetic FFAR1 agonist, attenuated histamine-induced MLC phosphorylation and cortical tension development in HASM cells. These physiological outcomes were unassociated with changes in histamine-evoked Ca2+ flux, protein kinase B (AKT) activation, or MLC phosphatase inhibition. Of note, TAK875-mediated inhibition of MLC phosphorylation was maintained in β2AR-desensitized HASM cells and across obese and non-obese donor-derived HASM cells. Taken together, our findings identified the FFAR1 agonist TAK875 as a novel bronchoprotective agent that warrants further investigation to treat difficult-to-control asthma and/or airway hyperreactivity in obesity.


A Facile Route to Indolo
Treatment of 1-(2'-bromobenzyl)-3,4-dihydroisoquinolines 2 in the presence of K(2)CO(3) in boiling DMF efficiently provided a variety of alkoxy-substituted indolo[2,1-a]isoquinolines 3. Application of this cyclization to 7-benzyloxyisoquinoline derivatives, followed by further elaboration of the resultant 2-benzyloxy-5,6-dihydroindolo[2,1-a]isoquinolines 16a,b, led to the formal synthesis of dibenzopyrrocoline alkaloids, (+/-)-cryptaustoline (1a) and (+/-)-cryptowoline (1b).


Ten years of progress in vaccination against cancer: the need to counteract cancer evasion by dual targeting in future therapies.
Although cancer immunology has made vigorous progress over the last decade, its future remains uncertain. Tumors have clearly proved subject to immune surveillance, leading to antigenic editing, and means of activating both T and B arms of the immune system have been devised. Therapeutic vaccination and monoclonal antibody therapy have so far proved disappointing, because tumors prove adept at evasion from immune control. Dual targeting could well counteract evasion, provided that the two targets are independent and are attacked simultaneously. This stage has nearly but not quite been reached in several forms of immunotherapy, particularly of B-cell cancers, although such treatment also carries hazards.


Risk of breast cancer according to use of antidepressants, phenothiazines, and antihistamines.
In laboratory studies, some antidepressants caused increased growth of mammary tumors. The relation of use of these drugs to the development of breast cancer was examined in a hospital-based case-control study. Information, including lifetime medication history, was collected by interview from 5,814 women with primary breast cancer diagnosed within the previous year, 5,095 women with primary malignancies of other sites, and 5,814 women with other conditions. Relative risks were estimated by using unconditional multiple logistic regression for regular use (> or =4 days per week for > or =4 weeks beginning > or =1 year before admission) of antidepressants and structurally similar drugs. With reference to never use of each drug, relative risks were statistically compatible with 1.0 for selective serotonin reuptake inhibitors (SSRI), tricyclics, other antidepressants, phenothiazines, and antihistamines; results were very similar using both control groups. There were no significant increases in risk for any category of regular use, stratified according to cumulative duration of use or time interval since the most recent use or for any individual drug within the broader classes. However, the estimate for regular SSRI use in the previous year, 1.8, was of borderline statistical significance (95% confidence interval: 1.0, 3.3). The findings do not support an overall association between the use of antidepressants, phenothiazines, or antihistamines and breast cancer. However, the results for SSRIs are not entirely reassuring.


Cardiovascular autonomic dysfunction in parkinsonian patients.
Cardiovascular dysfunction may occur in parkinsonian patients for a variety of reasons. Patients usually are more than 50 years old and on various drugs (both antiparkinsonian and for associated medical disorders), some of which may have cardiovascular effects. Autonomic failure increases with age and also is recognized in parkinsonian patients who have the disorder multiple system atrophy, in which there is substantial cardiovascular dysfunction. Thus, recognition of cardiovascular dysfunction and its causes in parkinsonian patients is of importance in diagnosis (in separating the various parkinsonian diseases), in determining prognosis, and finally in management. This article outlines the major areas of cardiovascular dysfunction, including disorders of blood pressure control, heart rate, and regional circulation, especially to vital organs. Clinical features and evaluation are described, together with abnormalities in different parkinsonian disorders and the principles of management.


Myelodysplastic syndrome with t(6;9)(p22;q34.1)/DEK-NUP214 better classified as acute myeloid leukemia? A multicenter study of 107 cases.
t(6;9)(p22;q34.1)/DEK-NUP214 is a recurrent genetic abnormality that occurs in 1-2% of patients with acute myeloid leukemia (AML), and rarely in myelodysplastic syndrome (MDS). It has been suggested by others that all myeloid neoplasms with t(6;9)/DEK-NUP214 may be considered as AML, even when blast count is <20%. In this study, we compared the clinicopathologic features of 107 patients with myeloid neoplasms harboring t(6;9)/DEK-NUP214: 33 MDS and 74 AML. Compared with patients with AML, patients with MDS were older (p = 0.10), had a lower white blood cell count (p = 0.0017), a lower blast count in the peripheral blood (p < 0.0001) and bone marrow (p < 0.0001), a higher platelet count (p = 0.022), and a lower frequency of FLT3-ITD mutation (p = 0.01). In addition, basophilia was not a common feature in the patients of this cohort. Although there was no difference in overall survival between MDS and AML patients (p = 0.18) in the entire cohort, the survival curves did show a trend toward favorable survival in MDS patients. Multivariate analyses showed that initial diagnosis of MDS vs. AML and allogeneic hematopoietic stem cell transplantation were prognostic factors for survival of patients with t(6;9)/DEK-NUP214 (p = 0.008 and p < 0.0001, respectively). Our data suggest that MDS with t(6;9)/DEK-NUP214 is prognostically not equivalent to AML with t(6;9)/DEK-NUP214. These data also show that stem cell transplantation greatly improves the survival of MDS and AML patients with myeloid neoplasms associated with t(6;9)/DEK-NUP214.


Aneurysm strength can decrease under calcification.
Aneurysms are abnormal dilatations of vessels in the vascular system that are prone to rupture. Prediction of the aneurysm rupture is a challenging and unsolved problem. Various factors can lead to the aneurysm rupture and, in the present study, we examine the effect of calcification on the aneurysm strength by using micromechanical modeling. The calcified tissue is considered as a composite material in which hard calcium particles are embedded in a hyperelastic soft matrix. Three experimentally calibrated constitutive models incorporating a failure description are used for the matrix representation. Two constitutive models describe the aneurysmal arterial wall and the third one - the intraluminal thrombus. The stiffness and strength of the calcified tissue are simulated in uniaxial tension under the varying amount of calcification, i.e. the relative volume of the hard inclusion within the periodic unit cell. In addition, the triaxiality of the stress state, which can be a trigger for the cavitation instability, is tracked. Results of the micromechanical simulation show an increase of the stiffness and a possible decrease of the strength of the calcified tissue as compared to the non-calcified one. The obtained results suggest that calcification (i.e. the presence of hard particles) can significantly affect the stiffness and strength of soft tissue. The development of refined experimental techniques that will allow for the accurate quantitative assessment of calcification is desirable.


Frailty Index Is a Significant Predictor of Complications and Mortality After Surgery for Adult Spinal Deformity.
Retrospective study of prospectively collected data. To determine if the modified Frailty Index (mFI) could be used to predict postoperative complications in patients undergoing surgery for adult spinal deformity (ASD). Surgery for patients with ASD is associated with high complication rates and significant concerns present during risk stratification with older patients. The mFI is an evaluation tool to describe the frailness of an individual and how their preoperative status may impact postoperative survival and outcomes. Using a large nationwide database, we assessed the utility of this instrument in patients undergoing surgery for ASD. The American College of Surgeons National Surgical Quality Improvement Program is a large multicenter clinical registry that prospectively collects preoperative variables, patient demographics, operative factors, and 30-day postoperative morbidity and mortality outcomes from about 400 hospitals nationwide. Current Procedural Terminology codes were used to query the database for adults who underwent fusion for spinal deformity. The previously described mFI was calculated based on the number of positive factors and univariate and multivariate logistic regression analysis were used to analyze the risk factors associated with mortality. Overall, 1001 patients were identified and the mean mFI score was 0.09 (range: 0-0.545). Increasing mFI score was associated with higher complication, reoperation, and mortality rates (P < 0.05). mFI of 0.09 and 0.18 was an independent predictor of any complication, mortality, requiring a blood transfusion, pulmonary embolism/deep vein thrombosis, and reoperation (all P < 0.05). In comparison with age >60 years obesity class III, mFI was a superior predictor of several postoperative complications and reoperation. Frailty was an independent predictor of postoperative complications, mortality, and reoperation in patients undergoing surgery for ASD. Preoperative assessment of the mFI in this patient population can be utilized to improve current risk models. 3.


Design and Application of Intelligent Reflecting Surface (IRS) for Beyond 5G Wireless Networks: A Review.
The existing sub-6 GHz band is insufficient to support the bandwidth requirement of emerging data-rate-hungry applications and Internet of Things devices, requiring ultrareliable low latency communication (URLLC), thus making the migration to millimeter-wave (mmWave) bands inevitable. A notable disadvantage of a mmWave band is the significant losses suffered at higher frequencies that may not be overcome by novel optimization algorithms at the transmitter and receiver and thus result in a performance degradation. To address this, Intelligent Reflecting Surface (IRS) is a new technology capable of transforming the wireless channel from a highly probabilistic to a highly deterministic channel and as a result, overcome the significant losses experienced in the mmWave band. This paper aims to survey the design and applications of an IRS, a 2-dimensional (2D) passive metasurface with the ability to control the wireless propagation channel and thus achieve better spectral efficiency (SE) and energy efficiency (EE) to aid the fifth and beyond generation to deliver the required data rate to support current and emerging technologies. It is imperative that the future wireless technology evolves toward an intelligent software paradigm, and the IRS is expected to be a key enabler in achieving this task. This work provides a detailed survey of the IRS technology, limitations in the current research, and the related research opportunities and possible solutions.


What's /depsilonr/? An anomalous error in a child with specific language impairment.
This longitudinal case study describes an anomalous error produced by a child with specific language impairment (SLI), MM, whose language development was documented from ages 3 through 7 years. Twelve spontaneous language samples were analysed. Across nine language samples MM produced the phonetic sequence /depsilonr/ in ungrammatical contexts as if it were the nominative third person plural pronoun, for example, with a past tense form (e.g. */depsilonr/ ate dinner). The phonetic sequence /depsilonr/ may have been either their, a case error, or they're, inclusion of a form of BE in an unexpected context. In this paper, we examine and describe the distribution of /depsilonr/ and the development of pronominal forms and the verb BE in order to account for the anomalous error.


Compliance, persistence, healthcare resource use, and treatment costs associated with aliskiren plus ARB versus ACE inhibitor plus ARB combination therapy: in US patients with hypertension.
Evidence is currently equivocal on the added benefits of dual blockade of the renin-angiotensin-aldosterone system with the combination of either an ACE inhibitor (ACEI) plus an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]) or aliskiren, the first-in-class direct renin inhibitor, plus an ARB. To compare the compliance, persistence, healthcare resource utilization, and healthcare costs associated with aliskiren plus ARB versus ACEI plus ARB combination therapies among adult patients diagnosed with hypertension. Patients (aged ≥18 years) initiated on either combination therapy were identified in the MarketScan Commercial and Medicare Supplemental Databases (1 July 2007 to 30 June 2008). The ARB components considered were candesartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan. The ACEI components included benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril. Outcomes measured during the 6-month study period included the proportion of days covered (PDC), treatment discontinuation, healthcare resource utilization, and changes in healthcare costs (study period minus 6-month baseline values). Risk-adjusted differences in outcomes between treatments and associated 95% confidence intervals (CIs) were estimated using multivariate regression models, controlling for demographics, region, co-morbidities, prescription drug use, and resource utilization during the baseline period. Adjusting for baseline characteristics, aliskiren plus ARB patients (n = 1395) demonstrated a significantly higher PDC (67.0% vs 54.3%; difference 12.7%; 95% CI 10.6, 14.7) and a significantly lower discontinuation rate (50.4% vs 68.6%; odds ratio 0.46; 95% CI 0.40, 0.54) than ACEI plus ARB patients (n = 16 507). Aliskiren plus ARB patients had significantly fewer all-cause hospitalizations (adjusted incidence rate ratio [IRR] 0.73; 95% CI 0.61, 0.86) and significantly fewer all-cause emergency room (ER) visits (adjusted IRR 0.72; 95% CI 0.61, 0.85) than ACEI plus ARB patients. Compared with ACEI plus ARB therapy, aliskiren plus ARB therapy was associated with significantly larger increases in prescription costs by $US264 post therapy initiation (95% CI 153, 375), but with non-significantly greater reductions in total healthcare costs by -$583 (95% CI -2409, 1242).[2008 values]. In adult hypertensive patients, treatment with aliskiren plus ARB was associated with significantly better compliance/persistence and fewer hospitalizations and ER visits compared with ACEI plus ARB therapy. Reductions in total healthcare costs were non-significantly different between patients treated with aliskiren plus ARB versus ACEI plus ARB, despite the increased prescription costs associated with aliskiren plus ARB therapy.


Risk and protective factors associated with youth problem gambling.
Risk factors for youth gambling problems are best understood within an ecological model recognizing the interwoven relationship that exists between the individual and their environment. Empirical studies covering individual, relationship, community, and societal factors associated with adolescent gambling problems are reviewed. The cumulative body of research suggests that males who are exposed to gambling at an earlier age are at greater risk of developing gambling problems. Individuals who report poor family cohesion, have family members or friends who also gamble, and those exposed to and engaged in a wider variety of gambling options are at greater risk. Adolescents with impulsive, high sensation-seeking personalities and exhibit emotion-focused coping styles are more likely to experience gambling problems. Anxiety, depression, ADHD, poor academic performance, substance use, and delinquency are also strong predictors. Many of these risk factors appear to predict a general behavior syndrome encompassed by overall mental health problems, substance abuse, delinquency, and problem gambling. Increased exposure to gambling opportunities and marketing of gambling is recognized as a potential risk factor at a community level while gambling-permissive cultures may instill positive attitudes and beliefs toward gambling. A call is made for more research that can identify the causal risk factors that lead to gambling problems among youth which will ultimately improve our prevention efforts.


Thermodynamic analysis of subunit interactions in Escherichia coli molybdopterin synthase.
The molybdopterin (MPT) synthase complex in Escherichia coli consists of two MoaE subunits and two MoaD subunits in a heterotetrameric structure with the two MoaE subunits forming a central dimer. Each MoaD subunit binds to a single MoaE molecule to form two identical MoaE/MoaD interfaces. Here we define the thermodynamic properties of the interaction between MoaE and MoaD in MPT synthase using a H/D exchange and matrix-assisted laser desorption/ionization (MALDI) mass spectroscopy based method termed SUPREX (stability of unpurified proteins from rates of H/D exchange). SUPREX-derived protein folding free energies and m values are reported for MoaE in the presence and absence of MoaD and MoaD-SH, the thiocarboxylated form of MoaD that is essential for the catalytic activity of MPT synthase. The protein folding free energy measurements were used to calculate a dissociation constant of 17 +/- 7 microM for the binding of MoaD to MoaE in inactive MPT synthase and a dissociation constant of 2.6 +/- 0.9 microM for the binding of MoaD-SH to MoaE in active MPT synthase. The increased binding affinity of MoaD-SH for MoaE is consistent with a previously proposed mechanism for the MPT synthase reaction. Using the increased m values exhibited by MoaE in the presence of either MoaD subunit, the solvent accessible surface area buried upon formation of the subunit interface in MPT synthase was estimated to be 2378 A(2) for inactive MPT synthase and 4117 A(2) for active MPT synthase.


Umbilical cord remnant infections in foals: 16 cases (1975-1985).
Infection of the umbilical cord remnants was diagnosed in 16 foals. The infection was found in the urachus alone in 3 foals, the umbilical arteries in 2 foals, the urachus and umbilical arteries in 3 foals, the urachus and umbilical vein in 2 foals, and the urachus, umbilical vein, and umbilical arteries in 2 foals. The specific location of the infection was not determined in 4 foals. Eleven foals developed an acquired patent urachus between 4 and 16 days of age. Seven foals had one or more joints infected. All foals with umbilical cord remnant infections were treated with orally, intramuscularly, or intravenously administered antibiotics and 9 foals had the umbilical cord remnants excised. Nine foals survived, 6 of which had had excision of the infected remnants. Only 2 foals with joint infections survived.


Functioning adrenal neoplasms.
Neoplasms of the adrenal gland may cause increased hormone activity, which has profound effects on the growing child. The adrenal gland should be viewed as two functionally separate glands: the adrenal medulla and adrenal cortex. Neoplasms of the adrenal cortex secrete excess glucocorticoids, mineralocorticoids, or androgens. Adrenal medulla neoplasms generally secrete excess catecholamines. Understanding the anatomy, embryology, and physiology of the adrenal cortex and medulla allows surgeons to diagnose these tumors, prepare the patients for surgery, and treat them effectively after resection. Because adjuvant therapy for adrenal cortical and medullary tumors is of limited effectiveness, the surgeon's role in the treatment of these neoplasms is extremely important.


Intraspecific trait variants determine the nature of interspecific interactions in a habitat-forming species.
Although the study of ecological interactions often takes into account functional variation between species, intraspecific variation is commonly ignored. Here, we investigate the importance of an intraspecific polymorphism in shaping interspecific interactions in a habitat-building species. Colonies of the social spider Anelosimus studiosus provide habitat for dozens of arthropod species, and colony members exhibit markedly polymorphic behavioral temperaments (BT): "aggressive" or "docile." We manipulated the phenotypic compositions of colonies (100% aggressive, 50% aggressive and 50% docile, 100% docile) and measured the nature and magnitude of interactions between A. studiosus and two heterospecific web associates, Larinioides cornutus and Agelenopsis emertoni. We found that BT composition significantly affected the outcome of interspecific interactions, changing the relationship between A. studiosus and its web associates from an ammensalism (where A. studiosus experiences reduced fecundity and survival) to a commensalism or mutualism. Our study successfully illustrates the potential of BTs to impact whole community dynamics, and conversely, for community structure to influence the maintenance of BTs.


Lumbar spine following successful surgical discectomy. Magnetic resonance imaging features and implications.
In an attempt to determine the expected long-term appearance of the lumbar spine in patients who have undergone successful lumbar discectomy, follow-up magnetic resonance (MR) examinations were performed on 23 patients (26 levels). All patients in the study had undergone at surgery at least one year prior to the study. All patients met rigorous criteria for a successful outcome. In nine cases, the postoperative study indicated a virtually total resolution of the previously identified disc herniations. In 13 cases, the study noted moderate, persistent posterior contour defects in the disc that contributed to persistent mass effect on the thecal sac or corresponding nerve root. In the remaining four cases, the postoperative study indicated virtually no change in the apparent contour of the posterior disc margin. Gadolinium contrast examinations demonstrated enhancement of the persistent contour abnormalities in 18 of 19 disc levels, suggesting the common presence of fibrosis, which was at times "mass-like," in these successful patients. These findings suggest that localized discal contour abnormalities morphologically simulating recurrent disc herniations and variably contributing to mass effect, may be commonly encountered in long-term follow-up imaging studies of successful discectomy patients.


Hollow Cathode Discharge Ionization Mass Spectrometry: Detection, Quantification and Gas Phase Ion-Molecule Reactions of Explosives and Related Compounds.
Mass spectrometry (MS) has become an essential analytical method in every sector of science and technology. Because of its unique ability to provide direct molecular structure information on analytes, an extra method is rarely required. This review describes fabrication of a variable-pressure hollow cathode discharge (HCD) ion source for MS in detection, quantification and investigation of gas-phase ion molecule reactions of explosives and related compounds using air as a carrier gas. The HCD ion source has been designed in such a way that by altering the ion source pressures, the system can generate both HCD and conventional GD. This design enables for the selective detection and quantification of explosives at trace to ultra-trace levels. The pressure-dependent HCD ion source has also been used to investigate ion-molecule reactions in the gas phase of explosives and related compounds. The mechanism of ion formation in explosive reactions is also discussed.


Host density drives spatial variation in parasitism of the alfalfa weevil, Hypera postica, across dryland and irrigated alfalfa cropping systems.
Classical biological control against the alfalfa weevil, Hypera postica (Gyllenhal), a destructive pest of alfalfa (Medicago sativa L.), has resulted in the establishment of nine parasitoid species in the United States. Despite widespread redistribution of a number of species, there remains little postrelease data on their establishment and potential effectiveness in many regions. I surveyed parasitoids associated with alfalfa weevil larvae across 30 or more sites in eastern Montana and western North Dakota over 2 yr. Replicate sites were sampled in two habitat types that differ in their physical characteristics, flood-irrigated and dryland alfalfa fields. Irrigated systems are more productive but also more intensively disturbed habitats because of increased harvest frequency and repeated flooding. Given evidence that both habitat disturbance and herbivore density, which often increases with productivity, can influence parasitoid dynamics, I predicted that parasitism levels, the relative importance of different species, or both, would differ across these two system types. Of four larval parasitoid species released previously or recovered in the region, two were found in this study, Bathyplectes curculionis (Thomson) and Oomyzus incertus (Ratzenberg), with average levels of parasitism across habitat types and years of 37.2 and 3.5%, respectively. Parasitism levels differed between habitat types, but the effect was driven by concomitant differences in host densities that were higher in irrigated than dryland fields. Parasitoid responses to host density varied across years and species. B. curculionis exhibited positive density dependence in parasitism across sites in 2009 and negative density dependence in 2010 when host densities were higher regionally. In contrast, O. incertus exhibited positive density dependence in 2010. Our results suggest that these species may be differentially effective at different host densities. Thus, variation in host density could represent an important axis along which parasitoids exhibit spatial complementarity in function.


Stabilization of disease after targeted therapy in a thymic carcinoma with KIT mutation detected by clinical next-generation sequencing.
Precision medicine uses individually determined genomic information to guide treatment in cancer and other diseases. We have implemented a clinical genomics assay that uses targeted next-generation sequencing of 25 cancer-related genes to guide the use of targeted therapies in diverse malignancies. We report the case of a 55-year-old woman with a poorly differentiated squamous cell carcinoma of thymic origin, with disease progression after standard treatment. Targeted tumor sequencing revealed the presence of a KIT codon 579 deletion (p.D579del). This specific mutation has not previously been associated with thymic tumors, but has been reported in gastrointestinal stromal tumors and has been associated with response to imatinib. Imatinib therapy was instituted for and resulted in stabilization of disease. This case illustrates the potential of clinical next-generation sequencing to open unexpected avenues for treatment and thereby improve patient outcomes.


Epidemiology and sequelae of head injury in San Marino Republic.
A study of head injuried patients was carried out in the smallest nation in the world (Republic of San Marino) from January 1981 to December 1982. The results show an epidemiological incidence of 468 cases/10(5) population/year in regards to Hospital admissions, whereas the cases are 694/10(5) population/year when taking into account also patients seen only by Accident and Emergency Department. The consequences of the head injury (Post Traumatic Syndrome, PTS) were studied in 187 patients having comparable features on admission and discharge, and being all residents of the Republic of San Marino. Factors significant in determining a PTS seem to be a history of previous head injuries, the presence of previous neuropsychiatric disturbances and an abnormal E.E.G. on admission. The time of onset of the syndrome, associated with the above mentioned factors, can be important in determining whether the PTS is of neurotic or organic origin.


Immunological response of mice to members of the autochthonous intestinal microflora.
Based on agglutination, complement fixation, bactericidal, and opsonization tests, it is evident that suspensions of a Bacteroides sp. isolated from the mouse intestine and given by parenteral routes do not initiate antibody formation in mice. Rats also respond poorly to the antigenic stimulus. In contrast, suspensions of other bacterial species isolated from the rodent intestine are highly immunogenic. Furthermore, high titers of antibody are produced in rabbits, guinea pigs, and sheep after parenteral injection of the Bacteroides suspensions. Marked differences in the absolute and relative numbers of Bacteroides in the intestinal contents of rodents and the latter three animal species have been demonstrated. It is proposed that the immunological unresponsiveness of rodents to this organism is related to its existence as a member of the autochthonous microflora in these animals.


A Preliminary Characterisation of Innovative Semi-Flexible Composite Pavement Comprising Geopolymer Grout and Reclaimed Asphalt Planings.
This article considers semi-flexible composite (SFC) pavement materials made with reclaimed asphalt planings (RAP) and geopolymer cement-based grouts. Geopolymer grouts were developed and used to fill the internal void structure of coarse RAP skeletons with varying levels of porosity. The geopolymer grouts were formulated at ambient temperature using industrial by-products to offer economic and environmental savings relative to conventional Portland cement-based grouting systems. They were characterised on flowability, setting time, and compressive strength. The effect of grout and RAP on SFC material performance was evaluated using permeable porosity, compressive strength, and ultrasonic pulse velocity. SFC performance was significantly influenced by both grout type and RAP content. Improved performance was associated with mixtures of high-flowability/high-strength grout and low RAP content. A practical limitation was identified for combination of grout with low-flowability/fast-setting time and well-compacted RAP skeletons. Solids content exceeding 49% by volume was not feasible, owing to inadequate grout penetration. A suite of SFC materials was produced offering performance levels for a range of practical pavement applications. Preliminary relationships enabling prediction of SFC elastic modulus based on strength and/or ultrasonic pulse velocity test data are given. A pavement design is given using SFC as a sub-base layer for an industrial hardstanding.


Control of ocular torsion in the rotational vestibulo-ocular reflexes.
Visual stabilization of the retina during rotational head movements requires that in far vision the eyes rotate about the same axis as the head but in opposite direction with a gain close to unity (optimal strategy). To achieve this goal the vestibulo-oculomotor system must be able to independently control all three rotational degrees of freedom of the eye. Studies of the human rotational vestibulo-ocular reflexes (VOR) have shown that its spatial characteristics are best explained by a strategy that lies halfway between the optimal image stabilization and perfect compliance with Listing's law. Here we argue that these spatial characteristics are fully compatible with an optimal strategy under the condition of a restrained gain of the torsional velocity-to-position integration. One implication of this finding is that the rotational VORs must override the default operation mode of the ocular plant that, according to recent findings, mechanically favours movements obeying Listing's law.


Systems development and difficulties in implementing procedures for elder abuse prevention among private community general support centers in Japan.
The present study examines differences in systems development and difficulties in implementing procedures for elder abuse prevention in 1,119 private and 606 public community general support centers under the public long-term care insurance program in Japan. The private community general support centers showed more difficulty implementing procedures than the public community general support centers. Controlling for the type of municipality, progress in systems development did not differ between the private and public community general support centers. Further research should examine how the characteristics of municipal governments are related to systems development in community general support centers.


Tricalcium citrate - a new brittle tableting excipient for direct compression and dry granulation with enormous hardness yield.
Tricalcium citrate (TCC) was characterized as a tableting excipient for direct compression (DC) and dry granulation (DG). Brittle materials usually lead to tablets of inferior mechanical strength compared to plastic deforming materials. A brittle material exhibiting a high tabletability with the ability to retain that behavior during recompression would represent a valuable alternative to the commonly used microcrystalline cellulose. Tablets of TCC and other common fillers were directly compressed for the purpose of compression analysis including Heckel analysis, speed dependency, and lubricant sensitivity. DG by roller compaction of TCC was first simulated via briquetting and experiments were subsequently repeated on a roller compactor. TCC appears as an excellent flowing powder of large agglomerates consisting of lower micron to submicron platelets. Despite the brittle deformation mechanism identified in the Heckel analysis, TCC demonstrated a very high mechanical strength up to 11 MPa in conjunction with an astonishingly low solid fraction of 0.85 at a compression pressure of 400 MPa. This was seen along with hardly any speed and lubricant sensitivity. Nevertheless, disintegration time was very short. TCC tablets suffered only a little from the re-compression: a slight loss in tensile strength of 1-2 MPa was observed for granules produced via roller compaction. TCC was found to be suitable for DC as a predominantly brittle deforming filler, nevertheless demonstrating an enormous hardness yield while being independent of lubrication and tableting speed. TCC furthermore retained enough bonding capacity after DG to maintain this pronounced tabletability.


Ligamentum Flavum Cyst With Acute Onset Motor Deficit: A Literature Review and Case Series.
Ligamentum flavum cysts have been rarely described in the literature and are one of the rare causes of neural compression and canal stenosis. Very few cases of their association with neurologic deficits are reported to date, and association with acute onset weakness is even rarer. We report our experience with 3 cases of ligamentum flavum cyst that presented with acute onset weakness and also present a comprehensive literature review on lumbar ligamentum flavum cysts reported to date. All 3 patients had symptoms of severe neurogenic claudication and presented to us with acute onset of motor weakness in lower limbs. Ligamentum flavum cyst was located in the midline in 2 cases and laterally in 1 case. We performed excision of the cyst and decompression with fusion in 2 cases and decompression alone in 1 case. All 3 cases had significant improvement in their neurologic status postoperatively. Histopathological examination confirmed ligamentum flavum cyst in all 3 cases. We performed a PUBMED and EMBASE database search using the MeSH (Medical Subject Headings) terms "ligamentum flavum" and "cysts" for articles published to April 2019. We could identify 7 studies describing 20 cases of lumbar ligamentum flavum cysts with motor weakness in the literature. Only 1 case had been described with an acute onset of weakness. Ligamentum flavum cysts should remain in the differential diagnosis of a patient who has symptoms of lumbar canal stenosis and presents with acute onset of neurological deficits. Such patients have a good improvement with surgery.


Evaluation of the Golgi trafficking protein VPS54 (wobbler) as a candidate for ALS.
VPS54 is a component of the Golgi-associated retrograde protein (GARP) complex of vesicle sorting proteins. A missense mutation of Vps54 is responsible for motor neuron disease in the wobbler mouse, but the human gene on chromosome 2p14-15 has not been evaluated as a disease gene. We completely sequenced the 22 coding exons from 96 individuals with sporadic ALS, 96 individuals with familial ALS, and 96 controls. Twenty-one novel SNPs were identified. The non-synonymous variant, T360A, was observed in one patient and 0/910 controls. Several polymorphic non-synonymous SNPs were also observed in patients and controls. These initial data suggest that mutations in VPS54 are not a major cause of ALS.


Terrestrial exposure of a fresh Martian meteorite causes rapid changes in hydrogen isotopes and water concentrations.
Determining the hydrogen isotopic compositions and H2O contents of meteorites and their components is important for addressing key cosmochemical questions about the abundance and source(s) of water in planetary bodies. However, deconvolving the effects of terrestrial contamination from the indigenous hydrogen isotopic compositions of these extraterrestrial materials is not trivial, because chondrites and some achondrites show only small deviations from terrestrial values such that even minor contamination can mask the indigenous values. Here we assess the effects of terrestrial weathering and contamination on the hydrogen isotope ratios and H2O contents of meteoritic minerals through monitored terrestrial weathering of Tissint, a recent Martian fall. Our findings reveal the rapidity with which this weathering affects nominally anhydrous phases in extraterrestrial materials, which illustrates the necessity of sampling the interiors of even relatively fresh meteorite falls and underlines the importance of sample return missions.


Radionuclide angiography in the management of asymptomatic aortic regurgitation.
Left ventricular systolic function is an important determinant of long-term prognosis in patients with chronic aortic regurgitation. In patients undergoing aortic valve replacement, those with preoperative left ventricular dysfunction have a greater risk of postoperative congestive heart failure and death than do those in whom preoperative left ventricular systolic function is normal. However, patients with preoperative left ventricular dysfunction are not a homogeneous group but may be further stratified according to risk on the basis of the severity of symptoms, exercise intolerance, and temporal duration of left ventricular dysfunction. Therefore, asymptomatic patients with reproducible and definite evidence of impaired left ventricular function should undergo operation without waiting for the development of symptoms or more severe left ventricular dysfunction. In addition, among asymptomatic patients with normal systolic function, indexes of left ventricular function are also helpful, especially when measured serially, in predicting the development of symptoms and the need for valve replacement surgery over the course of the next 5 to 10 years. Noninvasive imaging techniques should play a major role in this evaluation, and radionuclide angiography is ideally suited for the quantitative evaluation of systolic function in the volume-overloaded left ventricle. Although the prognostic value of left ventricular ejection fraction at rest is well established, ejection fraction during exercise has little value once age and left ventricular function at rest are accounted for and is of minor importance in formulating patient management decisions.


Nanometer scale fabrication and optical response of InGaN/GaN quantum disks.
In this work, we demonstrate homogeneously distributed In0.3Ga0.7N/GaN quantum disks (QDs), with an average diameter below 10 nm and a high density of 2.1 × 10(11) cm(-2), embedded in 20 nm tall nanopillars. The scalable top-down fabrication process involves the use of self-assembled ferritin bio-templates as the etch mask, spin coated on top of a strained In0.3Ga0.7N/GaN single quantum well (SQW) structure, followed by a neutral beam etch (NBE) method. The small dimensions of the iron cores inside ferritin and nearly damage-free process enabled by the NBE jointly contribute to the observation of photoluminescence (PL) from strain-relaxed In0.3Ga0.7N/GaN QDs at 6 K. The large blueshift of the peak wavelength by over 70 nm manifests a strong reduction of the quantum-confined Stark effect (QCSE) within the QD structure, which also agrees well with the theoretical prediction using a 3D Schrödinger equation solver. The current results hence pave the way towards the realization of large-scale III-N quantum structures using the combination of bio-templates and NBE, which is vital for the development of next-generation lighting and communication devices.


Monocular visual deprivation suppresses excitability in adult human visual cortex.
The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we employed TMS to trace plastic changes in adult visual cortex before, during, and after 48 h of monocular deprivation (MD) of the right dominant eye. In healthy adult volunteers, MD-induced changes in visual cortex excitability were probed with paired-pulse TMS applied to the left and right occipital cortex. Stimulus-response curves were constructed by recording the intensity of the reported phosphenes evoked in the contralateral visual field at range of TMS intensities. Phosphene measurements revealed that MD produced a rapid and robust decrease in cortical excitability relative to a control condition without MD. The cortical excitability returned to preinterventional baseline levels within 3 h after the end of MD. The results show that in contrast to the excitability increase in response to BD, MD acutely triggers a reversible decrease in visual cortical excitability. This shows that the pattern of visual deprivation has a substantial impact on experience-dependent plasticity of the human visual cortex.


The Blocking Flap for Ulnar Nerve Instability After In Situ Release: Technique and a Grading System of Ulnar Nerve Instability to Guide Treatment.
In situ ulnar nerve release has been gaining popularity as a simple, effective, and low-morbidity procedure for the treatment of cubital tunnel syndrome. One concern with the technique is how to manage the unstable ulnar nerve after release. It is unclear how much nerve subluxation will lead to problems and surprisingly there is no grading system to assess ulnar nerve instability. I propose such a grading system, as well as a new technique to stabilize the unstable ulnar nerve. The blocking flap technique consists of raising a rectangular flap off the flexor/pronator fascia and attaching it to the posterior subcutaneous flap so that it blocks the nerve from subluxation/dislocation.


Sanitary status and water quality of some drinking water sources and antibiogram of Shiga toxin-producing Escherichia coli O157:H7 isolated from Shika, Zaria, Nigeria.
This study assessed the sanitary condition and quality of selected wells and boreholes in Shika, Zaria Nigeria. Fifty samples each were collected during the dry and wet seasons. This involved sanitary survey, water quality assessment, isolation and characterization of Shiga toxin-producing Escherichia coli O157:H7 (STEC) and, antibiogram assay. Based on the risk of contamination, wells (72%) had a high risk of contamination, while boreholes (44%) had low risk of contamination. Their physicochemical quality varied with season and location, and mean total coliform (TC) and faecal coliform (FC) were significantly lower in the dry season (p < 0.05). STEC were isolated from only wells with a prevalence of 4%, and exhibited a multidrug resistance pattern (amoxicillin, erythromycin and tetracycline). There was a strong positive correlation between sanitary status and water quality. The high- and very high-risk categories (wells) were strongly correlated with TC, FC, BOD, phosphate, turbidity and pH. .


Genetics of psychosis; insights from views across the genome.
The major psychotic illnesses, schizophrenia and bipolar disorder (BD), are among the most heritable common disorders, but finding specific susceptibility genes for them has not been straightforward. The reasons are widely assumed to include lack of valid phenotypic definition, absence of good theories of pathophysiology for candidate gene studies, and the involvement of many genes, each making small contributions to population risk. Within the last year or so, a number of genome wide association (GWAS) of schizophrenia and BD have been published. These have produced stronger evidence for association to specific risk loci than have earlier studies, specifically for the zinc finger binding protein 804A (ZNF804A) locus in schizophrenia and for the calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C) and ankyrin 3, node of Ranvier (ANK3) loci in bipolar disorder. The ZNF804A and CACNA1C loci appear to influence risk for both disorders, a finding that supports the hypothesis that schizophrenia and BD are not aetiologically distinct. In the case of schizophrenia, a number of rare copy number variants have also been detected that have fairly large effect sizes on disease risk, and that additionally influence risk of autism, mental retardation, and other neurodevelopmental disorders. The existing findings point to some likely pathophysiological mechanisms but also challenge current concepts of disease classification. They also provide grounds for optimism that larger studies will reveal more about the origins of these disorders, although currently, very little of the genetic risk of either disorder is explained.


American Academy of Pediatrics. Nutrition Committee of the Canadian Paediatric Society and the Committee on Nutrition of the American Academy of Pediatrics. Breast-feeding. A commentary in celebration of the International Year of the Child, 1979.
1. Full-term newborn infants should be breastfed, except if there are specific contraindications or when breast-feeding is unsuccessful. 2. Education about breast-feeding should be provided in schools for all children, and better education about breast-feeding and infant nutrition should be provided in the curriculum of physicians and nurses. Information about breast-feeding should also be presented in public communications media. 3. Prenatal instruction should include both theoretical and practical information about breast-feeding. 4. Attitudes and practices in prenatal clinics and in maternity wards should encourage a climate which favors breast-feeding. The staff should include nurses and other personnel who are not only favorably disposed toward breast-feeding but also knowledgeable and skilled in the art. 5. Consultation between maternity services and agencies committed to breast-feeding should be strengthened. 6. Studies should be conducted on the feasibility of breast-feeding infants at day nurseries adjacent to places of work subsequent to an appropriate leave of absence following the birth of an infant.


Valproate-induced hyperammonemic encephalopathy treated by hemodialysis.
Valproate-induced hyperammonemic encephalopathy is an unusual but serious complication that may occur in people with normal liver-associated enzyme levels, despite normal therapeutic doses and serum levels of valproate. Here, we describe an adolescent girl who had absence seizure and complained about progressive dizziness and general malaise several days after restarting valproate. Then, she presented vomiting and decreased consciousness three weeks after valproate use. Notably, her serum ammonia level was five times the upper limit of normal (184 micrommol/L), with normal liver-associated enzyme and supra-therapeutic valproate level. EEG showed continuous generalized slowing. The tandem mass analysis revealed carnitine deficiency. Consciousness improved after emergent hemodialysis. Ammonia level and EEG also returned to normal. Possible mechanisms, risk factors and the treatments of valproate-induced hyperammonemic encephalopathy are described. Physicians should consider this possibility when consciousness disturbance occurs in patients treated with valproate.


The association between toddlerhood empathy deficits and antisocial personality disorder symptoms and psychopathy in adulthood.
The present study examined empathy deficits in toddlerhood (age 14 to 36 months) as predictors of antisocial personality disorder (ASPD) symptoms and psychopathy measured by the Levenson Self-Report Psychopathy scale (Levenson, Kiehl, & Fitzpatrick, 1995) in adulthood (age 23 years) in 956 individuals from the Colorado Longitudinal Twin Study. Consistent with the hypothesis that antisocial behavior is associated with "active" rather than "passive" empathy deficits, early disregard for others, not lack of concern for others, predicted later ASPD symptoms. Early disregard for others was also significantly associated with factor 1 of the Levenson Self-Report Psychopathy Scale, which includes items assessing interpersonal and affective deficits, but not with factor 2, which includes items assessing impulsivity and poor behavioral control. The association between early disregard for others and psychopathy factor 2 was near zero after controlling for the shared variance between psychopathy factors 1 and 2. These results suggest that there is a propensity toward adulthood ASPD symptoms and psychopathy factor 1 that can be assessed early in development, which may help identify individuals most at risk for stable antisocial outcomes.


Mechanisms of Moral Disengagement in the Transition from Cybergossip to Cyberaggression: A Longitudinal Study.
The internet is an area where young people establish relationships and develop socially, emotionally and morally, but it also gives rise to certain forms of online behaviour, such as cybergossip, which are associated with cyberaggression and other risky behaviour. The aims of this study were to verify whether a longitudinal association exists between cybergossip and cyberaggression, and to discover which mechanisms of moral disengagement may mediate this relationship. The final sample consisted of 1392 students (50% girls; Mage = 13.47; SD = 0.77), who were surveyed in a three-wave longitudinal study at six-month intervals. The results obtained confirmed a direct, positive relationship between cybergossip, subsequent cyberaggression and the mediation exerted by cognitive restructuring in this transition. We discuss the importance of recognizing and detecting the fine distinction between online gossip and cyberaggression with the intention of doing harm, and focus on the justifications used by young people to normalize online bullying. To sum up, there is a clear need to encourage ethical, responsible behaviour in online interactions in order to achieve well-balanced, more sustainable relationships in classrooms.


Perioperative Analgesia Using an Indwelling Catheter to Deliver an Inferior Alveolar Nerve Block: A Case Report.
A 74-year-old male was diagnosed with osteomyelitis of the left mandible requiring marginal mandibulectomy under general anesthesia. However, the patient's pulmonary function tests demonstrated findings consistent with severe chronic obstructive pulmonary disease, classified as stage III. The consulting pulmonologist explained the increased risk of respiratory complications associated with general anesthesia and advised against its use. Therefore, we opted to perform the surgery under moderate sedation using 0.2% ropivacaine administered via bilateral ultrasound-guided inferior alveolar nerve blocks (UGIANBs) and an indwelling catheter with a pump for continuous perioperative local anesthesia and prolonged postoperative analgesia. This approach delivered excellent local anesthetic effects without any need for rescue medications or complications. Use of UGIANBs along with an indwelling catheter and pump may provide adequate local anesthesia and postoperative analgesia in patients with contraindications for general anesthesia.