Impact of using multiple causes of death codes to compute site-specific, death certificate-based cancer mortality statistics in the United States.
Cancer mortality statistics, an important indicator for monitoring cancer burden, are traditionally restricted to instances when cancer is determined to be the underlying cause of death (UCD) based on information recorded on standard certificates of death. This study's objective was to determine the impact of using multiple causes of death codes to compute site-specific cancer mortality statistics. The state cancer registries of California, Colorado and Idaho provided linked cancer registry and death certificate data for individuals who died between 2002 and 2004, had at least one cancer listed on their death certificate and were diagnosed with cancer between 1993 and 2004. These linked data were used to calculate the site-specific proportion of cancers not selected as the UCD (non-UCD) among all cancer-related deaths (any mention on the death certificate). In addition, the retrospective concordance between the death certificate and the population-based cancer registry, measured as confirmations rates, was calculated for deaths with cancer as the UCD, as a non-UCD, and for any mention. Overall, non-UCD deaths comprised 9.5 percent of total deaths; 11 of the 79 cancer sites had proportions greater than 3 standard deviations from 9.5 percent. The confirmation rates for UCD and for any mention did not differ significantly for any of the cancer sites. The site-specific variation in proportions and rates suggests that for a few cancer sites, death rates might be computed for both UCD and any mention of the cancer site on the death certificate. Nevertheless, this study provides evidence that, in general, restricting to UCD deaths will not under report cancer mortality statistics.


Early age of first sexual intercourse and affiliation with deviant peers predict development of SUD: a prospective longitudinal study.
A recent study has reported that early sexual behavior predicts the development of substance use disorders (SUD). However, that relationship was considered by its authors to be only tentative, because it was based on cross-sectional data rather than longitudinal data. Another recent study reported that deviant activities of peers predict development of SUD, although that relationship has not yet been confirmed. The objective of this study was to assess whether early onset of sexual intercourse and affiliation with deviant peers serve as predictors of the development of SUD, using a prospective longitudinal study design. We conducted a prospective longitudinal study of adolescents. These subjects were recruited at the age of 10-12years, with follow-up evaluations at ages 14, 16, 19, 22, and 25. The sample included 136 male subjects. Cox regression analyses were performed, with age of first intercourse, neurobehavioral disinhibition, exposure to drugs in the neighborhood, and deviant activities of peers as factors in the analyses. Earlier age at first intercourse and deviant activities of peers each predicted a significantly higher risk of subsequently developing a SUD (Wald=8.3, df=1, p=0.004; Wald=7.5, df=1, p=0.006, respectively). The results of this study confirm that early onset of sexual intercourse and affiliation with deviant peers predict the early development of substance use disorders, using a prospective longitudinal study design.


Sugar addiction: An Achilles' heel of auto-immune diseases?
In this issue of Cell Metabolism, Hochrein et al. identify a metabolic checkpoint controlling the transcriptional programming of effector CD4+ T cells. The authors show that GLUT3-mediated glucose import and ACLY-dependent acetyl-CoA generation control histone acetylation and, hence, the epigenetic imprinting of effector gene expression in differentiated effector CD4+ T cells. These findings suggest a novel therapeutic target for inflammation-associated diseases.


Poly(allylamine) coated layer-by-layer assembly decorated 2D carbon backbone for highly sensitive and selective detection of Tau-441 using surface plasmon resonance biosensor.
The determination of clinically significant amounts of tau protein in bodily fluids is a major problem in Alzheimer's disease (AD) diagnosis. As a result, the present work aims to develop a simple, label-free, fast, highly sensitive, and selective 2D carbon backbone graphene oxide (GO) patterned surface plasmon resonance (SPR) mediated affinity biosensor for Tau-441 monitoring. Initially, non-plasmonic nanosized GO was made using a modified Hummers' method, whereas green synthesized gold nanoparticles (AuNPs) were subjected to a layer-by-layer (LbL) design employing anionic and cationic polyelectrolytes. Several spectroscopical evaluations were carried out to ensure the synthesis of GO, AuNPs, and LbL assembly. Following that, the Anti-Tau rabbit antibody was immobilized on the designed LbL assembly using carbodiimide chemistry, and various studies such as sensitivity, selectivity, stability, repeatability, spiked sample analysis, etc., were conducted using the constructed affinity GO@LbL-AuNPs-Anti-Tau SPR biosensor. As an output, it shows a broad concentration range and a very low detection limit of 150 ng/mL to 5 fg/mL and 13.25 fg/mL, respectively. The remarkable sensitivity of this SPR biosensor represents the merits of a combination of plasmonic AuNPs and a non-plasmonic GO. It also exhibits great selectivity for Tau-441 in the presence of interfering molecules, which may be because of the immobilization of the Anti-Tau rabbit on the surface of the LbL assembly. Furthermore, it ensured high stability and repeatability, while spiked sample analysis and AD-induced animal samples analysis confirmed the practicability of GO@LbL-AuNPs-Anti-Tau SPR biosensor for Tau-441 detection. In conclusion, fabricated sensitive, selective, stable, label-free, quick, simple, and minimally invasive GO@LbL-AuNPs-Anti-Tau SPR biosensor will provide an alternative for AD diagnosis in the future.


[Deeper skin tones rarely depicted in Dutch dermatology textbooks].
Within diverse populations such as in the Netherlands, medical education must prepare students to diagnose skin conditions on a broad range of skin tones. To develop the visual pattern recognition skills to do so, medical students need exposure to skin conditions on deeper skin tones. The purpose of this study is to assess the inclusion of images of brown skin in Dutch dermatology textbooks. Observational study. Two large Dutch student textbook web shops were searched for dermatology textbooks, and all available general dermatology textbooks explicitly aimed at medical students were selected. All images of skin were examined and divided into the categories 'light skin', 'light to medium brown skin', 'medium to deep brown skin', 'deep to very deep brown skin', and 'indeterminate'. Five textbooks, with a total of 2060 images of skin, were examined. 87.6% of images showed light skin, 7.0% showed light to medium brown skin, 2.9% showed medium to deep brown skin, and 0.5% showed deep to very deep brown skin. 2.0% was categorized as 'indeterminate'. Dutch dermatology textbooks currently include only small percentages of images of brown skin. Unfamiliarity with disease presentation on deeper skin tones can lead to delayed diagnosis and worse outcomes in Black and Brown patients. Future textbooks should include images of different skin tones, including deeper ones, for every skin condition.


Violent and criminal manifestations in dementia patients.
Although the older adults have been studied as victims of violence, geriatric patients can display violent behavior. The purpose of the present review was to explore the phenomenon of criminal violations and violent acts in people with dementia. The authors used PubMed to search the MEDLINE database and other sources for original research and review articles on criminal and violent manifestation in demented patients combining the terms "criminal manifestation," "violence, aggressive behavior," "homicide," "suicide" and "homicide-suicide" together with "dementia". Possible biomarkers of violence are considered. The present review highlights the risk factors for violence in patients suffering from dementia, and reviews the literature about criminal violations and homicidal/suicidal behavior in this patient group. Geriatr Gerontol Int 2016; 16: 541-549.


Dislocation rate and its risk factors in total hip arthroplasty with concurrent extensive spinal corrective fusion with pelvic fixation for adult spinal deformity.
Though there are several reports on the high dislocation rates following total hip arthroplasty (THA) before or after spinal surgery, the literature specific to extensive spinal corrective fusion with pelvic fixation for adult spinal deformity is limited. This study determined the rate and risk of hip dislocation after THA and extensive spinal corrective fusion. We retrospectively analyzed the data of 23 adults (27 hips) who underwent both extensive spinal corrective fusion with pelvic fixation and THA between 2010 and 2018. Surgery-related characteristics were investigated from medical records, while standing anteroposterior pelvic radiographs and lateral spinal radiographs were used to measure spinal alignment parameters and THA acetabular orientation. Patients were grouped based on the occurrence of dislocation, and the rate and risk of dislocation were compared. The rate of THA dislocations was extremely high-22% (6 of 27 hips) of patients. All dislocations occurred posteriorly in patients with prior THAs that were performed using the posterior approach. The pelvic tilt was significantly greater in patients with THA dislocations (p = 0.02) than in those without. Cup radiographic anteversion in the supine (p = 0.02) and standing (p = 0.05) positions was significantly smaller in patients with dislocations than in those without. Total hip arthroplasty concurrent with extensive spinal corrective fusion with pelvic fixation for adult spinal deformity has an extremely high rate of posterior hip dislocation. The posterior surgical approach and prior THA were high risk factors for dislocation. Hip and spine surgeons need focused pre-surgical planning to account for this risk.


Utilizing Dynamic Risk Stratification in Patients With Tall Cell Variant Papillary Thyroid Cancer.
Tall cell variant (TCV) papillary thyroid cancer (PTC) is a subtype of PTC associated with aggressive tumor behavior, advanced stage, and higher rates of recurrence and mortality. The present study aimed to test an established dynamic risk stratification tool in the TCV population, with the goal of better predicting the postoperative course of these patients. Retrospective chart review. A total of 94 patients with TCV who underwent total thyroidectomy with radioactive iodine ablation were retrospectively reviewed from 1998 through 2020. Biochemical, structural, and overall response to treatment was determined for each patient, based on postoperative thyroglobulin levels and imaging findings. Primary outcomes were locoregional and distant recurrence, presence of disease at final follow-up, need for additional intervention, and disease-specific mortality. Patients with TCV who were stratified as having an excellent overall response to treatment had lower rates of locoregional recurrence than indeterminate, biochemical incomplete, and structural incomplete responses (2.0%, 33.3%, 55.0%, and 85.7% at 5 years respectively, p < 0.001). The same was true for distant recurrence as well (2.0%, 9.0%, 35.1%, and 42.9%, p < 0.001). An excellent response was also associated with lower rates of presence of disease at final follow-up, need for additional intervention, and disease-specific mortality. Although TCV is an aggressive subtype associated with worse clinical outcomes than classical PTC, patients with an excellent overall response to treatment have significantly improved outcomes when compared to indeterminate, biochemical incomplete, and structural incomplete responses. 3 Laryngoscope, 133:2430-2438, 2023.


Characterization of CD34⁺ thymocytes in newborn dogs.
Using two-color flow cytometry, we characterized CD34(+) cells in the newborn canine thymus. CD34(+) thymic cells comprised approximately 5% of cells recovered by thymus tissue teasing and both large and small thymocytes have been present in this population, the former being 7-12 times more frequent. All CD34(+) cells expressed the pan-leukocyte antigen CD45. The expression of CD44 profile on the large and small CD34(+) thymocytes differed: almost all large CD34(+) cells were CD44(+), while only 75% of small CD34(+) thymocytes co-expressed the CD44 antigen. We have previously described that CD172α is present on the surface of CD34(+) bone marrow cells in dogs. In the thymus, CD172α was expressed on 5-10% and less than 5% of large and small CD34(+) cells, respectively. Some CD34(+) thymocytes also co-expressed T-lineage-specific markers like CD3, CD4, CD8, TCR1 and TCR2. Their expression increased during the large-to-small thymocyte transition. Based on our findings we suggest that thymocyte progenitors enter their primary differentiation center as large CD34(+), CD44(+), CD45(+) and CD172α(+) cells. T-cell specific markers appear on their surface at early stages of differentiation. As the size of progenitors decreases with terminal primary differentiation, the CD34, CD44, and CD172α surface markers are down-regulated.


Anterior segment optical coherence tomography and ultrasound biomicroscopy in the imaging of anterior segment tumors.
To evaluate the utility of anterior segment optical coherence tomography (OCT) in the imaging of anterior segment tumors and compare the images to ultrasound biomicroscopy (UBM). Prospective observational case series. Eighteen eyes of 18 patients with anterior segment tumors were evaluated at Princess Margaret Hospital. The evaluation included clinical examination, clinical photography, anterior segment OCT, and UBM. Comparison of images obtained by both methods was done. Anterior segment OCT imaged small hypopigmented tumors with complete penetration. Cysts were incompletely imaged behind the iris pigment epithelium. Highly pigmented tumors, large tumors, and ciliary body tumors were incompletely penetrated. Even without complete penetration it was possible to differentiate cystic lesions from solid lesions. UBM penetrated all tumors completely. Anterior segment OCT can penetrate small hypopigmented tumors and supply some information on internal characteristics of other tumors. UBM is preferable for clinical anterior tumor assessment and follow-up because of its superior ability to penetrate large tumors, highly pigmented tumors, and ciliary body tumors.


Calcitonin gene-related peptide depresses the growth and secretory activity of rat adrenal zona glomerulosa.
The bolus ip. injection of rat calcitonin gene-related peptide (CGRP) (5 pm. kg-1) significantly lowered plasma aldosterone concentration (PAC) in rats, despite a mild rise in plasma renin activity. Natremia, kalaemia and the blood levels of ACTH or corticosterone were not affected. Similar results were obtained after prolonged (5 days) sc. infusion of rats with CGRP (1 pm. kg-1. h-1). Moreover, CGRP infusion caused a notable atrophy of the zona glomerulosa (ZG) and its parenchymal cells, as well as a clearcut reduction in the surge of PAC evoked by a bolus injection of a high dose of angiotensin-II (100 micrograms. kg-1). From these results it is suggested that CGRP exerts an inhibitory effect on the growth and secretory activity of ZG in rats.


Effect of frozen storage on the lipid oxidation, protein oxidation, and flavor profile of marinated raw beef meat.
This study aimed to evaluate the effects of long-term frozen storage on the lipid oxidation, protein oxidation, and flavor profile of marinated raw beef meat. Twenty-eight volatiles were identified in all the samples during different times of frozen storage using HS-SPME-GC-MS. Frozen storage affected the contents of flavor compounds, in which their concentrations fluctuated along with the frozen storage. Partial least squares-discriminant analysis screened six flavors as markers, indicating the effect of frozen storage in all the beef samples. They included octanal, 2-ethyl-1-hexanol, benzeneacetaldehyde, 1-heptanol, isoeugenol, and hexanal. Most of the screened markers belonged to aldehydes and alcohols, indicating that these components were derived from lipid oxidation. Thiobarbituric acid reactive substances significantly increased in the first two months of frozen storage and then decreased slightly. Carbonyl content was increased linearly in all the samples during frozen storage.


In vivo targeting and positron emission tomography imaging of tumor vasculature with (66)Ga-labeled nano-graphene.
The goal of this study was to employ nano-graphene for tumor targeting in an animal tumor model, and quantitatively evaluate the pharmacokinetics and tumor targeting efficacy through positron emission tomography (PET) imaging using (66)Ga as the radiolabel. Nano-graphene oxide (GO) sheets with covalently linked, amino group-terminated six-arm branched polyethylene glycol (PEG; 10 kDa) chains were conjugated to NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid, for (66)Ga-labeling) and TRC105 (an antibody that binds to CD105). Flow cytometry analyses, size measurements, and serum stability studies were performed to characterize the GO conjugates before in vivo investigations in 4T1 murine breast tumor-bearing mice, which were further validated by histology. TRC105-conjugated GO was specific for CD105 in cell culture. (66)Ga-NOTA-GO-TRC105 and (66)Ga-NOTA-GO exhibited excellent stability in complete mouse serum. In 4T1 tumor-bearing mice, these GO conjugates were primarily cleared through the hepatobiliary pathway. (66)Ga-NOTA-GO-TRC105 accumulated quickly in the 4T1 tumors and tumor uptake remained stable over time (3.8 ± 0.4, 4.5 ± 0.4, 5.8 ± 0.3, and 4.5 ± 0.4 %ID/g at 0.5, 3, 7, and 24 h post-injection respectively; n = 4). Blocking studies with unconjugated TRC105 confirmed CD105 specificity of (66)Ga-NOTA-GO-TRC105, which was corroborated by biodistribution and histology studies. Furthermore, histological examination revealed that targeting of NOTA-GO-TRC105 is tumor vasculature CD105 specific with little extravasation. Successful demonstration of in vivo tumor targeting with GO, along with the versatile chemistry of graphene-based nanomaterials, makes them suitable nanoplatforms for future biomedical research such as cancer theranostics.


Painful os acromiale (or unfused acromial apophysis) in athletes.
Twelve male competitive athletes (fourteen shoulders) presented with persistent shoulder pain that interfered with athletic participation. Patient ages ranged from 18 to 25 years. Symptoms included impingement-like pain with overhead activity and weightlifting. Local tenderness was present over the acromion near the same coronal plane as the posterior border of the clavicle. In each case, plain radiographs revealed the presence of an unfused anterior meso-acromial fragment. Magnetic resonance images were obtained in 5 shoulders and revealed edema at the junction of the anterior acromial fragment and the body of the acromion. Nine patients (eleven shoulders) were treated with arthroscopic excision of the anterior acromial fragment. They were followed up for a minimum of 2 years after the procedure. All surgically treated patients were able to return to full athletic participation by 14 weeks after surgery. Isokinetic testing at the latest follow-up revealed no significant deficits in abduction, internal rotation, or external rotation strength compared with the opposite side.


Early oral colostrum administration in preterm infants.
Early administration of colostrum may provide preterm infants with immune components. Previous studies illustrating the effects of oral colostrum (OC) have been confounded by the coincidence of enteral feedings. To quantify OC absorption, as measured by urinary sIgA and lactoferrin, in preterm infants prior to enteral feedings. Colostrum was obtained from mothers delivering infants ≤32 weeks and ≤1500 g. sIgA and lactoferrin were measured in infant urine, and microflora in saliva and tracheal aspirates were characterized. Urinary sIgA and lactoferrin were significantly greater in infants receiving OC by syringe compared to swab (p < 0.002). Urinary sIgA correlated with the total number of doses in 72 h (R2 = 43%, p < 0.01). Administration of OC by syringe and higher cumulative dose are associated with increased absorption of sIgA and lactoferrin, and early dosing may contribute to a more diverse tracheal microbiome.


Gene-environment interaction identification via penalized robust divergence.
In high-throughput cancer studies, gene-environment interactions associated with outcomes have important implications. Some commonly adopted identification methods do not respect the "main effect, interaction" hierarchical structure. In addition, they can be challenged by data contamination and/or long-tailed distributions, which are not uncommon. In this article, robust methods based on γ$\gamma$ -divergence and density power divergence are proposed to accommodate contaminated data/long-tailed distributions. A hierarchical sparse group penalty is adopted for regularized estimation and selection and can identify important gene-environment interactions and respect the "main effect, interaction" hierarchical structure. The proposed methods are implemented using an effective group coordinate descent algorithm. Simulation shows that when contamination occurs, the proposed methods can significantly outperform the existing alternatives with more accurate identification. The proposed approach is applied to the analysis of The Cancer Genome Atlas (TCGA) triple-negative breast cancer data and Gene Environment Association Studies (GENEVA) Type 2 Diabetes data.


Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines.
Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) to decrease the risk of severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome, mucositis or myelosuppression). Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. The DPYD-gene activity score, determined by four DPYD variants, predicts DPD activity and can be used to optimize an individual's starting dose. The gene activity score ranges from 0 (no DPD activity) to 2 (normal DPD activity). In case it is not possible to calculate the gene activity score based on DPYD genotype, we recommend to determine the DPD activity and adjust the initial dose based on available data. For patients initiating 5-fluorouracil or capecitabine: subjects with a gene activity score of 0 are recommended to avoid systemic and cutaneous 5-fluorouracil or capecitabine; subjects with a gene activity score of 1 or 1.5 are recommended to initiate therapy with 50% the standard dose of 5-fluorouracil or capecitabine. For subjects initiating tegafur: subjects with a gene activity score of 0, 1 or 1.5 are recommended to avoid tegafur. Subjects with a gene activity score of 2 (reference) should receive a standard dose. Based on the DPWG clinical implication score, DPYD genotyping is considered "essential", therefore directing DPYD testing prior to initiating fluoropyrimidines.


Mini-navigator: a new system for navigated deformity corrections.
The purpose of this study is to present a new navigation device for deformity correction surgery and to evaluate its accuracy compared with a conventional electromagnetic navigation system in tracking the orientation of synthetic bony fragments. This system consists of three sensors and software which can be installed on any personal computer. One sensor is mounted about 1 m above the other sensors. The remaining two sensors are fixed to the bone fragments using Schanz screws. Data from all three sensors are computed using the software to estimate the change in position of the sensors. For the first part of the study 118 planned one and two plane deformities in 5° increments were created. For the second part of the study complex random 3-dimensional deformities were created (300 valid measurements). The mean absolute differences between measurements of the electromagnetic and mini-navigator were 1.8 ± 1.9° in the coronal, 1.1 ± 1.1° in the sagittal and 0.8 ± 0.7° in the transverse plane. Absolute differences between mini-navigator and Fastrak measurements were significantly affected by the magnitude of the deformity (P < 0.0001) with better accuracy for lower deformities. We believe that this new technology is appealing, because of its high accuracy and lower planned costs compared with conventional navigation devices.


Increased serum lactate dehydrogenase isoenzyme 1 and "flipped" LD-1/LD-2 ratio in myopathy associated with partial carnitine palmitoyltransferase deficiency.
We describe a case of a limb-girdle myopathy presenting with myoglobinuria. A partial deficiency of muscle carnitine palmitoyltransferase (EC 188.8.131.52) may also have been present. All "muscle-type" serum enzymes were markedly increased (to between 30- and 400-fold their respective upper reference limits) and creatine kinase (EC 126.96.36.199) isoenzyme 2 (CK-MB) was increased 130-fold but was still less than 2% of the total creatine kinase activity. The isoenzyme pattern of lactate dehydrogenase (EC 220.127.116.11) in serum was "anodic," with isoenzyme 1 greater than isoenzyme 2--an unusual pattern for myopathies. The possible physiological basis for such a finding is discussed.


Bone and mineral metabolism in patients with primary aldosteronism: A systematic review and meta-analysis.
Patients with primary aldosteronism (PA) tend to exhibit a high prevalence of osteoporosis (OP) that may vary by whether PA is unilateral or bilateral, and responsive to PA treatment. To explore relationships between bone metabolism, PA subtypes, and treatment outcomes, we performed a systematic review and meta-analysis. The PubMed, Embase, and Cochrane databases were searched for clinical studies related to PA and bone metabolism markers. Articles that met the criteria were screened and included in the systematic review; the data were extracted after evaluating their quality. R software (ver. 2022-02-16, Intel Mac OS X 11.6.4) was used for the meta-analysis. A total of 28 articles were subjected to systematic review, of which 18 were included in the meta-analysis. We found that PA patients evidenced a lower serum calcium level (mean difference [MD] = -0.06 mmol/L, 95% confidence interval [CI]: -0.10 ~ -0.01), a higher urine calcium level (MD = 1.29 mmol/24 h, 95% CI: 0.81 ~ 1.78), and a higher serum parathyroid hormone (PTH) level (MD = 2.16 pmol/L, 95% CI: 1.57 ~ 2.75) than did essential hypertension (EH) subjects. After medical treatment or adrenal surgery, PA patients exhibited a markedly increased serum calcium level (MD = -0.08 mmol/L, 95% CI: -0.11 ~ -0.05), a decreased urine calcium level (MD = 1.72 mmol/24 h, 95% CI: 1.00 ~ 2.44), a decreased serum PTH level (MD = 2.67 pmol/L, 95% CI: 1.73 ~ 3.62), and an increased serum 25-hydroxyvitamin D (25-OHD) level (MD = -6.32 nmol/L, 95% CI: -11.94 ~ -0.70). The meta-analysis showed that the ser um PTH level of unilateral PA patients was significantly higher than that of bilateral PA patients (MD = 0.93 pmol/L, 95% CI: 0.36 ~ 1.49) and the serum 25-OHD lower than that of bilateral PA patients (MD = -4.68 nmol/L, 95% CI: -7.58 ~ 1.77). There were, however, no significant differences between PA and EH patients of 25-OHD, or BMD of femoral neck and lumbar spine. BMDs of the femoral neck or lumbar spine did not change significantly after treatment. The meta-analytical results were confirmed via sensitivity and subgroup analyses. Excess aldosterone was associated with decreased serum calcium, elevated urinary calcium, and elevated PTH levels; these effects may be enhanced by low serum 25-OHD levels. The risks of OP and fracture might be elevated in PA patients, especially unilateral PA patients, but could be reduced after medical treatment or adrenal surgery. In view, however, of the lack of BMD changes, such hypothesis needs to be tested in further studies.


Musculoskeletal Disorders and Prescription Opioid Use Among U.S. Construction Workers.
Musculoskeletal disorders (MSDs) and opioid use are a combined burden for construction safety and health. This study examines both issues among construction workers using a large population-based survey. The prevalence of MSDs in construction was estimated using multi-year data from the Medical Expenditure Panel Survey. Prescription opioid use among workers with MSDs was compared to those without MSDs. About 34% of construction workers had at least one MSD symptom. Compared to those without MSDs, prescription opioid use tripled (aOR = 3.28, 95% CI: 2.44 to 4.41) among construction workers with MSDs. MSDs are prevalent among construction workers, and prescription opioid use significantly increased among workers with MSDs. It is critical to adopt ergonomic solutions in construction to reduce MSDs, and support workers in injury recovery with effective pain management.


Pediatric isolated oculomotor nerve schwannoma: a new case report and literature review.
Isolated schwannoma arising from the oculomotor nerve occurs rarely, and only 12 children with oculomotor nerve schwannoma without neurofibromatosis have been sufficiently documented. This article presents a 3-year-old boy in which a large isolated parasellar oculomotor nerve schwannoma causing parent nerve dysfunction. Complete resection of the tumor was achieved via a right pterion approach, but he developed complete palsy of the third nerve postoperatively, which had an incomplete recovery in 12-month follow-up. We review the pertinent literature about pediatric oculomotor nerve schwannoma and discuss its clinical features and management.


Special Issue "Viral Evasion or Suppression of Host Immunity".
Viruses have evolved to survive in hosts, presumably by devising meticulous strategies to elude or suppress host immunity [...].


Elevated resting heart rate, physical fitness and all-cause mortality: a 16-year follow-up in the Copenhagen Male Study.
To examine whether elevated resting heart rate (RHR) is an independent risk factor for mortality or a mere marker of physical fitness (VO2Max). This was a prospective cohort study: the Copenhagen Male Study, a longitudinal study of healthy middle-aged employed men. Subjects with sinus rhythm and without known cardiovascular disease or diabetes were included. RHR was assessed from a resting ECG at study visit in 1985-1986. VO2Max was determined by the Åstrand bicycle ergometer test in 1970-1971. Subjects were classified into categories according to level of RHR. Associations with mortality were studied in multivariate Cox models adjusted for physical fitness, leisure-time physical activity and conventional cardiovascular risk factors. 2798 subjects were followed for 16 years. 1082 deaths occurred. RHR was inversely related to physical fitness (p < 0.001). Overall, increasing RHR was highly associated with mortality in a graded manner after adjusting for physical fitness, leisure-time physical activity and other cardiovascular risk factors. Compared to men with RHR ≤ 50, those with RHR > 90 had an HR (95% CI) of 3.06 (1.97 to 4.75). With RHR as a continuous variable, risk of mortality increased with 16% (10-22) per 10 beats per minute (bpm). There was a borderline interaction with smoking (p = 0.07); risk per 10 bpm increase in RHR was 20% (12-27) in smokers, and 14% (4-24) in non-smokers. Elevated RHR is a risk factor for mortality independent of physical fitness, leisure-time physical activity and other major cardiovascular risk factors.


The 6-Item Cognitive Impairment Test as a bedside screening for dementia in general hospital patients: results of the General Hospital Study (GHoSt).
The objective of this study was to examine the psychometric quality of the 6-Item Cognitive Impairment Test (6CIT) as a bedside screening for the detection of dementia in general hospital patients. Participants (N = 1,440) were inpatients aged ≥65 of 33 randomly selected general hospitals in Southern Germany. The 6CIT was conducted at bedside, and dementia was diagnosed according to DSM-IV. Nursing staff was asked to rate the patients' cognitive status, and previous diagnoses of dementia were extracted from medical records. Completion rates and validity statistics were calculated. Two-hundred seventy patients had dementia. Cases with delirium but no dementia were excluded. Feasibility was 97.9% and 83.3% for patients without and with dementia, respectively, and decreased from moderate (93.8%) to severe dementia (53%). The area under the curve of the 6CIT was 0.98. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for the cutoffs 7/8 (0.96, 0.82, 0.85, 0.52, 0.99) and 10/11 (0.88, 0.95, 0.94, 0.76, 0.98). The nurse ratings and medical records information had lower validity statistics. Logistic regression analyses revealed that the 6CIT statistically significantly provided information above nurse ratings and medical records. Twenty-five and 37 additional patients were correctly classified by the 7/8 and 10/11 cutoffs, respectively. The 6CIT is a feasible and valid screening tool for the detection of dementia in older general hospital patients. The 6CIT outperformed the nurse ratings of cognitive status and dementia diagnoses from medical records, suggesting that standardized screening may have benefits with regard to case finding. Copyright © 2016 John Wiley & Sons, Ltd.


Relationship of chronic pelvic pain to psychiatric diagnoses and childhood sexual abuse.
Structured psychiatric and sexual abuse interviews were administered to 25 women with chronic pelvic pain and a comparison group of 30 women with specific gynecological conditions. All 55 patients underwent diagnostic laparoscopy, and the results of the fiberoptic pelvic examination were objectively classified by the study gynecologist, who was blind to the psychiatric diagnoses. The patients with chronic pelvic pain showed a significantly higher prevalence of major depression, substance abuse, adult sexual dysfunction, somatization, and history of childhood and adult sexual abuse than the comparison group. There were no significant differences between the groups in severity or type of pelvic pathology.


Solution structure of leptospiral LigA4 Big domain.
Pathogenic Leptospiraspecies express immunoglobulin-like proteins which serve as adhesins to bind to the extracellular matrices of host cells. Leptospiral immunoglobulin-like protein A (LigA), a surface exposed protein containing tandem repeats of bacterial immunoglobulin-like (Big) domains, has been proved to be involved in the interaction of pathogenic Leptospira with mammalian host. In this study, the solution structure of the fourth Big domain of LigA (LigA4 Big domain) from Leptospira interrogans was solved by nuclear magnetic resonance (NMR). The structure of LigA4 Big domain displays a similar bacterial immunoglobulin-like fold compared with other Big domains, implying some common structural aspects of Big domain family. On the other hand, it displays some structural characteristics significantly different from classic Ig-like domain. Furthermore, Stains-all assay and NMR chemical shift perturbation revealed the Ca(2+) binding property of LigA4 Big domain.


"Editing" Genes: A Case Study About How Language Matters in Bioethics.
Metaphors used to describe new technologies mediate public understanding of the innovations. Analyzing the linguistic, rhetorical, and affective aspects of these metaphors opens the range of issues available for bioethical scrutiny and increases public accountability. This article shows how such a multidisciplinary approach can be useful by looking at a set of texts about one issue, the use of a newly developed technique for genetic modification, CRISPRcas9.


Different expression of miR-29b and VEGFA in glioma.
Glioma is one of the most common carcinomas in terms of both incidence and mortality worldwide. This is a case-control study with 240 cases and age- and gender-matched controls in the rate of 1:1. The results of this present word indicated that the expressions of both miR-29b and VEGFA in blood were significantly different compared with the control group, and thus may help to differentiate glioma cases from the controls. In addition, the diagnostic role of miR-29b and VEGFA was important for the clinical application. In conclusion, circulating miR-29b and VEGFA could be used as diagnosis biomarkers.


The need for ventilatory support during bystander CPR.
To compare CPR with chest compressions plus ventilatory support (CC+V) and chest compressions alone (CC). Prospective, randomized study. Research laboratory. After 2 minutes of ventricular fibrillation, 18 domestic swine (20 to 35 kg) were treated first with CC or CC+V for 10 minutes, then with standard advanced cardiac life support. Hemodynamics, survival, and neurologic outcome were determined. All 8 swine subjected to CC+V and all 10 subjected to CC showed return of spontaneous circulation. One animal in each group died within 1 hour. Seven of 8 animals in the CC+V group survived for 24 and 48 hours, compared with 9 of 10 CC animals at 24 hours and 8 of 10 at 48 hours. All 48-hour survivors were neurologically normal. In this experimental model of bystander CPR, we could not detect a difference in hemodynamics, 48-hour survival, or neurologic outcome when CPR was applied with and without ventilatory support.


The risk of pulmonary embolism and deep venous thrombosis in systemic lupus erythematosus: A general population-based study.
To estimate the future risk and time trends of newly diagnosed venous thromboembolism (VTE) in individuals with incident systemic lupus erythematosus (SLE) in the general population. Using a population-based database that includes all residents of British Columbia, Canada we conducted a study cohort of all patients with incident SLE and up to 10 age-, sex-, and entry-time-matched individuals from the general population. We compared incidence rates of pulmonary embolism (PE), deep venous thrombosis (DVT), and VTE between the two groups according to SLE disease duration. We calculated hazards ratios (HR), adjusting for confounders. Among 4863 individuals with SLE (86% female; mean age, 48.9 years), the incidence rates (IRs) of PE, DVT, and VTE were 2.58, 3.33, and 5.32 per 1000 person-years, respectively, whereas the corresponding rates in the comparison cohort were 0.67, 0.57, and 1.11 per 1000 person-years. Compared with non-SLE individuals, the multivariable HRs among SLE patients were 3.04 (95% CI: 2.08-4.45), 4.46 (95% CI: 3.11-6.41), and 3.55 (95% CI: 2.69-4.69), respectively. The age-, sex-, and entry-time-matched HRs for PE, DVT, and VTE were highest during the first year after SLE diagnosis [13.57 (95% CI: 7.66-24.02), 11.13 (95% CI: 6.55-18.90), and 12.89 (95% CI: 8.56-19.41), respectively]. These findings provide population-based evidence that patients with SLE have a substantially increased risk of VTE, especially in the first year after SLE diagnosis. Awareness and increased vigilance of this potentially fatal, but preventable, complication is recommended.


Membrane lipoteichoic acid is not a precursor to wall teichoic acid in pneumococci.
The distribution of a pulse of teichoic acid-specific radiolabel between wall and membrane teichoic acids in pneumococci was constant over a subsequent chase period, suggesting that wall and membrane teichoic acids are biosynthesized simultaneously and independently.


Free distal volar forearm perforator flap: clinical application in digital reconstruction.
Soft tissue defects of the digits can be a challenging problem for the hand surgeon. For non-graftable defects, numerous local, regional and free flaps have been described for resurfacing, each with their own limitations - bulk, colour, texture mismatch, donor morbidity. Perforator flaps increasingly provide the optimal option for reconstruction of digital defects as they are thin, pliable and with low donor site morbidity. A thin, pliable fasciocutaneous flap can be raised from the distal volar forearm based on a perforator of the radial artery. The pedicle is up to 2-3 cm in length with a diameter of at least 0.5 mm in diameter, suitable for anastomosis to the digital artery. Venous drainage is via the venae comitante of the radial artery and superficial volar veins. A patient presented to our emergency department following circular saw injuries. He suffered multi-digit trauma with subsequent soft tissue defects over the dorsum of the digit. Reconstructive requirements were met utilizing a free fasciocutaneous flap raised on a distal volar forearm perforator from the radial artery. The recovery was uneventful with no donor site morbidity. Dorsal digital soft tissue reconstruction requires thin, pliable, ideally hairless and sensate skin. Most locoregional options are limited by the need for multi-stage surgery, bulk, limited reach or donor site morbidity. In our patient, the reconstructive requirements were met with preservation of the radial artery. While it requires microsurgical skill and instruments, this flap provides another option for the reconstructive hand surgeon.


Application of a modified drop method for high-resolution pachytene chromosome spreads in two Phalaenopsis species.
Preparation of good chromosome spreads without cytoplasmic contamination is the crucial step in cytogenetic mapping. To date, cytogenetic research in the Orchidaceae family has been carried out solely on mitotic metaphase chromosomes. Well-spread meiotic pachytene chromosomes can provide higher resolution and fine detail for analysis of chromosomal structure and are also beneficial for chromosomal FISH (fluorescence in situ hybridization) mapping. However, an adequate method for the preparation of meiotic pachytene chromosomes in orchid species has not yet been reported. Two Taiwanese native Phalaenopsis species were selected to test the modified drop method for preparation of meiotic pachytene chromosomes from pollinia. In this modified method, pollinia were ground and treated with an enzyme mixture to completely remove cell walls. Protoplasts were resuspended in ethanol/glacial acetic acid and dropped onto a wet inclined slide of 30° from a height of 0.5 m. The sample was then flowed down the inclined plane to spread the chromosomes. Hundreds of pachytene chromosomes with little to no cytoplasmic contamination were well spread on each slide. We also showed that the resolution of 45S rDNA-containing chromosomes at the pachytene stage was up to 20 times higher than that at metaphase. Slides prepared following this modified drop method were amenable to FISH mapping of both 45S and 5S rDNA on pachytene chromosomes and, after FISH, the chromosomal structure remained intact for further analysis. This modified drop method is suitable for pachytene spreads from pollinia of Phalaenopsis orchids. The large number and high-resolution pachytene spreads, with little or no cytoplasmic contamination, prepared by the modified drop method could be used for FISH mapping of DNA fragments to accelerate the integration of cytogenetic and molecular research in Phalaenopsis orchids.


MicroRNA Expression Analysis Using Small RNA Sequencing Discovery and RT-qPCR-Based Validation.
miRNAs are small noncoding RNA molecules that function as regulators of gene expression. Deregulated miRNA expression has been reported in various diseases including cancer. Due to their small size and high degree of homology, accurate quantification of miRNA expression is technically challenging. In this chapter, we present two different technologies for miRNA quantification: small RNA sequencing and RT-qPCR.


Stereoscopic contours and optokinetic nystagmus in normal and stereoblind subjects.
Moving stereoscopic contours in a dynamic random-dot stereogram have been previously shown to induce optokinetic nystagmus in subjects with normal stereopsis. For this to be validated as an objective test of stereopsis, stereoblind subjects must also be shown not to develop OKN, especially since it has been shown that the optomotor system of stereoblind individuals retains sensitivity to some cyclopean stimuli. In this report we verify that stereoblind subjects do not have an optomotor response to stereoscopic contours--regardless of the alignment angle at which the stereo image pair is presented.


Reported Levels of Exhaustion by the Graduate Nurse Midwife and Their Perceived Potential for Unsafe Practice: A Phenomenological Study of Australian Double Degree Nurse Midwives.
The experiences of graduate nurses and midwives transitioning into the clinical environment as beginning practitioners has been reported as a time period of great challenge. For the graduate double degree nurse midwife, often transitioning into two disciplines of practice concurrently, their experiences have the potential to be heightened. The aim of this research was to explore the transition to practice experiences of double degree graduate nurse midwives practicing in either or both nursing and midwifery in the Australian health care system. This research used a Husserlian descriptive phenomenological approach to understand the experiences of 23 double degree graduate nurse midwives working in 20 different health care facilities across Australia. The findings showed that most participants experienced exhaustion from an emotional, physical, and mental perspective during their first year of practice. These experiences were linked with cognitive saturation, professional loneliness, sleep deprivation, and an inability to achieve a work-life balance. The data also highlighted the graduate nurse midwife's concerns for safe practice when feeling mentally, physically, and emotionally depleted. Safe practice is paramount for both patient and health care worker. The levels of exhaustion described by the participants in this study influenced their perceived ability to practice safely. As a result, it should be recognized that the graduate nurse midwife's health and well-being is central to their perceptions of safe practice and is fundamental to a positive transition to practice experience.


Three years after transplants in human mandibles, histological and in-line holotomography revealed that stem cells regenerated a compact rather than a spongy bone: biological and clinical implications.
Mesenchymal stem cells deriving from dental pulp differentiate into osteoblasts capable of producing bone. In previous studies, we extensively demonstrated that, when seeded on collagen I scaffolds, these cells can be conveniently used for the repair of human mandible defects. Here, we assess the stability and quality of the regenerated bone and vessel network 3 years after the grafting intervention, with conventional procedures and in-line holotomography, an advanced phase-imaging method using synchrotron radiation that offers improved sensitivity toward low-absorbing structures. We found that the regenerated tissue from the graft sites was composed of a fully compact bone with a higher matrix density than control human alveolar spongy bone from the same patient. Thus, the regenerated bone, being entirely compact, is completely different from normal alveolar bone. Although the bone regenerated at the graft sites is not of the proper type found in the mandible, it does seem to have a positive clinical impact. In fact, it creates steadier mandibles, may well increase implant stability, and, additionally, may improve resistance to mechanical, physical, chemical, and pharmacological agents.


Potentiated action on the progression of OSMF by hypoxia mediated signaling pathway by the epithelial mesenchymal transition and angiogenic apparatus.
Epithelial-mesenchymal transition (EMT) is a complex process, in which epithelial cells acquire the characteristics of invasive mesenchymal cells. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. The aim of the study was to ascertain the role of hypoxia-mediated signaling pathways influencing EMT and angiogenesis in progression of oral submucous fibrosis (OSMF). Evaluation of the immunoexpression of alpha-smooth muscle actin (α-SMA), E-cadherin, vimentin, and factor VIII receptor antigen in OSMF and oral squamous cell carcinoma (OSCC) arising from OSMF was done. Differences between the different variables were analyzed using ANOVA test and Pearson's Chi-square test, and Mann-Whitney test was also calculated. The mean α-SMA positive myofibroblasts increased from Group 1 (OSMF) to Group 2 (OSCC), especially those in the deeper connective tissue stroma. The mean labeling index of vimentin and mean vessel density immunoexpression was more in Group 2 (OSCC) as compared to Group 1 (OSMF). Mean α-SMA correlated negatively with E-cadherin expression and positively with vimentin and factor VIII immunoexpression. E-cadherin expression correlated negatively with factor VIII and positively with Vimentin expression. The molecular mechanisms responsible for the development of OSCC in patients with OSMF require unification of multiple progressive pathogenetic mechanisms involved in the progression of the disease.


Density functional theory study of epoxy polymer chains adsorbing onto single-walled carbon nanotubes: electronic and mechanical properties.
We performed first principles calculations based on density functional theory (DFT) to investigate the effect of epoxy monomer content on the electronic and mechanical properties of single-walled carbon nanotubes (SWCNTs). Our calculation results reveal that interfacial interaction increases with increasing numbers of epoxy monomers on the surface of SWCNTs. Furthermore, density of states (DOS) results showed no orbital hybridization between the epoxy monomers and nanotubes. Mulliken charge analysis shows that the epoxy polymer carries a positive charge that is directly proportional to the number of monomers. The Young's modulus of the nanotubes was also studied as a function of monomer content. It was found that, with increasing number of monomers on the nanotubes, the Young's modulus first decreases and then approaches a constant value. The results of a SWCNT pullout simulation suggest that the interfacial shear stress of the epoxy/SWCNT complex is approximately 68 MPa. These results agreed well with experimental results, thus proving that the simulation methods used in this study are viable.


Leber's hereditary optic neuropathy-associated ND6 14484T > C mutation caused pleiotropic effects on the complex I, RNA homeostasis, apoptosis and mitophagy.
Leber's hereditary optic neuropathy (LHON) is a maternally inherited eye disease due to mitochondrial DNA (mtDNA) mutations. LHON-linked ND6 14484T > C (p.M64V) mutation affected structural components of complex I but its pathophysiology is poorly understood. The structural analysis of complex I revealed that the M64 forms a nonpolar interaction Y59 in the ND6, Y59 in the ND6 interacts with E34 of ND4L, and L60 of ND6 interacts with the Y114 of ND1. These suggested that the m.14484T > C mutation may perturb the structure and function of complex I. Mutant cybrids constructed by transferring mitochondria from lymphoblastoid cell lines of one Chinese LHON family into mtDNA-less (ρo) cells revealed decreases in the levels of ND6, ND1 and ND4L. The m.14484T > C mutation may affect mitochondrial mRNA homeostasis, supported by reduced levels of SLIRP and SUPV3L1 involved in mRNA degradation and increasing expression of ND6, ND1 and ND4L genes. These alterations yielded decreased activity of complex I, respiratory deficiency, diminished mitochondrial ATP production and reduced membrane potential, and increased production of reactive oxygen species in the mutant cybrids. Furthermore, the m.14484T > C mutation promoted apoptosis, evidenced by elevating Annexin V-positive cells, release of cytochrome c into cytosol, levels in apoptotic proteins BAX, caspases 3, 7, 9 and decreasing levels in anti-apoptotic protein Bcl-xL in the mutant cybrids. Moreover, the cybrids bearing the m.14484T > C mutation exhibited the reduced levels of autophagy protein LC3, increased levels of substrate P62 and impaired PINK1/Parkin-dependent mitophagy. Our findings highlighted the critical role of m.14484T > C mutation in the pathogenesis of LHON.


Photoreaction of indole-containing mycotoxins to fluorescent products.
Photochemical reaction of the non-fluorescent mycotoxin cyclopiazonic acid (CPA) to fluorescent products was recently reported. Because CPA contains an indole moiety, believed to contribute to the fluorescence, it was of interest to determine whether the effect might be more generally applicable to indole-containing mycotoxins. Three indole-containing tremorgens (penitrem A, paxilline, verruculogen) that have not previously been reported to be fluorescent were rendered fluorescent by exposure to ultraviolet light in a photoreactor. Naturally fluorescent ergot alkaloids, which also contain an indole-moiety, exhibited a diminished response after exposure. This suggests that the phenomenon may be most useful for detection of indole-containing tremorgens that are non-fluorescent, rather than for the enhancement of materials that are already fluorescent, such as the ergot alkaloids. The extent to which fluorescence enhancement was seen was strongly influenced by the reaction environment, in particular the solvent used and whether cyclodextrins were present. In an HPLC format, placement of the photoreactor post-column allowed for the fluorescence detection of penitrem A, paxilline, and verruculogen. The ability to photoreact indole-containing tremorgens and detect them by fluorescence may open up new avenues for detection of these mycotoxins alone or in combination.


A DNA sequence conferring high postmeiotic segregation frequency to heterozygous deletions in Saccharomyces cerevisiae is related to sequences associated with eucaryotic recombination hotspots.
The meiotic behavior of two graded series of deletion mutations in the ADE8 gene in Saccharomyces cerevisiae was analyzed to investigate the molecular basis of meiotic recombination. Postmeiotic segregation (PMS) was observed for a subset of the deletion heterozygosities, including deletions of 38 to 93 base pairs. There was no clear relationship between deletion length and PMS frequency. A common sequence characterized the novel joint region in the alleles which displayed PMS. This sequence is related to repeated sequences recently identified in association with recombination hotspots in the human and mouse genomes. We propose that these particular deletion heterozygosities escape heteroduplex DNA repair because of fortuitous homology to a binding site for a protein.


Effect of magnesium hydroxide on the absorption of tolfenamic and mefenamic acids.
The effect of various antacids on the absorption of tolfenamic and mefenamic acids has been investigated in three separate crossover studies, each consisting of four phases. Single doses of magnesium hydroxide (85 mg, 425 mg and 1700 mg) or of water (150 ml) were given by mouth to 6 healthy volunteers immediately after tolfenamic acid 400 mg (Study 1), and, using an identical study design, after mefenamic acid 500 mg (Study 3). In Study 2 sodium bicarbonate 1 g, aluminium hydroxide 1 g, an antacid preparation containing both aluminium and magnesium hydroxides, or water alone were ingested with tolfenamic acid 400 mg. Plasma concentrations of tolfenamic and mefenamic acids and their cumulative excretion in urine were determined up to 24 h. Magnesium hydroxide greatly accelerated, in a dose-dependent manner the absorption of both tolfenamic and mefenamic acids. The peak times in plasma were shortened by about 1 h by 425 mg and 1700 mg magnesium hydroxide, and the peak plasma concentrations of both fenamates were elevated up to 3-fold. The area under the plasma concentration-time curve between 0 and 1 h of tolfenamic acid was increased up to 7-fold and that of mefenamic acid up to 3-fold. The total bioavailability of tolfenamic and mefenamic acids was only slightly increased. Aluminium hydroxide alone and in combination with magnesium hydroxide significantly retarded the absorption and lowered the peak plasma concentration of tolfenamic acid. Sodium bicarbonate had no significant effect on its absorption. The interaction with magnesium hydroxide leads to higher and earlier peak plasma concentrations of the fenamates.(ABSTRACT TRUNCATED AT 250 WORDS)


Catalyst-free diboration and silaboration of alkenes and alkynes using bis(9-heterofluorenyl)s.
Diboration and silaboration reactions are prominent tools to introduce valuable functional groups into organic substrates. To date, most diboranes(4) and silylboranes used for this purpose are electronically and/or kinetically stabilized and require activation by a catalyst. We show here that the tetraaryl (μ-hydrido)diborane(4) anion [3]- and the silyl (hydrido)borate ([4]-)/Me3SiBr system react spontaneously with the archetypal olefin ethylene in the absence of a catalyst. The actual active species in both cases are the valence isoelectronic intermediates [FluB-B(H)Flu]- ([1]-) and FluB-Si(H)Flu (2), which consist of two 9-heterofluorenyl halves that get attached to the 1 and 2 positions of ethylene. At room temperature, [1]- is present in a dynamic equilibrium with its isolable isomer [3]-, while 2 has to be released in situ at low temperatures by H- abstraction from [4]-. Quantum-chemical calculations show qualitatively identical reaction mechanisms for [1]- and 2. Since the reactions start with π coordination of the ethylene molecule to a vacant B(pz) orbital, the high Lewis acidity and low steric hindrance of the 9-borafluorenyl fragments are the keys to success. As the reaction proceeds, back-donation from the B-E bond into the ethylene π* orbital becomes increasingly important (E = B, Si). The scope of the reactions has been extended to tBu(H)C[double bond, length as m-dash]CH2 and tBuC[triple bond, length as m-dash]CH on the one hand and FluB-Si(Cl)Flu as well as FluB-Si(Cl)Ph2 on the other.


Development and distribution of serotonin in the central nervous system of Manduca sexta during embryogenesis. II. The ventral ganglia.
The distribution of serotonin (5-HT) immunoreactive cells and their projections was mapped in the ganglia of the ventral nerve cord of the tobacco hornworm, Manduca sexta, during embryonic development, using an antiserum to 5-HT. Immunoreactive cells were first seen at 60% development. By 75% of embryonic development, a total of 94 immunoreactive cells were found in the ventral ganglia, including the suboesophageal ganglion. This number decreased to 80 neurons by 100% of development. About 50% of these cells were arranged in the abdominal ganglia and the rest were located in both the suboesophageal and thoracic ganglia. The suboesophageal ganglion exhibited immunoreactive segmental interneurons in areas corresponding to the mandibular, maxillary and labial neuromeres. Two pairs of immunoreactive interneurons were also observed to occur bilaterally in each of the thoracic and abdominal ganglia, with the exception of the prothoracic ganglion. This ganglion contained three pairs of bilaterally arranged immunoreactive neurons as early as 60% of embryonic development. Serotonin immunoreactivity was also found in a number of efferent neurons in the mandibular and labial neuromeres of the suboesophageal ganglion and in the prothoracic, mesothoracic and posterior abdominal ganglia. The occurrence of 5-HT in these efferent neurons suggests an involvement of serotonin in fore- and hindgut function via its effect on the visceral muscles. Immunoreactive lateral longitudinal fibers extended along the entire length of the ventral nerve cord together with dense segmental arborizations. The latter had regressed by the time the embryo was fully developed. This regression of the arborizations in the ganglia at the end of embryonic development indicates that a reorganization of 5-HT innervation occurs to support new larval functions. The time of appearance of 5-HT immunoreactive cells and fibers suggests that serotonin may play a role in the development of the ventral nerve cord.


[The Göttinger minipig as a laboratory animal. 3. Communication: iron-, copper- and zinc-values in blood-serum].
Serumvalues of iron, copper and zinc were determined by atomic absorption. The results of two collectives (juvenile and adult animals) which were kept under SPF-conditions were compared with the corresponding values of man.


Degree centrality and functional connections in presbycusis with and without cognitive impairments.
Presbycusis is a major public issue that affecting elderly adults. However, the neural substrates between normal cognition and cognitive deficits in these patients need to be illustrated. 47 patients with presbycusis and 33 well-matched healthy controls were recruited in present study. Each subject underwent pure-tone audiometry (PTA), MRI scanning and cognition evaluations, then we found 22 patients with cognitive deficits and 25 patients with common cognition. We analyzed the Degree centrality (DC) characteristics among three groups, and try to recognize key nodes which contribute significantly. Subsequent functional connectivity analysis was applied using the key nodes as seeds. Compared with controls, presbycusis without cognitive impairments showed deceased DC in superior temporal gyrus (STG), inferior frontal gyrus (IFG) and supramarginal gyrus (SMG). Additionally, presbycusis with cognitive impairments showed enhanced DC in fusiform gurus (FFG), cerebellum and para-hippocampal gyrus (PHG), while weakened DC in SMG, middle frontal gyrus (IFG) and inferior Parietal lobule (IPL). Compared with normal cognition, increased DC value of cerebellum and STG, as well as decreased DC value of IPL in presbycusis with cognitive impairments were observed. We noticed that SMG may play an important role. Then the left and right SMG were used as seeds in functional connections analysis. With the seed set at left SMG, presbycusis without cognitive impairments showed decreases connections with cerebellum, temporal pole (TP), superior temporal gyrus (STG) and median cingulate cortex (MCC). Presbycusis with cognitive impairments showed weakened connectivity with cerebellum, IFG, IPL and superior frontal gyrus (SFG). The right SMG showed decrease connections with cerebellum, middle temporal gyrus (MTG), STG and increase connection with middle frontal gyrus (MFG) in presbycusis without cognitive impairments. While the right SMG showed enhanced connections with left TP, caudate, anterior cingulate cortex (ACC), angular, SFG and weakened connectivity with right SFG presbycusis with cognitive impairments. In comparison with normal cognition and impaired cognition, MFG, IFG, PHG, rolandic operculum and cerebellum were involved. These findings enriched our understanding of the neural mechanisms underlying cognitive impairments associated with presbycusis and may serve as a potential imaging biomarker for investigating and predicting cognitive difficulties.


White light phase shifting interferometric microscopy with whole slide imaging for quantitative analysis of biological samples.
In this paper, we demonstrate the white light phase shifting interferometer employed as whole slide scanner and phase profiler for determining qualitative and quantitative information over large field-of-view (FOV). Experiments were performed on human erythrocytes and MG63 Osteosarcoma cells. Here, we have recorded microscopic images and phase shifted white light interferograms simultaneously in a stepped manner. Sample slide is translated in transverse direction such that there exists a correlation between the adjacent frames, and they were stitched together using correlation functions. Final stitched image has a FOV of 0.24 × 1.14 mm with high resolution ~0.8 μm. Circular Hough transform algorithm is implemented to the resulting image for cell counting and five-step phase shifting algorithm is utilised to retrieve the phase profiles over a large FOV. Further, this technique is utilised to study the difference between normal and anaemic erythrocytes. Significant changes are observed in anaemic cells as compared to normal cells.


Use of the MILLIPLEX® bovine cytokine/chemokine multiplex assay to identify Mycobacterium bovis-infection biomarkers in African buffaloes (Syncerus caffer).
As a recognized Mycobacterium bovis maintenance host, the African buffalo (Syncerus caffer) poses transmission risks to livestock, humans and other wildlife. Early detection of M. bovis infection is critical for limiting its spread. Currently, tests detecting cell-mediated immune responses are used for diagnosis in buffaloes. However, these may have suboptimal sensitivity or specificity, depending on the blood stimulation method. Recent evidence suggests that assays using combinations of host cytokine biomarkers may increase diagnostic performance. Therefore, this study aimed to investigate the application of a MILLIPLEX® bovine cytokine/chemokine multiplex assay to identify candidate biomarkers of M. bovis infection in buffaloes. Whole blood from twelve culture-confirmed M. bovis-infected buffaloes, stimulated with the QuantiFERON® TB Gold Plus in-tube system, was tested using the MILLIPLEX® platform. Results indicated binding of bovine antibodies to fifteen buffalo cytokine/chemokine targets. Moreover, there was a significant difference in concentrations between unstimulated and TB antigen-stimulated buffalo samples for seven cytokines/chemokines included in the kit. Although these preliminary results require further investigation in larger sample sets and a comparison between M. bovis-infected and uninfected cohorts, the utility of the MILLIPLEX® platform in a novel species was demonstrated, in addition to identifying potential African buffalo cytokines for future research.


Glucagon-like peptide containing pathways in the regulation of feeding behaviour.
The pre-proglucagon derived peptides, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are both involved in a wide variety of peripheral functions, such as glucose homeostasis, gastric emptying, intestinal growth, insulin secretion as well as the regulation of food intake. Pre-proglucagon is also found in the brainstem in a small population of nerve cells in the nucleus of the solitary tract (NTS) that process the pre-propeptide as in the gut to yield GLP-1 and GLP-2. GLP-1 containing nerve fibres and the GLP-1 receptor are found predominantly in hypothalamic midline nuclei. GLP-1 given centrally to naive rats results in a marked induction of c-Fos protein in the supraoptic nucleus, paraventricular nucleus of the hypothalamus (PVN) and central nucleus of the amygdala, but only a moderate increase in the arcuate nucleus. The pattern of c-Fos activation is compatible with the appetite suppressing effects of GLP-1. This anorectic effect of GLP-1 appears to be mediated by the PVN, as direct injections of GLP-1 into this nucleus cause anorexia without concomitant taste aversion, suggesting a specific action upon neuronal circuits involved in the regulation of feeding. Recent experiments have also shown that GLP-1 is implicated in mediating signals from the gastrointestinal tract pertaining to discomfort and malaise. The distribution of the co-localised peptide, GLP-2, displays a perfect overlap with GLP-1 in the CNS with the highest concentration in the diffuse ventral part of the dorsomedial nucleus (DMHv). In contrast to the widely distributed GLP-1 receptor mRNA, GLP-2 receptor mRNA is exclusively expressed in the compact part of the DMH (DMHc). Interestingly, the DMHc is also the only nucleus responding to central administration of GLP-2 with a significant increase in the number of c-Fos positive cells. When injected into the lateral ventricle, GLP-2 has a marked inhibitory effect on feeding. The effect of GLP-2 on feeding is both behaviourally and pharmacologically specific. Future experiments will elucidate whether or not GLP-1 and GLP-2 are involved in the long-term or short-term regulation of feeding behaviour and hence have an impact on bodyweight.


Diagnostic and prognostic role of plasma and urinary sialic acid in human carcinoma of uterine cervix.
In different stages of carcinoma of uterine cervix, the plasma total sialic acid (TSA), lipid bound sialic acid (LSA) and urinary sialic acid levels were studied before and after radiation treatment. Glycocomponents of glycoproteins were found to be increased progressively as the disease advances. The increased levels of glycocomponents were found to be decreased to near normal levels after radiotherapy. This may be a better indicator of the disease in conjunction with the studies of cervical smear rather than the latter alone.


Four-dimensional translabial ultrasound concordance with digital palpation and surface electromyography during dynamic pelvic floor muscles assessment: A cross-sectional study.
To investigate whether pelvic floor muscle (PFM) morphological changes obtained through four-dimensional translabial ultrasound (4D TLUS) correlate with a PFM contraction as evaluated by digital palpation and PFM electromyographic activity evaluated by surface electromyography (sEMG). The secondary objective was to investigate which ultrasound parameter is more strongly associated with digital palpation. This cross-sectional study included 210 women and their PFMs were evaluated by digital palpation (graded according to the Modified Oxford Scale), sEMG and 4D TLUS. Offline analysis of ultrasound volume datasets was performed for measuring the change in levator plate angle, bladder neck elevation, hiatal area narrowing, puborectalis strain, and puborectalis muscle thickness at rest and during PFM contraction. Statistical analysis included Kruskal-Wallis, Dunn, and Spearman's tests in addition to univariate and multivariate logistic regression, adopting a significance level of 5%. A weak but significant correlation between the change in levator plate angle and sEMG (P = .04; r = 0.14) was found. All 4D TLUS measurements, except the puborectalis muscle thickness, significantly correlated with digital palpation (P < .0001); with the puborectalis strain and the change in levator plate angle having the strongest combined parameters associated with digital palpation (R2 = 21.77%), despite the low coefficient of determination. We found that 4D TLUS significantly correlates with digital palpation and sEMG, being the change in the levator plate angle the parameter that best correlates with both methods. While digital palpation is essential during a PFM functional assessment, 4D TLUS is recommended as a beneficial noninvasive clinical tool for a more in-depth evaluation.


Radiation induced free radicals as molecular probes in synthetic apatites.
Free radicals generated in synthetic apatitic calcium phosphates by X-ray radiation were investigated by electron spin resonance (ESR) spectroscopy. Among the species stable enough at -188 degrees C to be identified were hydrogen atoms, phosphate radicals, and oxygen anion radicals. The ESR spectra were markedly dependent on the specific surface of the mineral. Oxygen radicals dominated the spectra of low specific surface samples while phosphate radicals were the predominant species at higher specific surfaces. Our studies suggest that the oxygen radicals are more stable in the bulk of the crystal while the hydrogen atoms and the phosphate radicals are stabilized at or near the crystal surface. It was concluded that the surface species are potentially capable of serving as probes of biologically relevant mineral-organic interfaces.


Should Gastric Decompression be a Routine Procedure in Patients Who Undergo Pylorus-Preserving Pancreatoduodenectomy?
Nasogastric tube placement after abdominal surgery has been a standard procedure for many decades. In pancreatoduodenectomy, delayed gastric emptying (DGE) is still a leading postoperative complication, often resulting in patient anxiety or depression and prolonged hospital stays. Such complications have led many surgeons to prefer postoperative nasogastric decompression because of the greater risk of DGE. Therefore, the goal of this study was to evaluate the DGE and perioperative outcomes after pylorus-preserving pancreatoduodenectomy (PPPD) with or without routine gastrostomy. From May 2009 to December 2014, 228 patients underwent PPPD at the Department of Surgery, Gangnam Severance Hospital, Yonsei University. The first cohort of 116 patients underwent surgery before June 2012 and uniformly underwent gastric decompression as a part of postoperative management. The second cohort of 112 patients underwent operation after July 2012, and gastric decompression was selectively used to facilitate exposure during operation and was removed in the operating room at the end of surgery. We evaluated DGE incidence, time to dietary tolerance, length of hospital stay, and postoperative gastric tube reinsertion rates. Gastric re-decompression was necessary in 38 patients (16.7 %), and there was a significant difference between the two groups (p = 0.006). Eleven (9.8 %) patients in the no-tube gastrostomy group required nasogastric tube reinsertion, and 27 (23.3 %) in the routine gastrostomy group required that the gastrostomy tube be re-drainage. There were no statistically significant differences in the frequency or severity of complications such as delayed gastric emptying or pancreatic leakage. Our study demonstrates that routine postoperative gastric decompression can be safely avoided in patients who undergo PPPD.


Short term triiodo-L-thyronine treatment inhibits cardiac myocyte apoptosis in border area after myocardial infarction in rats.
Thyroid hormone (TH) levels decline after a myocardial infarction (MI). Treatment with TH has been shown to improve left ventricular (LV) function in MI and other cardiovascular diseases, but the mechanisms are not clear. We have previously shown that TH can prevent myocyte apoptosis via Akt signaling in cultured neonatal rat cardiomyocytes. In this study, the effects of triiodo-L-thyronine (T3) on LV function and myocyte apoptosis after MI was examined in rats. After surgery, MI rats were treated with T3 for 3 days. Compared with sham-operated rats, MI rats showed significantly increased LV chamber dimension during systole and decreased LV function. T3 treatment increased LV +/-dP/dt but did not change LV chamber dimensions. MI rats also showed significantly increased myocyte apoptosis in the border area as assessed by DNA laddering and TUNEL assay. T3 treatment decreased the amount of DNA laddering, and reduced TUNEL positive myocytes in the border area, which was associated with phosphorylation of Akt at serine 473. These results suggest that T3 can protect myocytes against ischemia-induced apoptosis, which may be mediated by Akt signaling.


Internal calibration as an emerging approach for endogenous analyte quantification: Application to steroids.
The use of mass spectrometry methods with triple quadrupole instruments is well established for quantification. However, the preparation of calibration curves can be time-consuming and prone to analytical errors. In this study, an innovative internal calibration (IC) approach using a one-standard calibration with a stable isotope-labeled (SIL) standard version of the endogenous compound was developed. To ensure optimal quantitative performance, the following parameters were evaluated: the stability of the analyte-to-SIL response factor (RF), the chemical and isotopic purities of the SIL, and the instrumental reproducibility. Using six clinically important endogenous steroids and their respective SIL standards, we demonstrated that RFs obtained on different LC-MS platforms were consistent. The quantitative performance of the proposed approach was determined using quality control samples prepared in depleted serum, and showed both satisfactory precision (1.3%-12.4%) and trueness (77.5%-107.0%, with only 3 values outside ±30%). The developed method was then applied to human serum samples, and the results were similar to those obtained with the conventional quantification approach based on external calibration: the Passing-Bablok regression showed a proportional bias of 6.8% and a mean difference of -5.9% between the two methodologies. Finally, we showed that the naturally occurring isotopes of the SIL can be used to provide additional calibration points and increase the accuracy for analytes with low concentrations.


Studies on genome size estimation, chromosome number, gametophyte development and plant morphology of salt-tolerant halophyte Suaeda salsa.
Soil salinization and alkalization are among the major agricultural threats that affect crop productivity worldwide, which are increasing day by day with an alarming rate. In recent years, several halophytes have been investigated for their utilization in soil remediation and to decipher the mechanism of salt-tolerance in these high salt tolerant genetic repositories. Suaeda salsa is an annual halophytic herb in the family Amaranthaceae, displaying high salt and alkali-resistance and having nutritive value. However, the fundamental biological characteristics of this valuable plant remain to be elucidated until today. In this study, we observed the morphology and development of Suaeda salsa, including seed morphology, seed germination, plant morphology, and flower development. Using microscopy, we observed the male and female gametophyte developments of Suaeda salsa. Also, chromosome behaviour during the meiosis of male gametophyte was studied. Eventually, the genome size of Suaeda salsa was estimated through flow cytometry using Arabidopsis as reference. Our findings suggest that the male and female gametophyte developments of Suaeda salsa are similar to those of the model plant Arabidopsis, and the diploid Suaeda salsa contains nine pairs of chromosomes. The findings also indicate that the haploid genome of Suaeda salsa is approximately 437.5 MB. The observations and results discussed in this study will provide an insight into future research on Suaeda salsa.


The circadian clock and cell cycle: interconnected biological circuits.
The circadian clock governs biological timekeeping on a systemic level, helping to regulate and maintain physiological processes, including endocrine and metabolic pathways with a periodicity of 24-hours. Disruption within the circadian clock machinery has been linked to numerous pathological conditions, including cancer, suggesting that clock-dependent regulation of the cell cycle is an essential control mechanism. This review will highlight recent advances on the 'gating' controls of the circadian clock at various checkpoints of the cell cycle and also how the cell cycle can influence biological rhythms. The reciprocal influence that the circadian clock and cell cycle exert on each other suggests that these intertwined biological circuits are essential and multiple regulatory/control steps have been instated to ensure proper timekeeping.


Method for quantitative extraction of copper hydroxide nanoparticles from farmland soil.
With the development of nanotechnology, nano-pesticides have been developed and show better application effects than traditional pesticides, which have a good development prospect. Copper hydroxide nanoparticles (Cu(OH)2 NPs) are one of the specific fungicides. However, there is still no reliable method to evaluate their environmental processes, which is essential for the broad application of new pesticides. Since soil is a vital link between pesticides and crops, this study took linear and slightly soluble Cu(OH)2 NPs as the research object and established a method to quantitatively extract Cu(OH)2 NPs from the soil. Five essential parameters in the extraction process were optimized first, and then the extraction effect of this optimal method was further tested under different nanoparticles and soil conditions. The optimal extraction method was determined, including (i) Dispersant: 0.2 % carboxymethyl cellulose (CMC) with a molecular weight of 250,000; (ii) Mixing conditions of soil and dispersant: water bath shaking for 30 min, water bath ultrasonication for 10 min (energy of the ultrasonication = 6 kJ/ml); (iii) Phase separation conditions: settlement for 60 min; (iv) Solid-to-liquid ratio: 1:20; (v) 1 extraction cycle. After optimization, 81.5 % of the supernatant was Cu(OH)2 NPs, and 2.6 % was dissolved copper ions (Cu2+). This method showed good applicability to different concentrations of Cu(OH)2 NPs and different farmland soils. It also showed significant differences in the extraction rates of copper oxide nanoparticles (CuO NPs), Cu2+, and other copper sources. The addition of a small amount of silica was confirmed to improve the extraction rate of Cu(OH)2 NPs. The establishment of this method lays the foundation for the quantitative analysis of nano-pesticides and other non-spherical and slightly soluble nanoparticles.


Amino acid sequence of a low molecular weight, high affinity calcium-binding protein from the optic lobe of the squid Loligo pealei.
The amino acid sequence was determined for squid calcium-binding protein (CaBP), a low molecular weight, high affinity calcium-binding protein from squid optic lobe. The sequence shows this protein to consist of 149 amino acids with an N-acetylated N terminus. The protein has a molecular weight of 16,894 and is homologous to calmodulin, which is also present in squid optic lobe (Head, J. F., Spielberg, S., and Kaminer, B. (1983) Biochem. J. 209, 797-802). When the sequences of squid CaBP and bovine brain calmodulin are appropriately aligned, the proteins are found to share 68% identity, with a single residue insertion in squid CaBP, between domains III and IV. The four-domain structure of calmodulin appears to be retained in squid CaBP, which is consistent with the previously reported presence of four calcium-binding sites per molecule (Sheldon, A., and Head, J. F. (1988) J. Biol. Chem. 263, 14384-14389). The two tyrosines of squid CaBP are located in different halves of the molecule, one at the position corresponding to Tyr-138 in calmodulin, the other in an equivalent position in domain II. In addition, squid CaBP exhibits several differences in the region corresponding to the long central helix of calmodulin. These differences include the replacement of Lys-77 by glycine, Asp-78 by proline, and Ser-81 by proline. The sequence of this portion of the squid CaBP molecule suggests the protein is unlikely to possess the continuous long central helix found in calmodulin.


A follow-up of the survivors of mechanical ventilation in a paediatric intensive care unit.
Fifty-eight long-term survivors of mechanical ventilation have been traced and examined for evidence of auditory, visual, behavioural, developmental and central nervous system abnormalities. There were four children with serious neurological or intellectual handicaps, the causes of which did not seem to be related to deficiencies of their ventilator treatment but rather to events preceding ventilation or to the disease which had necessitated ventilation. There were an additional eight children who may have some intellectual damage. The occurrence of convulsions or hypoxic episodes during or preceding the period of treatment was significantly more common among the 12 children with a poor outcome, than those with a good outcome.


The effect of hypoxia on the central light reflex of retinal arteries and veins.
Computerized scanning microdensitometry was used on fundus photographs of 40 men (aged 18-23 years) and effects of hypoxia on intensity profiles of the 'light reflex' in 140 arteries and 138 veins were analysed. Changes from sea level to four levels of acute hypoxia of simulated altitude were studied: 8000 feet (ft) (2438 meters) (m), 10,000 ft (3048 m), 12,500 ft (3810 m), and 15,000 ft (4572 m) using a low-pressure chamber. The intensity of the reflex increased at 12,500 ft and 15,000 ft by 24% (P less than 0.05) and 39% (P less than 0.01) in arteries and 50% and 33% in veins (P less than 0.05), respectively. As an overall response from sea level to all four altitudes, the width of the reflex was reduced. The reduction in width was negatively correlated to the diameter of the arteries (P less than 0.0001) and veins (P less than 0.001) at sea level, and the variability of changes was larger in veins (P less than 0.01). Funduscopic light reflected from intravascular blood columns of retinal vessels is thus influenced by hypoxic stress, and 12,500 ft of simulated altitude represents a threshold value of circulatory interest.


Men and Women Repeatedly Infected With Chlamydia trachomatis Have a Lower Urogenital Bacterial Load.
We assessed whether patients repeatedly infected with Chlamydia trachomatis (CT) have a lower urogenital or anorectal CT load. A CT-positive retest was independently associated with higher vaginal and higher urine Cq values (P<0.01). Partial immunity could play a role in repeat urogenital infections, potentially not in anorectal infections.


Single-dose darbepoetin administration to anemic preterm neonates.
Darbepoetin is longer acting and more potent than recombinant erythropoietin (rEpo). In certain situations, preterm neonates might benefit from rEpo, and for such patients darbepoetin would require fewer doses at a lower cost. However, the proper dose and dosing interval have not been established. We performed a prospective trial in two level III Neonatal Intensive Care Units. Patients <32 weeks gestation at birth, with a birth weight (BW) <1500 g, were eligible for participation if they were >21-days-old and had a hemoglobin (Hgb) concentration </or=10.5 g/dl. In all, 12 were to receive a single subcutaneous (s.c.) dose at either 1 or 4 microg/kg. Once before the dose was given, and at two preset intervals after, blood was obtained for immature reticulocyte fraction (IRF) and absolute reticulocyte count (ARC). Once before and at four preset intervals after, blood was obtained for pharmacokinetic studies. The 12 subjects had BWs of 1129+/-245 g (mean+/-SD), were 29.2+/-1.2 weeks gestation at delivery, and were 43+/-12 days old with an Hgb concentration of 9.6+/-1.0 g/dl when the darbepoetin was given. Six received 1 microg/kg and six 4 microg/kg. The IRF increased (p<0.05) as did the ARC (p<0.05). The increases in IRF were somewhat greater among the 4 microg/kg recipients (P=0.06). The highest recorded concentrations of drug occurred 6 to 12 hours after administration. The combined 6 and 12 hours values were 185+/-106 mU/ml in the 1 microg/kg group vs 597+/-238 in the 4 microg/kg group (p<0.002). The t(1/2) was 26 hours (range 10 to 50). The biovailability-normalized clearance was 19 ml/hour/kg (range 5 to 54). A single s.c. dose of darbepoetin given to preterm neonates accelerated effective erythropoiesis. The pharmacodynamic and pharmacokinetic findings suggest that darbepoetin dosing in neonates would require a higher unit dose/kg and a shorter dosing interval than are generally used for anemic adults.


Efficiency and profitability in US not-for-profit hospitals.
This article examines the relationship between hospital profitability and efficiency. A cross-section of 1317 U.S. metropolitan, acute care, not-for-profit hospitals for the year 2015 was employed. We use a frontier method, stochastic frontier analysis, to estimate hospital efficiency. Total margin and operating margin were used as profit variables in OLS regressions that were corrected for heteroskedacity. In addition to estimated efficiency, control variables for internal and external correlates of profitability were included in the regression models. We found that more efficient hospitals were also more profitable. The results show a positive relationship between profitability and size, concentration of output, occupancy rate and membership in a multi-hospital system. An inverse relationship was found between profits and academic medical centers, average length of stay, location in a Medicaid expansion state, Medicaid and Medicare share of admissions, and unemployment rate. The results of a Hausman test indicates that efficiency is exogenous in the profit equations. The findings suggest that not-for-profit hospitals will be responsive to incentives for increasing efficiency and use market power to increase surplus to pursue their objectives.


Victimization experiences and the stabilization of victim sensitivity.
People reliably differ in the extent to which they are sensitive to being victimized by others. Importantly, "victim sensitivity" predicts how people behave in social dilemma situations: Victim-sensitive individuals are less likely to trust others and more likely to behave uncooperatively-especially in socially uncertain situations. This pattern can be explained with the sensitivity to mean intentions (SeMI) model, according to which victim sensitivity entails a specific and asymmetric sensitivity to contextual cues that are associated with untrustworthiness. Recent research is largely in line with the model's prediction, but some issues have remained conceptually unresolved so far. For instance, it is unclear why and how victim sensitivity becomes a stable trait and which developmental and cognitive processes are involved in such stabilization. In the present article, we will discuss the psychological processes that contribute to a stabilization of victim sensitivity within persons, both across the life span ("ontogenetic stabilization") and across social situations ("actual-genetic stabilization"). Our theoretical framework starts from the assumption that experiences of being exploited threaten a basic need, the need to trust. This need is so fundamental that experiences that threaten it receive a considerable amount of attention and trigger strong affective reactions. Associative learning processes can then explain (a) how certain contextual cues (e.g., facial expressions) become conditioned stimuli that elicit equally strong responses, (b) why these contextual untrustworthiness cues receive much more attention than, for instance, trustworthiness cues, and (c) how these cues shape spontaneous social expectations (regarding other people's intentions). Finally, avoidance learning can explain why these cognitive processes gradually stabilize and become a trait: the trait which is referred to as victim sensitivity.


Targeting Inflammation in Acne: Current Treatments and Future Prospects.
Acne is a common, chronic inflammatory condition affecting millions of people worldwide, with significant negative impact on quality of life and mental health. Acne is characterized by comedones, inflammatory papules, pustules, and nodulocystic lesions, with long-lasting sequelae including scarring and dyspigmentation, the latter of which is more common in skin of color. The four main pillars of acne pathophysiology include alteration of sebum production and concentration, hyperkeratinization of the follicular unit, Cutibacterium acnes strains, and an inflammatory immune response. Newer research has provided greater insight into these pathophysiologic categories. This greater understanding of acne pathogenesis has led to numerous new and emerging treatment modalities. These modalities include combinations of existing treatments, repurposing of existing agents historically used for other conditions, new topical treatments, novel antibiotics, topical and oral probiotics, and various procedural devices. This article will provide an overview of emerging treatments of acne and their link to our current and improved understanding of acne pathogenesis.


No benefits of hypothermia in patients treated with hemicraniectomy for large ischemic stroke.
Background Space-occupying middle cerebral artery brain infarcts are associated with the development of brain edema, which may lead to cerebral herniation and death despite early hemicraniectomy. Aims To evaluate the benefit of therapeutic hypothermia in patients with space-occupying cerebral infarction treated with hemicraniectomy within 48 h of stroke onset. Methods Patients aged 18-60 years with space-occupying cerebral infarction treated with hemicraniectomy within 48 h and hypothermia (33-34°C) were selected from a single university hospital between 2001 and 2010 (n = 53). Patients treated with hemicraniectomy alone served as comparison group (n = 58), originating from three randomized controlled trials evaluating the effects of early decompressive surgery (DECIMAL, DESTINY, HAMLET). Primary outcome was the score on the modified Rankin scale at 12 months dichotomized between modified Rankin scale 0-3 and modified Rankin scale 4-6. Secondary outcome measures were modified Rankin scale score 0-4 and survival. Risk ratios were adjusted with Poisson regression. Results Mean patient age was 48 years. Median time from stroke onset to hemicraniectomy was 23.5 h in both treatment groups. Treatment with hypothermia had no effect on the primary outcome (modified Rankin scale 0-3 versus 4-6 (13/53 (25%) versus 24/58 (41%)); adjusted risk ratio 0.66, 95% confidence interval 0.38-1.13). Fewer patients treated with hypothermia had a modified Rankin scale score of 0-4 (21/53 (40%) versus 42/58 (72%); adjusted risk ratio 0.53, 95% confidence interval 0.37-0.76) and fewer patients survived (26/53 (49%) versus 46/58 (79%); adjusted risk ratio 0.60, 95% confidence interval 0.44-0.82). Conclusions In patients with space-occupying cerebral infarction, treatment with hypothermia had no additional benefit on functional outcome compared with treatment with hemicraniectomy alone.


Mechanisms of platelet activating factor-induced aggregation and secretion in human platelets.
The role of TXA2 in PAF-induced aggregation and secretion of human platelets is unclear. We have studied the relationship between aggregation, synthesis of TXA2 and release of 5-HT during the time course of aggregation induced by PAF and collagen. For PAF-induced aggregation there was strong aggregation and secretion with minimal production of TXA2 in contrast to collagen in which a surge in TXA2 synthesis preceded both aggregation and secretion. To determine the role of calcium flux in PAF-induced aggregation we have similarly studied the temporal relationships between aggregation, secretion and TXA2 synthesis for calcium ionophore A23187 induced aggregation but found these to be distinctly different from those determined for PAF. A method for measuring absolute amounts of 5HT released from platelets in small volumes of plasma is described. We conclude that TXA2 is not important in the mechanism of PAF induced aggregation and that an increase in the level of intraplatelet calcium per se is not sufficient to explain the mediation of PAF-induced aggregation.


[Urinary stress incontinence after radical prostatectomy in treatment reality : Results of a rehabilitation clinic-2009 compared to 2016].
Based on the work of Lent et al., the aim of this study was to compare and to evaluate the 2009 outcomes of maintaining continence after radical prostatectomy (rp) with those of patients from 2016. The data of all patients who underwent follow-up treatment 1 to 8 weeks after rp in 2016 (n = 1392) were evaluated by quantitative measuring all day incontinence under a defined graduation and compared to the results of 2009 (n = 1750). The basic data of the patients including age (p < 0.001), prostate-specific antigen (PSA) value (median 10.8/13.76 ng/ml in 2009/2016), cancer stage (p = 0.001) and Gleason score (p = 0.001) were significantly higher in 2016. Robot-assisted prostatectomy (RARP; 12% in 2009 to 45% in 2016) was performed much more often than radical retropubic prostatectomy. Laparoscopic and perineal prostatectomy were rarely performed. Significantly fewer patients achieved pad-free continence at discharge in 2016 (23%) vs. 33.9% in 2009; p ≤ 0.001. Within the same age group, there was a significant worsening of continence (p = 0.01). The results of maintaining continence did not significantly differ between patients with open retropubic prostatectomy and RARP (p = 0.078). The certification type of a clinic had no effect on continence preservation (p = 0.12). Incontinence rates after discharge from a rehabilitation clinic are high and have not improved over time or with new surgical techniques. The patient should be prepared for this in the patient information discussion prior to the surgery.


Effects of verapamil and diltiazem on dopamine release in the central nervous system of spontaneously hypertensive rats.
1. The purpose of the present study was to investigate the effects of Ca(2+)-antagonists (verapamil and diltiazem) on dopamine release in the central nervous system in hypertension. 2. Striatal slices obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were prelabelled with [3H]-dopamine, and superfused with Krebs-Ringer solution in vitro. The slices were stimulated electrically at a frequency of 1 Hz. 3. Stimulation-evoked release of [3H]-dopamine from striatal slices was significantly decreased in SHR compared with WKY rats. 4. Exposure of slices to verapamil and diltiazem significantly increased the stimulation-evoked [3H]-dopamine release. The facilitatory effects of the Ca(2+)-antagonists on dopamine release were significantly greater in SHR than in WKY rats. 5. Because central nervous system dopaminergic mechanisms appear to be depressor, the results suggest that the pronounced effects of verapamil and diltiazem on dopamine release in SHR might be involved in the central hypotensive mechanisms of the Ca(2+)-antagonists.