Changes in phenolic profile and anti-inflammatory activity of Baccharis beebread during gastrointestinal digestion/intestinal permeability in vitro.
Knowledge about the fate of beebread bioactive compounds throughout the human gastrointestinal tract are scarce. The present study aimed at assessing the effects of gastrointestinal digestion followed by intestinal permeability in vitro on phenolic profile and anti-inflammatory activity of Baccharis beebread. Palynological analysis confirmed the beebread is predominantly composed by pollen grains from Baccharis species, which are endemic in south and southeast Brazil. Flavonols and phenylamides were found in beebread hydroalcoholic extract by HPLC-ESI-QTOF-MS analysis. Moreover, simulated digestion lead to compounds' breakage, releasing both aglycones from glycosylated flavonols and p-coumaric acid, but not caffeic acid from phenylamides. Only spermidines crossed the Caco-2 cell monolayer, possibly due to spermine oxidation. Free p-coumaric acid was released after digestion, and epithelial transport. Concomitantly, NF-κΒ activation and TNF-α level was decreased by beebread even after Caco-2 transport, which indicates spermidines conjugated with p-coumaric acid may be bioavailable compounds with anti-inflammatory activity.


Variation in Patient-reported Outcomes Across Hospitals Following Surgery.
Although there is growing interest in applying patient-reported outcomes (PROs) toward surgical quality, the extent to which PROs vary across hospitals following surgical procedures is unknown. We examined variation in PROs, specifically health-related quality of life (HRQOL), across hospitals performing bariatric surgery. A retrospective cohort study. The Michigan Bariatric Surgery Collaborative is a statewide consortium of 39 hospitals performing laparoscopic gastric bypass, gastric banding, or sleeve gastrectomy (n=11,420 patients between 2008 and 2012). We examined generic and disease-specific HRQOL measured by the Health and Activities Limitations Index (HALex) and Bariatric Quality of Life index (BQL) preoperatively and at 1 year. We measured the variation in postoperative HRQOL across hospitals, and the effect of risk and reliability adjustment on hospital ranking. In this cohort, HRQOL varied by 56% (HALex) and 37% (BQL) across hospitals. Patient factors accounted for 58% (HALex) to 71% (BQL) of the variation in HRQOL across hospitals. After risk and reliability adjustment, HRQOL varied by 18% (by HALex) and 14.5% (by BQL) across hospitals, and the proportion of patients who experienced a large improvement in HRQOL by HALex ranged from 33% to 69% and 67% to 92% by BQL. After adjusting for patient factors and reliability, these differences diminished to 55%-64% (HALex) and 79%-84% (BQL). Patient factors explain a large proportion of hospital-level variation in PROs following bariatric surgery, underscoring the importance of risk adjustment. However, some variation in PROs across hospitals remains unexplained, suggesting PROs may represent a viable indicator of hospital performance.


Caveolin-1-derived peptide attenuates cigarette smoke-induced airway and alveolar epithelial injury.
Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease with no effective treatment that can reduce mortality or slow the disease progression. COPD is the third leading cause of global death and is characterized by airflow limitations due to chronic bronchitis and alveolar damage/emphysema. Chronic cigarette smoke (CS) exposure damages airway and alveolar epithelium and remains a major risk factor for the pathogenesis of COPD. We found that the expression of caveolin-1, a tumor suppressor protein; p53; and plasminogen activator inhibitor-1 (PAI-1), one of the downstream targets of p53, was markedly increased in airway epithelial cells (AECs) as well as in type II alveolar epithelial (AT2) cells from the lungs of patients with COPD or wild-type mice with CS-induced lung injury (CS-LI). Moreover, p53- and PAI-1-deficient mice resisted CS-LI. Furthermore, treatment of AECs, AT2 cells, or lung tissue slices from patients with COPD or mice with CS-LI with a seven amino acid caveolin-1 scaffolding domain peptide (CSP7) reduced mucus hypersecretion in AECs and improved AT2 cell viability. Notably, induction of PAI-1 expression via increased caveolin-1 and p53 contributed to mucous cell metaplasia and mucus hypersecretion in AECs, and reduced AT2 viability, due to increased senescence and apoptosis, which was abrogated by CSP7. In addition, treatment of wild-type mice having CS-LI with CSP7 by intraperitoneal injection or nebulization via airways attenuated mucus hypersecretion, alveolar injury, and significantly improved lung function. This study validates the potential therapeutic role of CSP7 for treating CS-LI and COPD. NEW & NOTEWORTHY Chronic cigarette smoke (CS) exposure remains a major risk factor for the pathogenesis of COPD, a debilitating disease with no effective treatment. Increased caveolin-1 mediated induction of p53 and downstream plasminogen activator inhibitor-1 (PAI-1) expression contributes to CS-induced airway mucus hypersecretion and alveolar wall damage. This is reversed by caveolin-1 scaffolding domain peptide (CSP7) in preclinical models, suggesting the therapeutic potential of CSP7 for treating CS-induced lung injury (CS-LI) and COPD.


Bilayer oxidized regenerated cellulose/poly ε-caprolactone knitted fabric-reinforced composite for use as an artificial dural substitute.
A novel bilayer knitted fabric-reinforced composite for potentially being used as a dural substitute was developed by solution infiltration of oxidized regenerated cellulose knitted fabric (ORC) with poly ε-caprolactone (PCL) solution at various concentrations ranging 10-40 g/100 mL. It was found that the density of all formulations did not differ significantly and was lower than that of the human dura. Microstructure of the samples typically comprised a bilayer structure having a nonporous PCL layer on one side and the ORC/PCL composite layer on another side. Tensile modulus and strength of the samples initially decreased with increasing PCL solution concentration for up to 20 g/100 mL and re-increased again with further increasing PCL solution concentration. Strain at break of all formulations were not significantly different. Watertight test revealed that all composites could prevent leakage at the pressure within the normal range of intracranial pressure. In vitro degradation study revealed that the weight loss percentage and change in tensile properties of all samples displayed biphasic profile comprising an initially rapid decrease and followed by a gradual decrease with incubation times afterward. Micro and macro porous channels were observed to be in situ generated in the composite layer by ORC dissolution and PCL resorption during degradation while nonporous layer remained relatively unchanged. The degradation rate was found to decrease with increasing PCL solution concentration. In vitro biocompatibility using alamar blue assay on selected samples showed that fibroblasts could attach and proliferate well at all incubation periods.


A content analysis of views of self-control: relation to positive and negative valence, and implications for a working definition.
It has been argued that one important variable that hampers research on self-control strategies is the absence of a working definition of self-control. Part of the difficulty involves the ambiguous and self-reflexive nature of the term itself, and part of the difficulty involves tautological imprecision equating the construct and definition of self-control with the effects of a self-control strategy. In order to begin to bring order to what has heretofore been a linguistic morass, an effort was made to assess individuals' views of self-control and then to perform a content analysis of the different aspects and dimensions actually embedded within these views. This study offered partial confirmation for six previously identified dimensions: choice, responsibility, awareness, discipline, skill, and goal. These dimensions provide us with a beginning phenomenological framework for assessing how individuals view self-control, and thereby help refine the position endorsed by Mahoney and Arnkoff (1979) that "self-control is a social label which is differentially applied to some behavior patterns." Further, individuals were requested to list positive and negative aspects of self-control, in order to assess whether, as Mahoney and Arnkoff suggest, self-control is necessarily applied to behavior perceived as (a) being socially appropriate or desirable and (b) originating from noble ideals. The study found that there were both positively and negatively valenced aspects thought to be associated with self-control, and that the mention of a certain dimension of self-control (discipline) was found to be significantly correlated with a specific negatively valenced view (rigidity). The study concludes with implications for developing a working definition of self-control, and with guidelines and suggestions for future research.


Sequential diets, metabolic costs, and growth of Spodoptera eridania (Lepidoptera: Noctuidae) feeding upon dill, lima bean, and cabbage.
This study illustrates the diversity of feeding responses of individually polyphagous southern armyworms, Spodoptera eridania, to plants with differing allelochemics. In spite of the near optimal leaf water and nitrogen contents of the young foliage, it is apparent that vastly different larval growth performance results from dill, lima bean, and cabbage. Cabbage is the poorest food (as measured by larval growth rates and metabolic costs of processing the plant biomass). Unlike the case with certain other plant species or cultivars that are costly to process, with cabbage, S. eridania does not compensate for low efficiencies (E.C.D.'s) with increased consumption rates (R.C.R.'s). Biochemical or physiological reasons for this inability are unknown.A sequence of foods (changed each 18-24 h) apparently did not add sufficient stress upon the MFO system to be detected in the respiratory expenditures of S. eridania larvae, in spite of the fact that dill is known to contain insecticidal and synergistic chemicals (Lichtenstein et al. 1974). The larval growth performances and metabolic expenditures in these sequences were intermediate between the best food (dill) and the worse (cabbage). Significant differences were observed however between the sequential switching sequences, perhaps indicating that particular periods during the instar are especially more sensitive to certain allelochemics. Actual respiratory costs of the lima bean-cabbage-dill (i.e. B-C-D) sequence were 40-50% higher than observed for the other two sequences and more than 50% higher than the theoretical metabolic costs based on the proportions actually eaten and known costs associated with each food.This study and a related one (Scriber 1981a) illustrate how consumption rates, feeding efficiences, and larval growth of Spodoptera eridania are not species, population, or even individual characteristics, (cf. Fox and Morrow 1981), but instead depend largely upon variations in plant allelochemics and plant nutritional quality (Wolfson 1978; Scriber, 1981 b; Scriber and Slansky 1981). More significantly they illustrate that the food consumed in earlier instars (Scriber 1981 a) as well as the food consumed earlier in an instar can be a major influence upon the observed armyworm growth performances under a given set of environmental conditions.


Characterization of cake layer structure on the microfiltration membrane permeability by iron pre-coagulation.
A cake layer is formed by coagulation aggregates under certain transmembrane pressure in the coagulation-microfiltration (MF) process. The characteristics of humic acid aggregates coagulated by different iron-based coagulants, such as charge, size, fractal dimension and compressibility, have an effect on the cake layer structure. At the optimum iron dose of 0.6 to 0.8 mmol/L for ferric chloride (FC) and polymer ferric sulfate (PFS) pre-coagulation, at the point of charge neutralization for near zero zeta potential, the aggregate particles produced possess the greatest size and highest fractal dimension, which contributes to the cake layer being most loose with high porosity and low compressibility. Thus the membrane filterability is better. At a low or high iron dose of FC and PFS, a high negative or positive zeta potential with high charge repulsion results in so many small aggregate particles and low fractal dimension that the cake layer is compact with low porosity and high compressibility. Therefore the membrane fouling is accelerated and MF permeability becomes worse. The variation of cake layer structure as measured by scanning electric microscopy corresponds with the fact that the smaller the coagulation flocs size and fractal dimension are, the lower the porosity and the tighter the cake layer conformation. This also explains the MF membrane flux variation visually and accurately.


Supportive Care for Patients with Lymphoma Undergoing CAR-T-cell Therapy: the Advanced Practice Provider's Perspective.
The purpose of our paper is to describe the all-encompassing supportive care for patients with relapsed or refractory lymphoma undergoing cellular therapy, with a focus on the advanced practice provider's (APPs) perspective. Chimeric antigen receptor-T (CAR-T) cell therapy has become more available for treating relapsed or refractory B-cell hematologic malignancies, requiring proficient and adequate treatment of side effects, complications, and infections that may occur during therapy. APPs often meet these patients during the initial referral and help to support them through the CAR-T cell therapy process. As APPs acquire a complete understanding and comprehensive knowledge of how to treat, support, and guide patients with B-cell malignancies through CAR-T cell therapy, they play a pivotal role in these patients throughout their treatment. Standardization of supportive care is paramount.


Effects of 13-cis retinoic acid and Ara-C on differentiation and proliferation of non-promyelocytic acute myelogenous leukemia.
An alternative to a cell-kill strategy for eradication of acute myelogenous leukemia, is to restore normal differentiation. Vitamin A derivatives demonstrate differentiation-inducing activity both in vitro and in vivo on promyelocytic leukemic cells. We tested the ability of 13-cis retinoic acid to reduce proliferation and induce differentiation in 10 samples from patients with acute non-promyelocytic leukemia. DNA synthesis and leukemia colony formation were affected to varying degrees by a prolonged exposure to the vitamin A compound. Morphologically and cytochemically no differentiation was determined either after 48 h in suspension cultures or 7 additional days in semi-solid cultures. Alkaline leukocyte phosphatase, a biochemical marker of differentiation, was significantly increased in five samples. DNA synthesis in these samples was significantly reduced as compared to samples failing to express alkaline leukocyte phosphatase following 13-cis retinoic acid treatment. DNA synthesis of these same 5 samples was also strongly inhibited by Ara-C. Expression of alkaline leukocyte phosphatase following 13-cis retinoic acid exposure may be a useful indicator for cells amenable to 13-cis retinoic acid or Ara-C treatment.


Microscope in modern spinal surgery: advantages, ergonomics and limitations.
The surgical microscope has revolutionized the practice of modern spine surgery. The major advantages of the microscope include better illumination, magnification and coaxial vision. It has also contributed to the welfare of the surgeon through improved ergonomics and opportunities to demonstrate surgical nuances to a training resident. However, there are limitations to its role in complex, long segment fixations and a potential for higher risk of surgical infections secondary to intraoperative contamination.


[Socioeconomic disparities for maternal serum screening of Down's syndrome: trends between 1998 and 2003 in France].
To compare trends in the use of and the opportunity for making an informed choice, regarding maternal serum screening for Down's syndrome. Data were based on the national perinatal surveys of 1998 and 2003, which comprise representative samples of births in France. We used logistic regression models and likelihood ratio tests for testing the statistical significance of interactions between time trends and socioeconomic factors. We found a generalized increase between 1998 and 2003 in both the use of screening and in the opportunity for making an informed choice. The use of screening increased more however, for women with primary or no education (OR=3.0; 95% CI, 2.2-4.1) as compared with those with education levels beyond a high school diploma (OR: 1.8; 95% CI, 1.7-2.0). On the contrary, trends in informed choice were comparable across socioeconomic groups. Hence, disparities in the opportunity for informed choice were essentially unchanged. The use of serum screening, and the opportunity for informed choice regarding the test, became more widespread for women from all socioeconomic categories between 1998 and 2003. These trends were accompanied by a decrease in socioeconomic disparities in the use of screening but not in the opportunity for making an informed choice.


Results of simulation of non-homogeneous ventilatory mechanics for a patient-computer arrangement.
A model of the ventilatory mechanic system was realised on the MEDA TC 41 analogue computer; it consists of 2 structurally identical compartments, differing in the values of their coefficients. By changing the values of coefficients and the relations between the 2 compartments, it was possible to simulate the non-homogeneity of a real, pathologically-changed system of the body afflicted by disease. Complex resistance loops with phase shifts. identical with those really registered from patients, were realised; this was impossible for models with only 1 compartment. By changing the non-homogeneity of the model., it was possible to simulate the past and future development of the state of the diseased patient with sufficient reliability.


Suprasellar chordoid neoplasm with expression of thyroid transcription factor 1: evidence that chordoid glioma of the third ventricle and pituicytoma may form part of a spectrum of lineage-related tumors of the basal forebrain.
Chordoid glioma of the third ventricle is a rare neuroepithelial tumor characterized by a unique histomorphology and exclusive association with the suprasellar/third ventricular compartment. Variously interpreted as either astrocytic- or ependymal-like, and speculatively ascribed to the lamina terminalis/subcommissural organ, its histogenesis remains, nevertheless, unsettled. Here, we report on a suprasellar chordoid glioma occurring in a 52-year-old man. Although displaying otherwise typical morphological features, the tumor was notable for expression of thyroid transcription factor 1, a marker of tumors of pituicytic origin in the context of the sellar region. We furthermore found overlapping immunoprofiles of this example of chordoid glioma and pituicytic tumors (pituicytoma and spindle cell oncocytoma), respectively. Specifically, phosphorylated ribosomal protein S6, a marker of mTOR pathway activation, was expressed in both groups. Based on these findings, we suggest that chordoid glioma and pituicytic tumors may form part of a spectrum of lineage-related neoplasms of the basal forebrain.


Diagnostic plasma miRNA-profiles for ovarian cancer in patients with pelvic mass.
Ovarian cancer is the fifth most common cancer in women worldwide. Moreover, there are no reliable minimal invasive tests to secure the diagnosis of malignant pelvic masses. Cell-free, circulating microRNAs have the potential as diagnostic biomarkers in cancer. Here, we performed and validated a miRNA panel with the potential to distinguish OC from benign pelvic masses. The profile of plasma microRNA was determined with a panel of 46 candidates in a discovery group and a validation group, each consisting of 190 pre-surgery plasma samples from age-matched patients with malignant (n = 95) and benign pelvic mass (n = 95), by real time RT-qPCR. Four up-regulated (miR-200c-3p, miR-221-3p, miR-21-5p, and miR-484) and two down-regulated (miR-195-5p and miR-451a) microRNAs were discovered. From those, miR-200c-3p and miR-221-3p were further confirmed in a validation cohort. A combination of these 2 microRNAs together with CA-125 yielded an overall diagnostic accuracy of AUC = 0.96. We showed consistent plasma microRNA profiles that provide independent diagnostic information of late stage OC.


Reduced surround inhibition in musicians.
To investigate whether surround inhibition (SI) in the motor system is altered in professional musicians, we performed a transcranial magnetic stimulation (TMS) study in 10 professional musicians and 15 age-matched healthy non-musicians. TMS was set to be triggered by self-initiated flexion of the index finger at different intervals ranging from 3 to 1,000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest and expressed as a percentage. Normalized MEP amplitudes of the abductor digiti minimi (ADM) muscles were compared between the musicians and non-musicians with the primary analysis being the intervals between 3 and 80 ms (during the movement). A mixed-design ANOVA revealed a significant difference in normalized ADM MEPs during the index finger flexion between groups, with less SI in the musicians. This study demonstrated that the functional operation of SI is less strong in musicians than non-musicians, perhaps due to practice of movement synergies involving both muscles. Reduced SI, however, could lead susceptible musicians to be prone to develop task-specific dystonia.


Neurocysticercosis presenting as a locked-in lateral ventricle: A case report and evidence-based review.
Human neurocysticercosis is one of the most prevalent parasitic infestations of the central nervous system. It is considered the most frequent underlying etiology of acquired epilepsy in endemic areas in Central and South America, East Europe, Africa, and Asia, with over 50 million people affected globally. Ventricular involvement is a severe form of neurocysticercosis commonly manifests as arachnoiditis, raised intracranial pressure, or hydrocephalus, secondary to CSF flow obstruction of the ventricular system by cysts of Taenia solium, hence requiring prompt, aggressive intervention to alleviate the increased intracranial pressure to prevent imminent lethal complications. Ventricular neurocysticercosis can involve any brain ventricle but with a paramount preference for the fourth ventricle, causing non-communicating hydrocephalus and symmetric ventriculomegaly. However, in this clinical report, we present an uncommon case of trapped (locked-in) lateral ventricle caused by an isolated cysticercus trapped at the ipsilateral foramen of Monro, which is an atypical location for neurocysticercosis, adding more challenges to diagnosis and during the process of surgical extraction. We additionally provide a comprehensive, evidence-based review of the clinical course and management options relevant to the entity of ventricular neurocysticercosis, besides recent relevant clinical updates.


Two sandwich arsenomolybdates based on the new building block As(iii)Mo(7)O(27)(9-): [Cr(2)(AsMo(7)O(27))(2)](12-) and [Cu(2)(AsMo(7)O(27))(2)](14-).
The polyanions [Cr(2)(AsMo(7)O(27))(2)](12-) () or [Cu(2)(AsMo(7)O(27))(2)](14-) () have sandwich-like structures wrapping two transition metals between two [As(iii)Mo(7)O(27)](9-) fragments, and the fragment is unprecedented and can be viewed as a mono-capped hexavacant B-alpha-Keggin subunit with a central AsO(3) group.


[Prevention of deep venous thrombosis by physical methods. Use of an external electrical stimulator. Initial results in surgery of the hip].
The aim of this study is to demonstrate the importance of the fight against venous stasis in the prevention of post-operative deep venous thrombosis. The study is based on two perfectly matched groups of 75 patients undergoing surgery for the complete replacement of the hip. As well as the usual preventive methods, one group was given external electric stimulus of the muscles of the lower limbs during the operation, in the immediate post-operative period and for the ten days following, achieving maximum venous drainage which was virtually permanent. The results make it apparent that external electric stimulus meant that 16% of deep venous thromboses were avoided in the group on which it was used.


Size and power required for motion with implication for the evolution of early hominids.
The fossil record of early hominids (early human ancestors) suggests that their stature and weight had a tendency to increase, but their robusticity (the proportion of radius to length) to decrease. Using a simple musculo-skeletal model, this paper explores possible relationships between size, power required for motion (PRM) and cycle-time, deriving relationships which indicate that PRM per unit of mass and velocity is proportional to robusticity, but inversely proportional to stature. The results derived appear to be in general agreement with published data from physiological experiments. If the material properties of early hominids were similar to those of modern humans and the achievement of minimum PRM was the selective criterion, human stature might tend to increase slightly in human evolution (and, if selective pressures are not removed, might do so in the future but at lower rate). If mobility and stability under loading are the selective criteria, however, human size should not substantially increase in the future.


Endoscopic sphincterotomy for common bile duct calculi in patients without stones in the gallbladder.
Endoscopic sphincterotomy (ES) was performed in 25 patients for common bile duct (CBD) calculi in the absence of stones in the gallbladder. Eighteen of these patients were considered unfit for surgery because of age or concomitant disease. All ES procedures were technically successful with complete evacuation of the CBD in all cases. Early complications occurred in only one patient, a 91-year-old female who died from nonbiliary tract disease. Long-term follow up over a period of 42 months was available in 19 of the 24 patients. Late complications occurred in two patients (10%), both of whom developed cholecystitis; they underwent surgery without subsequent morbidity or mortality. This 10% incidence of long-term complications is similar to that of other series that did not differentiate between patients with isolated CBD calculi and those with stones also present in the gallbladder. The observed complication rate does not justify routine prophylactic cholecystectomy after ES for isolated CBD stones.


The strategic benefits of revenue cycle improvement.
Leveraging revenue cycle financial and process improvements can result in a variety of benefits, including: A continuous learning culture that maintains performance improvements over the long term. Ability to attract and retain key personnel. Resources to invest in employee education and training. Expansion of strategic programs.


Sevoflurane for ENT-surgery in children. A comparison with halothane.
Sevoflurane, a new volatile anesthetic agent, is of great potential interest in pediatric anesthesia. Its use for ENT surgery in children was compared with halothane in this study. Altogether 40 children participated in the investigation. In 18 (median age 4.2 years), halothane was used. The remainder (median age 4.0 years) were anesthetized with sevoflurane. After rectal premedication with midazolam and atropine, anesthesia was induced by mask (the agent in O2/N2O, 40/60) using a Mapleson D system. The trachea was intubated without the use of muscle relaxants and the children were then allowed to breathe spontaneously at fresh gas flows set high enough to avoid rebreathing. Hemoglobine oxygen saturation (SpO2), inspired and expired gas concentrations, respiratory rate (RR), heart rate (HR), ECG and blood pressure were followed. Equianesthetic concentrations of the agents were used and induction characteristics were comparable between the two agents. RR and end-tidal CO2 tensions were similar in the two groups. HR and systolic blood pressures were, however, higher with sevoflurane. Cardiac arrhythmias were seen more frequently with halothane (61%) than with sevoflurane (5%). During emergence, postoperative nausea/vomiting was more frequent after halothane anesthesia. Initially, postoperative excitement occurred more often after sevoflurane, when paracetamol was given during anesthesia, which was reduced (P < 0.01) when paracetamol was given at the time for premedication. It is concluded that sevoflurane is an excellent induction agent, and maintains heart rate and systolic blood pressure better than when halothane is used. The incidence of cardiac arrhythmia is lower with sevoflurane than with halothane.(ABSTRACT TRUNCATED AT 250 WORDS)


(E)-3-(2-Nitro-phen-yl)-1-{1-phenyl-sulfonyl-2-[(phenyl-sulfon-yl)meth-yl]-1H-indol-3-yl}prop-2-en-1-one.
In the title compound, C(30)H(22)N(2)O(7)S(2), the configuration about the propene C=C bond is E. The indole unit is essentially planar, with a maximum deviation of 0.031 (3) Å. The dihedral angle between the planes of the phenyl rings of the two phenyl-sulfonyl groups is 80.95 (19)°. The central prop-2-ene-1-one group is oriented at a dihedral angle of 44.26 (11)° with respect to the nitro-phenyl ring and at 39.24 (8)° with respect to the indole unit. The S atoms are in a distorted tetra-hedral configuration. In the crystal, mol-ecules are linked into centrosymmetric dimers via pairs of C-H⋯O hydrogen bonds with an R(2) (2)(24) graph-set motif. The crystal structure is stabilized by further C-H⋯O inter-actions. Short intra-molecular C-H⋯O contacts result in several S(6) rings.


Glucose availability enhances lipopolysaccharide production and immunogenicity in the opportunistic pathogen Acinetobacter baumannii.
Acinetobacter baumannii can cause sepsis with high mortality rates. We investigated whether glucose sensing might play a role in A. baumannii pathogenesis. We carried out transcriptome analysis and extracellular polysaccharide determination in an A. baumannii clinical isolate grown on complex medium with or without glucose supplementation, and assessed its ability to induce production of inflammatory cytokines in human macrophages. Growth in glucose-supplemented medium strongly enhanced A. baumannii sugar anabolism, resulting in increasing lipopolysaccharide biosynthesis. In addition, glucose induced active shedding of lipopolysaccharide, in turn triggering a strong induction of inflammatory cytokines in human macrophages. Finally, hemolytic activity was strongly enhanced by growth in glucose-supplemented medium. We propose that sensing of exogenous glucose might trigger A. baumannii pathogenesis during sepsis.


Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic review.
Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females, suggesting that drug addiction is a sexually differentiated disorder. The neurobiological bases of sex differences in SUD include sex-specific reward system activation, influenced by interactions between gonadal hormone level changes, dopaminergic reward circuits, and epigenetic modifications of key reward system genes. This systematic review, adhering to PICOS and PRISMA-P 2015 guidelines, highlights the sex-dependent roles of estrogens, progesterone, and testosterone in SUD. In particular, estradiol elevates and progesterone reduces dopaminergic activity in SUD females, whilst testosterone and progesterone augment SUD behavior in males. Finally, SUD is associated with a sex-specific increase in the rate of opioid and monoaminergic gene methylation. The study reveals the need for detailed research on gonadal hormone levels, dopaminergic or reward system activity, and epigenetic landscapes in both sexes for efficient SUD therapy development.


Epidermal Langerhans' cells and dermal dendritic cells in human fetal and neonatal skin: an immunohistochemical study.
The dendritic cells in skin biopsies from 36 fetuses (from 16 weeks' gestational age on) and neonatal infants of different ages were investigated using a number of markers for various cells of the immune system and immunohistochemistry. Epidermal Langerhans' cells were found in all cases in a predominantly basal localization. The number of OKT6-positive Langerhans' cells and the development of their dendritic processes gradually increased with age. Dermal dendritic cells were present as well. Both HLA-DR-positive and Leu-10-positive dermal dendritic cells were found in the superficial and deep dermis, often in a perivascular distribution. The OKT6-positive dermal dendritic cells were few in number and occurred only in the upper dermis.


POSTOPERATIVE MOVEMENT OF THE FOVEA AFTER SUCCESSFUL SURGERY IN PATIENTS WITH IDIOPATHIC EPIRETINAL MEMBRANES.
To evaluate the change in the fovea's postoperative location after successful pars plana vitrectomy with combined epiretinal and internal limiting membrane peeling in patients with idiopathic epiretinal membranes (iERMs). In this prospective study 32 eyes of 32 patients with iERMs were followed from baseline before until 3 months after surgery. Study measures included 4-m Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, enhanced-depth imaging-optical coherence tomography, and intraoperative fundus photographs. Foveal movement was assessed by measuring the change in the papillofoveal distance (∆PFD). Mean ∆PFD in the study eye was -124 µm (±138) and -272 µm (±213) one day and 3 months after surgery, respectively. Mean ∆PFD after 3 months was greater in the study than in the fellow eye (P < 0.001). ∆PFD at Month 3 did not correlate with the internal limiting membrane area peeled (P = 0.78). Foveal movement starts immediately after surgery and causes a statistically significant reduction in PFD after uneventful macular pucker surgery. ∆PFD correlates statistically significantly with baseline best-corrected visual acuity and baseline central retinal thickness. The internal limiting membrane peeling size had no significant effect on the amount of postoperative foveal dislocation.


Retention of Escherichia coli in municipal sewage by means of planted soil filters in two-stage pilot plant systems.
Different types of constructed wetlands in a pilot-plant system were fed with identical municipal waste water to compare the sanitisation process in two-stage systems. With combinations of a vertical and a horizontal flow filter an E. coli reduction of 5 log10 with an E. coli influent concentration of 10(7) MPN/100 ml was achieved. Using different filter materials in each stage the total performance of the two-stage system was independent from the sequence of these materials. However, using coarser filter material in the first stage makes the filter less prone to clogging and is thus the preferential option with regard to operational reliability.


Multiplexed protease assays using element-tagged substrates.
Inductively coupled plasma-mass spectrometry (ICP-MS)-based assays lend themselves to multiplexing due to the high resolution between mass channels, the sensitivity, and the reliability of the technique. Here the potential of ICP-MS-based protease assays is demonstrated with a quadruplex assay of cysteine proteases and metalloproteases. Four orthogonal peptide substrates were synthesized for the proteases calpain-1, caspase-3, matrix metalloprotease-9 (MMP-9), and a disintegrin and metalloprotease-10 (ADAM10). Each substrate carries a biotin tag at the C terminus and a diethylenetriaminepentaacetic acid (DTPA)-based lanthanide complex at the N terminus. The results demonstrate that this is a simple and reproducible analysis technique with excellent correlation between the single and multiplex assay formats.


Intrinsic and environmental factors modulating autonomous robotic search under high uncertainty.
Autonomous robotic search problems deal with different levels of uncertainty. When uncertainty is low, deterministic strategies employing available knowledge result in most effective searches. However, there are domains where uncertainty is always high since information about robot location, environment boundaries or precise reference points is unattainable, e.g., in cave, deep ocean, planetary exploration, or upon sensor or communications impairment. Furthermore, latency regarding when search targets move, appear or disappear add to uncertainty sources. Here we study intrinsic and environmental factors that affect low-informed robotic search based on diffusive Brownian, naive ballistic, and superdiffusive strategies (Lévy walks), and in particular, the effectiveness of their random exploration. Representative strategies were evaluated considering both intrinsic (motion drift, energy or memory limitations) and extrinsic factors (obstacles and search boundaries). Our results point towards minimum-knowledge based modulation approaches that can adjust distinct spatial and temporal aspects of random exploration to lead to effective autonomous search under uncertainty.


Analysis of late complications after rapid hyperfractionated radiotherapy in advanced head and neck cancers.
Late effects were analyzed in a series of 39 patients with a 2-year minimal follow-up who were treated by rapid hyperfractionated radiotherapy. The total dose was 66-72 Gy delivered in two series of 33-36 Gy separated by a 2-4 week rest interval. The number of daily fractions ranged from 8 to 6 and the interval between each fraction was 2 hr. Late complications consisted of cervical fibrosis, mucosal necrosis, bone necrosis, trismus, and laryngeal edema. Seventy percent of patients experienced late complications, and in 54% of cases, these reactions were considered severe, causing death in 13% of patients. No relationship was found between field sizes, dosimetric data and type and frequency of late effects. It is therefore suggested that the interval between two daily sessions in any multifractionated protocol may be of critical importance.


The association of padded headgear with concussion and injury risk in junior Australian football: A prospective cohort study.
To assess whether padded headgear was associated with incidence of suspected sports-related concussion, non-sports-related concussion head injury, and injuries to other body regions in junior Australian football. Prospective cohort injury surveillance. There were 400 junior players (42.5% female) enrolled across two seasons. Suspected sports-related concussion was defined by detection of observable signs on the field and medical assessment or missed match(es) due to suspected sports-related concussion. Non-sports-related concussion head injury and injuries to other body regions were defined as those that received medical assessment or resulted in a missed match. There were 20 teams monitored over 258 matches. 204 players (2484 player hours) wore mandated headgear throughout the season and 196 (2246 player hours) did not. The incidence rate of suspected sports-related concussion was 3.17 (95% confidence interval: 3.04-3.30) per 1000 player-hours and no differences were observed between males and females (risk ratio 1.11; 95% confidence interval: 0.40-3.06). Headgear use was not associated with suspected sports-related concussion (risk ratio 1.09; 95% confidence interval: 0.41-2.97), non-sports-related concussion head injury (risk ratio 0.27; 95% confidence interval: 0.06-1.31), or injuries to other body regions (risk ratio 1.41; 95% confidence interval: 0.79-2.53). Headgear use was not associated with reduced risk of suspected sports-related concussion, non-sports-related concussion head injury or injuries to other body regions. There was no difference in the rate of suspected sports-related concussion in female compared to male players, however, rates of non-sports-related concussion head injury and injuries to other body regions were higher in male players.


Louse-borne relapsing fever: II. Combined penicillin and tetracycline therapy in 160 Sudanese patients.
One hundred and sixty patients with louse-borne relapsing fever were treated with a combination therapy of procaine penicillin and tetracycline. Fortified procaine penicillin B.P. was given as 400,000 units in the first day. This was followed the next day by 2 g tetracycline orally in divided doses for seven days. A mild rise in temperature was observed in 22 (13-7%) patients within four hours of administering penicillin. Rigors and hypotension occurred in one patient. Relapse occurred in two patients, of whom one had concomitant typhoid and one visceral leishmaniasis. The combined therapy has been found to be effective and safe. It lacks the disadvantages of penicillin (relapses) and tetracycline (severe reaction), when each drug is used alone.


Nomogram for predicting delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage in the Chinese population.
Delayed cerebral ischemia is a serious complication of aneurysmal subarachnoid hemorrhage with debilitating and fatal consequences. Lack of well-established risk factors impedes early identification of high-risk patients with delayed cerebral ischemia. A nomogram provides personalized, evidence-based, and accurate risk estimation. To offset the lack of a predictive tool, we developed a nomogram to predict delayed cerebral ischemia before performing surgical interventions for aneurysmal subarachnoid hemorrhage to aid surgical decision-making. We retrospectively collected data from 887 consecutive eligible Chinese patients who underwent surgical clipping or endovascular coiling for aneurysmal subarachnoid hemorrhage. Patients who previously underwent surgery formed the training cohort (n = 621) for nomogram development; those who underwent surgery later formed the validation cohort (n = 266) to confirm the performance of the model. A multivariate logistic regression analysis identified the independent risk factors associated with delayed cerebral ischemia, which were then incorporated into the nomogram. Delayed cerebral ischemia was identified in 158/621 patients (25.4%) in the training cohort and in 66/266 patients (24.8%) in the validation cohort. Preoperative factors associated with delayed cerebral ischemia were age > 65 years, modified Fisher grade of 3-4, ruptured aneurysm in the anterior circulation, Hunt-Hess grade of 4-5, high blood pressure on admission, and plasma homocysteine level ≥ 10 μmol/L. Incorporating these six factors in the nomogram achieved efficient concordance indices of 0.73 (95% confidence interval, 0.68-0.77) and 0.65 (95% confidence interval, 0.57-0.72) in predicting delayed cerebral ischemia in the training and validation cohorts, respectively. Our model can help determine an individual's risk of developing delayed cerebral ischemia in the Chinese population, and thereby, facilitate reasonable treatment-related decision-making.


Associations of the APOC3 rs5128 polymorphism with plasma APOC3 and lipid levels: a meta-analysis.
Studies of the association between the apolipoprotein C3 gene (APOC3) rs5128 polymorphism and plasma levels of apolipoprotein C3 (APOC3) and lipids have reported apparently conflicting findings. This meta-analysis aimed to investigate the associations of the rs5128 polymorphism with fasting APOC3 and lipid levels. The following information was abstracted for each study: ethnicity, age, sex, health condition, sample size, genotyping and lipid assay methods, mean and standard deviation or standard error by genotypes for APOC3 and lipid variables. There were 42 eligible studies with 23846 subjects included in this meta-analysis. A dominant model was used for this meta-analysis. The results showed that the carriers of the variant allele G had higher levels of APOC3 [standardized mean difference (SMD): 0.22, 95% confidence interval (CI): 0.12-0.31, P<0.00001], triglycerides (TG) (SMD: 0.33, 95% CI: 0.23-0.44, P<0.00001), total cholesterol (TC) (SMD: 0.15, 95% CI: 0.09-0.22, P<0.00001), and low-density lipoprotein cholesterol (LDL-C) (SMD: 0.11, 95% CI: 0.04-0.17, P=0.001) than the non-carriers. No significant association between the APOC3 rs5128 polymorphism and lower levels of high-density lipoprotein cholesterol (HDL-C) was detected under the dominant model (SMD: -0.03, 95% CI: -0.06-0.01, P=0.156). The results from the present meta-analysis demonstrate a significant association between the APOC3 rs5128 polymorphism and higher levels of APOC3, TG, TC and LDL-C, but further studies are needed to elucidate the underlying mechanisms.


Fighting to the death: Does hockey fighting in the NHL affect players' longevity?
Hockey is a sport known for its violent nature. Specifically, hockey fights have consistently been an integral part of the National Hockey League. Past research has demonstrated that players are likely to be involved in fighting as a mechanism to gain fan support, generate game momentum or enhance team camaraderie. However, fighting naturally has negative health ramifications. In the current study, we sought to investigate if players' involvement in hockey fights throughout their career was associated with shorter life spans. Previous mortality studies have not distinguished hockey fighting from other aggressive aspects of this sport (e.g., in game physical contact with other players). We conducted an archival study examining the frequency of hockey fighting during the 1957-1971 NHL seasons and player longevity. A Kaplan-Meier survival analysis log-rank method and a subsequent Cox regression accounting for correlates showed no relationship between an elevated number of fights and a reduced lifespan. The lack of effect may indeed demonstrate a negligible influence on long-term health consequences in the context of a generally very physical game. However, with the relatively moderate levels of fighting in the period studied we recommend that the association be explored also in a subsequent era when NHL fighting peaked.


Anatomic considerations and the relationship between the piriformis muscle and the sciatic nerve.
STATING BACKGROUND: The piriformis syndrome is one of the non-discogenics causes of sciatica. It results from the compression of the sciatic nerve (SN) by the piriformis muscle (PM) in the neutral and piriformis stretch test position. The evidence of the increase in pain in the test position requires a detailed anatomical study addressing the changes that occurred in the SN and PM anatomy during the test position. The aim of this study is to examine this relationship morphometrically. A total of 20 right and left lower limbs of ten adult cadavers were examined. The SN and the PM were made visible. The location of the SN was evaluated with respect to the consistent bony landmarks, including the greater and the lesser trochanter of the femur, the ischial tuberosity, the ischial spine of the hip bone, the posterior inferior iliac spine of the hip bone and the posterior superior iliac spine of the hip bone. The study was done in both neutral and test positions (i.e., 30 degrees adduction 60 degrees flexion and approximately 10 degrees medial rotation position of the hip joint). The width of the greater sciatic notch was 63.09 +/- 13.59 mm. The length of the lower edge of the PM was 95.49 +/- 6.21 mm, and whereas the diameter of the SN where it emerged from the infrapiriforme was 17.00 +/- 3.70 mm, the diameter decreased to 11.03 +/- 2.52 mm at the level of the lesser trochanter of the femur. The SN intersected the PM most commonly in its medial second quarter anatomically. The vertical distance between the medial edge of the SN-PM intersection point and the ischial tuberosity was 85.62 +/- 17.23 and 72.28 +/- 7.56 mm (P < 0.05); the angle between the SN and the transverse plane was 66.36 degrees +/- 6.68 degrees and 71.90 +/- 8.48 degrees (P < 0.05); and the vertical distance between the medial edge of the SN and the apex of the ischial spine of the hip bone was 17.33 +/- 4.89 and 15.84 +/- 4.63 mm (P > 0.05), before and after the test position, respectively. This study provides helpful information regarding the course and the location of the SN. The presented morphometric data also revealed that after stretch test position, the infrapiriforme foramen becomes narrower; the SN becomes closer to the ischial spine of the hip bone, and the angle between the SN and the transverse plane increases. This study confirmed that the SN is prone to be trapped in the test position, and diagnosis of this situation requires dynamic MR and MR neurography study.


Effect of workstation configuration on musculoskeletal discomfort, productivity, postural risks, and perceived fatigue in a sit-stand-walk intervention for computer-based work.
Compare musculoskeletal discomfort, productivity, postural risks, and perceived fatigue for a sit-stand-walk intervention between two workstation configurations - one, individually customized for office workers according to ergonomic guidelines (Ergo-Fit); another, self-adjusted by office workers according to their preference (Self-Adjusted). 36 participants performed a 60-min computer typing task in both configurations using a within-participants, counterbalanced design. Musculoskeletal discomfort and perceived fatigue were reported through surveys; productivity was operationalized by typing speed and typing error; postural risks were assessed by RULA for seated work, and REBA for standing work. Musculoskeletal discomfort and perceived fatigue did not vary significantly between configurations. Postural risks for seated and standing work were significantly lower for Ergo-Fit configuration; productivity was significantly higher for Self-Adjusted configuration. Use of Ergo-Fit configuration for a sit-stand-walk intervention can facilitate postural transitions and increase physical activity, while enabling neutral postures in seated and standing work to minimize postural risks.


Vaccinia viruses isolated from skin infection in horses produced cutaneous and systemic disease in experimentally infected rabbits.
The susceptibility of rabbits to two isolates of Vaccinia virus (VACV) recovered from cutaneous disease in horses in Southern Brazil was investigated. Rabbits were inoculated in the ear skin with both VACV isolates, either in single or mixed infection. All inoculated animals presented local skin lesions characterized by hyperaemia, papules, vesicles, pustules and ulcers. Infectious virus was detected in the lungs and intestine of rabbits that died during acute disease. Histological examination of the skin revealed changes characteristic of those associated with members of the genus Orthopoxvirus. These results demonstrate that rabbits develop skin disease accompanied by systemic signs upon intradermal inoculation of these two equine VACV isolates, either alone or in combination, opening the way for using rabbits to study selected aspects of the biology and pathogenesis of VACV infection.


Introduction of an online approach to flexible learning for on-campus and distance education students: lessons learned and ways forward.
While flexible delivery techniques, including online technologies, are becoming widely used to cater for the differing needs of students, they are not always met with enthusiasm, and can cause anxiety in students who are unfamiliar with the online environment. Online delivery of a first year nursing course (for distance learning and face-to-face provision) was introduced to facilitate reliable student-staff and student-student communication and streamline assessment procedures during a period in which class sizes increased (from 500 in 2003 to more than 650 in 2004 and 2005). Results of an evaluation exercise are presented, which aimed to: (1) trial online methods for course delivery and assignment submission; (2) canvass both student and staff responses to these innovations; (3) identify areas requiring change/improvement; and (4) formulate a strategy for improvement and continuing use of the technologies. Results suggested a positive response to the innovations by both staff and students. However, several implementation issues were identified, as were suggestions to overcome these initial hurdles. Iterative re-evaluation and continual development will examine the total benefit of these improvements. Taken together, this process has highlighted the importance of open communication, reducing anxiety and resistance to innovation, formal and informal evaluation processes and continued systems development.


Family Caregiver Depressive Symptom and Grief Outcomes From the ENABLE III Randomized Controlled Trial.
Little is known about whether early palliative care (EPC) support for family caregivers (CGs) impacts depressive symptoms and grief after care recipients die. To assess after-death CG depressive symptom and grief scores for early compared to delayed group CGs. We conducted a randomized controlled trial (10/2010-9/2013) of an EPC telehealth intervention for CGs (n = 123) initiated at the time of care recipients' advanced cancer diagnosis (early group) or 12 weeks later (delayed group) in a rural comprehensive cancer center, affiliated clinics, and a Veterans Administration medical center. The ENABLE [Educate, Nurture, Advise, Before Life Ends] CG intervention consisted of three weekly sessions, monthly follow-up, and a bereavement call. CGs completed the Center for Epidemiological Study-Depression (CES-D) scale and the Prigerson Inventory of Complicated Grief-Short Form (PG13) 8-12 weeks after care recipients' deaths. Crude and covariate-adjusted between-group differences were estimated and tested using general linear models. For care recipients who died (n = 70), 44 CGs (early: n = 19; delayed: n = 25) completed after-death questionnaires. Mean depressive symptom scores (CES-D) for the early group was 14.6 (SD = 10.7) and for the delayed group was 17.6 (SD = 11.8). Mean complicated grief scores (PG13) for the early group was 22.7 (SD = 4.9) and for the delayed group was 24.9 (SD = 6.9). Adjusted between-group differences were not statistically significant (CES-D: d = 0.07, P = 0.88; PG13: d = -0.21, P = 0.51). CGs' depressive symptom and complicated grief scores 8-12 weeks after care recipients' deaths were not statistically different based on the timing of EPC support. The impact of timing of CG EPC interventions on CGs bereavement outcomes requires further investigation.


Direct ethanolic extraction of polar lipids and fractional crystallization from whey protein phospholipid concentrate.
Polar lipids, including sphingomyelin (SM) and other sphingolipids, have nutritional implications in many important metabolic pathways. Milk and whey are valuable sources of these bioactive lipids, differing in SM content compared with other plant-based lecithins in the food industry. Dairy lipids were extracted from whey protein phospholipid concentrate powder by direct exposure to a food-grade solvent, ethanol. A total of 20 mass equivalents of solvent was required to completely recover all lipid material of the original whey protein phospholipid concentrate sample. Using a minimal apparatus, absolute ethanol, and heating to a boiling point, a final total lipid extract composed of 37.7% phospholipids (PL) by mass was achieved. The method was developed with potential pilot-scale and industry application in mind. Investigations into fractional crystallization showed limited success at purifying PL from triglyceride content (<1% increase in percent PL by mass). However, the relative percentage of SM was increased in the fractionated sample compared with the total lipid extract. Fatty acid analysis of the PL fraction reported a composition of 33.3% monounsaturated fatty acids and 9.8% polyunsaturated fatty acids. Additional work is needed to investigate different conditions for lipid recovery, PL recovery, and PL purification by fractional crystallization in ethanol.


Infrared (1.2-1.6 microm) luminescence in Cr4+:Yb3Al5O12 single crystal with 940 nm diode pumping.
Infrared (1.2-1.6 microm) luminescence in a ytterbium aluminium garnet (YbAG) crystal, doped with Cr (0.05at.%) ions, was investigated under CW laser diode pumping (lambda=940 nm). The Cr4+ emission band was observed with its peak at 1.34 microm and measured to be about 1.3 times with respect to Yb3+ IR luminescence (lambda=1.03 microm). We demonstrate that for the excitation wavelength of 940 nm Yb3+ ions act as sensitizers of the 3B2(3T2)-3B1(3A2) emission of Cr4+ ions. This crystal is promising as a high-efficient system for tunable laser (1.2-1.6 microm) output.


Kinetic properties and stereospecificity of the monomeric dUTPase from herpes simplex virus type 1.
Kinetic properties of the monomeric enzyme dUTPase from herpes simplex virus type 1 (HSV) were investigated and compared to those previously determined for homotrimeric dUTPases of bacterial and retroviral origins. The HSV and Escherichia coli dUTPases are equally potent as catalysts towards the native substrate dUTP with a kcat/K(M) of about 10(7) M(-1) s(-1) and a K(M) of 0.3 microM. However, the viral enzymes are less specific than the bacterial enzyme. The HSV and E. coli dUTPases show the same stereospecificity towards the racemic substrate analogue dUTPalphaS (2'-deoxyuridine 5'-(alpha-thio)triphosphate), suggesting that they have identical reaction mechanisms.


Cleavage specificity of Saccharomyces cerevisiae flap endonuclease 1 suggests a double-flap structure as the cellular substrate.
Flap endonuclease 1 (FEN1) is a structure-specific nuclease that cleaves substrates containing unannealed 5'-flaps during Okazaki fragment processing. Cleavage removes the flap at or near the point of annealing. The preferred substrate for archaeal FEN1 or the 5'-nuclease domains of bacterial DNA polymerases is a double-flap structure containing a 3'-tail on the upstream primer adjacent to the 5'-flap. We report that FEN1 in Saccharomyces cerevisiae (Rad27p) exhibits a similar specificity. Cleavage was most efficient when the upstream primer contained a 1-nucleotide 3'-tail as compared with the fully annealed upstream primer traditionally tested. The site of cleavage was exclusively at a position one nucleotide into the annealed region, allowing human DNA ligase I to seal all resulting nicks. In contrast, a portion of the products from traditional flap substrates is not ligated. The 3'-OH of the upstream primer is not critical for double-flap recognition, because Rad27p is tolerant of modifications. However, the positioning of the 3'-nucleotide defines the site of cleavage. We have tested substrates having complementary tails that equilibrate to many structures by branch migration. FEN1 only cleaved those containing a 1-nucleotide 3'-tail. Equilibrating substrates containing 12-ribonucleotides at the end of the 5'-flap simulates the situation in vivo. Rad27p cleaves this substrate in the expected 1-nucleotide 3'-tail configuration. Overall, these results suggest that the double-flap substrate is formed and cleaved during eukaryotic DNA replication in vivo.


Uncertainty quantification of microcirculatory characteristic parameters for recognition of cardiovascular diseases.
Cardiovascular disease is one of the leading causes of death worldwide. However, according to studies, 90% of cardiovascular diseases can be prevented. Cardiovascular function parameters are an important basis for the diagnosis of cardiovascular diseases. The pulse wave also contains a wealth of physiological and pathological information, which can reflect the trend of cardiac function parameters at an early stage, so the measurement and analysis of the pulse wave signal becomes more and more important. The wearable pulse signal acquisition device has gradually become a new trend. In the mobile health scenario, convenient use is the prerequisite for long-term and rapid health monitoring. The data containing diverse pulse wave signals is the basis for obtaining more comprehensive and accurate human physiopathological information. Accurate data analysis and processing is the key to realizing the important goal of cardiovascular health monitoring. Based on the concept of mobile health care, wearable devices are developed to obtain physiological signals. The zero-dimensional model and the optimization algorithm are combined to complete the uncertainty quantification of the microcirculation parameters. Then, a feature set containing the cardiovasvular parameters can be constructed. The machine learning algorithm can be used to build a model that can accurately realize cardiovascular disease identification. This paper adopts laboratory-developed equipment to acquire the wrist pulse wave and fingertip volume pulse wave. A total of 323 samples were collected from healthy populations, hypertensive patients and patients with coronary heart disease (CHD). The pulse blood flow model in fingertip microcirculation is established, and the uncertainty quantification of model parameters is completed based on slime mold algorithm (SMA). After comparing and analyzing the performance of four algorithms on pulse wave classification, the identification model of cardiovascular diseases is established based on the microcirculatory characteristic parameter set and random forest algorithm (RF). RF showed good classification performance among the four classification algorithms. The identification accuracy of the model built on the microcirculatory characteristic parameter set and RF algorithm all reached more than 88%. The highest recognition accuracy was 95.51% for coronary heart disease samples, 92.11% for healthy samples, and 88.55% for hypertensive samples. It can be seen that the model based on RF algorithm has a good ability to distinguish the characteristic parameters in different cardiovascular health states. The wearable device designed in this paper can facilitate the daily health monitoring of cardiovascular disease. By using the combination of the physical model and machine learning model, the uncertainty quantification of microcirculation parameters and the identification of cardiovascular disease was finally completed. The recognition model based on machine learning provides a new idea and method for the research of cardiovascular health monitoring through pulse waves.


Complete genome sequence of a novel avian orthoreovirus isolated from gosling, China.
Avian orthoreovirus (ARV) has been considered as a significant pathogen causing great infectious diseases to the avian, like broiler and waterfowl. The genome of this novel ARV(Reo/SDPY/Goose) was completely sequenced by next-generation sequencing. The complete genome was found to be 23517 bp in length with 10 segments. Although the Reo/SDPY/Goose was isolated from the gosling, it shares great similarity, no matter which segment within the genome, with those published as avian-origin reovirus. Genomic analysis revealed that this virus was distinct from published ARV strains and met criteria to become a novel ARV strain.


Severity of Diabetic Retinopathy and the Risk of Future Cerebrovascular Disease, Cardiovascular Disease, and All-Cause Mortality.
To determine the relationship between the severity of diabetic retinopathy and the future risk of cerebrovascular accident (CVA), myocardial infarction (MI), congestive heart failure (CHF), and all-cause mortality in patients with type 2 diabetes mellitus. Retrospective cohort study. Patients with type 2 diabetes who underwent diabetic retinopathy screening via fundus photography. The relationship between retinopathy status and the 5-year risk of first-time CVA, MI, CHF, and all-cause mortality was investigated using multivariate Cox proportional hazards regressions that controlled for age, gender, race or ethnicity, hemoglobin A1c, duration of diabetes, high-density lipoprotein level, low-density lipoprotein level, history of hypertension, systolic blood pressure, diastolic blood pressure, tobacco use, statin use, body mass index, urine microalbumin-to-creatinine ratio, and estimated glomerular filtration rate. Five-year risk of first-time CVA, MI, CHF, and all-cause mortality. Seventy-seven thousand three hundred seventy-six patients were included in this study. The average age was 59.8 years with 53.6% male, 31.2% non-Hispanic White, and 41.4% Hispanic patients. Diabetic retinopathy was significantly associated with all outcomes on multivariate analysis. Compared with patients with no retinopathy, those with minimal nonproliferative diabetic retinopathy (NPDR) had a higher risk of CVA (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.18-1.46), MI (HR, 1.30; 95% CI, 1.15-1.46), CHF (HR, 1.29; 95% CI, 1.19-1.40), and death (HR, 1.15; 95% CI, 1.05-1.25). Similarly, patients with moderate to severe NPDR had a higher risk of each outcome (CVA: HR, 1.56; 95% CI, 1.29-1.89; MI: HR, 1.92; 95% CI, 1.57-2.34; CHF: HR, 1.90; 95% CI, 1.66-2.18, and death: HR, 1.55; 95% CI, 1.32-1.82), as did patients with proliferative diabetic retinopathy (CVA: HR, 2.53; 95% CI, 1.84-3.48; MI: HR, 1.89; 95% CI, 1.26-2.83; CHF: HR, 1.96; 95% CI, 1.47-2.59; and death: HR, 1.87; 95% CI, 1.36-2.56). Diabetic retinopathy is significantly associated with future risk of CVA, MI, CHF, and death, with higher degrees of retinopathy appearing to carry a heightened risk for each outcome. Retinal information may provide valuable insights into patients' risk of future vascular disease and death.


Small ruminant lentivirus infections and diseases.
Small ruminant lentiviruses include viruses with diverse genotypes that frequently cross the species barrier between sheep and goats and that display a great genetic variability. These characteristics stress the need to consider the whole host range and to perform local surveillance of the viruses to opt for optimum diagnostic tests, in order to establish control programmes. In the absence of effective vaccines, a comprehensive knowledge of the epidemiology of these infections is of major importance to limit their spread. This article intends to cover these aspects and to summarise information related to characteristics of the viruses, pathogenesis of the infection and description of the various syndromes produced, as well as the diagnostic tools available, the mechanisms involved in transmission of the pathogens and, finally, the control strategies that have been designed until now, with remarks on the drawbacks and the advantages of each one. We conclude that there are many variables influencing the expected cost and benefits of control programs that must be evaluated, in order to put into practice measures that might lead to control of these infections.


In vitro translation of rat lung surfactant apoprotein mRNA.
Rat pulmonary surfactant contains apoproteins of molecular weights 38,000, 32,000, 26,000 and 10,000-12,000. The structural and metabolic interrelationships of these proteins are not clear as yet. In order to investigate if they arise from a single or multiple precursor protein (s), we isolated total poly(A)RNA from rat lungs, performed its translation in vitro in the presence of [35s]-methionine and reticulocyte lysate, immunoprecipitated the translation products with anti-rat surfactant antibody, and analyzed them by SDS-polyacrylamide gel electrophoresis and autoradiography. A single translation product of molecular weight 35,000 was detected. Since the antibody used in the immunoprecipitation recognizes the 38,000, 32,000 and 26,000 dalton proteins, it is concluded that at least these three proteins arise from the 35,000 dalton precursor by post-translational modifications.


High efficient adsorption of W(VI) with a novel lignin-based biosorbent functionalized with Zn2+ and polyamine.
Functionalized lignin-based biosorbent has become popular in wastewater treatment and extraction of valuable metals. Amination and metallization modification can effectively improve the adsorption performance of adsorbent. Zn2+/polyamine lignin for adsorption of W(VI) was synthesized by quaternization, amination and metallization from lignin with 3-chloro-2-hydroxypropyl trimethylammonium chloride, tetraethylenepentamine and ZnCl2. The adsorbent was characterized by SEM-EDS, FTIR and XRD. The adsorption performance of Zn2+/polyamine lignin for W(VI) was investigated in batch system. The adsorption mechanism was revealed by zeta potential, SEM-EDS and FTIR and XPS. It was shown that Zn2+/polyamine lignin exhibited great adsorption capacity at pH of 2, 25 °C, oscillation rate of 400 r/min, initial tungsten concentration of 700 mg·L-1 and adsorption time of 720 min. The maximum adsorption capacity of 0.5 g·L-1 Zn2+/polyamine lignin for W(VI) reached 488.28 mg·g-1. The adsorption followed Langmuir model and quasi-second-order kinetic model, indicating that the adsorption was monolayer homogeneous chemisorption. W(VI) was adsorbed through electrostatic attraction of hydrogen bond and Zn2+, ion exchange with Cl- and coordination with -NH2. The adsorption capacity reduced by only 6.47 % after seven cycles of adsorption-desorption, which indicated that Zn2+/polyamine lignin had a great application prospect.


Engineering conditionally replication-competent adenoviral vectors carrying the cytosine deaminase gene increases the infectivity and therapeutic effect for breast cancer gene therapy.
We constructed a conditionally replication-competent adenoviral vector Ad.Lp-CD-IRES-E1A(control) in which the expression of both the prodrug-activating cytosine deaminase gene and the viral replication E1A gene were driven by the L-plastin tumor-specific promoter. In order to overcome the low infectivity of the adenoviral vectors for breast cancer cells, and to increase the safety and efficacy for cancer gene therapy, this vector was further modified on a transductional level by simultaneously ablating the native tropism of the vector to the primary CAR receptor and inserting a RGD-4C peptide into the HI loop of the fiber, which allows the vector to use the alphavbeta3 and alphavbeta5 receptors as alternative receptors. The resulting vector was named Ad.Lp-CD-IRES-E1A(MRGD). The transduction efficiency of the vector for breast cancer cell lines which have low expression level of CAR was increased both in vitro and in vivo. The Ad.Lp-CD-IRES-E1A(MRGD) vector produces a higher vector particle yield and a greater cytotoxic effect in tumor cells which have a low expression level of CAR, than did the Ad.Lp-CD-IRES-E1A(control) vector. Intratumoral injection of the Ad.Lp-CD-IRES-E1A(MRGD) vector following the intraperitoneal injection of 5FC into xenotransplanted human breast cancer cell lines which have low expression level of CAR led to greater degree of tumor regression in vivo than did the intratumoral injection of control adenoviral vectors not so modified.


The influence of binding capacity and affinity on the improved performance of N-terminally extended hCG peptides, determined by ELISA-based procedures.
The improvement of peptide-ELISA responses by the use of small synthetic peptides elongated at the N-terminus with an Ata-group or a (Lys)7 extension has been analyzed. For this purpose, binding capacity and affinity were evaluated by specific ELISA procedures. The ELISA experiments on binding capacity, performed with saturating antibody concentrations, revealed a difference of more than three orders of magnitude in binding capacity between the parent peptides and the N-terminally linked peptides, in favor of the latter peptides. Antibody affinity values were determined by a liquid-phase equilibrium method as well as by a solid-phase equilibrium method. N-terminal extension of the peptides had almost no effect on the affinity when equilibrium between the peptide and the antibody was reached in solution. In contrast, solid-phase affinity was greatly enhanced when the N-terminally linked peptides were adsorbed to the polystyrene surface. This enhancement was determined by the N-terminal extension and the peptide amino acid sequence (40 to 600 times higher). Thus, the use of N-terminally extended peptides can greatly increase the performance of a peptide-ELISA through improved surface effects, resulting in higher binding capacity and functional affinity.


Biological function and research progress of N6-methyladenosine binding protein heterogeneous nuclear ribonucleoprotein A2B1 in human cancers.
N6-methyladenosine (m6A) is the most prevalent internal modification found in both mRNA and lncRNA. It exerts reversible regulation over RNA function and affects RNA processing and metabolism in various diseases, especially tumors. The m6A binding protein, hnRNPA2B1, is extensively studied as a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) protein family. It is frequently dysregulated and holds significant importance in multiple types of tumors. By recognizing m6A sites for variable splicing, maintaining RNA stability, and regulating translation and transport, hnRNPA2B1 plays a vital role in various aspects of tumor development, metabolism, and regulation of the immune microenvironment. In this review, we summarized the latest research on the functional roles and underlying molecular mechanisms of hnRNPA2B1. Moreover, we discussed its potential as a target for tumor therapy.


Variation in adoption of skin and nipple sparing mastectomy: An opportunity to enhance patient outcomes.
Nipple-sparing mastectomies (NSM) for breast cancer are under-utilized. We sought to investigate NSM utilization. Females with nonmetastatic breast cancer undergoing mastectomy in the Legacy Health System from 2007 to 2020 were identified. Multivariable logistic regression was utilized to evaluate odds of receiving NSM. Three-thousand-four-hundred-seventeen mastectomies were performed with 772 undergoing NSM. On multivariable analysis, later year (OR 1.22/year, P < 0.001), neoadjuvant chemotherapy (OR 1.33, P = 0.04), HR+ (OR 1.61, P = 0.001) and surgeon volume (OR 1.16/10 yearly mastectomies, P < 0.001) were independently associated with increased odds of receiving a NSM while age (OR 0.94/year, P < 0.001), IDC (OR 0.58, P = 0.01), T3/T4 stage (OR 0.36, P = 0.009), and clinical node positivity (OR 0.63, P = 0.003) were independently associated with decreased odds. Surgeon volume was not associated with odds of receiving a non-NSM with reconstruction (OR 1.01 P = 0.48). NSM is under-utilized by low-volume breast surgeons. Understanding barriers to adoption is an is an opportunity to enhance patient-centered outcomes.


Synthesis and structure-activity relationship studies of naphthoquinones as STAT3 inhibitors.
Based on previous studies, we synthesized a novel class of ortho- and para-naphthoquinones derivatives bearing a phenolic hydroxy or sulfonamide moiety and evaluated their in vitro antiproliferative and signal transducer and activator of transcription-3 (STAT3) phosphorylation inhibitory activities. The biological evaluations of these naphthoquinones revealed that ortho-naphthoquinones containing a phenolic hydroxyl group exhibited greater antiproliferative activity compared to compounds without a phenolic hydroxyl group. Among the synthesized para-naphthoquinones, 21, which has a condensed sulfonamide structure, showed substantially higher antiproliferative activity than that of the parent compound, and was also found to inhibit the phosphorylation of STAT3(Y705) in a dose-dependent manner. A docking simulation using AutoDock Vina suggested that 21 could directly bind to the hinge region of STAT3.


Effect of taurine on some pharmacological properties of ethanol.
Taurine was effective in reducing the hypnotic effect of ethanol but did not antagonize the effect of ethanol on seizure susceptibility, body temperature, or brain 5-HIAA concentration.


A possible role of the specialized conduction system in the conversion of ventricular tachycardia to ventricular fibrillation.
Electrode recordings from the right bundle branch, His bundle, and right atrium in a canine preparation enabled us to observe the activation of the ventricular myocardium and the specialized conduction system during the conversion of ventricular tachycardia to ventricular fibrillation. At times when ventricular tachycardia degenerated to ventricular fibrillation, asynchronous activation of the right bundle branch and the ventricular myocardium was frequently noted. Such asynchrony of activation was not seen during the spontaneous conversion of ventricular tachycardia to sinus rhythm. We suggest that this asynchronous activity produces increasing fractionation of ventricular activation fronts, which in turn yields fibrillation.


The impact of human pregnancy on perceptual responses to chemoreflex vs. exercise stimulation of ventilation: a retrospective analysis.
We examined the impact of human pregnancy on breathlessness intensity at matched levels of ventilation (V˙E) during isoxic hyperoxic CO₂ rebreathing and incremental cycle exercise tests in 21 healthy women in the third trimester (TM₃) and again ∼5 months post-partum (PP). Pregnancy had no significant (P > 0.05) effect on the slope or threshold of the breathlessness intensity-V˙E relationship during both exercise and rebreathing. By contrast, the slope of the breathlessness intensity-V˙E relationship was significantly higher, while the threshold of this relationship was consistently lower during rebreathing vs. exercise (both P < 0.05), regardless of pregnancy status (P > 0.05). As a result, breathlessness intensity was markedly higher at any given V˙E (e.g., by ∼4 Borg units at 40 L/min) during rebreathing vs. exercise, regardless of pregnancy status. Inter-subject variation in breathlessness intensity-V˙E slopes during exercise was not associated with inter-subject variation in breathlessness intensity-V˙E slopes during rebreathing or with increased central chemoreflex responsiveness during pregnancy (both P > 0.05). In conclusion, the intensity of perceived breathlessness for a given V˙E depends, at least in part, on the nature and source of increased central respiratory motor command output, independent of pregnancy status; and pregnancy-induced increases in activity-related breathlessness cannot be easily explained by increased central chemoreflex responsiveness.


Microbial bioreporters of trace explosives.
Since its introduction as an explosive in the late 19th century, 2,4,6-trinitrotoluene (TNT), along with other explosive compounds, has left numerous environmental marks. One of these is widespread soil and water pollution by trace explosives in military proving grounds, manufacturing facilities, or actual battlefields. Another dramatic impact is that exerted by the millions of landmines and other explosive devices buried in large parts of the world, causing extensive loss of life, injuries, and economical damage. In this review we highlight recent advances in the design and construction of microbial bioreporters, molecularly engineered to generate a quantifiable dose-dependent signal in the presence of trace amounts of explosives. Such sensor strains may be employed for monitoring environmental pollution as well as for the remote detection of buried landmines.


Deuterated phospholipids as nonperturbing components for Raman studies of biomembranes.
The deuterated phospholipid, 1,2-dipalmitoyl-d62-phosphatidylcholine is shown by Raman spectroscopic measurements to be useful for obtaining information concerning phospholipid conformation in complex phospholipid and lipidprotein mixtures. The Raman bands of the deuterated phospholipid are assigned, and the sensitivity of these vibrational modes to conformational changes in the bilayer is demonstrated. Deuteration of the alkyl chains reveals the CH vibrations of the head group. A change in these bands is observed at the melting temperature and is assigned to alteration of the glycerol backbone conformation upon melting.


Synthesis of β-cyclodextrin conjugated superparamagnetic iron oxide nanoparticles for selective binding and detection of cholesterol crystals.
Water-soluble, β-cyclodextrin conjugated superparamagnetic nanoparticles have been constructed. These particles showed selective binding to cholesterol crystals, which opens the door for the detection of cholesterol crystal-related diseases such as atherosclerosis by magnetic resonance imaging (MRI).


A bright single-cell resolution live imaging reporter of Notch signaling in the mouse.
Live imaging provides an essential methodology for understanding complex and dynamic cell behaviors and their underlying molecular mechanisms. Genetically-encoded reporter expressing mouse strains are an important tool for use in live imaging experiments. Such reporter strains can be engineered by placing cis-regulatory elements of interest to direct the expression of desired reporter genes. If these cis-regulatory elements are downstream targets, and thus activated as a consequence of signaling pathway activation, such reporters can provide read-outs of the signaling status of a cell. The Notch signaling pathway is an evolutionary conserved pathway operating in multiple developmental processes as well as being the basis for several congenital diseases. The transcription factor CBF1 is a central evolutionarily conserved component of the Notch signaling pathway. It binds the active form of the Notch receptor (NICD) and subsequently binds to cis-regulatory regions (CBF1 binding sites) in the promoters of Notch responsive genes. In this way, CBF1 binding sites represent a good target for the design of a Notch signaling reporter. To generate a single-cell resolution Notch signaling reporter, we used a CBF responsive element to direct the expression of a nuclear-localized fluorescent protein. To do this, we linked 4 copies of a consensus CBF1 binding site to the basal simian virus 40 (SV40) promoter, placed this cassette in front of a fluorescent protein fusion comprising human histone H2B linked to the yellow fluorescent protein (YFP) Venus, one of the brightest available YFPs. We used the CBF:H2B-Venus construct to generate both transgenic embryonic mouse stem (ES) cell lines and a strain of transgenic mice that would report Notch signaling activity. By using multiple CBF1 binding sites together with a subcellular-localized, genetically-encoded fluorescent protein, H2B-Venus, we have generated a transgenic strain of mice that faithfully recapitulates Notch signaling at single-cell resolution. This is the first mouse reporter strain in which individual cells transducing a Notch signal can be visualized. The improved resolution of this reporter makes it ideal for live imaging developmental processes regulated by the Notch signaling pathway as well as a short-term lineage tracer of Notch expressing cells due to the perdurance of the fluorescent reporter. Taken together, the CBF:H2B-Venus mouse strain is a unique tool to study and understand the morphogenetic events regulated by the Notch signaling pathway.


Cardiac biopsy of Kawasaki disease.
Two hundred one patients (138 boys, 63 girls), 1 month to 11 years old, with Kawasaki disease underwent coronary angiography, ultrasonic tomography, myocardial imaging, and biopsy of right ventricular myocardium. Aneurysms of epicardial coronary arteries, mostly left, occurred in 26 cases (12.9%). Degeneration and proliferation of endothelium, edema, scarring, and fibrosis, slight to moderate, involved the tunicae of intramural small vessels in all cases. These changes tended to abate with time. The basic lesion of Kawasaki disease, round-cell myocarditis and fibrosis, involved all cases and persisted. Disarrangement, abnormal branching, disarray, and hypertrophy of myocytes correlated significantly with myocarditis, but not with epimural or intramural coronary angitis. As a consequence of the myocardial changes, it is suggested that some cases may terminate as myocardiopathy. Scoring criteria for vascular and myocardial changes in biopsy specimens are included.


Perforated Meckel's diverticulum presenting as a gastrointestinal stromal tumor: a case report.
Tumors and perforation of Meckel's diverticulum are rare manifestations. A gastrointestinal stromal tumor in a Meckel's diverticulum causing perforation and subsequent peritonitis in a 75-year-old man is presented. The literature on tumors in Meckel's diverticulum is extensively reviewed and discussed.


Highly sensitive visual colorimetric sensor for xanthine oxidase detection by using MnO2-nanosheet-modified gold nanoparticles.
In this study, a highly sensitive colorimetric assay has been constructed for the determination of xanthine oxidase (XOD) activity by the GNP@MnO2 core-shell nanoparticles as probe. In the presence of XOD, xanthine can be oxidized to produce H2O2, which makes the MnO2 shell fallen off. With the single particle detection (SPD) based dark field microscopy (DFM), the scattering color of GNP@MnO2 NP probe shows obvious change before and after etching process. At the single particle level, noticeable color change of the single probe can be easily detected in the existence of trace XOD. This SPD-based colorimetric strategy displays broad linear dynamic range (0.02-4 mU/mL) and low detection limit of 7.82 μU/mL, which is more sensitive than the results from ensemble sample measurement. In addition, we tested the inhibitory effect of quercetin on the activity of XOD and obtained good inhibition effect. As a consequence, this SPD-based colorimetric strategy provides new perception for the ultrasensitive detection of molecules in complex system.


Soluble cytochrome P-450 from housefly microsomes. Partial purification and characterization of two hemoprotein forms.
Housefly microsomes contain two spectrally different forms of cytochrome P-450 which we have termed P-450 and P-450I. Methods have been developed for the fractionation and chromatographic purification of these two hemoprotein forms. Microsomes are solubilized first with Triton X-100 in the presence of glycerol, dithiothreitol, ethylenediaminetetra-acetic acid, and phenobarbital. Cytochrome P-450 is recovered in a floating pellet after the addition of 25% ammonium sulfate followed by centrifugation, whereas cytochrome P-450I remains in the 25% ammonium sulfate supernatant fluid. Cytochrome P-450 is purified further by Sephadez G-200 and DEAE-Sephadex A-50 column chromatography, which also allows the isolation of cytochrome b5 and NADPH-dependent cytochrome P-450 reductase in good yields and with little cross-contamination. Cytochrome P-450 apparently is free of cytochromes b5 and P-420 as well as of reductase and is obtained in a final yield of approximately 16% with a 6.9-fold purification. Its maximum absorbance is at 45 mn in the CO-difference spectrum and its average extinction coefficient is 103 cm-1 nm-1. Cytochrome P-450I is purified by Sephadex G-25 column chromatography but still contains some cytochromes b5 and P-420 as well as reductase. Its maximum absorbance is at 448.5 nm in the CO-difference spectrum and its extinction coefficient is 83 to 86 cm-1 mM-1. Both cytochromes hydroxylate type I substrates such as aminopyrine. Sufficient amounts of reductase are present in the cytochrome P-450I preparation to sustain activity, but the reductase has to be added to cytochrome P-450 in a reconstituted system for activity. Cytochrome P-450 is fairly stable, whereas cytochrome P-450I can be isolated only when protected by a substrate (phenobarbital). Detergent-solubilized housefly cytochromes P-450 and P-450I seem to correspond to either aggregates or oligomeric proteins. Cytochrome P-450 appears to correspond to a tetramer, each subunit having a molecular weight of 45,000, whereas cytochrome P-450I may correspond to an aggregate of at least 10 subunits. The cytochrome P-450 aggregate is dissociated by 6 M urea, but cytochrome P-450I remains as such.


Amperometric and spectrophotometric determination of carbaryl in natural waters and commercial formulations.
The work presented describes the development and evaluation of two flow-injection analysis (FIA) systems for the automated determination of carbaryl in spiked natural waters and commercial formulations. Samples are injected directly into the system where they are subjected to alkaline hydrolysis thus forming 1-naphthol. This product is readily oxidised at a glassy carbon electrode. The electrochemical behaviour of 1-naphthol allows the development of an FIA system with an amperometric detector in which 1-naphthol determination, and thus measurement of carbaryl concentration, can be performed. Linear response over the range 1.0 x 10(-7) to 1.0 x 10(-5) mol L(-1), with a sampling rate of 80 samples h(-1), was recorded. The detection limit was 1.0 x 10(-8) mol L(-1). Another FIA manifold was constructed but this used a colorimetric detector. The methodology was based on the coupling of 1-naphthol with phenylhydrazine hydrochloride to produce a red complex which has maximum absorbance at 495 nm. The response was linear from 1.0 x 10(-5) to 1.5 x 10(-3) mol L(-1) with a detection limit of 1.0 x 10(-6) mol L(-1). Sample-throughput was about 60 samples h(-1). Validation of the results provided by the two FIA methodologies was performed by comparing them with results from a standard HPLC-UV technique. The relative deviation was <5%. Recovery trials were also carried out and the values obtained ranged from 97.0 to 102.0% for both methods. The repeatability ( RSD, %) of 12 consecutive injections of one sample was 0.8% and 1.6% for the amperometric and colorimetric systems, respectively.


A Third Note: Helmholtz, Palestrina, and the Early History of Musicology.
This contribution focuses on Hermann von Helmholtz's work on Renaissance composer Giovanni Pierluigi da Palestrina. Helmholtz used his scientific concept of distortion to analyze this music and, reversely, to find corroboration for the concept in his musical analyses. In this, his work interlocked with nineteenth-century aesthetic and scholarly ideals. His eagerness to use the latest products of historical scholarship in early music reveals a specific view of music history. Historical documents of music provide the opportunity for the discovery of new experimental research topics and thereby also reveal insights into hearing under different conditions. The essay argues that this work occupies a peculiar position in the history of musicology; it falls under the header of "systematic musicology," which eventually emerged as a discipline of musicology at the end of the nineteenth century. That this discipline has a history at all is easily overlooked, as many of its contributors were scientists with an interest in music. A history of musicology therefore must consider at least the following two caveats: parts of it take place outside the institutionalized field of musicology, and any history of musicology must, in the last instance, be embedded in a history of music.


The comparative results of treatment in idiopathic thoracolumbar and lumbar scoliosis using the Harrington, Dwyer, and Zielke instrumentations.
Forty-five patients with idiopathic thoracolumbar or lumbar scoliosis were treated with the Harrington, Dwyer, or Zielke instrumentation and fusion. The Harrington group achieved a 55% correction of the primary curves, while the Dwyer and the Zielke groups achieved 88 and 91%, respectively. Overcorrection of the curves occurred in a total of nine cases in the latter two groups. The Dwyer and Zielke instrumentations enabled better correction of the curves with a shorter fusion. At subsequent follow-up, the 'adding on' phenomenon as a result of the shorter fusion in the Dwyer group was unchanged, while that in the Zielke group became gradually resolved. The Zielke instrumentation appears to be the apparatus of choice for treatment of thoracolumbar and lumbar scoliosis.


Comparison between 60 matched pairs of postmenopausal black and white women: analysis of risk factors related to bone mineral density.
Osteoporosis is a systemic disease in which bone density is reduced, leading to weakness of the skeleton and increased vulnerability to fractures. The purpose of this study was to compare known or suspected risk factors (medical, gynecological, and lifestyle characteristics) related to bone loss between 60 matched pairs of black and white postmenopausal women. The two racial groups were matched one for one on selective anthropometric variables [age (years), standing height (cm), and body weight (kg)] in order to equate age and body size between groups. Information on risk factors was obtained from an orally administered questionnaire and body composition variables (in addition to those used for matching) assessed by anthropometry and total body dual energy X-ray absorptiometry (DXA). Four skinfold sites (chest, triceps, mid-axillary, and abdomen) were measured with Harpendon calipers and four body circumferences (chest, forearm contracted, waist, and gluteal) were assessed with a Gulick tape. DXA radius, spine, femur, and whole body measurements were obtained on a Hologic QDR-2000 with software version 7.20. White women reported significantly higher proportions of alcohol use, family history of broken bones, and a greater utilization of hormones, calcium and vitamins than did black women. Black women reported a greater numbers who had other diseases (i.e., overactive thyroid, diabetes, rheumatoid arthritis, or kidney stones). Although age and body weight were similar in both groups, black women had greater lean tissue and less body fat than white women. Blacks had significantly higher bone mineral density across all body sites with the exception of the mid- and ultra-distal radius. On the basis of these data, it was concluded that part of the difference often observed in bone density between black and white postmenopausal women might be due to lifestyle factors.


Distribution of two metabolically related fluorophors in human lens measured by laser microprobe.
Automated Raman microprobe spectrometry revealed the distribution of a major fluorophor, 3-OH-L-kynurenine-O-beta-glucoside, in human lenses from 0.38 to 71 yr. A three-dimensional perspective grid map with fluorescence intensity as the third dimension shows maximum fluorescence in the infant lens nucleus. At 12 yr the fluorescence peak is broadened and a toroid-shaped maximum occurs also in the outer cortex, creating a toroid-shaped minimum between the two maxima. By 71 yr the nuclear maximum is lower but a new (green) fluorophor (excitation 488 nm: emission 530 nm) has appeared as a toroidal maximum in the same location as the blue minimum, suggesting the conversion of the blue fluorophor to the unidentified green fluorophor.


Neurofeedback with low-cost, wearable electroencephalography (EEG) reduces symptoms in chronic Post-Traumatic Stress Disorder.
The study examines the effectiveness of both neurofeedback and motor-imagery brain-computer interface (BCI) training, which promotes self-regulation of brain activity, using low-cost electroencephalography (EEG)-based wearable neurotechnology outside a clinical setting, as a potential treatment for post-traumatic stress disorder (PTSD) in Rwanda. Participants received training/treatment sessions along with a pre- and post- intervention clinical assessment, (N = 29; control n = 9, neurofeedback (NF, 7 sessions) n = 10, and motor-imagery (MI, 6 sessions) n = 10). Feedback was presented visually via a videogame. Participants were asked to regulate (NF) or intentionally modulate (MI) brain activity to affect/control the game. The NF group demonstrated an increase in resting-state alpha 8-12 Hz bandpower following individual training sessions, termed alpha 'rebound' (Pz channel, p = 0.025, all channels, p = 0.024), consistent with previous research findings. This alpha 'rebound', unobserved in the MI group, produced a clinically relevant reduction in symptom severity in NF group, as revealed in three of seven clinical outcome measures: PCL-5 (p = 0.005), PTSD screen (p = 0.005), and HTQ (p = 0.005). Data collection took place in environments that posed difficulties in controlling environmental factors. Nevertheless, this limitation improves ecological validity, as neurotechnology treatments must be deployable outside controlled environments, to be a feasible technological treatment. The study produced the first evidence to support a low-cost, neurotechnological solution for neurofeedback as an effective treatment of PTSD for victims of acute trauma in conflict zones in a developing country.


Safety and efficacy of continuous intravenous morphine for severe cancer pain.
To study the efficacy and safety of continuously administered intravenous morphine for cancer pain unrelieved by standard narcotic therapy, bolus intravenous injections of 2 to 5 mg of morphine were given every 10 minutes until pain relief was achieved. Within the next hour, continuous intravenous morphine infusion was begun with the hourly dose equal to the cumulative bolus dose. Respiratory rate, pulse, blood pressure, arterial blood gas values, mental status, and pain relief were recorded at baseline and during the study period. A reduction in arterial oxygen pressure (PaO2) and/or increase in arterial carbon dioxide pressure PaCO2 of more than 20 percent of baseline values occurred, during the first 24 hours of infusion, in a minority of patients. This did not require changes in hourly morphine dose. Despite subsequent increases in morphine dose, blood gas values tended to remain at or return toward baseline values. Severe toxicity occurred during one trial and was heralded by bradypnea and marked somnolence. Major pain relief was achieved in 11 of 15 trials. Therefore, continuous intravenous morphine is effective and safe therapy. Bradypnea associated with marked somnolence is a cause for dose reduction.