Comparative grazing behavior of lactating Holstein-Friesian, Jersey, and Jersey x Holstein-Friesian dairy cows and its association with intake capacity and production efficiency.
The objectives of this study were to investigate differences in grazing behavior among Holstein-Friesian (HF), Jersey (JE), and Jersey x Holstein-Friesian (F(1)) cows under an intensive, seasonal, grass-based environment and to determine whether associations exist among grazing behavior, intake capacity, and production efficiency. Data from a total of 108 animals (37 HF, 34 JE, and 37F(1)) were available for analysis. Measurements included milk production, body weight (BW), intake, and grazing behavior. Breed group had a significant effect on all of the production, grass dry matter intake, and efficiency parameters investigated. No differences were observed among the breeds for grazing time, number of grazing bouts, grazing bout duration, and total number of bites. Grazing mastications were higher for the JE cows compared with the HF cows. Grass dry matter intake per bite and rate of intake per minute were higher for the HF cows compared with the JE cows. Large differences between the breeds were apparent when grazing behavior measurements were expressed per unit of BW and per unit of intake. In absolute terms, the HF cows spent more time ruminating and had more mastications during rumination than the JE cows. However, when expressed per unit of BW, ruminating time was greater for the JE cows and they tended to have more ruminating mastications compared with the HF cows. Despite these differences, ruminating time and ruminating mastications per unit of intake were similar for the 2 breeds. For the most part, the F(1) cows tended to be similar to the mid-parent mean, but results showed an increase in biting rate, lower grazing duration per bout, and a tendency to achieve a high intake per bite compared with the average of the parent breeds. The results obtained also indicate that inherent grazing and ruminating differences exist between cows varying in intake capacity and production efficiency. Cows with higher intake capacities have increased grazing time and rate of intake per unit of BW. Increased production efficiency, on the other hand, appears to be aided, in particular by improvements in mastication behavior during grazing.


Effect of Impression Technique and Operator Experience on Impression Time and Operator-Reported Outcomes.
To investigate the effect of impression technique (conventional preliminary alginate and digital scan) and operator experience in impression making (experienced in digital and conventional, experienced in conventional and inexperienced in digital, and inexperienced in conventional and digital) on impression time, satisfaction and stress levels, and the preference of the operators. One patient was assigned for each of the 60 operators, who were experienced in impression techniques at different levels (Group 1: experienced in conventional and digital, Group 2: experienced in conventional and inexperienced in digital, Group 3: inexperienced in conventional and digital). They made conventional impressions (irreversible hydrocolloid) and digital scans (Trios 3) from the same patient. The impression times were recorded at each step (patient registration, maxillary arch, mandibular arch, and bite registration) and in total. A visual analog scale (VAS) was used for the operator satisfaction for applicability, comfort, and hygiene; the State-Trait Anxiety Inventory form (STAI-TX1) was used for stress, and a questionnaire was completed to measure the operator's impression preference. The data were analyzed with a 2-way ANOVA and Chi-square test (α = 0.05). A significant interaction was found between the operator experience in impression making and the impression technique on time for maxillary and mandibular arch impressions and total time (p ≤ 0.002). Operator experience and impression technique interaction had a significant effect on comfort and average VAS scores (p ≤ 0.016). Whereas, no significant effect of this interaction was found on stress (p ≥ 0.195). Operator experience in impression making had a significant effect on applicability (p < 0.001), and the impression technique had a significant effect on hygiene VAS scores (p < 0.001). Operators in Group 1 and Group 3 preferred the digital scans, however, operators in Group 2 had no preference (p = 0.022). Operator experience in impression making and impression technique had varying effects on clinician's impression time, comfort, applicability, hygiene, and preference. Operators needed less time for the impressions they were experienced with. Operator stress level was not affected by the operator experience in impression making and the impression technique. Dental students and operators experienced in both techniques were satisfied with the digital scans and they preferred digital scans. Operators experienced with conventional impressions were satisfied with conventional impressions but didn't have a preference for the impression type.


Isolated cortical venous thrombosis--discrepancy between clinical features and neuroradiologic findings. A case report.
Isolated cortical venous thrombosis (CVT) is rare, and the discrepancy between clinical features and neuroradiologic findings has not been adequately emphasized. A thirty-one-year-old woman presented with focal seizures and occasionally secondary generalization. There was no focal neurologic deficit except for Todd's paralysis. Electroencephalography showed intermittent theta waves at the left frontoparietal area. Brain computed tomography (CT) and magnetic resonance imaging (MRI) disclosed a large lesion in the left frontoparietal area. An extensive occlusion of the superior cerebral veins of the left hemisphere with a patency of the dural sinuses was noted in the cerebral angiography. Eight months later, the CT hypodense lesion disappeared. Her neurologic status was stationary, but the seizures, mostly focal, still occurred occasionally. In this report, the authors emphasize the dissociation between minor clinical features and larger CT and MRI lesions in isolated CVT.


Highly efficient removal of organic pollutants via a green catalytic oxidation system based on sodium metaborate and peroxymonosulfate.
The development of highly efficient and green catalytic oxidation process based on peroxymonosulfate (PMS) activation has been identified to be a significant yet challenging objective in the environmental catalysis field. A simple, environmentally benign and highly effective catalytic oxidation system was innovatively constructed by coupling NaBO2 and PMS for the removal of Acid Red 1. The catalytic mechanism in the NaBO2/PMS system was elucidated by electron paramagnetic resonance (EPR) combined with several radical capture reagents (ascorbic acid, methanol, tert-butyl alcohol, ethanol and l-histidine). The experimental results indicated that singlet oxygen (1O2) severed as the predominant reactive oxygen species (ROS) rather than the HO or during the catalytic oxidation process, at variance with the reported radical pathway in the Co2+/PMS system. Inspiringly, p-benzoquinone (p-BQ) as a trapping agent in most advanced oxidation process could be turned into the positive one in the NaBO2/PMS system, achieving a nearly 3-times enhancement in terms of the rate constant for AR1 removal. More interestingly, sodium chloride (NaCl) presented the same enhancement effect as p-benzoquinone due to generation of hypochlorous acid (HOCl) and more 1O2, which was completely different from the reported. This study develops a highly efficient green oxidation process and opens up a new insight in the remediation of contaminated water.


Chronic heart failure and micronutrients.
Heart failure (HF) is associated with weight loss, and cachexia is a well-recognized complication. Patients have an increased risk of osteoporosis and lose muscle bulk early in the course of the disease. Basal metabolic rate is increased in HF, but general malnutrition may play a part in the development of cachexia, particularly in an elderly population. There is evidence for a possible role for micronutrient deficiency in HF. Selective deficiency of selenium, calcium and thiamine can directly lead to the HF syndrome. Other nutrients, particularly vitamins C and E and beta-carotene, are antioxidants and may have a protective effect on the vasculature. Vitamins B6, B12 and folate all tend to reduce levels of homocysteine, which is associated with increased oxidative stress. Carnitine, co-enzyme Q10 and creatine supplementation have resulted in improved exercise capacity in patients with HF in some studies. In this article, we review the relation between micronutrients and HF. Chronic HF is characterized by high mortality and morbidity, and research effort has centered on pharmacological management, with the successful introduction of angiotensin-converting enzyme inhibitors and beta-adrenergic antagonists into routine practice. There is sufficient evidence to support a large-scale trial of dietary micronutrient supplementation in HF.


Nanocrystalline brookite with enhanced stability and photocatalytic activity: influence of lanthanum(III) doping.
Metastable TiO(2) polymorphs are more promising materials than rutile for specific applications such as photocatalysis or catalysis support. This was clearly demonstrated for the anatase phase but still under consideration for brookite, which is difficult to obtain as pure phase. Moreover, the surface doping of anatase with lanthanum ions is known to both increase the thermal stability of the metastable phase and improve its photocatalytic activity. In this study, TiO(2) nanoparticles of almost only the brookite structure were prepared by a simple sol-gel procedure in aqueous solution. The nanoparticles were then doped with lanthanum(III) ions. The thermal stability of the nanoparticles was analyzed by X-ray diffraction and kinetic models were successfully applied to quantify phases evolutions. The presence of surface-sorbed lanthanum(III) ions increased the phase stability of at least 200 °C and this temperature shift was attributed to the selective phase stabilization of metastable TiO(2) polymorphs. Moreover, the combination of the surface doping ions and the thermal treatment induces the vanishing of the secondary anatase phase, and the photocatalytic tests on the doped brookite nanoparticles demonstrated that the doping increased photocatalytic activity and that the extent depended on the duration of the sintering treatment.


Recombinant interleukin-2 and lymphokine-activated killer cell treatment of advanced bladder cancer: clinical results and immunological effects.
The purpose of this study was to evaluate the efficacy of treatment with recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells in patients with advanced bladder cancer and to study the induced changes in the distribution of leukocyte subsets in blood and tumor. Nine patients with metastatic transitional cell cancer of the bladder were treated with a continuous infusion of rIL-2 combined with lymphocytes stimulated in vitro with rIL-2. None of the patients responded to the therapy despite substantial changes observed in the immunological cells, both in tumor and blood. The rIL-2 infusion induced migration of leukocytes to the tumors, which was related to increased expression of the adhesion molecule VLA-1 on both peripheral blood mononuclear cells and the endothelial cells of small tumor vessels. Only T-cells, predominately expressing IL-2 receptors, and macrophages infiltrated the tumors. Natural killer cells remained few or absent in the tumors, even though the natural killer cells in peripheral blood were activated by the treatment. This study shows that the present technique of rIL-2 and lymphokine-activated killer cell therapy is able to induce substantial changes in the immune system of patients with metastatic bladder cancer. However, this treatment did not induce tumor regression, which may be due to the advanced stage of disease.


LiGa5O8:Cr-based theranostic nanoparticles for imaging-guided X-ray induced photodynamic therapy of deep-seated tumors.
Using X-ray as the irradiation source, a photodynamic therapy process can be initiated from under deep tissues. This technology, referred to as X-ray induced PDT, or X-PDT, holds great potential to treat tumors at internal organs. To this end, one question is how to navigate the treatment to tumors with accuracy with external irradiation. Herein we address the issue with a novel, LiGa5O8: Cr (LGO:Cr)-based nanoscintillator, which emits persistent, near-infrared X-ray luminescence. This permits deep-tissue optical imaging that can be employed to guide irradiation. Specifically, we encapsulated LGO:Cr nanoparticles and a photosensitizer, 2,3-naphthalocyanine, into mesoporous silica nanoparticles. The nanoparticles were conjugated with cetuximab and systemically injected into H1299 orthotopic non-small cell lung cancer tumor models. The nanoconjugates can efficiently home to tumors in the lung, confirmed by monitoring X-ray luminescence from LGO:Cr. Guided by the imaging, external irradiation was applied, leading to efficient tumor suppression while minimally affecting normal tissues. To the best of our knowledge, the present study is the first to demonstrate, with systematically injected nanoparticles, that X-PDT can suppress growth of deep-seated tumors. The imaging guidance is also new to X-PDT, and is significant to the further transformation of the technology.


A Point-of-Care Immunosensor Based on a Quartz Crystal Microbalance with Graphene Biointerface for Antibody Assay.
We present a sensitive and low-cost immunoassay, based on a customized open-source quartz crystal microbalance coupled with graphene biointerface sensors (G-QCM), to quantify antibodies in undiluted patient serum. We demonstrate its efficacy for a specific antibody against the phospholipase A2 receptor (anti-PLA2R), which is a biomarker in primary membranous nephropathy. A novel graphene-protein biointerface was constructed by adsorbing a low concentration of denatured bovine serum albumin (dBSA) on the reduced graphene oxide (rGO) sensor surface. The dBSA film prevents the denaturation of the protein receptor on the rGO surface and serves as the cross-linker for immobilization of the receptor for anti-PLA2R antibodies on the surface. The detection limit and selectivity of this G-QCM biosensor was compared with a commercial QCM system. The G-QCM immunoassay exhibited good specificity and high sensitivity toward the target, with an order of magnitude better detection limit (of 100 ng/mL) compared to the commercial system, at a fraction of the cost and with considerable time saving. The results obtained from patient sera compared favorably with those from enzyme-linked immunosorbent assay, validating the feasibility of use in clinical applications. The multifunctional dBSA-rGO platform provides a promising biofunctionalization method for universal immunoassay and biosensors. With the advantages of inexpensive, rapid, and sensitive detection, the G-QCM sensor and instrument form an effective autoimmune disease screening tool.


The topographical and age distributions of neuroendocrine cells in the normal human appendix.
In order to clarify the histogenesis of appendiceal carcinoid tumours, epithelial (ENC) and subepithelial (SNC) neuroendocrine cells were counted at four sites in 50 normal appendices stained by standard argyrophil and argentaffin techniques. In general, ENC were present in similar number at all sites within the appendix, whereas SNC were more numerous at the tip than at the base. The number of ENC was similar throughout life, apart from an increase in one neonate and some elderly patients, whereas SNC were maximal in young adults. Thus, the topographical and age distributions of SNC, but not those of ENC, parallels the topographical and age incidence of appendiceal carcinoid tumours, suggesting that most appendiceal carcinoid tumours arise from SNC rather than ENC.


Intravesical transurethral electrotherapy for the neurogenic bladder.
Intravesical transurethral bladder stimulation is a rehabilitative and diagnostic technique for the neurogenic bladder. The goal of therapy is 3-fold: 1) to achieve the sensation of bladder filling or the urge to void, 2) to initiate a detrusor contraction and 3) to achieve conscious urinary control. The procedure combines direct electrical stimulation of bladder receptors with visual biofeedback using patient observance of a water manometric representation of the detrusor response. Since November 1984 we have evaluated and/or treated 24 patients with a neurogenic bladder. An electrocatheter is passed transurethrally into the bladder and the bladder is filled to a third of its capacity with normal saline. We then deliver 2 to 6 mA. every 3 seconds for 90 minutes. Full treatment usually requires 30 to 90 sessions. Of the 24 patients 13 had only 1 evaluation and 10 had 3 to 39 sessions. Of those 10 patients 7 had significant detrusor activity that had not been present before treatment and 4 have a sensation to void. The remaining child underwent 110 sessions. He has controlled detrusor contractions resulting in a normal voiding pattern. It appears that intravesical transurethral bladder stimulation may be helpful diagnostically to determine the stimulus response of bladder function and therapeutically to rehabilitate the neurogenic bladder toward full control.


The good, the bad and the dubious: VHELIBS, a validation helper for ligands and binding sites.
Many Protein Data Bank (PDB) users assume that the deposited structural models are of high quality but forget that these models are derived from the interpretation of experimental data. The accuracy of atom coordinates is not homogeneous between models or throughout the same model. To avoid basing a research project on a flawed model, we present a tool for assessing the quality of ligands and binding sites in crystallographic models from the PDB. The Validation HElper for LIgands and Binding Sites (VHELIBS) is software that aims to ease the validation of binding site and ligand coordinates for non-crystallographers (i.e., users with little or no crystallography knowledge). Using a convenient graphical user interface, it allows one to check how ligand and binding site coordinates fit to the electron density map. VHELIBS can use models from either the PDB or the PDB_REDO databank of re-refined and re-built crystallographic models. The user can specify threshold values for a series of properties related to the fit of coordinates to electron density (Real Space R, Real Space Correlation Coefficient and average occupancy are used by default). VHELIBS will automatically classify residues and ligands as Good, Dubious or Bad based on the specified limits. The user is also able to visually check the quality of the fit of residues and ligands to the electron density map and reclassify them if needed. VHELIBS allows inexperienced users to examine the binding site and the ligand coordinates in relation to the experimental data. This is an important step to evaluate models for their fitness for drug discovery purposes such as structure-based pharmacophore development and protein-ligand docking experiments.


Ca2+-independent activity of nitric oxide synthase.
Ca2+-independent forms of nitric-oxide synthase have significant activity when the endogenous calmodulin subunit is Ca2+ free. Further activation is seen when Ca2+ is added. We have examined the activation of a Ca2+-independent nitric-oxide synthase variant and its two point mutants that are more dependent on Ca2+ for activation using mutant calmodulins containing non-functional Ca2+-binding sites. These studies provide evidence that the Ca2+-independent activity of these enzymes can be exerted through specific adapted interactions between the enzyme and the Ca2+-binding site 2 of calmodulin. Further, the results suggest that EGTA-sensitive metals other than Ca2+ complexed to calmodulin may be involved in maximal activation of these nitric-oxide synthase variants.


Atrial natriuretic peptide and cyclic nucleotides affect glucose-induced Ca2+ responses in single pancreatic islet beta-cells: correlation with (Ca[2+] + Mg2+)-ATPase activity.
Glucose stimulation of pancreatic islets is characterized by an initial decline in intracellular Ca2+ concentration ([Ca2+]i) (phase 0), followed by an increase in peak [Ca2+]i (phase 1). The effect of atrial natriuretic peptide (ANP) and cyclic nucleotides on the glucose-induced phase 0 [Ca2+]i was investigated by Fura-2 fluorescent imaging in single beta-cells from isolated islets of rats maintained at 1.67 mmol/l glucose. ANP (1 nmol/l to 1 micromol/l) inhibited the glucose (8.2 mmol/l)-induced phase 0 [Ca2+], in a concentration-dependent manner. Forskolin, 8-bromo-cyclic AMP (8BrcAMP), and 8-bromo-cyclic guanosine monophosphate (8BrcGMP) also inhibited the glucose-induced phase 0 [Ca2+]i. The Ca2+ channel blocker, D 600, prevented the response to 8BrcAMP but not to ANP or 8BrcGMP on phase 0 [Ca2+]i. Thapsigargin (TG) also inhibited phase 0 [Ca2+]i by 90%. ANP, 8BrcGMP, and TG also reduced the time required for glucose to initiate the phase 1 increase in [Ca2+]i, and each of these agents potentiated the effect of glucose on peak [Ca2+]i. Furthermore, sarco(endo)-plasmic reticulum (Ca[2+] + Mg2+)-ATPase (SERCA) activity in RINm5F insulinoma cells was inhibited by 8BrcGMP and TG, but not 8BrcAMP. Thus, ANP and cGMP modulate [Ca2+]i regulation in pancreatic beta-cells perhaps through mechanisms involving changes in SERCA activity and Ca2+ influx.


Can We Release All Calcaneal Attachments of the Superior Peroneal Retinaculum During Extensile Lateral Approach to the Calcaneus?
During extensile lateral approach to the calcaneus, in order to see all fractured fragments and subtalar joint, all soft tissues including insertion site of superior peroneal retinaculum (SPR) on the calcaneus should be released. The aim of this study was to evaluate the probability of peroneal tendon dislocation by releasing all soft tissues attached to the calcaneus. In 10 fresh cadavers, after standard extensile lateral approach to the calcaneus in right side, all soft tissues attached to the lateral wall of the calcaneus were excised. In the left side of each cadaver, all soft tissues inserted to the superior border of calcaneal tuberosity in addition to the lateral wall of the calcaneus were cut out. Probable anterior dislocation of peroneal tendons in the retromalleolar groove was assessed by placing a clamp into the peroneal tendon sheath from distal to proximal and advancing it to the retromalleolar groove. Also by careful dissection, any instability of peroneal tendons was visualized. Not any anterior dislocation of peroneal tendons to the lateral malleolus tip was seen in any stage of the procedure. Insertions of the SPR to the fascia of the deep posterior compartment of the leg and the Achilles tendon sheath are the main soft tissue stabilizer of the peroneal tendons in the retromalleolar groove. So resection of the insertion site of the SPR to the calcaneus might not result in the peroneal tendon instabilities.


Impaired dimerization of von Willebrand factor subunit due to mutation A2801D in the CK domain results in a recessive type 2A subtype IID von Willebrand disease.
The CK domain of von Willebrand factor (VWF) is involved in the dimerization of the protein. We identified the homozygous substitution A2801D of the CK domain in two siblings. Patients had low levels of VWF in plasma, abnormal ristocetin-induced binding to platelets and abnormal multimeric pattern with a lack of high molecular weight (HMW) forms and the presence of intervening bands between normal multimers. Accordingly, they were classified in type 2A, subtype IID, von Willebrand disease (VWD). Both asymptomatic parents carried the mutation at the heterozygous state. Their plasmaVWF exhibited the full range of multimers found in normal plasma. When analyzed by high resolution gel electrophoresis, very faint bands corresponding to the position of intervening bands of the propositus can be observed. The mutated recombinant (r)VWF-D2801, the hybrid rVWF-A/D2801 and the mutated C-terminal VWF fragment rSPII-D2801 were expressed in COS-7 cells. rVWF-D2801 showed an abnormal multimeric distribution similar to that of the propositus'VWF with intervening bands and a lack of HMW species. rVWF-A/D2801 exhibited the full range of multimers and the aberrant sized forms observed both in propositus'VWF and in rVWF-D2801. rSPII-WT assembled correctly into a dimer of 220 kDa. rSPII-D2801 appeared as a mixture of monomeric and dimeric forms which may be related to the abnormal multimeric pattern of the propositus and both mutated rVWF. We concluded that mutation A2801D disturbs the folding of the CK domain, which may result in a mixture of monomers and dimers of VWF. Multimers containing either an odd or even number of mature subunits are produced, and the presence of monomers appears to limit the degree of multimerization. In the heterozygousVWF, the presence of normal dimers improves the multimerization process. In conclusion, the mutation A2801D appears to be responsible for a recessive type 2A, subtype IID, VWD.


Treatment patterns and healthcare costs among biologic-naive patients initiating apremilast or biologics for the treatment of psoriatic arthritis: results from a US claims analysis.
Objective: Information on treatment costs for psoriatic arthritis (PsA) can be valuable for payers and providers who make treatment and formulary decisions. This study compared real-world treatment patterns and healthcare costs among biologic-naive patients with PsA initiating apremilast or biologics.Methods: A retrospective cohort study was conducted using the Optum Clinformatics™ claims database. The study included biologic-naive patients with PsA who initiated treatment with apremilast or a biologic between 1 January 2014, and 31 December 2015. Propensity score matching was used to adjust for selection bias. Treatment persistence/adherence and all-cause healthcare costs were evaluated. Cost differences were determined using Wilcoxon rank-sum tests.Results: In all, 125 biologic-naive patients initiating treatment with apremilast were matched to 245 biologic-naive patients initiating treatment with a biologic. Twelve-month treatment persistence was similar for apremilast vs. biologic users (43.2 vs. 36.7%; p = .2277). While persistent on treatment for up to 12 months, total healthcare costs (from all utilizations) were significantly lower among apremilast vs. biologic users ($28,130 vs. $37,093; p < .0001). Likewise, per-patient per-month costs while persistent on treatment were significantly lower among apremilast vs. biologic users whether they switched treatments ($2,455 vs. $3,497; p = .0103), remained persistent on treatment ($2,434 vs. $3,521; p < .0001), or discontinued but did not switch treatments ($2,178 vs. $2,696; p = .0082).Conclusions: Apremilast patients had significantly lower healthcare costs than biologic patients, even when they switched to a biologic, during the 12-month post-index period. These results may be useful to payers and providers seeking to optimize PsA care while reducing healthcare costs.


Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291.
A new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative, varioloid A (1), was isolated from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291. Its structure was elucidated on the basis of extensive analysis of 1D and 2D NMR data and the absolute configuration was determined by time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations. A similar compound, whose planar structure was previously described but the relative and absolute configurations and 13C NMR data were not reported, was also identified and was tentatively named as varioloid B (2). Both compounds 1 and 2 exhibited cytotoxicity against A549, HCT116, and HepG2 cell lines, with IC50 values ranging from 2.6 to 8.2 µg/mL.


[The demographic behavior of linguistic groups in Quebec during].
"The purpose of this paper is to analyse simultaneously, according to what is known as the multiregional approach, the interactions between fertility, migration and mortality, for each of the main linguistic groups of Quebec [Canada]. Results show that, on the basis of the demographic regime observed between 1976 and 1981, while migration probably has reduced regional disparities in fertility and mortality behavior, it also has markedly amplified the demographic impact of linguistic disparities in this behavior." (SUMMARY IN ENG AND SPA)


Role of yeast Rad5 and its human orthologs, HLTF and SHPRH in DNA damage tolerance.
In the yeast Saccharomyces cerevisiae, the Rad6-Rad18 DNA damage tolerance pathway constitutes a major defense system against replication fork blocking DNA lesions. The Rad6-Rad18 ubiquitin-conjugating/ligase complex governs error-free and error-prone translesion synthesis by specialized DNA polymerases, as well as an error-free Rad5-dependent postreplicative repair pathway. For facilitating replication through DNA lesions, translesion synthesis polymerases copy directly from the damaged template, while the Rad5-dependent damage tolerance pathway obtains information from the newly synthesized strand of the undamaged sister duplex. Although genetic data demonstrate the importance of the Rad5-dependent pathway in tolerating DNA damages, there has been little understanding of its mechanism. Also, the conservation of the yeast Rad5-dependent pathway in higher order eukaryotic cells remained uncertain for a long time. Here we summarize findings published in recent years regarding the role of Rad5 in promoting error-free replication of damaged DNA, and we also discuss results obtained with its human orthologs, HLTF and SHPRH.


Amyloid precursor protein and tau transgenic models of Alzheimer's disease: insights from the past and directions for the future.
During the last 20 years, our understanding of the mechanisms underlying Alzheimer's disease (AD) has considerably improved, in part owing to both in vitro and in vivo model systems. Studies in mice expressing both human amyloid precursor protein and human tau have provided clear evidence that amyloid-beta and tau interact in the pathogenesis of AD. Moreover, amyloid-beta toxicity has been shown to be tau-dependent since reducing tau levels prevents behavioral deficits and sudden death in amyloid precursor protein transgenic mice. As tau pathology preferentially develops in specific sites and spreads in a predictable manner across the brain, understanding the mechanism underlying tau dysfunction should be a focus in AD mouse modeling. A defined effort must be made to develop therapies that directly address the impact of tau dysfunction in the pathogenesis of AD. Finally, early diagnosis of AD is essential and this must be made possible by identification of early biomarkers, behavioral changes or use of novel imaging techniques.


Ultrastructural localization of substance P, met-enkephalin, and somatostatin immunoreactivity in lamina X of the primate spinal cord.
The ultrastructural localization of substance P (SP), met-enkephalin (MENK), and somatostatin (SS) in the lamina X area surrounding the central canal of the macaque monkey was examined by the indirect peroxidase-antiperoxidase method. The most common synaptic terminals in lamina X were simple terminals (S) with small rounded or pleomorphic clear vesicles; one to two dense-core vesicles were occasionally also present. These were found on soma, dendrites, and dendritic spines, in all regions of lamina X. A second class of terminal with round or oval clear vesicles was glomerular (G) in shape, with scalloped edges, and contained many mitochondria. These large terminals had several synaptic contacts onto dendrites, spines, and small terminals and were found mainly in the lateral region. The third class (L) contained small clear vesicles and several vesicles with large, dense cores (100-125 nm), and also contacted dendrites, mainly lateral to the canal. The fourth class of terminal (D) contained small clear vesicles and several vesicles with small, dense cores (75-100 nm); these contacted dendrites and somata in all areas. Very few terminals with flat vesicles were identified. There was an unequal distribution of immunoreactivity among the several terminal classes identified in lamina X. Most SP terminals were S terminals, but SP L terminals were also common; few were D terminals. MENK terminals were usually either S terminals or D terminals; L terminals were rarely MENK positive. SS terminals were commonly D terminals or S terminals; L terminals were also rarely SS positive. Only SP terminals were identified as G terminals. Synaptic targets of SP, MENK, and SS terminals were most commonly dendrites. In addition to unlabelled neurons, peptidergic neurons and their processes were also synaptic targets of terminals containing the same peptide. The distributions of these peptides in primate lamina X differ from that of the same peptides in primate superficial dorsal horn. These differences are important, in consideration of some of the parallels that may be drawn between the lamina X area and the superficial dorsal horn; both areas have high concentrations of the same peptides, receive nociceptive primary afferents, and contain spinothalamic and other projection neurons. Nevertheless, comparison of the distribution of immunoreactivity among terminal classes indicates that neurochemical organization at the ultrastructural level is quite distinct in each of the two areas. This may also reflect other roles of the lamina X area, including its involvement in visceral functions, although it would be expected that this element might be less prominent at the cervical levels we investigated.


The effect of salvage therapy on survival in a longitudinal study with treatment by indication.
We consider using observational data to estimate the effect of a treatment on disease recurrence, when the decision to initiate treatment is based on longitudinal factors associated with the risk of recurrence. The effect of salvage androgen deprivation therapy (SADT) on the risk of recurrence of prostate cancer is inadequately described by the existing literature. Furthermore, standard Cox regression yields biased estimates of the effect of SADT, since it is necessary to adjust for prostate-specific antigen (PSA), which is a time-dependent confounder and an intermediate variable. In this paper, we describe and compare two methods which appropriately adjust for PSA in estimating the effect of SADT. The first method is a two-stage method which jointly estimates the effect of SADT and the hazard of recurrence in the absence of treatment by SADT. In the first stage, PSA is predicted in the absence of SADT, and in the second stage, a time-dependent Cox model is used to estimate the benefit of SADT, adjusting for PSA. The second method, called sequential stratification, reorganizes the data to resemble a sequence of experiments in which treatment is conditionally randomized given the time-dependent covariates. Strata are formed, each consisting of a patient undergoing SADT and a set of appropriately matched controls, and analysis proceeds via stratified Cox regression. Both methods are applied to data from patients initially treated with radiation therapy for prostate cancer and give similar SADT effect estimates.


Exercise-induced asthma.
Exercise-induced bronchospasm is a common condition of patients who have asthma. Its mechanism appears to be related to cooling of the airways. Clinically, it can be managed by pretreatment with beta-adrenergic medications or cromolyn. Measures to protect the airway from excessive loss of heat, such as the use of scarves or participating in indoor activity, are also effective strategies in its management.


[Assessment of the selected, late phase of angiogenesis factors' concentration in colorectal cancer patients].
Angiogenesis is a process of new blood vessels creating based on existing already vascularisation. This composed and multistage mechanism, which is responsible for growth of the tissues and organs, plays a crucial role in neoplasia. The exact role of particular cells, cytokines and extracellular matrix in cancerogenesis is still discussing. An identification of it is the key to searching the antiangiogenic substances breaking simultaneously neoplastic proliferation. THE AIM OF THE STUDY was to compare the angiopoietin-1(Ang-1), angiopoietin-2 (Ang-2) and Tie-2 receptor (rec. Tie-2) concentrations in the serum of colorectal cancer patients with concentrations of these factors in the serum of healthy people. Moreover the aim of the study was to assess the correlation between the concentrations of these factors and stage of clinical neoplasm progression. The study included 35 patients hospitalized in the Department of General Surgery due to confirmed by histopatological examination colorectal cancer, between 2006 to 2007. The group of examined patients consisted of 9 women and 26 men with ages between 39 to 81 (average 67.20+/-8.85). The control group consisted of 11 healthy people. The examinations relied on the 10 ml of blood sampling from all the patients, in fasting state, one day before the operation. 10 ml of blood, in the healthy group was also sampled in fasting state. Afterwards all blood samples, 30 minutes after collecting, were centrifuged with velocity 6000 rotation per minute. The gaining serum was freezed in temperature -80 degrees C. The concentrations of Ang-1, Ang-2 and rec.Tie-2 were measured with ELISA method. Among examined patients with colorectal cancer, the statistically significant, higher concentration of Ang-2 in comparison with control group was revealed (6239.7+/-3482.3 pg/ml vs. 2954.9+/-9624.2 pg/ml). The concentration of Ang-2 among the patients from III and IV group according to the clinical and pathomorfological progression classification was statistically significant, higher than in I and II group of the patients (III: 8668,8+/-4938.57 pg/ml; IV: 9002.1+/-5380.92 pg/ml vs. I: 4672.3+/-1808.7 pg/ml; II: 5284.8+/-3204.2 pg/ml). The concentration of Ang-1 and rec. Tie-2 in blood of all the patients with colorectal cancer didn't statistically differ from the control group (Ang-1: 42339.9+/-20197.2 pg/ml vs. 48976.4+/-2284.5 pg/ml; rec.Tie-2; 14.4+/-5.1 vs. 16.8+/-6.2 ng/ml). The concentration of Ang-2 in the colorectal patients was statistically higher than in the control group. The increase concentration of Ang-2 correlated with the stage of colorectal cancer's clinical progression. The higher concentration of Ang-2 may eventually become a helpful marker in diagnostic and assessment of colorectal cancer's clinical progression stage.


Surgical Management of a Patient with Anterior Megalophthalmos, Lens Subluxation, and a High Risk of Retinal Detachment.
The early development of lens opacities and lens subluxation are the most common causes of vision loss in patients with anterior megalophthalmos (AM). Cataract surgery in such patients is challenging, however, because of anatomical abnormalities. Intraocular lens dislocation is the most common postoperative complication. Patients with AM also seem to be affected by a type of vitreoretinopathy that predisposes them to retinal detachment. We here present the case of a 36-year-old man with bilateral AM misdiagnosed as simple megalocornea. He had a history of amaurosis in the right eye due to retinal detachment. He presented with vision loss in the left eye due to lens subluxation. Following the removal of the subluxated lens, it was deemed necessary to perform a vitrectomy in order to prevent retinal detachment. Seven months after surgery, an Artisan® Aphakia iris-claw lens was implanted in the anterior chamber. Fifteen months of follow-up data are provided.


A noninvasive approach to quantitative functional brain mapping with H2 (15)O and positron emission tomography.
Positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) with intravenously administered 15O-labeled water and an adaptation of the Kety autoradiographic model are well suited to the study of functional-anatomical correlations within the human brain. This model requires arterial blood sampling to determine rCBF from the regional tissue radiotracer concentration (Cr) recorded by the tomograph. Based upon the well-defined, nearly linear relation between Cr and rCBF inherent in the model, we have developed a method for estimating changes in rCBF from changes in Cr without calculating true rCBF and thus without arterial sampling. This study demonstrates that quantitative functional brain mapping does not require the determination of rCBF from Cr when regional neuronal activation is expressed as the change in rCBF from an initial, resting-state measurement. Patterned-flash visual stimulation was used to produce a wide range of increases in rCBF within the striate cortex. Changes in occipital rCBF were found to be accurately estimated directly from Cr over a series of 56 measurements on eight subjects. This adaptation of the PET/autoradiographic method serves to simplify its application and to make it more acceptable to the subject.


Evaluation of antibacterial efficacy of Chitosan, Chlorhexidine, Propolis and Sodium hypochlorite on Enterococcus faecalis biofilm : An in vitro study.
Long term successful root canal treatment requires effective debridement and disinfection of root canal system. Persistent periradicular lesions are usually associated with Enterococccus faecalis. Prompt research for natural alternatives for irrigation is mainly due to the constant increase in antibiotic resistant strains and side effects caused by synthetic drugs. Sodium hypochlorite; the gold standard for irrigation has many disadvantages. Therefore, the present study was aimed to explore newer irrigants probably be as more effective and at the same time would be less irritating to the tissues than NaOCl. Ninety extracted human mandibular premolars were biomechanically prepared, vertically sectioned, placed in tissue culture wells exposing the root canal surface to E. faecalis to form a biofilm. At the end of 3rd week, all groups were irrigated with 3 ml of test solutions and control for 10 minutes. The samples were then scraped with a scalpel, inoculated on tryptone soy agar plates and incubated for 24 hours at 37ºC. The plates were then subjected to digital colony counter and evaluated for E. faecalisgrowth. The growth was statistically analysed by ANOVA & Post Hoc Tukey tests. Chitosan + Chlorhexidine, NaOCl and Chlorhexidine showed no statistically significant difference, whereas all the other inter‑group differences were statistically significant (P<0.05). Chitosan + Chlorhexidine, Chlorhexidine and Propolis were found to be as efficacious as sodium hypochlorite. The use of natural alternatives as root canal irrigation solutions might prove to be advantageous considering several unfavorable properties of NaOCl. Key words:Antibacterial efficacy, Chitosan, Enterococcus faecalis, Root canal irrigation.


Fetal deaths in Brazil: What changed in the last decade and what can we learn from the current situation?
To determine fetal death rates (FDRs) according to maternal characteristics in Brazil. A serial cross-sectional analysis was conducted based on vital statistics of the Brazilian population from 2007 to 2019. FDRs were estimated according to maternal and pregnancy characteristics. Annual percent change (APC) of FDR was assessed by joinpoint regression model. Causes of death were compared between the ante-/intrapartum periods. A significant reduction in FDR occurred in Brazil during 2007-2019 (11.1 and 10.43 in 2007 and 2019, respectively; APC -0.44). Only the northern region showed an increase in FDR. In 2019, the northeast and southeast had the highest and lowest FDRs, respectively (11.4 and 7.8/1000 live births). In adolescents, FDR increased from 2007 to 2016 (APC 1.75). In 2019, missing information was significantly high for maternal skin color (99.7%), schooling (17.0%), and age (7.0%) in fetal death registries. The most common causes of fetal death in the ante-/intrapartum periods were fetus and newborn affected by maternal conditions. A reduction in FDR has been achieved in Brazil over the last decade. However, there is an unmet need for decreasing social and regional disparities. A better system to attribute causes of death is needed to identifying priorities in maternal-fetal health care.


Subadult dietary variation at Trino Vercellese, Italy, and its relationship to adult diet and mortality.
Early-life nutrition is a predisposing factor for later-life outcomes. This study tests the hypothesis that subadults from medieval Trino Vercellese, Italy, who lived to adulthood consumed isotopically different diets compared with subadults who died before reaching adulthood. We have previously used a life history approach, comparing dentine and bone of the same adult individuals ("subadults who lived"), to elucidate dietary variation across the life span. Here, we examine diets of "subadults who died" from the same population, estimated from subadult rib collagen, to explore whether dietary behaviors of subadults who lived differed from those of subadults who died. Forty-one subadults aged six months to 14.5 years were studied through stable carbon and nitrogen isotope analysis of collagen. Individuals were weaned by age 4 years, with considerable variation in weaning ages overall. Post-weaning, diets of subadults who died comprised significantly less animal protein than diets of subadults who lived. Isotopic values of the two oldest individuals, 13.5 and 14.5 years, show the same status-based variation in diet as do adults from the population. Our results suggest that incorporating animal protein in diet during growth and development supported medieval subadults' ability to survive to adulthood. Isotopic similarities between adults and older subadults suggest "adult" dietary behaviors were adopted in adolescence. Stable isotope evidence from subadults bridges a disparity between ontogenetic age categories and socioculturally meaningful age categories in the past, and sheds light on the underpinnings of health, mortality, growth, and disease in the bioarchaeological record. Am J Phys Anthropol 160:653-664, 2016. © 2016 Wiley Periodicals, Inc.


Key features of inhibitor binding to the human mitochondrial pyruvate carrier hetero-dimer.
The mitochondrial pyruvate carrier (MPC) has emerged as a promising drug target for metabolic disorders, including non-alcoholic steatohepatitis and diabetes, metabolically dependent cancers and neurodegenerative diseases. A range of structurally diverse small molecule inhibitors have been proposed, but the nature of their interaction with MPC is not understood, and the composition of the functional human MPC is still debated. The goal of this study was to characterise the human MPC protein in vitro, to understand the chemical features that determine binding of structurally diverse inhibitors and to develop novel higher affinity ones. We recombinantly expressed and purified human MPC hetero-complexes and studied their composition, transport and inhibitor binding properties by establishing in vitro transport assays, high throughput thermostability shift assays and pharmacophore modeling. We determined that the functional unit of human MPC is a hetero-dimer. We compared all different classes of MPC inhibitors to find that three closely arranged hydrogen bond acceptors followed by an aromatic ring are shared characteristics of all inhibitors and represent the minimal requirement for high potency. We also demonstrated that high affinity binding is not attributed to covalent bond formation with MPC cysteines, as previously proposed. Following the basic pharmacophore properties, we identified 14 new inhibitors of MPC, one outperforming compound UK5099 by tenfold. Two are the commonly prescribed drugs entacapone and nitrofurantoin, suggesting an off-target mechanism associated with their adverse effects. This work defines the composition of human MPC and the essential MPC inhibitor characteristics. In combination with the functional assays we describe, this new understanding will accelerate the development of clinically relevant MPC modulators.


New combination of IntraSPINE device and posterior lumbar interbody fusion for rare skipped-level lumbar disc herniation: a case report and literature review.
Posterior lumbar interbody fusion is an open surgical technique that has been widely used for the treatment of degenerative lumbar disease. However, traditional lumbar spinal fusion, especially long-segment fusion surgery, is associated with several complications. The IntraSPINE (Cousin Biotech, Wervicq-Sud, France) is a new device for non-fusion lumbar spine surgery that is used as an alternative for the treatment of degenerative lumbar disease. Although the designer of the IntraSPINE proposed indications for its use, including combination of the device with lumbar spinal fusion for the treatment of degenerative lumbar disease, use of the IntraSPINE has not been reported in the clinical literature. In the present case, we boldly combined the IntraSPINE device and posterior lumbar interbody fusion for the treatment of skipped-level lumbar disc herniation to explore the indications of the IntraSPINE and report its clinical outcomes.


High purity factor VIII concentrates for the treatment of HIV-positive patients with haemophilia.
Some factor VIII concentrates cause downregulation of the immune system in HIV-positive haemophilia patients. This effect appears to be related to the purity of the concentrate, but not to its method of preparation. The optimum purity for preventing downregulation is not known at present.


A simple method for automated allele binning in microsatellite markers.
High-throughput fluorescent genotyping requires a considerable amount of automation for accurate and efficient processing of genetic markers. Automated DNA sequencers and corresponding software products are commercially available that contribute substantially to increased throughput rates for large-scale genotyping projects. However, some conceptually simple tasks still require time-consuming manual intervention that imposes bottlenecks on throughput capacity. One of these tasks is the conversion of imprecise DNA fragment sizes determined by commercial software programs to the underlying discrete alleles that the sizes represent. Here we describe a simple method for assigning allele sizes into their appropriate allele "bins" using least-squares minimization procedures. The method requires no special treatment of family data on plates, internal/external size standards, or electropherogram data manipulation. Tests of the method using the ABI 373A automated DNA sequencer and accompanying Genescan/Genotyper software resulted in accurate automatic classification of all alleles in >80% of 208 markers analyzed, with the remaining 20% being appropriately identified as requiring additional attention to laboratory conditions. Specific characteristics of different markers, including differences in PCR product size and inexact repeat lengths (e.g., 1. 9 bp for a dinucleotide repeat), are accommodated by the method and their properties discussed.


A mother and son with Noonan syndrome resulting from a PTPN11 mutation: first report of molecularly proven cases from Turkey.
Noonan syndrome is an autosomal dominant disorder characterized by short stature, typical craniofacial features, and congenital heart defects. The underlying genetic defects were not clear until 2001. This report is the first to describe a molecular analysis and associated clinical features of a Turkish mother and son, who were clinically diagnosed as Noonan syndrome when the boy was referred to our department due to short stature. The analysis revealed an A --> G transition at position 923 in exon 8 of the PTPN11 gene, indicating an Asn308Ser substitution.


Duodenal ulcers preceding cervical tuberculous lymphadenitis.
Lymphadenitis is the most common presentation of extra pulmonary tuberculosis, whereas gastrointestinal localization, particularly duodenal involvement, is rare. We report a case of extra pulmonary tuberculosis with association between cervical lymphadenitis and duodenitis with multiple ulcers, not responsive to treatment with protonic pump inhibitors, in a human immunodeficiency virus-seronegative adult woman of Eritrean origin. Clinical patterns of duodenal TB, diagnostic difficulties and aetiopathogenesis are discussed according to the literature. In this case report it is suggested that tuberculous infection must be considered when duodenal ulcers fail to respond to proton pump inhibitors, especially when the patient comes from an endemic area.


A review of accidental poisoning in Barbados--a new perspective (1981-1985).
A retrospective study is presented of accidental poisoning in 348 children who were admitted to the Queen Elizabeth Hospital during the 5-year period 1981-1985. These cases represented 4% of all admissions to the paediatric medical ward, with 56% of patients being boys and 43% girls. Most fell into the age group 13 months to 3 years, and all were aged between 6 months and 12 years. In the majority of cases, complications were mild or absent and no deaths were recorded. Their admission to hospital, however, did contribute greatly to the National Health Budget, costing more than BDS$130,000 over the 5-year period. Most of the children required only gastric decontamination and supportive treatment. Thirty-four per cent of the poisonings were due to medications prescribed for friends or family. Common household and garden products were involved in a similar number (33%). Fortunately, kerosene poisoning has declined in importance, but still accounted for 20% of cases. These ratings contrast with previous studies where kerosene ingestion was the most frequent cause of poisoning. With the ever increasing variety of toxic drugs and chemicals now available, there is a greater need to continue to stress the prevention of accidental poisoning. This will decrease the likelihood of mortality and morbidity resulting from accidental ingestion and likewise decrease the cost of hospital admissions for a largely preventable condition.


An Empirical Analysis of Indoor Tanners: Implications for Audience Segmentation in Campaigns.
Tanning bed use before age 35 has been strongly associated with several types of skin cancer. The current study sought to advance an understanding of audience segmentation for indoor tanning among young women. Panhellenic sorority systems at two universities in the Southeastern United States participated in this study. A total of 1,481 young women took the survey; 421 (28%) had tanned indoors in the previous 12 months and were the focus of the analyses reported in this article. Results suggested two distinct tanner types: regular (n = 60) and irregular (n = 353) tanners. Regular tanners tanned more frequently (M = 36.2 vs. 8.6 times per year) and reported significantly higher positive outcome expectations (p < .001) and lower negative outcome expectations (p < .01) than irregular tanners, among other significant differences. Hierarchical logistic regression analysis revealed several significant (p < .001) predictors of regular tanning type, with tanning dependence emerging as the strongest predictor of this classification (OR = 2.25). Implications for developing anti-tanning messages directed at regular and irregular tanners are discussed.


Targeting Fluorescence Imaging of RGD-Modified Indocyanine Green Micelles on Gastric Cancer.
Early diagnosis and complete resection of the tumor is an important way to improve the quality of life of patients with gastric cancer. In recent years, near-infrared (NIR) materials show great potential in fluorescence-based imaging of the tumors. To realize a satisfying intraoperative fluorescence tumor imaging, there are two pre-requirements. One is to obtain a stable agent with a relatively longer circulation time. The second is to make it good biocompatible and specific targeting to the tumor. Here, we developed an RGD-modified Distearyl acylphosphatidyl ethanolamine-polyethylene glycol micelle (DSPE-PEG-RGD) to encapsulate indocyanine green (ICG) for targeting fluorescence imaging of gastric cancer, aimed at realizing tumor-targeted accumulation and NIR imaging. 1H NMR spectroscopy confirmed its molecular structure. The characteristics and stability results indicated that the DSPE-PEG-RGD@ICG had a relatively uniform size of <200 nm and longer-term fluorescence stability. RGD peptides had a high affinity to integrin αvβ3 and the specific targeting effect on SGC7901 was assessed by confocal microscopy in vitro. Additionally, the results of cytotoxicity and blood compatibility in vitro were consistent with the acute toxicity test in vivo, which revealed good biocompatibility. The biodistribution and tumor targeting image of DSPE-PEG-RGD@ICG were observed by an imaging system in tumor-bearing mice. DSPE-PEG-RGD@ICG demonstrated an improved accumulation in tumors and longer circulation time when compared with free ICG or DSPE-PEG@ICG. In all, DSPE-PEG-RGD@ICG demonstrated ideal properties for tumor target imaging, thus, providing a promising way for the detection and accurate resection of gastric cancer.


The relevance of breakfast: concluding remarks.
The disease preventive role of breakfast emerges from epidemiological surveys. Thus, to accustom children to a regular breakfast consumption, and to maintain such behavior throughout the life-span, may have a significant health impact. Strategies to implement this dietary habit should be developed, as well as knowledge of the metabolic impact of different breakfast types according to local traditions and genetic background.


From aMCI to AD: The Role of Visuo-Spatial Memory Span and Executive Functions in Egocentric and Allocentric Spatial Impairments.
A difficulty in encoding spatial information in an egocentric (i.e., body-to-object) and especially allocentric (i.e., object-to-object) manner, and impairments in executive function (EF) are typical in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). Since executive functions are involved in spatial encodings, it is important to understand the extent of their reciprocal or selective impairment. To this end, AD patients, aMCI and healthy elderly people had to provide egocentric (What object was closest to you?) and allocentric (What object was closest to object X?) judgments about memorized objects. Participants' frontal functions, attentional resources and visual-spatial memory were assessed with the Frontal Assessment Battery (FAB), the Trail Making Test (TMT) and the Corsi Block Tapping Test (forward/backward). Results showed that ADs performed worse than all others in all tasks but did not differ from aMCIs in allocentric judgments and Corsi forward. Regression analyses showed, although to different degrees in the three groups, a link between attentional resources, visuo-spatial memory and egocentric performance, and between frontal resources and allocentric performance. Therefore, visuo-spatial memory, especially when it involves allocentric frames and requires demanding active processing, should be carefully assessed to reveal early signs of conversion from aMCI to AD.


Binocular visual function after staged implantation of extended-depth-of-focus intraocular lens targeting emmetropia and -0.5 diopter: A prospective comparison.
The prospective comparative case series aimed to evaluate the binocular uncorrected visual acuities (BUCVAs) after staged implantations of extended-depth-of-focus intraocular lenses (EDOF IOLs) targeting emmetropia and -0.5 diopter (D). Diffractive EDOF IOLs with an add power of +1.75 D were implanted in the first eyes targeting emmetropia or -0.5 D according to the patients' preferences, then the targets for the second eyes were determined 1 week or longer after the implantation. IOL powers were determined with the SRK/T formula. Consequently, the subjects were divided into 3 groups: those with emmetropia targeted bilaterally (group EE, 22 patients), those with -0.5 D targeted bilaterally (group MM, 21 patients), and those with monovision of emmetropia and -0.5 D (group EM, 21 patients). Manifest refraction spherical equivalent (MRSE), BUCVA from 0.3 to 5 meters, spectacle use, and questionnaire regarding photic symptoms and patient satisfaction were assessed 3 months postoperatively. No significant differences were seen in the mean BUCVAs at any distance (P > 0.23), spectacle use (P = 0.13), or photic symptoms and patient satisfaction (P>0.65). When the EE and MM groups were assigned based on the MRSE, the EE group was better at 5 m (P = 0.005) while the MM group at 0.5 m (P = 0.031). The effect of different targeted refractions was not identified due to insufficient accuracy in the use of the SRK/T power calculation.


cDNA sequence, map, and expression of the murine homolog of GTBP, a DNA mismatch repair gene.
DNA mismatch repair genes (MMR) have been actively studied in humans for their role in cancer susceptibility. Recently, GTBP, a new member of the MMR gene family, has been cloned and found to encode a 160-kDa protein that forms a heterodimer with hMSH2. Our group has isolated and characterized the mouse homolog of GTBP. The transcript, termed Gtmbp (G/T mismatch-binding protein), encodes a protein highly similar to its human counterpart. The gene is markedly conserved across species and maps to the distal portion of mouse chromosome 17, in a region homologous to human 2p. One Gtmbp-related sequence maps to proximal mouse chromosome 4. Studies of the expression of Gtmbp suggest that its regulated transcription is tightly linked to the level of DNA replication, consistent with the protein's DNA proofreading function.


Calorimetric study on the temperature dependence of the formation of mixed ionic/nonionic micelles.
The differential excess enthalpy of mixed micelle formation was measured at different temperatures by mixing nonionic hexa(ethylene glycol) mono n-dodecyl ether with anionic sodium dodecyl sulfate or cationic dodecylpyridinium chloride. The experimental data were obtained calorimetrically by titrating a concentrated surfactant solution into a micellar solution of nonionic surfactant. The composition and the size of the mixed nonionic/ionic micelles at different surfactant concentrations were also determined. Pronounced differences in both composition and excess enthalpy were found between the anionic and the cationic mixed system. For both systems, the excess enthalpies become more exothermic with increasing temperature, but for the anionic mixed system an additional exothermic contribution was found which was much less temperature dependent. Temperature dependence of the excess enthalpy was attributed to the effect of the ionic headgroup on the hydration of the ethylene oxide (EO) groups in the mixed corona. Ionic headgroups located in the ethylene oxide layer cause the dehydration of the EO chains resulting in an additional hydrophobic contribution to the enthalpy of mixing. A high affinity of sodium dodecyl sulfate for nonionic micelles and an extra exothermic and less temperature dependent contribution to the excess enthalpy found for the SDS-C(12)E(6) system might be attributed to specific interactions (hydrogen bonds) between the sulfate headgroup and the partly dehydrated EO chain.


Perceived barriers to medical care and mental health care among veterans with serious mental illness.
This study examined perceived barriers to mental health care and medical care and the relationship between demographic and clinical characteristics and perceived barriers among veterans with serious mental illness. Veterans diagnosed as having serious mental illnesses, hospitalized for psychiatric concerns, and at risk for treatment dropout (N=136) completed an interview as part of a larger study of a critical time intervention. Many participants perceived barriers to accessing mental health care (67%) and medical care (60%). Personal factors were cited most often as barriers; overall, however, personal barriers were more likely to be perceived to impede mental health care (56%) than medical care (43%). Psychiatric symptoms were associated with greater perceived barriers to mental health care and medical care. Veterans with serious mental illness at risk of treatment dropout perceived barriers to mental health care and medical services. Strategies to overcome barriers are needed and should target illness-related factors that may impede service use.


One for All, All for One: A Mixed Methods Case Study into the Role Organisational and Personal Interests Play on Cooperation in Dutch Integrated Dementia Care Networks.
Cooperation is key to provide integrated dementia care. However, different kinds of (personal and organisational) interests will affect collaboration in integrated dementia care (IDC) networks. Hence, it is crucial to understand how interests influence relations in IDC-networks in order to shape future policies. A sequential mixed methods single case study design was used, in three phases: a Social Network Analysis (SNA) based on data from questionnaires (n = 24-26), explorative interviews with network partners (n = 14) and a focus group with network coordinators (n = 7) to explore the conceptual generalisability of the single case of the IDC-network. The SNA revealed that highly connected organisations were often established care organisations that deliver case management, while smaller care organisations or welfare organisations tend to be less connected. Care-related, strategic, and financial interests influence participation of organisations in the IDC-network, while personal intrinsic motivations determine a representative's contribution to the network. Especially conflicting interests strongly influence the network structure. We conclude that conflicting interests in IDC-networks stand in the way of reaching the collective goal of an IDC-network, i.e., optimising the wellbeing of people with dementia and their informal caregivers in the region. Thus, IDC-networks should act to manage, resolve and prevent disputes arising from conflicting interests.


Precise GNSS Positioning Using Smart Devices.
The recent access to GNSS (Global Navigation Satellite System) phase observations on smart devices, enabled by Google through its Android operating system, opens the possibility to apply precise positioning techniques using off-the-shelf, mass-market devices. The target of this work is to evaluate whether this is feasible, and which positioning accuracy can be achieved by relative positioning of the smart device with respect to a base station. Positioning of a Google/HTC Nexus 9 tablet was performed by means of batch least-squares adjustment of L1 phase double-differenced observations, using the open source goGPS software, over baselines ranging from approximately 10 m to 8 km, with respect to both physical (geodetic or low-cost) and virtual base stations. The same positioning procedure was applied also to a co-located u-blox low-cost receiver, to compare the performance between the receiver and antenna embedded in the Nexus 9 and a standard low-cost single-frequency receiver with external patch antenna. The results demonstrate that with a smart device providing raw GNSS phase observations, like the Nexus 9, it is possible to reach decimeter-level accuracy through rapid-static surveys, without phase ambiguity resolution. It is expected that sub-centimeter accuracy could be achieved, as demonstrated for the u-blox case, if integer phase ambiguities were correctly resolved.


Phosphorylated and cleaved TDP-43 in ALS, FTLD and other neurodegenerative disorders and in cellular models of TDP-43 proteinopathy.
Transactivation response (TAR) DNA-binding protein of Mr 43 kDa (TDP-43) is a major component of the tau-negative and ubiquitin-positive inclusions that characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration which is now referred to as FTLD-TDP. Concurrent TDP-43 pathology has been reported in a variety of other neurodegenerative disorders such as Alzheimer's disease, forming a group of TDP-43 proteinopathy. Accumulated TDP-43 is characterized by phosphorylation and fragmentation. There is a close relationship between the pathological subtypes of FTLD-TDP and the immunoblot pattern of the C-terminal fragments of phosphorylated TDP-43. These results suggest that proteolytic processing of accumulated TDP-43 may play an important role for the pathological process. In cultured cells, transfected C-terminal fragments of TDP-43 are more prone to form aggregates than full-length TDP-43. Transfecting the C-terminal fragment of TDP-43 harboring pathogenic mutations of TDP-43 gene identified in familial and sporadic ALS cases into cells enhanced the aggregate formation. Furthermore, we found that methylene blue and dimebon inhibit aggregation of TDP-43 in these cellular models. Understanding the mechanism of phosphorylation and truncation of TDP-43 and aggregate formation may be crucial for clarifying the pathogenesis of TDP-43 proteinopathy and for developing useful therapeutics.


Skeletal Diversity in Combinatorial Fashion: A New Format for the Castagnoli-Cushman Reaction.
A new format for the Castagnoli-Cushman reaction of structurally diverse dicarboxylic acids, amines, and aldehydes in the presence of acetic anhydride as dehydrating agent is described. The reaction is distinctly amenable to parallel format: the combinatorial array of 180 reactions delivered 157 products of >85% purity without chromatographic purification (of this number, 143 compounds had >94% purity). The new method offers a convenient preparation of the skeletally and peripherally diverse, lead- and druglike γ- and δ-lactam carboxylic acids with high diastereoselectivity in combinatorial fashion.


[Clinical treatment and prognosis of 52 cases of neurinoma in parotid region].
To investigate the clinical features, diagnosis, and treatment, as well as prognosis of neurinoma in parotid region, in order to provide references for clinical treatment. Fifty-two cases of neurinoma in parotid region treated between June 2000 to December 2013 were retrospectively investigated, including their clinical characteristics, imaging examination, diagnosis, therapies and prognosis. SPSS13.0 software package was used for Fisher's exact test. Nine cases (17.31%) in all had facial paralysis, discomfort and other neural symptoms before operation. Eleven cases(21.15%) was preoperatively diagnosed. All patients were treated with surgery, pathologically diagnosed and followed up for 42 months to 206 months. No recurrence and malignant transformation were found. Twenty-eight cases (53.85%) had symptoms of facial nerve injury postoperatively, but 18 cases (64.29%) were improved functionally. When there was no obvious correlation between the tumor and facial nerve, no facial nerve paralysis was found. When the tumor was located on the facial nerve, the rate of preserving facial nerve function was 22.22%, the rate of intracapsular enucleation of the neurinoma was 85.71%, and the effective rate of excision followed by facial nerve reconstruction was 85.71%. The diagnosis of neurinoma in parotid region is difficult and needed to be confirmed by postoperative pathology. The preservation of facial nerve function should be the utmost procedure during operation while intracapsular enucleation is the first choice. However, in order to restore the function of facial nerve, nerve reconstruction should be performed as soon as possible.


Biochemical identification of the bovine blood group M' antigen as a major histocompatibility complex class I-like molecule.
Absorption and elution experiments showed that it was impossible to separate antibodies against blood group factor M' from antibodies against bovine lymphocyte antigen (BoLA) A16 in an antiserum showing haemolytic activity against M' as well as lymphocytotoxic activity against BoLA-A16. To elucidate the structural relationship between BoLA-A16 and blood group antigen M', immunoprecipitation experiments on red and white cell lysates isolated from M'-A16 positive and negative cattle were carried out. These results showed that M(r) 44,000 and M(r) 12000 polypeptides can be precipitated from both red and white cells isolated from M'-A16 positive animals, whereas no bands were seen in M'-A16 negative animals in precipitations with the same antibody. Precipitation with a crossreacting human beta 2-microglobulin (beta 2-m) specific antibody confirmed a class-I-like structure associated with beta 2-m on M' positive red cells and the absence of such a structure on M' negative red cells. Sequential precipitations gave analogous results. Proteolytic degradation by papain and V8 protease did not reveal any substantial difference between red and white M'-A16 positive cells, but a slight difference in the pI of the immunoprecipitable components of red and white cells was observed. All together, this indicates that either the blood group antigen M' is the BoLA-A16 class I antigen or M' and BoLA-A16 are two different class I polypeptides with the same relative mass, sharing identical epitopes and both associated with beta 2-m. Comparable results were obtained with M1 and BoLA-A24.


Low levels of transthyretin in the CSF of depressed patients.
Transthyretin plays an important role in the transport and distribution of thyroid hormone in the central nervous system (CNS). This study replicated and extended to patients with nonrefractory depressive illness a pilot study indicating that patients with refractory major depression have significantly lower levels of CSF transthyretin than do healthy comparison subjects. Lumbar punctures were performed in drug-free subjects with DSM-III-R major depression (N = 18), DSM-III-R bipolar disorder, depressed phase (N = 1), and healthy comparison subjects (N = 24). CSF concentrations of transthyretin, determined by a quantitative dot-immunobinding assay, of the depressed patients and comparison subjects were compared by analysis of covariance (ANCOVA). The relationship between CSF transthyretin levels and Hamilton Depression Rating Scale scores was determined in a subset of the depressed patients. CSF concentrations of transthyretin were significantly lower in the depressed patients than in the comparison subjects by ANCOVA. Within the depressed group there was no significant overall correlation between CSF transthyretin levels and Hamilton depression scale scores, but there was a significant inverse correlation in male depressed patients (N = 8) between CSF transthyretin concentrations and Hamilton depression scores. Lower CSF transthyretin concentrations in depressed patients may reflect either a stable trait in this population or a state change secondary to depression or other factors. Lower CSF transthyretin concentrations may result in altered CNS thyroid hormone homeostasis. Such alteration could account for certain mood and neurovegetative symptoms of depression and might contribute to failure of standard antidepressant treatment.


Study of acute hepatotoxicity of Equisetum arvense L. in rats.
To evaluate the acute hepatotoxicity of Equisentum arvense L. in rats. Fifty Wistar rats were used, these being divided in four groups, one being the control (receiving only water) and the other groups receiving graded doses of Equisentum arvense L. (30, 50, and 100mg/kg respectively) for 14 days. Blood samples were obtained to determine TGO, TGP, FA, DHL and GT-gamma activities. After that, hepatic tissue samples were collected for the anatomopathologic analysis. The anatomopathologic exam of the hepatic tissue showed organ with preserved lobular structure. In the same way, there was no significant change in the seric activities of the hepatic enzymes when compared to control group. The oral treatment with graded doses of Equisentum arvense L. was not able to produce hepatic changes. Further studies are necessary to evaluate the chronic hepatotoxicity of Equisentum arvense L. in rats.


[False asthmas of the adult].
Many conditions may simulate asthma, particularly tracheobronchial lesions that are dominated by tumoral stenoses, laryngeal anomalies and cardio-vascular diseases. At the time of the initial assessment of all sibilant dyspneas, certain other complementary examinations should systematically be made: pulmonary radiography, ORL examination and exploration of respiratory function.


Giant angiofibroma without accompanying tuberous sclerosis.
Angiofibromas occur in a variety of settings but can be markers for underlying tuberous sclerosis. We report an unusual giant angiofibroma occurring in a patient without associated disease. The suggested work-up for patients with tuberous sclerosis is also reviewed.


Medicare program; solicitation of hospitals and medical centers to participate in a study of heart transplants: Health Care Financing Administration. Notice.
This notice invites hospitals and medical centers to participate in a study of heart transplants to be conducted by HCFA. The purpose of the study is to examine, in general, all aspects of heart transplants, including the scientific, social, economic, and ethical issues, and, in particular, the impact of a possible Medicare decision to pay for heart transplants on the Medicare program, Medicare beneficiaries, and providers of health care. The study will be done in two related parts--the selection and participation of hospitals and medical centers, to which this notice is addressed, and an analysis of pertinent data and issues, to be conducted by an independent contractor. Hospitals and medical centers selected to participate in this study, under this notice, may be reimbursed for a limited number of heart transplants performed for Medicare beneficiaries during the course of the study. In addition, these institutions will furnish data about heart transplants performed at their facilities and will be reimbursed for the costs of furnishing this information. This notice contains information about the study, the availability of funds, and the procedures by which interested institutions can communicate their willingness to participate in the study. This notice also contains the criteria for the selection of hospitals and medical centers for heart transplant funding.


Early responsiveness to stimuli paired with different stages within the state of alcohol intoxication.
Infant rats quickly learn to avoid a sensory cue paired with alcohol as an unconditioned stimulus, particularly when the drug reaches peak blood concentrations. In this study, a tactile cue paired with the onset of alcohol intoxication preceded subsequent presentations of a gustatory conditioned stimulus (CS). The goal was to address the possibility of differential conditioning depending on when stimuli were introduced during the course of the toxic state. In experiment 1, rat pups received sequential presentations of a salient texture (sandpaper) and a gustatory cue (saccharin) while intoxicated with a 2.5 g/kg alcohol dose or after receiving saline. Texture location tests and saccharin intake assessments were then performed. A third modality of assessment was defined by a saccharin intake test while pups simultaneously experienced sandpaper. In experiment 2, alcohol-mediated conditioning was followed by tests similar to those of experiment 1, but after pups were re-exposed to either the tactile CS or the alcohol-unconditioned stimulus. Conditioned taste aversions, due to pairing saccharin and the later stage of alcohol intoxication, were reliably established in both experiments. Also in both experiments, this excitatory aversive response was dramatically inhibited when the association between the texture CS and the earlier stage of alcohol intoxication was activated. There were no indications of conditioned motor responses to the tactile CS that might compete with intake behavior of saccharin or distort measurement of an appetitive memory derived from pairing the texture and the earlier stage of intoxication. Rat pups' expression of an association between a taste signaling aversive consequences of alcohol was eliminated by the presence of a tactile stimulus that originally had signaled the absence of aversive consequences of alcohol intoxication. The results suggest the interaction of inhibitory and excitatory conditioning involving the aversive properties of alcohol.


Total synthesis of a key series of vinblastines modified at C4 that define the importance and surprising trends in activity.
The total synthesis and evaluation of a key systematic series of vinblastines that incorporate the first deep-seated changes to the substituent at C4 are detailed. The synthetic approach features an expanded and redefined scope of a 1,3,4-oxadiazole [4 + 2]/[3 + 2] cycloaddition cascade in which electronically mismatched electron-deficient trisubstituted alkenes and unactivated trisubstituted alkenes were found to productively initiate the cycloaddition cascade with tethered electron-deficient 1,3,4-oxadiazoles. Such cycloaddition cascades were used to directly introduce altered C4 substituents, providing the basis for concise total syntheses of a series of C4 modified vindolines and their subsequent single-step incorporation into the corresponding synthetic vinblastines in routes as short as 8-12 steps. Evaluation of the synthetic vinblastines revealed a surprisingly large impact and role of the C4 substituent on activity even though it was previously not thought to intimately interact with the biological target tubulin. Only the introduction of a C4 methyl ester, a constitutional isomer of vinblastine in which the carbonyl carbon and ester oxygen of the C4 acetate are transposed, provided a synthetic vinblastine that matched the potency of the natural product. In contrast, even introduction of a C4 acetamide or N-methyl carboxamide, which incorporate single heavy atom exchanges (amide NH for ester oxygen) in vinblastine or the C4 methyl ester, provided compounds that were ≥10-fold less active than vinblastine. Other C4 acetate replacements, including a C4 amine, carboxylic acid, hydroxymethyl or acetoxymethyl group, led to even greater reductions in potency. Even replacement of the C4 acetoxy group or its equally active C4 methyl ester with an ethyl or isopropyl ester led to 10-fold or more reductions in activity. These remarkable trends in activity, which correlate with relative tubulin binding affinities, retrospectively may be ascribed to the role the substituent serves as a H-bond acceptor for α-tubulin Lys336 and Asn329 side chains at a site less tolerant of a H-bond donor, placing the methyl group of the C4 acetate or C4 methyl ester in a spatially restricted and well-defined hydrophobic half pocket created by a surrounding well-ordered loop. This remarkable impact of the C4 substituent, its stringency, and even the magnitude of its effect are extraordinary, and indicate that its presence was selected in Nature to enhance the effects of vinblastine and related natural products.


The 3' to 5' Exoribonuclease DIS3: From Structure and Mechanisms to Biological Functions and Role in Human Disease.
DIS3 is a conserved exoribonuclease and catalytic subunit of the exosome, a protein complex involved in the 3' to 5' degradation and processing of both nuclear and cytoplasmic RNA species. Recently, aberrant expression of DIS3 has been found to be implicated in a range of different cancers. Perhaps most striking is the finding that DIS3 is recurrently mutated in 11% of multiple myeloma patients. Much work has been done to elucidate the structural and biochemical characteristics of DIS3, including the mechanistic details of its role as an effector of RNA decay pathways. Nevertheless, we do not understand how DIS3 mutations can lead to cancer. There are a number of studies that pertain to the function of DIS3 at the organismal level. Mutant phenotypes in S. pombe, S. cerevisiae and Drosophila suggest DIS3 homologues have a common role in cell-cycle progression and microtubule assembly. DIS3 has also recently been implicated in antibody diversification of mouse B-cells. This article aims to review current knowledge of the structure, mechanisms and functions of DIS3 as well as highlighting the genetic patterns observed within myeloma patients, in order to yield insight into the putative role of DIS3 mutations in oncogenesis.


Progress and future perspectives in mechanical circulatory support.
Progress in several types of artificial organs in the cardiovascular field has significantly contributed to advancements in cardiac surgery. Due to the progress of high technology in fields other than medicine, both cardiac surgery and artificial organs have shown rapid and remarkable advances. In recent years, several types of blood pumps have been developed that are widely used not only as the main pump of cardiopulmonary bypass but also for circulatory support of postcardiotomy cardiogenic shock. In this article, the progress and current status of percutaneous cardiopulmonary support systems and ventricular assist devices (VADs) are described. In addition, new centrifugal and axial pumps, which are compact and implantable clinical use devices, are introduced. I believe that by making developments toward the clinical application of artificial hearts or VADs, not only in Japan but also in cooperation with colleagues at various institutions throughout the world, we will be able to make some contributions to the progress in the field of cardiac surgery. In the 20th century, medical research showed remarkable advances, mainly in medical electronics and pathophysiology. However, in the next century, we have to focus on other research fields, namely artificial organs and gene technology.


The efficacy of lapatinib in patients with metastatic HER2 positive breast cancer who received prior therapy with monoclonal antibodies and antibody-drug conjugate: a single institutional experience.
The choice of the anti-HER2 agent depends on country-specific availability, the specific, previously administered anti-HER2 therapy and the relapse-free interval, although there is not much published data on the use of lapatinib after progression on pertuzumab and/or T-DM1. The aim of this research is to determine efficacy of lapatinib in this setting. This research included 111 patients with metastatic HER2 positive breast cancer who received lapatinib with capecitabine at The Oncology Institute of Vojvodina. Lapatinib was given to 83 patients after trastuzumab without prior exposure to pertuzumab or T-DM1 while 28 patients received lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1. In order to determine efficacy of lapatinib in both groups, we measured progression free survival (PFS) and overall survival (OS), as well as by subsets: hormonal status (ER-positive and/or PR-positive tumours versus ER-negative and PR-negative tumours), the number of positive axillary lymph nodes (four or more positive axillary lymph nodes versus less than four positive axillary lymph nodes), marker of proliferation (Ki-67 ≥ 30 versus Ki-67 < 30), disease free interval (metastatic recurrence ≤ 1 year after initial diagnosis versus metastatic recurrence > 1 year after initial diagnosis or de novo metastatic disease. Median PFS was 5.6 months (95% CI 4.6-6.6) in the group of patients who received lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM 1 and 7.4 months (95% CI 6.1-10.2) in the group of patients who received lapatinib after trastuzumab (HR, 0.79; 95% CI 0.61-0.98; P = 0.09). The patients with negative prognostic factors such as hormone receptor negativity, more than four positive axillary lymph nodes, marker of proliferation Ki 67 ≥ 30 and metastatic recurrence ≤ 1 year after initial diagnosis, had a similar PFS, regardless of receiving lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1 or without prior exposure. Median OS was 10.1 months (95% CI 8.6-NR) in the group that received lapatinib after exposure to trastuzumab, pertuzumab and/or T-DM1 and 16.3 months (95% CI 14.4-20.2) in the group of patients who received lapatinib after trastuzumab (HR, 0.76; 95% CI, 0.59-0.94; P = 0.04). Patients with negative prognostic factors such as hormone receptor negativity, more than four positive axillary lymph nodes and marker of proliferation Ki 67 ≥ 30, had no distinctly worse OS, regardless of receiving lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1 or without prior exposure. Lapatinib with capecitabine is an effective therapeutic option, especially in patients with negative prognostic factors, who have received prior chemotherapy, trastuzumab, pertuzumab, T-DM1 and remains an acceptable option for HER2 positive metastatic breast cancer until the novel drugs are approved in developing countries.


Efficient and unbiased estimation of volume and area of tissue components and cell number in gingival biopsies.
Recently, the methodology for volume and cell number estimation from sectioned tissue has undergone rapid progress. To date there are no indications in the literature that investigators in periodontal research are aware of this progress, published mainly in the disciplines of stereology and morphometry. This is unfortunate, as these developments could be profitably exploited in periodontal pathology. In this review we discuss the dangers of some currently used quantitative methods and indicate how simple unbiased methods together with an appropriate systematic sampling scheme lead to an efficient estimation of cell number and volume of tissue or tissue components.


Specific Anion Effects on Na+ Adsorption at the Aqueous Solution-Air Interface: MD Simulations, SESSA Calculations, and Photoelectron Spectroscopy Experiments.
Specific ion effects of the large halide anions have been shown to moderate anion adsorption to the air-water interface (AWI), but little quantitative attention has been paid to the behavior of alkali cations. Here we investigate the concentration and local distribution of sodium (Na+) at the AWI in dilute (<1 M) aqueous solutions of NaCl, NaBr, and NaI using a combination of molecular dynamics (MD) and SESSA simulations, and liquid jet ambient pressure photoelectron spectroscopy measurements. We use SESSA to simulate Na 2p photoelectron intensities on the basis of the atom density profiles obtained from MD simulations, and we compare the simulation results with photoelectron spectroscopy experiments to evaluate the performance of a nonpolarizable force field model versus that of an induced dipole polarizable one. Our results show that the nonpolarizable force model developed by Horinek and co-workers (Chem. Phys. Lett. 2009, 479, 173-183) accurately predicts the local concentration and distribution of Na+ near the AWI for all three electrolytes, whereas the polarizable model does not. To our knowledge, this is the first interface-specific spectroscopic validation of a MD force field. The molecular origins of the unique Na+ distributions for the three electrolytes are analyzed on the basis of electrostatic arguments, and shown to arise from an indirect anion effect wherein the identity of the anion affects the strength of the attractive Na+-H2O electrostatic interaction. Finally, we use the photoelectron spectroscopy results to constrain the range of inelastic mean free paths (IMFPs) for the three electrolyte solutions used in the SESSA simulations that are able to reproduce the experimental intensities. Our results suggest that earlier estimates of IMFPs for aqueous solutions are likely too high.


Crystallography on curved surfaces.
We study static and dynamical properties that distinguish 2D crystals constrained to lie on a curved substrate from their flat-space counterparts. A generic mechanism of dislocation unbinding in the presence of varying Gaussian curvature is presented in the context of a model surface amenable to full analytical treatment. We find that glide diffusion of isolated dislocations is suppressed by a binding potential of purely geometrical origin. Finally, the energetics and biased diffusion dynamics of point defects such as vacancies and interstitials are explained in terms of their geometric potential.


Partitioning of Polymerizing Fluids in Random Microporous Media: Application of the Replica Ornstein-Zernike Equations.
We have investigated a model for a polymerizing fluid in which each of the particles has two bonding sites, such that chains can be formed via a chemical association mechanism. The fluid model is considered to be in a random quenched microporous matrix. The matrix species are assumed to be either impermeable to adsorbed fluid particles or permeable, such that the surface of the matrix particles represents a permeable membrane of finite width. We have studied the influence of the matrix species on the formation of chains due to association. The model is investigated by means of the associative replica Ornstein-Zernike equations with the Percus-Yevick closure and the ideal chain approximation. We have observed that the average chain length is longer in the presence of an impermeable matrix than in the case where the matrix is absent. Matrix is therefore conducive to the growth of the polymerizing species in micropores. There is a decrease in the average chain length with increasing permeability of matrix species. This behavior reaffirms the attenuating role of the permeable matrix species as a whole. Copyright 1999 Academic Press.


Exploring the Relationship Between Value Modularity, Knowledge Transfer, and Firm Innovation Performance: Evidence From China.
This study aimed to explore the influence the value modularity and a firm's innovation performance, directly and indirectly, using knowledge management as mediating variable. Moreover, in this study, we used the resource integration ability as a moderator between the relationship value modularity and firm innovation performance. We collected data from the Chinese state-owned and state-controlled high-tech firms from 2011 to 2018. In this study, we used the gray comprehensive evaluation method to test the degree of value modularity, and hierarchical regression analysis is used to analyze the relationship among variables. The outcomes of this study indicate that value modularity and firm innovation performance has inverted U-shaped and significant association. Similarly, results also confirm that knowledge acquisition and knowledge internalization mediate the relationship between value modularity and firm innovation performance. The finding of this research also confirms that resource integration ability negatively affects the relationship between value modularity and firm innovation performance. This paper enriches the research of the value modularity and gives certain inspiration to knowledge management. At the end of this study, we also suggest some significant practical implications.


[Use of aminoglycoside antibiotic gentamycin in extremely premature infants--administration schedule and suggested dosage based on pharmacokinetic studies in plasma].
The pharmacokinetics of Gentamycin administered to 22 infants intravenously at currently recommended doses (2-2.5 mg every 24 h for infants less than 7 days of life and 28 g.a. and 12 h for infants 32 g.a). The results showed a statistically significant relation between half-life and postconsiptional age and direct correlation between total body clearance and postconsiptional age. These pharmacokinetics data were used to calculate a new dosage schedule for preterm infants. Ondoing therapeutic drug monitoring is essential to tailor the dosage to the individual patient. Gentamycin.


Dissolution of tradition: a reprise.
Last summer, within the pages of this journal, an essay described the uncertainty surrounding the future of our small but independent VNA ("Dissolution of Tradition into Fantasy: A Lament," May/June, 1996). Supposedly, harsh financial pressures bombarded us and our Board began an inexorable movement toward affiliation with a powerful local hospital. When professional staff became jittery, Board representatives soothed us. This anxious period, given the decidedly unromantic coinage "due diligence," was likened to a courtship phase, an arranged engagement of sorts. Cold feet, second thoughts, panic attacks, and troubled dreams--all were to be expected, considered perfectly natural. All would be forgotten in the bliss of connubial union. Be patient and trust, we were advised; the consummation would make it all worthwhile. And we tried. What has transpired between last summer and this spring, however, exceeded our most vivid nightmare. Betrayed and angry, we scrambled to save what we could of our VNA before it was consigned to obsolescence in this, the year of our centennial.