Induction of CC and CXC chemokines in human antigen-presenting dendritic cells by the pneumococcal proteins pneumolysin and CbpA, and the role played by toll-like receptor 4, NF-kappaB, and mitogen-activated protein kinases.
Choline-binding protein A (CbpA) and pneumolysin (Ply) can induce the expression and release of chemokines by human cells, which might modulate specific immune responses. In dendritic cells (DCs), such effects could be important for the size and character of the immunity induced if administered as vaccines. We studied the induction of CCL and CXCL chemokines by CbpA and Ply in DCs and related signaling pathways. Proteins derived from bacterial cultures and cloning were used as stimulants. DCs were generated from CD14+ human monocytes by negative selection, followed by coculture with recombinant human granulocyte-macrophage colony-stimulating factor and recombinant interleukin-4. The role played by Toll-like receptors (TLRs) was assessed using anti-TLR antibodies. Likewise, specific inhibitors (given in parentheses) of signaling molecules were used: NF-kappaB (SN50), extracellular signal-regulated kinase (PD98059), p38 (SB203580), and Jun N-terminal kinase (SP600125). Both CbpA and Ply significantly up-regulated DC mRNA of several CCL (2, 4, 5, and 8) and CXCL (8 and 10) chemokines studied as well as the expression of 3 proteins studied: CCL2, CCL5, and CXCL8. Ply stimulation was blocked by anti-TLR4. Inhibition of NF-kappaB and several mitogen-activated protein kinase signaling pathways also reduced chemokine release. Chemokine induction in DCs by CbpA and Ply may be important for their potential use in future pneumococcal vaccines.


Differential diagnosis of solitary gastric Peutz-Jeghers-type polyp with stomach cancer: a case report.
Solitary Peutz-Jeghers-type polyps of the stomach are extremely rare. They are defined as unique polyps that are not associated with Peutz-Jeghers syndrome (PJS). A 37-year-old woman presented at our hospital with anemia and epigastric discomfort. Esophagogastroduodenoscopy to determine the cause of anemia revealed a 5 × 6-cm pedunculated polypoid tumor at the greater curvature of the upper gastric body. Pathological examination of a biopsy specimen confirmed a Group 1 hyperplastic polyp. Computed tomography revealed neither lymph node swelling nor distant metastasis. A malignant component of the polypoid tumor was difficult to deny because of its size. The patient underwent local resection of the stomach. Her postoperative course was uneventful. A pathological examination of the surgical specimen revealed a Peutz-Jeghers-type, hamartomatous polyp containing an enlarged crypt with hyperplastic foveolar epithelium and smooth muscle proliferating into the lamina propria. No atypical cells were found in the overlying epithelium. Based on these findings, we performed colonoscopy and capsule endoscopy of the intestine. No polyps were found in the intestine or colon. She had no family history of any type of tumor and no mucocutaneous pigmentation. There were only 10 reports of solitary gastric Peutz-Jeghers polyps published to date. Although most of them did not have atypical cells, one case has proliferative component. A few reports have described relationship with malignant tumor. Solitary gastric PJ-type polyps are rare. Careful follow-up should be recommended and further studies are needed to evaluate cancer risk of solitary gastric PJ-type polyps.


Behavioral effects of lesions of precommissural and postcommissural fornix.
Lesions which sever different parts of precommissural or postcommissural fornix were compared to the effects of control lesions in several behavioral tasks. Spatial learning and avoidance was impaired by lesions of the descending columns, or by lesions which sever the precommissural communications passing to and from medial septum. Damage to precommissural fibers through lateral septum produced a measurable change only on the avoidance task. This pattern of deficits, considered together with the anatomical relationship of the system, suggests a model in which the medial septum relays kinesthetic information to dorsal hippocampus, which in turn serves as a memory system in the performance of spatial habits. It is less clear what kind of information is relayed by lateral septum, but it may communicate with ventral hippocampus regarding the consequences of punishment, and thus serve as part of a system for defensive suppression of behavior.


The loss-of-function mutation of CETP affects HDLc levels but not ApoA1 in patients with acute myocardial infarction.
Loss of the cholesteryl ester transfer protein (CETP) function affects HDLc levels, but its effects on major HDL protein component ApoA1 are not well understood in patients with acute myocardial infarction (AMI). We investigated the effects of an East Asian loss-of-function variant (rs2303790; p.D442G) in CETP gene on HDLc and ApoA1 levels and its relationship with AMI. A total of 2327 AMI patients and 2615 age- and sex-matched controls from INTERHEART-China study were included. In controls, both levels of HDLc (1.24 vs. 1.04 mmol/L, P = 0.001) and ApoA1 (1.48 vs. 1.37 mmol/L, P = 0.042) were significantly higher in CETP variant G allele carriers compared to CETP wildtype D allele carriers. In AMI patients, levels of HDLc were significantly higher (1.14 vs. 1.01 mmol/L, P = 0.013) while levels of ApoA1 were not statistically difference (1.31 vs. 1.32 mmol/L, P = 0.468) in CETP variant group compared to CETP wildtype group. Moreover, CETP variant is associated with HDLc increase, but is not associated with AMI risk (P = 0.564), even after adjusting for age, sex, history of hypertension and diabetes, waist to hip ratio, smoking, total cholesterol, LDL cholesterol, triglycerides, physical activity, depression, alcohol, vegetables and fruit consumption. Loss of CETP function is associated with increased HDLc and ApoA1 levels in healthy subjects, and in AMI patients, it is associated with HDLc levels but not ApoA1 levels. The lack of association of CETP variant with AMI may be related to the inability to increase ApoA1 levels and warranted further studies.


Phosphorus-calcium carbonate saturation relationships in a lowland chalk river impacted by sewage inputs and phosphorus remediation: an assessment of phosphorus self-cleansing mechanisms in natural waters.
The relationship between calcium carbonate saturation and phosphorus concentrations for seven sites on the upper reaches of the River Kennet are examined. The findings are related to issues of groundwater supplies and the introduction of phosphorus treatment of effluent from the Marlborough sewage treatment works (STW) at part of the way along the study reach. Being supplied from a Cretaceous Chalk aquifer, the Kennet is mainly of a calcium-bicarbonate type and has a relatively constant composition of many major water quality determinands. Typically, the waters average a pH of approximately eight (range approx. 7.5-8.5) during the day with the lowest values occurring at the upstream site. Dissolved carbon dioxide varies from approximately 5 to 35 times atmospheric pressure during the late morning with the highest values occurring at the upstream site. However, in-stream biological activity gives rise to marked diurnal fluctuations in pH and dissolved carbon dioxide concentrations and during the summer months, by mid to late afternoon, pH is at its maximum and dissolved carbon dioxide is at its lowest: this is shown by continuous measurements at one of the river sites. Alkalinity and calcium concentrations remain relatively constant at approximately 4,700 microEq/l (range 3,500-6,000 microEq/l) and 120 mg/l (range 85-150 mg/l), respectively, and the waters are oversaturated with respect to calcium carbonate (calcite) typically by a factor of six (range 2-25). Along the reach, soluble reactive phosphate (SRP) increases from the first to the second site with the introduction of sewage supplies from the Marlborough STW, and then declines further downstream as sewage dilution and uptake by the river bed/aquatic plants increases. The differences in concentration decrease after phosphorus removal from Marlborough STW. Despite this change, there is no clear indication of any calcite solubility control except perhaps at times of extreme baseflow during the growing season when within-stream photosynthesis is maximal and within-stream residence times are longer. A comparison of river and groundwater data shows that the groundwaters have similar alkalinities and calcium concentrations. However, the groundwaters have (a) higher carbon dioxide saturations (a factor of 2-5 times the value for the river), (b) lower pHs (0.5-1.5 units), (c) lower SRP concentrations (a quarter or less of the river values) and (d) waters near calcite saturation (unlike the surface waters which are oversaturated). The findings indicate a river system dominated by the input carbon dioxide laden groundwaters in approximate equilibrium with calcite attenuated by within-channel biological and physical processes. Within the river: (a) the waters degas carbon dioxide increasing the pH, producing oversaturated conditions; and (b) oscillating pH-dissolved carbon dioxide levels occur between day and night due to changing balances between photosynthesis and respiration. It seems that lowering the phosphorus levels have not resulted in calcite precipitation within the water column and that no significant within-stream self-cleansing mechanisms are occurring that might be predicted from theory: other components in the water such as dissolved organic carbon may inhibit calcite nucleation. However, the low SRP levels in the groundwater coupled with calcite saturation, may well indicate that phosphorous concentrations within the groundwater are regulated by such processes: the number of calcite nucleating sites are orders of magnitude higher and the calcite inhibitors may be less prevalent.


Fluid-structure interaction study of hemodynamics and its biomechanical influence on carotid artery atherosclerotic plaque deposits.
Atherosclerotic plaque deposits are common causes of blood flow disruption in the carotid artery bifurcation and the associated fluid mechanics has been extensively studied using Computational Fluid Dynamics (CFD) and Fluid Structure Interaction (FSI). However, the elastic responses of plaques to hemodynamics in the carotid artery bifurcation has not been deeply studied using either of the above-mentioned numerical techniques. In this study, a two-way FSI study was coupled with CFD technique, using Arbitrary-Lagrangian-Eulerian method, to study the biomechanics of blood flow on nonlinear and hyperelastic calcified plaque deposits in a realistic geometry of the carotid sinus. FSI parameters such as total mesh displacement and von Misses stress on the plaque, as well as flow velocity and blood pressure around the plaques, were analyzed and compared to variables such as velocity streamline, pressure and wall shear stress obtained from CFD simulation in a healthy model. The blood flow simulations reveal complete reversed blood flow behavior in the internal carotid artery, ICAs and external carotid artery, ECAs for both cases. In particular, this study suggests that plaques, irrespective of the masses, possess a high yielding response to hemodynamic forces at the attaching edges, while the surfaces are vulnerable to rupture.


[Description of bulimic behaviors].
This report describes and comments the definitions which have been proposed for Bulimia nervosa in three recent classifications: DSM III, DSM III-R and ICD-10.


Draft Genome Sequences of Eight Nontypeable Haemophilus influenzae Strains Previously Characterized Using an Electrophoretic Typing Scheme.
Nontypeable Haemophilus influenzae is an important cause of human disease. Strains were selected for genome sequencing to represent the breadth of nontypeable strains within the species, as previously defined by the electrophoretic mobility of 16 metabolic enzymes.


BRCA1 mutations and polymorphisms in a hospital-based consecutive series of breast cancer patients from Apulia, Italy.
Hereditary breast cancer has been partly attributed to germline mutations in the BRCA1 gene that are deleterious for BRCA1 protein activity. This paper analyzes the incidence and characteristics of detectable BRCA1 mutations and polymorphisms in a hospital-based consecutive series of breast cancer patients from southern Italy to investigate the incidence and the association of these molecular alterations with breast cancer biology and family history. One hundred cases with familial characteristics were selected from a consecutive series of 511 patients with a first diagnosis of breast cancer. DNA from peripheral blood was screened for whole BRCA1 gene mutations utilizing dHPLC as a pre-screening analysis and automatic DNA sequencing for the identification of specific alterations. In the overall series of 511 patients, 100 had a family history of breast cancer and were investigated for BRCA1 mutations. Two types of BRCA1 mutations were identified, 5382insC in six cases and 4566delA in one case. The 5382insC mutation was present in two out of six cases with ovarian cancer while 4566delA in one case of male cancer. The most frequent missense polymorphisms were E1038G, P871L, K1183R in exon 11, S1613G, M1652I in exon 16 and D1778G in exon 22. Confirming what found in previous studies, patients in whom pathological BRCA1 mutations were detected had early-onset breast cancer (p=0.05), positive nodal status (p=0.05), lower ER (p=0.02) and PgR (p=0.01) content. Interestingly, the K1183R polymorphism and, less strongly, S1613G polymorphism were associated to mutational risk (K1183R: OR 0.1 p=0.03; S1613G: OR 2.7 p=0.08). Mutations in the BRCA1 gene are frequent also in our consecutive series of patients from southern Italy. An association between two detected single nucleotide polymorphisms (SNPs) and BRCA1 mutational risk was ascertained. Finally, we confirm the fact that peculiar clinical-pathological features seem to characterize patients with a family history of breast cancer and BRCA1 alterations.


Safety of irrigation with 5-fluorouracil in a sealed-capsule irrigation device in the rabbit eye.
To study the safety of irrigation with 5-fluorouracil (5-FU) in the Perfect Capsule sealed-capsule irrigation device (Milvella, Ltd., Epping, Australia). St. Erik's Eye Hospital, Stockholm, Sweden. Thirty 8-week-old rabbits were divided into 4 groups. Clear lens extraction was performed and the Perfect Capsule was applied in 1 eye in Groups 1, 2 and 3. The sealed system was flushed with balanced salt solution (BSS) in Group 1, 5-FU 50 mg/mL in Group 2, and 5-FU followed by BSS in Group 3. In Group 4, the Perfect Capsule was not applied; instead, 0.2 mL of 5-FU was instilled in the capsule and left there for 30 seconds. An endothelial cell count and pachymetry were performed preoperatively and 24 hours postoperatively. At 24 or 48 hours (half of each group at each time point), the rabbits were killed and the retina and trabecular meshwork histopathologically examined. The endothelial cell count and pachymetry were compared between the Perfect Capsule eye and the control eye in Group 1. There was no difference between the groups in endothelial cell count (P = .96) or pachymetry (P = .32). Histologic evaluation showed no damage from the 5-FU. The comparison between eyes in Group 1 showed that the use of the Perfect Capsule did not cause more endothelial cell loss (P = .86) or increase pachymetry more (P = .28) than in the control eye. Irrigation with 5-FU 50 mg/mL in the sealed-capsule irrigation device was safe and caused no apparent damage to the adjacent intraocular tissues.


Long-term reproducibility of Edinger-Westphal stimulated accommodation in rhesus monkeys.
If longitudinal studies of accommodation or accommodation restoration procedures are undertaken in rhesus monkeys, the methods used to induce and measure accommodation must remain reproducible over the study period. Stimulation of the Edinger-Westphal (EW) nucleus in anesthetized rhesus monkeys is a valuable method to understand various aspects of accommodation. A prior study showed reproducibility of EW-stimulated accommodation over 14 months after chronic electrode implantation. However, reproducibility over a period longer than this has not been investigated and therefore remains unknown. To address this, accommodation stimulation experiments in four eyes of two rhesus monkeys (13.7 and 13.8 years old) were evaluated over a period of 68 months. Carbachol iontophoresis stimulated accommodation was first measured with a Hartinger coincidence refractometer (HCR) two weeks before electrode implantation to determine maximum accommodative amplitudes. EW stimulus-response curves were initially measured with the HCR one month after electrode implantation and then repeated at least six times for each eye in the following 60 months. At 64 months, carbachol iontophoresis induced accommodation was measured again. At 68 months, EW stimulus-response curves were measured with an HCR and photorefraction every week over four consecutive weeks to evaluate the short-term reproducibility over one month. In the four eyes studied, long-term EW-stimulated accommodation decreased by 7.00 D, 3.33 D, 4.63 D, and 2.03 D, whereas carbachol stimulated accommodation increased by 0.18 D-0.49 D over the same time period. The short-term reproducibility of maximum EW-stimulated accommodation (standard deviations) over a period of four weeks at 68 months after electrode implantation was 0.48 D, 0.79 D, 0.55 D and 0.39 D in the four eyes. Since the long-term decrease in EW-stimulated accommodation is not matched by similar decreases in carbachol iontophoresis stimulated accommodation, the decline in accommodation cannot be due to the progression of presbyopia but is likely to result from variability in EW electrode position. Therefore, EW-stimulated accommodation in anesthetized monkeys is not appropriate for long-term longitudinal studies of age-related loss of accommodation or accommodation restoration procedures.


Molecular classification of borderline ovarian tumors using hierarchical cluster analysis of protein expression profiles.
Ovarian tumors range from benign to aggressive malignant tumors, including an intermediate class referred to as borderline carcinoma. The prognosis of the disease is strongly dependent on tumor classification, where patients with borderline tumors have much better prognosis than patients with carcinomas. We here describe the use of hierarchical clustering analysis of quantitative protein expression data for classification of this type of tumor. An accurate classification was not achieved using an unselected set of 1,584 protein spots for clustering analysis. Different approaches were used to select spots that were differentially expressed between tumors of different malignant potential and to use these sets of spots for classification. When sets of proteins were selected that differentiated benign and malignant tumors, borderline tumors clustered in the benign group. This is consistent with the biologic properties of these tumors. Our results indicate that hierarchical clustering analysis is a useful approach for analysis of protein profiles and show that this approach can be used for differential diagnosis of ovarian carcinomas and borderline tumors.


A traveler-centric mobility game: Efficiency and stability under rationality and prospect theory.
In this paper, we study a routing and travel-mode choice problem for mobility systems with a multimodal transportation network as a "mobility game" with coupled action sets. We formulate an atomic routing game to focus on the travelers' preferences and study the impact on the efficiency of the travelers' behavioral decision-making under rationality and prospect theory. To control the innate inefficiencies, we introduce a mobility "pricing mechanism," in which we model traffic congestion using linear cost functions while also considering the waiting times at different transport hubs. We show that the travelers' selfish actions lead to a pure-strategy Nash equilibrium. We then perform a Price of Anarchy and Price of Stability analysis to establish that the mobility system's inefficiencies remain relatively low and the social welfare at a NE remains close to the social optimum as the number of travelers increases. We deviate from the standard game-theoretic analysis of decision-making by extending our mobility game to capture the subjective behavior of travelers using prospect theory. Finally, we provide a detailed discussion of implementing our proposed mobility game.


Intravenous sulforhodamine B reduces alveolar surface tension, improves oxygenation, and reduces ventilation injury in a respiratory distress model.
In the neonatal respiratory distress syndrome (NRDS) and acute respiratory distress syndrome (ARDS), mechanical ventilation supports gas exchange but can cause ventilation-induced lung injury (VILI) that contributes to high mortality. Further, surface tension, T, should be elevated and VILI is proportional to T. Surfactant therapy is effective in NRDS but not ARDS. Sulforhodamine B (SRB) is a potential alternative T-lowering therapeutic. In anesthetized male rats, we injure the lungs with 15 min of 42 mL/kg tidal volume, VT, and zero end-expiratory pressure ventilation. Then, over 4 h, we support the rats with protective ventilation-VT of 6 mL/kg with positive end-expiratory pressure. At the start of the support period, we administer intravenous non-T-altering fluorescein (targeting 27 µM in plasma) without or with therapeutic SRB (10 nM). Throughout the support period, we increase inspired oxygen fraction, as necessary, to maintain >90% arterial oxygen saturation. At the end of the support period, we euthanize the rat; sample systemic venous blood for injury marker ELISAs; excise the lungs; combine confocal microscopy and servo-nulling pressure measurement to determine T in situ in the lungs; image fluorescein in alveolar liquid to assess local permeability; and determine lavage protein content and wet-to-dry ratio (W/D) to assess global permeability. Lungs exhibit focal injury. Surface tension is elevated 72% throughout control lungs and in uninjured regions of SRB-treated lungs, but normal in injured regions of treated lungs. SRB administration improves oxygenation, reduces W/D, and reduces plasma injury markers. Intravenous SRB holds promise as a therapy for respiratory distress.NEW & NOTEWORTHY Sulforhodmaine B lowers T in alveolar edema liquid. Given the problematic intratracheal delivery of surfactant therapy for ARDS, intravenous SRB might constitute an alternative therapeutic. In a lung injury model, we find that intravenously administered SRB crosses the injured alveolar-capillary barrier thus reduces T specifically in injured lung regions; improves oxygenation; and reduces the degree of further lung injury. Intravenous SRB administration might help respiratory distress patients, including those with the novel coronavirus, avoid mechanical ventilation or, once ventilated, survive.


Structural analysis of monoclonal anti-arsonate antibodies: idiotypic specificities are determined by the heavy chain.
Hybrid immunoglobulin molecules were constructed from the isolated heavy and light chains of monoclonal anti-arsonate antibodies which differed in their expression of a cross-reactive idiotype. The reconstructed molecules were tested for public and private idiotypic determinants associated with the A-strain response to the hapten p-azophenylarsonate and it was found that both an appropriate heavy chain and an appropriate light chain were required for expression of idiotypic determinants. While appropriate heavy chains could be derived only from idiotype-positive antibodies, appropriate light chains could be derived not only from idiotype positive antibodies, but also from certain idiotype-negative molecules. Similarly, recombinant (hybrid) molecules constructed from two idiotype-positive immunoglobulins differing quantitatively in the degree of idiotypic character, expressed the character at a level which correlated with that of the heavy chain donor. Thus, while the serological expression of idiotypic determinants occurs only in the context of the appropriate VHVL combination, these data demonstrate that the determinants comprising the major cross-reactive idiotype of the anti-arsonate response of A/J mice have their bases in heavy chain structures.


Concomitant use of clopidogrel and statins and risk of major adverse cardiovascular events following coronary stent implantation.
• The CYP3A4 inhibition by lipophilic statins may attenuate the effectiveness of clopidogrel. • No studies have measured drug exposure in a time-varying manner that detects discontinuation and restart of clopidogrel and statin therapy, allowing clinical quantification of the interaction effect. • Clopidogrel and CYP3A4-metabolizing statin use were each associated with a substantially reduced rate of major adverse cardiovascular events within 12 months after coronary stent implantation. • Although we observed an interaction between use of clopidogrel and statins, statin use vs. non-use was not associated with an increased rate of major adverse cardiovascular events in patients using clopidogrel after coronary stent implantation. To examine whether CYP3A4-metabolizing statin use modified the association between clopidogrel use and major adverse cardiovascular events (MACE) after coronary stent implantation, using time-varying drug exposure ascertainment. We conducted this population-based cohort study in Western Denmark (population: 3 million) using medical databases. We identified all 13 001 patients with coronary stent implantation between 2002 and 2005 and their comorbidities. During 12 months of follow-up, we tracked the use of clopidogrel and CYP3A4-metabolizing statins and the rate of MACE. We used Cox regression to compute hazard ratios (HRs) controlling for potential confounders. The rate of MACE per 1000 person years was 104 for concomitant clopidogrel and statin use, 130 for clopidogrel without statin use, 108 for statin without clopidogrel use and 446 for no use of either drug. The adjusted HR comparing clopidogrel use with non-use was 0.68 (95% confidence interval (CI) 0.58, 0.79) among statin users and 0.34 (95% CI 0.29, 0.40) among statin non-users, yielding an interaction effect (i.e. relative rate increase) of 1.97 (95% CI 1.59, 2.44). The adjusted HR for MACE comparing statin use with non-use was 0.97 (95% CI 0.83, 1.13) among clopidogrel users and 0.49 (95% CI 0.42, 0.57) among clopidogrel non-users. Clopidogrel and CYP3A4-metabolizing statin use were each associated with a substantially reduced rate of MACE within 12 months after coronary stent implantation. Although we observed an interaction between use of clopidogrel and statins, statin use vs. non-use was not associated with an increased rate of MACE in patients using clopidogrel after coronary stent implantation.


Selective degeneration of two out of the nine types of synapses in cat caudate nucleus after cortical lesions.
In the cat caudate nucleus the same nine types of synapses are found as in putamen and fundus striati. The three parts of the striatum in the strict sense do not differ in the morphological differentiation of synapse types but only in their quantitative distribution. One-third of all synapses in the caudate nucleus are axo-spinous type IV synapses with a curved and divided asymmetric contact. This strongly suggests that the caudate nucleus interneuronal apparatus is dominated by centre-median input, in contrast to the putamen which is controlled by the cortico-striatal input to its internuncial cells and by its strong intrastriatal feedback mechanism. Extensive destruction of the convexity of the cortex and the medial cortex in one hemisphere results in dark degeneration of a large proportion of two of the nine types of caudate synapses: a) the axo-dendritic type VII synapses exciting the large spiny caudate neurons and b) the axo-spinous type III synapses making contact with the small spiny neurons of the interneuronal cell apparatus.


Primary structure of the adult human skeletal muscle voltage-dependent sodium channel.
The gene encoding the principal voltage-dependent sodium channel expressed in adult human skeletal muscle (SCN4A) has recently been linked to the pathogenesis of human hyperkalemic periodic paralysis and paramyotonia congenita. We report the cloning and nucleotide sequence determination of the normal product of this gene. The 7,823 nucleotide complementary DNA, designated hSkM1, encodes a 1,836 amino acid protein that exhibits 92% identity with the tetrodotoxin-sensitive rat skeletal muscle sodium channel alpha subunit, but lower homology with either the human heart sodium channel or with other sodium channels from immature rat muscle or rat brain. Specific hSkM1 RNA transcripts are expressed in adult human skeletal muscle but not in heart, brain, or uterus. The SCN4A gene product, hSkM1, is the human homologue of rSkM1, the tetrodotoxin-sensitive sodium channel characteristic of adult rat skeletal muscle. This structural information should provide the necessary backdrop for identifying and evaluating mutations affecting the function of this channel in the periodic paralyses.


Occurrence of phosphorylated forms of an acidic protein in the large ribosomal subunit of rat liver.
An acidic protein from rat liver 60-S ribosomal subunits was selectively extracted with 50% ethanol. It was revealed as three different spots by two-dimensional gel electrophoresis, two of them being attributable to phosphorylated forms since they disappeared after alkaline phosphatase treatment. The relationship between this protein and similar acidic proteins found in eucaryotic cells is discussed.


Nicotinic acetylcholine receptor subtypes in human frontal cortex: changes in Alzheimer's disease.
Molecular genetic and pharmacological studies have suggested that several subtypes of nicotinic acetylcholine receptors exist in the mammalian and avian brain. Combining 3H-(-)-nicotine, 125I-alpha-bungarotoxin, and 125I-kappa-bungarotoxin as ligands, we report here the first evidence for the existence in human frontal cortex of at least three different subtypes of nicotinic receptors. Autoradiographic analysis shows that specific 125I-kappa-bungarotoxin binding sites are concentrated mainly in several cortical layers. We also show that kappa-bungarotoxin, but not alpha-bungarotoxin decreases the evoked release of 3H-acetylcholine in rat cortical slices, indicating a likely presynaptic localization for some of the alpha-bungarotoxin-insensitive kappa-bungarotoxin sites in mammalian brain. The brains of patients with Alzheimer's disease show marked decreases in Bmax values for low-affinity 125I-kappa-bungarotoxin sites and both high- and low-affinity 3H-nicotine sites, whereas 125I-alpha-bungarotoxin sites are not significantly different in number from age-matched control brains. We conclude that Alzheimer's disease does not affect all subtypes of nicotinic receptors in the frontal cortex to the same extent.


Quadrupole moments of highly deformed structures in the A approximately 135 region: probing the single-particle motion in a rotating potential.
The latest generation gamma-ray detection system, GAMMASPHERE, coupled with the Microball charged-particle detector, has made possible a new class of nuclear lifetime measurement. For the first time differential lifetime measurements free from common systematic errors for over 15 different nuclei ( >30 rotational bands in various isotopes of Ce, Pr, Nd, Pm, and Sm) have been extracted at high spin within a single experiment. This comprehensive study establishes the effective single-particle transition quadrupole moments in the A approximately 135 light rare-earth region. Detailed comparisons are made with theoretical calculations using the self-consistent cranked mean-field theory which convincingly demonstrates the validity of the additivity of single-particle quadrupole moments in this mass region.


Use of osteochondral bone graft in coronoid fractures.
Results of the treatment of the deficient coronoid and chronic elbow instability have not been reported. The purpose of this study was to analyze the results of structural bone graft for reconstruction of the coronoid process. Structural bone graft was used to reconstruct the coronoid process of 6 patients. All injuries were of the terrible triad: fracture of the coronoid, radial head fracture, and collateral ligament disruption. All cases had persistent posterior subluxation averaging 6 months (range, 1-13 months before reconstruction. Patient charts, surgical records, and radiographs were reviewed. All patients were contacted at a mean of 64 months after treatment to answer a specific set of questions to determine the Mayo Elbow Performance score. In 1 patient, radiographs showed complete resorption of the graft and severe osteoarthritis of the elbow at 54 months after surgery (case 4). The Mayo Elbow Performance score showed 1 excellent, 2 good, 1 fair, and 2 poor results. Structural bone graft may be a useful option for a deficient coronoid process and an unstable elbow, but the outcome is unpredictable.


Hyperactivation of mTORC1 disrupts cellular homeostasis in cerebellar Purkinje cells.
Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolism. The importance of mTORC1 signaling in neuronal development and functions has been highlighted by its strong relationship with many neurological and neuropsychiatric diseases. Previous studies demonstrated that hyperactivation of mTORC1 in forebrain recapitulates tuberous sclerosis and neurodegeneration. In the mouse cerebellum, Purkinje cell-specific knockout of Tsc1/2 has been implicated in autistic-like behaviors. However, since TSC1/2 activity does not always correlate with clinical manifestations as evident in some cases of tuberous sclerosis, the intriguing possibility is raised that phenotypes observed in Tsc1/2 knockout mice cannot be attributable solely to mTORC1 hyperactivation. Here we generated transgenic mice in which mTORC1 signaling is directly hyperactivated in Purkinje cells. The transgenic mice exhibited impaired synapse elimination of climbing fibers and motor discoordination without affecting social behaviors. Furthermore, mTORC1 hyperactivation induced prominent apoptosis of Purkinje cells, accompanied with dysregulated cellular homeostasis including cell enlargement, increased mitochondrial respiratory activity, and activation of pseudohypoxic response. These findings suggest the different contributions between hyperactivated mTORC1 and Tsc1/2 knockout in social behaviors, and reveal the perturbations of cellular homeostasis by hyperactivated mTORC1 as possible underlying mechanisms of neuronal dysfunctions and death in tuberous sclerosis and neurodegenerative diseases.


Sensory Evolution: Making Sense of the Noni Scent.
A recent study identifies the neuronal and molecular underpinnings of a key ecological difference between two Drosophila species using a remarkable genetic toolbox for a non-model species.


Damage control surgery.
Damage control is a staged approach to severely injured patients predicated on treatment priorities. Initially, life-threatening injuries are addressed expediently, and procedures are truncated. Normal physiology is restored in the ICU, and patients subsequently are returned to the operating room for definitive management. This strategy breaks the bloody vicious cycle and results in improved outcomes. Novel technologies like CAVR and rFVIIa contribute to the effectiveness of damage control.


Ambulatory treatment of suspected pelvic inflammatory disease with Augmentin, with or without doxycycline.
Sixty-three women with suspected pelvic inflammatory disease were treated as outpatients with Augmentin with or without doxycycline. Initially, doxycycline was added only after a direct test for Chlamydia trachomatis was positive. Because chlamydial infections were frequent, all patients received doxycycline during the last two thirds of the study. Neisseria gonorrhoeae or Chlamydia trachomatis were recovered from 15 (65%) of 23 women classified as probably having pelvic inflammatory disease. Among 47 women reexamined after starting therapy, three rapidly became worse and were hospitalized, nine (20%) discontinued therapy because of gastrointestinal side effects, and all of the remaining 35 women who completed therapy were either cured or improved.


Corrigendum: Moderate and Deep Hypothermic Circulatory Arrest Have Comparable Effects on Severe Systemic Inflammatory Response Syndrome After Total Aortic Arch Replacement in Patients With Type A Aortic Dissection.
[This corrects the article DOI: 10.3389/fsurg.2021.758854.].


Combination of levofloxacin and cisplatin enhances anticancer efficacy via co-regulation of eight cancer-associated genes.
Chemosensitizer or combined chemotherapy can sensitize cancer cells to therapy and minimize drug resistance. We reveal that levofloxacin has broad-spectrum anticancer activity. Here we report that combination of levofloxacin and cisplatin further enhanced cytotoxicity in cancer cells by further promotion of apoptosis. Levofloxacin concentration-dependently promoted the inhibition of clone formation in cancer cells treated by cisplatin, and their combination further suppressed the tumor growth in mice. Levofloxacin and cisplatin co-regulated genes in directions supporting the enhancement of anticancer efficacy, of which, THBS1, TNFAIP3, LAPTM5, PI3 and IL24 were further upregulated, NCOA5, SRSF6 and SFPQ were further downregulated. Out of the 24 apoptotic pathways significantly enriched in the combination group, TNFAIP3, THBS1, SRSF6 and SFPQ overlapped in 14, 13, 3 and 1 pathway respectively. Jak-STAT/Cytokine-cytokine receptor interaction pathway network and extrinsic apoptotic signaling pathway were significantly enriched in levofloxacin group, cisplatin group and combination group. Jak-STAT/Cytokine-cytokine receptor interaction/Focal adhesion/EMC-receptor interaction pathway network was significantly enriched in the combination group, and IL24 and THBS1 were the overlapped genes. In conclusion, enhancement of anticancer efficacy in combination group was associated with the further regulation of THBS1, TNFAIP3, LAPTM5, PI3, IL24 and NCOA5, SFPQ, SRSF6. Targeting of Jak-STAT/Cytokine-cytokine receptor interaction/Focal adhesion/EMC-receptor interaction pathway network was correlated to the enhancement. With additional benefit to cancer patients for treatment or prophylaxis of an infectious syndrome, levofloxacin can benefit cancer chemotherapy no matter it is used independently or used with other chemotherapeutic drugs.


Microwave-assisted quick synthesis of microcrystalline cellulose from black tea waste (Camellia sinensis) and characterization.
Tea wastes generated in the industries during tea production processes show excellent potential to be used as a renewable, abundant, and cheap source for the extraction of microcrystalline cellulose. In the current work, MCC was isolated from black tea waste through microwave heating instead of using conventional heating and avoiding the traditional acid hydrolysis method. Microwave increased the reaction speed significantly and resulted in very quick delignification and bleaching of black tea waste to isolate MCC in white powdered form. FTIR, XRD, FESEM, and TGA analysis were then carried out to investigate the chemical functionality, crystallinity, morphology, and thermal properties, respectively, of the synthesized tea waste MCC. The characterization results demonstrated that cellulose with a short rough fibrous structure having an average particle size of around 23.06 μm was extracted. The results of FTIR and XRD demonstrated unequivocally that all amorphous non-cellulosic compounds had been eliminated. The microwave-extracted black tea waste MCC showed 89.77 % crystallinity and good thermal properties, indicating that it could be a promising filler material for preparing polymer composites. Therefore, microwave-assisted delignification and bleaching can be used as a suitable, energy-efficient, time-saving and low-cost method for extracting MCC from the black tea waste produced in tea factories.


Nonoperative Management of Lateral Epicondyle Tendinopathy: An Umbrella Review.
The primary objective of this review was to summarize systematic reviews and meta-analyses reporting on nonoperative management of lateral epicondyle tendinopathy. An umbrella review of all published systematic reviews and meta-analyses was performed. Three databases were searched using the key words "tennis elbow," "lateral epicondylitis," "non-operative," and "non-surgical modalities." The search was limited to English-language systematic reviews and meta-analyses between the years of 2000 and 2022. There were 114 systematic reviews/meta-analyses, of which 35 met our inclusion criteria. These articles reviewed the following nonoperative management strategies: ultrasound, shockwave therapy, injection procedures, low-level laser therapy, joint mobilizations, exercise therapy, and electrophysical modalities. Exercise therapy was beneficial in decreasing pain regardless of dosage or type. Conflicting results were seen with ultrasound, laser, and shockwave therapy. Corticosteroid injections provided the most short-term pain relief, and platelet-rich plasma and autologous blood injections were most effective in the long term. A variety of nonoperative interventions were found to be effective for short- and long-term pain relief as well as functional improvement, with most interventions indicating mixed results. Due to variations in study populations and study quality, results should be interpreted with caution.


The molecular evolution and DNA profiling of toxic cyanobacteria.
Rapid and sensitive methods for the detection and genetic characterization of cyanobacteria have been developed based on DNA amplification techniques. This article describes the molecular methods that have been used to characterize cyanobacteria and their use as tools to identify toxin-producing strains. Different species and strains were compared using restriction fragment length polymorphism (RFLP) of amplified fragments of the phycocyanin gene and the 16S-23S rRNA internal transcribed spacer.


CR/periphilin is a transcriptional co-repressor involved in cell cycle progression.
CR/periphilin (CR) retards cell cycle progression mainly at the S-phase in part by transcriptionally repressing expression of Cdc7, the key regulator of DNA replication, and in part by unknown mechanisms. In this study, we show that enforced expression of CR inhibits Cdc7 promoter activity. The attachment of the DNA-binding domain of the yeast GAL4 transcription factor to CR that appears without DNA-binding sequences, enables CR to repress GAL4 promoter-mediated transcription in a histone deacetylase (HDAC) activity-dependent manner. CR forms a complex with mSin3A, a common component in transcriptional repressor complexes, as well as with HDAC1, suggesting that CR may behave as a co-repressor by functional interaction with the Sin3/HDAC co-repressor complex. We also demonstrate that an alternatively spliced variant of CR, CR-S, which is without a region encoded by exon 4 of the CR gene and is a weak interactor with HDAC1, shows a suppressing effect on CR activity.


Beraprost sodium, a prostacyclin (PGI) analogue, ameliorates concanavalin A-induced liver injury in mice.
Prostacyclin (PGI(2)) is a potent mediator in the inflammatory and coagulation processes. The aim of this study was to test whether beraprost sodium, a PGI(2) analogue, could prevent experimental hepatic injury induced by concanavalin A (Con A), which is a model of fulminant hepatic failure. Beraprost (100 microg/kg) was administered intraperitoneally simultaneously with Con A (40 mg/kg) in C57B6J mice. Blood circulation in the liver was determined by laser-Doppler flowmetry. Plasma levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-6 were determined. Levels of TNF-alpha and IFN-gamma in culture supernatant of splenocytes were also determined. Beraprost administration reduced the incidence of death following hepatic failure (76.5% vs. 29.4%, P<0.05). Plasma levels of ALT were significantly lower in the beraprost-treated group than in the control group, and in the former, there was concomitant suppression of the histological features of injury. Beraprost significantly increased hepatic blood flow volume in Con A-treated mice. Plasma levels of TNF-alpha and IFN-gamma were significantly reduced at 6 and 12 h after Con A injection, respectively, but the levels of IL-6 were increased at 6 h. In vitro, beraprost also suppressed Con A-induced TNF-alpha production in splenocytes, while it stimulated IFN-gamma production. These findings imply that beraprost suppresses Con A-induced liver injury. These data also suggest that beraprost, which is clinically effective in treating pulmonary hypertension, may have therapeutic potential for preventing hepatic injury.


GITR/GITRL reverse signalling modulates the proliferation of hepatic progenitor cells by recruiting ANXA2 to phosphorylate ERK1/2 and Akt.
Hepatic stem/progenitor cells are the major cell compartment for tissue repair when hepatocyte proliferation is compromised in chronic liver diseases, but the expansion of these cells increases the risk of carcinogenesis. Therefore, it is essential to explore the pathways restricting their expansion and abnormal transformation. The ligand of glucocorticoid-induced tumour necrosis factor receptor (GITRL) showed the most highly increased expression in hepatic progenitor cells treated with transforming growth factor (TGF)-β1. If overexpressed by hepatic progenitor cells, GITRL stimulated cell proliferation by activating the epithelial-mesenchymal transition pathway and enhancing ERK1/2 and Akt phosphorylation via GITRL binding to ANXA2. However, GITR, the specific GITRL receptor, suppressed the epithelial-mesenchymal transition pathway of GITRL-expressing cells and decreased their growth by dissociating ANXA2 from GITRL and reducing downstream ERK1/2 and Akt phosphorylation. This study identifies GITR/GITRL reverse signalling as a cross-interaction pathway between immune cells and hepatic stem/progenitor cells that restricts the expansion of hepatic stem/progenitor cells and reduces the possibility of carcinogenesis.


Disparity in outcomes of melanoma adjuvant immunotherapy by demographic profile.
Randomized comparisons have demonstrated survival benefit of adjuvant immunotherapy in node-positive melanoma patients but have limited power to determine if this benefit persists across various demographic factors. We assessed the impact of demographic factors on the survival benefit of adjuvant immunotherapy in a database of 38,189 node-positive melanoma patients using the Kaplan-Meier method and Cox proportional hazards models. All assessed demographic factors other than race significantly impacted survival of node-positive melanoma patients in univariate analysis. In multivariable analysis, only the age group interacted with immunotherapy. Analysis of this large database of unselected node-positive melanoma patients demonstrated a positive survival benefit of immunotherapy across all demographic factors assessed and the impact was greater for patients 65 years of age and older.


Prefrontal hypoperfusion and cognitive dysfunction correlates in spinocerebellar ataxia type 6.
The aim of this study is to evaluate the correlation between brain perfusion and cognitive dysfunction in spinocerebellar ataxia type 6 (SCA6) patients. Thirteen genetically confirmed SCA6 patients and 21 age- and education-matched control subjects were subjected to single photon emission computed tomography (SPECT) and neuropsychological tests. Brain perfusion was examined with SPECT analysis, while general cognition, verbal and visual memory, attention, visuospatial ability, language, executive function, depression, and anxiety were examined with the neuropsychological tests. SCA6 patients showed prefrontal hypoperfusion, and impairments of visual memory, verbal fluency, and executive function compared to control subjects. These neuropsychological impairments in SCA6 patients were significantly correlated with a decrease in prefrontal perfusion. This relation was not correlated to other factors, such as age, education and severity of cerebellar ataxia, which are possible relevant factors associated with cognitive performance. SCA6 patients have mild cognitive impairment, and correlating prefrontal hypoperfusion. These results indicate cognitive impairment in SCA6 patients resulting from prefrontal hypoperfusion.


Medication-related osteonecrosis of the jaw associated with implant and regenerative treatments: Systematic review.
The aim of this study was to determine if the treatment with bisphosphonates other anti-resorptive and antiangiogenic agents influences the success of regenerative and / or implant treatments. We reviewed the literature from the last 5 years in the PubMed database, using the following words: "Sinus Floor Augmentation"[Mesh] OR "Dental Implants"[Mesh]) OR "Guided Tissue Regeneration"[Mesh]) AND "Osteonecrosis"[Mesh]. The articles were selected following the inclusion and exclusion criteria and were evaluated using the 22 items of the STROBE declaration. The following PICO clinical question was applied: Does the treatment with agents associated with drug osteonecrosis influence the success of regenerative and implant treatments? The initial search resulted in a total of 27 articles. After eliminating those that did not refer to the topic, were duplicated or did not meet the inclusion / exclusion criteria, a full reading of the articles was made evaluating their methodological quality, obtaining six studies with high methodological quality and two with moderate. The literature regarding this topic is scarce, randomized clinical trials would be necessary to establish protocols relative to implant treatment in patients on antiresorptive treatments. The risk of developing an osteonecrosis associated with the regeneration / implant placement in patients with benign bone diseases is scarce, but it exists and it should not be underestimated. Especially, in the posterior areas of the jaw, if the duration of treatment with BP is greater than 3 years, and if the patient is under therapy with systemic corticosteroids.


Molecular technology and pancreatic cancer.
Pancreatic cancer is the fifth leading cause of cancer death in the Western world. Despite improvement in operative mortality rates, little impact has been made on overall 5-year survival. This review discusses the molecular changes peculiar to pancreatic cancer and how the use of molecular technology might affect detection, screening, diagnosis and treatment of the disease. A literature review was performed using the National Library of Medicine's Pubmed database; this was combined with ongoing work within the Queen Elizabeth Hospital, Birmingham. Over the past 20 years great strides have been made in our understanding of the molecular basis of disease. Advances in molecular biology are now reshaping how diseases are screened for, diagnosed, investigated and treated. In recent years collaboration between clinicians and basic scientists has revealed a unique pattern of genetic and molecular events in pancreatic cancer. This review discusses how these advances may impact on patients with this disease. The past decade has seen some improvement in outlook for patients with pancreatic cancer, but the 'molecular age' promises to deliver even better results.


Mesenteric ischemia: a radiologic perspective.
Mesenteric ischemia is a broad term encompassing several clinical conditions leading to impaired vascularity of bowel loops. Absence of specific clinical presentation and a definitive laboratory marker often lead to delayed diagnosis with high morbidity and mortality in the acute setting. Imaging plays a crucial role in the diagnosis and management. Multi-detector CT (MDCT) is the first line imaging modality for the evaluation of patients with suspected mesenteric ischemia and plays an important role for assessing its severity and complications. This review article highlights the causes, pathophysiology, imaging features and possible endovascular treatment options of mesenteric ischemia.


Virtual screening for novel quorum sensing inhibitors to eradicate biofilm formation of Pseudomonas aeruginosa.
The automated docking program DOCK 5.3.0 was applied to screening for quorum sensing inhibitors (QSIs) of Peudomonus aeruginosa from a database containing 51 active components of Traditional Chinese Medicines with antibacterial activity. Five potential QSIs were revealed by the computer-based virtual screening. The compounds 3, 4, 5, 6, 7 inhibit biofilm formation of P. aeruginosa at a concentration of 200 microM. Compound 4 (baicalein) does not inhibit the growth of P. aeruginosa; however, it significantly inhibits biofilm formation of the bacteria at a lower concentration of 20 microM and promoted proteolysis of the signal receptor TraR protein in Escherichia coli at 4-40 mM. Baicalein and ampicillin showed synergistic activity against P. aeruginosa. These results suggested that baicalein can interfere with quorum sensing system of P. aeruginosa and will be developed as antibacterial agent with novel target.


[Changes in the population composition and the rates of proliferation and specialization of erythroid cells in rats with experimental anemia].
Cytomorphologic, morphometric and population analyses have revealed that during acute anemia, induced by phenylhydrazin, the proliferative activity of erythroblasts increases, an abrupt change in the structures of erythroid populations of both bone marrow and peripheral blood is observed, together with the increase in the rates of their specialization. Also, the ratio of the stem cells which differentiate by the erythroid pathway is increased, and the macro- and microcytosis mechanisms, which are essentially salient in normal conditions, are switched on. The roles of macro- and microcytes in the restoration of the normal amount of erythroid cells and haemoglobin contents in the blood are discussed.


Long-term cost-effectiveness of quality of diabetes care; experiences from private and public diabetes centers in Iran.
The quality of health care has a significant impact on both patients and the health system in terms of long-term costs and health consequences. This study focuses on determining the long-term cost-effectiveness in quality of diabetes care in two different settings (private/public) using longitudinal patient-level data in Iran. By extracting patients intermediate biomedical markers in under-treatment type 2 diabetes patients(T2DP) in a longitudinal retrospective study and by applying the localized UKPDS diabetes model, lifetime health outcomes including life expectancy, quality-adjusted Life expectancy (QALE) and direct medical costs of managing disease and related complications from a healthcare system perspective was predicted. Costs and utility decrements had derived on under-treatment T2DP from 7 private and 8 Public diabetes centers. We applied two steps sampling mehods to recruit the needed sample size (cluster and random sampling). To cope with first and second-order uncertainty, we used Monte-Carlo simulation and bootstrapping techniques. Both cost and utility variables were discounted by 3% in the base model. In a 20-year time horizon, according to over 5 years of quality of care data, outcomes-driven in the private sector will be more effective and more costly (5.17 vs. 4.95 QALE and 15,385 vs. 8092). The incremental cost-effectiveness ratio (ICER) was $33,148.02 per QALE gained, which was higher than the national threshold. Although quality of care in private diabetes centers resulted in a slight increase in the life expectancy in T2DM patients, it is associated with unfavorable costs, too. Private-sector in management of T2DM patients, compared with public (governmental) diabetic Centers, is unlikely to be cost-effective in Iran.


Accelerated evolution of SARS-CoV-2 in free-ranging white-tailed deer.
The zoonotic origin of the COVID-19 pandemic virus highlights the need to fill the vast gaps in our knowledge of SARS-CoV-2 ecology and evolution in non-human hosts. Here, we detected that SARS-CoV-2 was introduced from humans into white-tailed deer more than 30 times in Ohio, USA during November 2021-March 2022. Subsequently, deer-to-deer transmission persisted for 2-8 months, disseminating across hundreds of kilometers. Newly developed Bayesian phylogenetic methods quantified how SARS-CoV-2 evolution is not only three-times faster in white-tailed deer compared to the rate observed in humans but also driven by different mutational biases and selection pressures. The long-term effect of this accelerated evolutionary rate remains to be seen as no critical phenotypic changes were observed in our animal models using white-tailed deer origin viruses. Still, SARS-CoV-2 has transmitted in white-tailed deer populations for a relatively short duration, and the risk of future changes may have serious consequences for humans and livestock.


Nitrate reductase activity in some subarctic species and UV influence in the foliage of Betula pendula Roth. seedlings.
Nitrate reductase (NR) activity was studied in the foliage of five subarctic species: mature trees of European white birch (Betula pubescens Erch. S.S.), Scots pine (Pinus sylvestris L.), Norway spruce (Picea abies L. Karst), Ericaceous shrub bilberry (Vaccinium myrtillus L.), naturally growing in a forest, and seed-grown silver birch (Betula pendula Roth.) seedlings in an ultraviolet (UV) exclusion field experiment at the Pallas-Ounastunturi National Park in Finnish Lapland (68 degrees N). Mean NR activity ranged from 0 in bilberry to 1477 (S.D. = 277.7) and 1910 (S.D. = 785.4) nmol g(-1) DW h(-1) in mature trees of European white birch and silver birch seedlings, respectively. Significant differences due to UV exclosure treatments were determined for the NR activity of silver birch seedlings (F = 3.62, P= 0.025*) after three growing seasons (191 days) of UV exclusion. The ambient and control silver birch seedlings had or tended to have higher NR activity than those grown under UV exclusion. No relationship was found between the foliage NR activity and total nitrogen content, which ranged from 0.61 to 1.35% per seedling. The present study suggests large differences in NR activity between the species and the induction of NR activity in silver birch seedlings due to ambient UV radiation.


Ethanol-dependent induction of bilirubin UDP-glucuronosyl-transferase in rat liver is mediated by Kupffer cells.
Recently we have reported that bilirubin UDP-glucuronosyltransferase (UGT1A1) is induced in rat liver by chronic ethanol treatment. Several studies have shown that Kupffer cells play a central role in the mediation of various hepatic effects of chronic alcohol consumption. In the present work, the participation of Kupffer cells in the ethanol dependent induction of UGT1A1 was investigated. A group of rats was pretreated with gadolinium chloride, a known Kupffer-cell-depleting agent. We compared the effect of chronic ethanol ingestion on UGT1A1 expression in the liver of normal and gadolinium chloride treated rats. The effect of ethanol on bilirubin glucuronidation was completely prevented in Kupffer cell deficient rats. The western and northern blot analyses showed that the increase of both the protein and mRNA of UGT1A1 was prevented in these animals. These results suggest that Kupffer cells play a major role in the mediation of ethanol-stimulated induction of UGT1A1 in liver parenchymal cells.


Knowledge-assisted recognition of cluster boundaries in gene expression data.
DNA microarray technology has made it possible to determine the expression levels of thousands of genes in parallel under multiple experimental conditions. Genome-wide analyses using DNA microarrays make a great contribution to the exploration of the dynamic state of genetic networks, and further lead to the development of new disease diagnosis technologies. An important step in the analysis of gene expression data is to classify genes with similar expression patterns into the same groups. To this end, hierarchical clustering algorithms have been widely used. Major advantages of hierarchical clustering algorithms are that investigators do not need to specify the number of clusters in advance and results are presented visually in the form of a dendrogram. However, since traditional hierarchical clustering methods simply provide results on the statistical characteristics of expression data, biological interpretations of the resulting clusters are not easy, and it requires laborious tasks to unveil hidden biological processes regulated by members in the clusters. Therefore, it has been a very difficult routine for experts. Here, we propose a novel algorithm in which cluster boundaries are determined by referring to functional annotations stored in genome databases. The algorithm first performs hierarchical clustering of gene expression profiles. Then, the cluster boundaries are determined by the Variance Inflation Factor among the Gene Function Vectors, which represents distributions of gene functions in each cluster. Our algorithm automatically specifies a cutoff that leads to functionally independent agglomerations of genes on the dendrogram derived from similarities among gene expression patterns. Finally, each cluster is annotated according to dominant gene functions within the respective cluster. In this paper, we apply our algorithm to two gene expression datasets related to cell cycle and cold stress response in budding yeast Saccharomyces cerevisiae. As a result, we show that the algorithm enables us to recognize cluster boundaries characterizing fundamental biological processes such as the Early G1, Late G1, S, G2 and M phases in cell cycles, and also provides novel annotation information that has not been obtained by traditional hierarchical clustering methods. In addition, using formal cluster validity indices, high validity of our algorithm is verified by the comparison through other popular clustering algorithms, K-means, self-organizing map and AutoClass.


Erratum: Therapeutic Plasma Exchange Practices in Intensive Care Unit.
[This corrects the article on p. 336 in vol. 23, PMID: 31406443.].


Effect of increasing trypsin concentrations on seminal coagulum dissolution and sperm parameters in spider monkeys (Ateles geoffroyi).
Seminal coagulum formation in spider monkeys (Ateles geoffroyi) interferes with the efficient recovery and evaluation of spermatozoa. The main objective was to assess the effect of increasing concentrations of trypsin on dissolution of seminal coagulum and spermatic parameters. Seminal coagulum was incubated at 37 °C without trypsin or in the presence of increasing trypsin concentrations (0.1%, 1.0%, and 5.0%). For each sample, coagulum dissolution time was measured, and sperm concentration, viability, motility, and morphology were evaluated using light microscopy and/or transmission electronic microscopy (TEM). Trypsin concentrations of 1.0% and 5.0% more rapidly liquefied seminal coagulum, averaging 32 and 21 min, respectively, compared with nontrypsinized controls, with maintenance of greater sperm viability (70.8% and 72.5%, respectively). Coagulum treated with 1.0% trypsin and the liquid ejaculate fraction averaged higher sperm motility (40.1% and 55.6%, respectively) than control samples, and both 1.0% and 5.0% trypsin treatment allowed recovery of increased numbers of motile spermatozoa. There was greater sperm fragmentation at the head and midpiece level after treatment with 1.0% and 5.0% trypsin (55.8% and 55.9%); however, the percentage of normal morphology in structurally intact spermatozoa did not differ relative to controls. With transmission electronic microscopy imaging, there were similar percentages of spermatozoa with plasma membrane swelling in the midpiece and acrosomal regions in trypsin-treated samples and controls. In conclusion, trypsin treatment of spider monkey seminal coagulum exerted a concentration-dependent effect on dissolution time and various spermatic parameters. Higher trypsin concentrations caused more rapid liquefaction of coagulum and recovery of greater numbers of motile spermatozoa, but may adversely affect fragmentation of spermatozoa and could compromise sperm function and cryopreservation potential.


Pediatric COVID-19 case with regard to the family infection chain and the psychosocial context.
The role of children in households, spreading SARS-CoV-2, may differ from measles or influenza, and therefore, these diseases are not directly comparable to COVID-19. The psychosocial aspect of infection and quarantine for families and children suggests that fear of social stigmatization can lead to not disclosing the infection.


Methods for diagnosis and treatment of stimulus-correlated motion in generic brain activation studies using fMRI.
Movement-related effects in realigned fMRI timeseries can be corrected by regression on linear functions of estimated positional displacements of an individual subject's head during image acquisition. However, this entails biased (under)estimation of the experimental effect whenever subject motion is not independent of the experimental input function. Methods for diagnosing such stimulus-correlated motion (SCM) are illustrated by application to fMRI data acquired from 5 schizophrenics and 5 normal controls during periodic performance of a verbal fluency task. The schizophrenic group data were more severely affected by SCM than the control group data. Analysis of covariance (ANCOVA) was used, with a voxelwise measure of SCM as a covariate, to estimate between-group differences in power of periodic signal change while controlling for variability in SCM across groups. Failure to control for SCM in this way substantially exaggerated the number of voxels, apparently demonstrating a between-group difference in task response.


Effect of culture conditions on the phenotype of THP-1 monocyte cell line.
Macrophage function has many implications in a variety of diseases. Understanding their biology becomes imperative when trying to elucidate immune cell interactions with their environment, and in vitro cell lines allow researchers to manipulate these interactions. A common cell line used is THP-1, a promyeloid cell line suggestive to outside factors, and therefore sensitive to culture conditions. In this study, we describe how culture conditions can alter THP-1 morphology and in turn affect their response to differentiation stimuli. THP-1 cells were cultured in two conditions and treated with phorbol 12-myristate 13-acetate (PMA) or MCSF. CD14 surface expression was determined by flow cytometry and cytokine/chemokine production determined by multiplex analysis. Culture conditions of THP-1 affect their response to PMA. Highly confluent THP-1 cells differentiate into a heterogeneous population responsive to PMA as seen by an increase in CD14 expression. However, these cells, cultured in low confluence, remain as a homogenous population and do not gain CD14. Additionally, there are major differences in the constitutive cytokine profile. We demonstrate that the culture conditions of THP-1 cells can alter their response PMA. This suggests that culture techniques may account for the discrepancy in the literature of both basal THP-1 phenotype and their response to PMA.


Determination of diltiazem in human whole blood and plasma by high-performance liquid chromatography using a polymeric reversed-phase column and utilizing a salting-out extraction procedure.
A rapid, simple and sensitive reversed-phase high-performance liquid chromatography method for the separation and measurement of the concentration of diltiazem in human whole blood and plasma has been developed. The method involves a simple one-step solvent extraction of the drug from biological samples followed by salting-out the organic solvent using ammonium sulfate. A 15 cm x 4.1 mm, PRP-1, pH-stable (pH 1-13) polymeric reversed-phase column was used with an isocratic elution of acetonitrile-0.01 M tetrabutylammonium hydroxide (60:40, v/v). Diltiazem was monitored at 254 nm and 0.50-0.005 a.u.f.s. The completion time for assay was less than 15 min, and the limit of detection was 10 ng/ml at a signal-to-noise ratio of 3 for a 50-microliters injection volume. Using this method, the pharmacokinetic parameters (elimination rate constant, elimination half-life and area under the curve) were calculated from a whole blood concentration versus time profile of diltiazem.


The physiological effects of aerobic dance. A review.
Aerobic dance exercise is currently one of the most commonly practised adult fitness activities. The majority of the research pertaining to this form of exercise supports its application as a valid cardiovascular training alternative, especially for adult females if performed according to the American College of Sports Medicine (ACSM) guidelines. If, however, the participant is interested in modifying body composition, training frequency, duration, or efforts toward caloric restriction may need to be increased or altered beyond those employed in the aerobic dance training investigations. The amount of energy expended during a bout of aerobic dance can vary dramatically according to the intensity of the exercise. 'Low intensity' dance exercise is usually characterised by less large muscle activity and/or less lower extremity impact, and music of slower tempo. Dance exercise representative of this variety requires a cost of approximately 4 to 5 kcal/minute. Several trials, however, have shown that vigorous 'high intensity' aerobic dance which entails using the large muscle groups can require 10 to 11 kcal/minute. The associated training outcomes could be affected by such differences in dance exercise intensity and style.


A refined method for assessing 99mTc-MDP whole body retention in prostate cancer patients.
Whole body retention (WBR) of 99mTc labeled methylene diphosphonate (MDP) has been shown to significantly differentiate various clinical stages of prostate cancer. Whole body measurements, when performed at 5 min and 24 h after i.v. administration of 99mTc-MDP, allows for the calculations of percentage whole body retention (% WBR) after one day. The latter can be expressed relative to either the anterior or posterior projection, or in combination as the geometric mean value. In an attempt to better describe the clinical course of prostate cancer patients with bone metastases we have refined the % WBR calculations to include a normalization factor. The latter consists of the mean 24-h value of WBR's as obtained from 10 prostate cancer patients without bony metastases as determined by bone scintigram. These values were determined for each projection to be: anterior = 26.5 +/- 4.7%, posterior = 37.5 +/- 7.4%, and geometric mean = 31.5 +/- 5.7%. The % WBR is then divided by the normalization factor of choice and expressed as (% WBR)N. These data are used to better express 99mTc MDP 24-h whole body retentions when following the clinical course of patients with metastatic carcinoma of the prostate. Caution should be exercised when interpreting these data when metabolic bone pathology is present. A false negative (% WBR)N value will result if an infiltration of the 99mTc-MDP occurs during administration.


Cytological and histological features in a case of endometrial adenocarcinoma.
We have examined a case of endometrial adenocarcinoma in which the cytological sample was indicative for a histotype which was not the predominant component in the histological examination of the uterus. The cytological diagnosis was: pattern concerning adenocarcinoma poorly differentiated; the histological diagnosis was: moderately differentiated endometrial adenocarcinoma. The Authors underline the usefulness of the integration of histological and cytological examinations for a better prognostic evaluation of endometrial adenocarcinoma.


Psychosocial factors and perceived tremor disability in essential tremor.
Growing evidence suggests that patients with essential tremor (ET) show impairment in psychosocial functions and subsequently increasing vulnerability to anxiety. Here we review evidence supporting a positive relationship between self-reported motor disability and psychological symptoms in ET and critically analyze evidence suggesting how psychosocial factors enhance tremor disability in ET. Theories related to motor competency, behavioral conditioning, and social anxiety have been proposed to relate self-concepts to self-reported tremor disability. We review these theories and then propose a new model in an effort to focus on the self-concepts among ET patients as a factor in tremor disability. Patients with ET exhibited cognitive abnormalities, depression, anxiety, and a higher prevalence of avoidant personality types. Although anxiety, depression and personality types may influence tremor disability in ET, self-concepts may better explain perceived tremor disability in social situations. We conclude by discussing a proposed biopsychosocial model and suggesting future research on ET specific assessment tools and intervention methods.


The role of phosphoenolpyruvate and lactate production in insulin secretion.
There is a positive correlation between lactate output and insulin secretion but there is no correlation between total islet PEP content and insulin secretion and no correlation between cAMP production and insulin release. Neither PEP or cAMP seem to be primary triggers to insulin release but may rather act as positive modulators of insulin secretion. Potentially, PEP can maintain an elevated cytoplasmic Ca++ concentration by inhibiting Ca++ uptake in the mitochondria, increase the concentration of cAMP in the beta-cells by activating the adenylate cyclase (11) and change the phosphorylation state of the plasma membrane (12). The possible trigger effect of an increased glycolytic flux on insulin secretion may be mediated perhaps via changes in the NADH/NAD+ ratio (13). As regards the mechanism of potentiation of insulin release: in the fed state potentiation may be related to an increased glycolytic flux whereas this is not the case during starvation. Here enhancement of cAMP may play a role.


Output feedback H∞ control for singular hybrid systems with partly unknown transition rates and input saturation.
This paper investigates dynamic output feedback H∞ control for singular Markovian jump systems with partly unknown transition rates and input saturation. Necessary and sufficient conditions that singular Markovian jump system satisfies stochastic admissibility and H∞ performance index are successfully deduced in terms of linear matrix inequalities under the two different conditions of completely known transition rates and partly unknown transition rates. Mode-dependent dynamic output feedback controller is designed to ensure that the closed-loop singular Markovian jump system satisfies stochastic admissibility and H∞ performance index. Novel set invariant condition is proposed, and it not only provides an estimate of the attractive domain of the closed-loop system but also allows the analysis of performance outside the stability region within this invariant set. Furthermore, the estimation of the attraction domain comes down to the determination of the largest contractively invariant ellipsoid satisfying the necessary and sufficient conditions and the novel set invariant condition, and it is solved as an optimization problem with linear matrix inequality constraints. Finally, the effectiveness and utility of the proposed method are verified by a numerical example and an oil catalytic cracking process.


Characterisation of partial volume effect and region-based correction in small animal positron emission tomography (PET) of the rat brain.
Accurate quantification of PET imaging data is required for a useful interpretation of the measured radioactive tracer concentrations. The partial volume effect (PVE) describes signal dilution and mixing due to spatial resolution and sampling limitations, which introduces bias in quantitative results. In the present study we investigated the magnitude of PVE for volumes of interest (VOIs) in the rat brain and the effect of positron range. In simulated (11)C-raclopride studies we examined the influence of PVE on time activity curves in striatal and cerebellar VOIs and binding potential estimation. The performance of partial volume correction (PVC) was studied using the region-based geometric transfer matrix (GTM) method including the question of whether a spatially variant point spread function (PSF) is necessary for PVC of a rat brain close to the centre of the field of view. Furthermore, we determined the effect of spillover from activity outside the brain. The results confirmed that PVE is significant in rat brain PET and showed that positron range is an important factor that needs to be included in the PSF. There was considerable bias in time activity curves for the simulated (11)C-raclopride studies and significant underestimation of binding potential even for very small centred VOIs. Good activity recovery was achieved with the GTM PVC using a spatially invariant simulated PSF when no activity was present outside the brain. PVC using a simple Gaussian fit point spread function was not sufficiently accurate. Spillover from regions outside the brain had a significant impact on measured activity concentrations and reduced the accuracy of PVC with the GTM method using rat brain regions alone, except for the smallest VOI size but at the cost of increased noise. Voxel-based partial volume correction methods which inherently compensate for spillover from outside the brain might be a more suitable choice.


The biological standard of living and mortality in Central Italy at the beginning of the 19th century.
The biological standard of living in Central Italy at the beginning of the 19th century is analyzed using newly collected data on the height of recruits in the army of the Papal States. The results reveal a decline in height for the cohorts born under French rule (1796-1815). Although this trend was common to many parts of Europe, the estimated magnitude of the decline suggests a worsening of the biological standard of living of the working classes in the Papal States even relative to that of other countries. Despite the differences in the economic systems within the Papal States, no significant geographical variation in height has been found: even the most dynamic and advanced regions experienced a dramatic height decline. Mortality also increased during the period under consideration.


[New aspects of causal therapy of hearing and speech development disorders caused by cleft palate].
Seromucous effusions were found in the tympanum in 91% of 208 cases of cleft palate. The incidence of recurrent mucosal effusions after paracentesis alone, in addition to drainage of the middle ear and poor speech results after veloplasty alone (according to Schweckendieck), led to the realization that hearing and speech disturbances in patients with cleft palates must be treated with a combination of morphologically correct veloplasty and tympanic drainage. Taking into consideration the fact that the auditory canal reaches maturation at the end of the first year of life, this procedure should be performed before the patient is 12 months old.


Topoisomerase I inhibitors from the Streptomyces sp. strain KM86-9B isolated from a marine sponge.
The crude extract of Streptomyces sp. strain KM86-9B, isolated from a marine sponge, displayed significant inhibition on topoisomerase I activity. Investigation of the causative components by bioactivity-directed fractionation resulted in the isolation of a series of iso- and anteiso-fatty acids.


Apoptosis.
Apoptosis is a process of cell suicide, the mechanisms of which are encoded in the genomes of all higher eukaryotes. The mechanisms involved in apoptosis suggest that the process is based on a viral defense originally developed in primitive multicelled eukaryotes and that the fundamental execution platform of the process involves 1) inhibition of protein synthesis at the level of translation initiation, 2) proteolysis specifically involving degradation of DNA repair mechanisms, and 3) polynucleotide degradation. In mammals this execution platform is regulated by a complex molecular signaling system that includes feedback mechanisms tending toward activation of all elements of the execution platform if only one element is initially engaged. Tissue ischemia and reperfusion activate elements of the apoptosis system, which thus represents a therapeutic target for emerging treatment approaches to preserve cellular integrity in critical organs such as the heart and brain.


Hofmeister effect-based soaking strategy for gelatin hydrogels with adjustable gelation temperature, mechanical properties, and ionic conductivity.
As a natural polymer with good biocompatibility, gelatin hydrogel has been widely used in the field of biomedical science for a long time. However, the lack of suitable gelation temperature and mechanical properties often limit the clinical applicability in diverse and complex environments. Here, we proposed a strategy based on the Hofmeister effect that gelatin hydrogels were soaked in the appropriate concentration of sodium sulfate solution, and the change in molecular chain interactions mainly guided by kosmotropic ions resulted in a comprehensive adjustment of multiple properties. A series of gelatin hydrogels treated with different concentrations of the salt solution gave rise to microstructural changes, which brought a decrease in the number and size of pores, a wide range of gelation temperature from 32 °C to 46 °C, a stress enhancement of about 40 times stronger to 0.8345 MPa, a strain increase of about 7 times higher to 238.05 %, and a certain degree of electrical conductivity to be utilized for versatile applications. In this regard, for example, we prepared microneedles and obtained a remarkable compression (punctuation) strength of 0.661 N/needle, which was 55 times greater than those of untreated ones. Overall, by integrating various characterizations and suggesting the corresponding mechanism behind the phenomenon, this method provides a simpler and more convenient performance control procedure. This allowed us to easily modulate the properties of the hydrogel as per the intended purpose, revealing its vast potential applications such as smart sensors, electronic skin, and drug delivery.


[Cytochrome P450 2C19 gene polymorphism in four Chinese nationality populations].
To study the cytochrome P450 2C19(CYP2C19) gene polymorphism in 4 Chinese nationality populations. The genotypes of the unrelated Miao, Buyi, Tu and Dulong subjects were analyzed by polymerase chain reaction and restriction fragment length polymorphism (RFLP). CYP2C19*2 allele frequencies were 0.291, 0.329, 0.315 and 0.349 in Miao, Buyi, Tu and Dulong population, respectively. The four populations were consistent with Hardy-Weinberg expectations (P>0.05). The frequencies of CYP2C19*2 were in agreement with those of other published data on Asian, but were different from those data on European and African.


The impact of macular edema on microvascular and metabolic alterations in retinitis pigmentosa.
The primary aim of our study was to evaluate retinal microvascular anomalies recorded with optical coherence tomography angiography (OCTA) and the retinal metabolic function measured with retinal oximetry (RO) in patients with retinitis pigmentosa (RP). The secondary aim of the study was to link the presence of macular edema to microvascular and metabolic parameters in RP. OCTA and RO were performed on 94 eyes: 64 eyes diagnosed with RP with (ME-RP) and without (no-ME-RP) macular edema were compared with 30 control eyes. Study end points were as follows: mean superficial (FAZ-S) and deep foveal avascular zone (FAZ-D) determined by OCTA. In addition, we evaluated the mean arterial (A-SO2; %), venular (V-SO2; %) oxygen saturation, their difference (A-V SO2; %), as well as the corresponding mean diameter of the retinal arterioles (D-A; μm) and venules (D-V; μm). RP patients differed from controls by enlarged FAZ-S and FAZ-D (p ≤ 0.001), attenuated retinal vessels (p ≤ 0.001), and increased retinal vessel oxygen saturation (p ≤ 0.010). Subgroup analyses within RP patients revealed more pronounced alterations of microvascular parameters and metabolic function in the presence of macular edema. In the no-ME-RP subgroup, significant interactions were present between FAZ-S, A-SO2, and V-SO2, whereas in the ME-RP subgroup, we found significant correlations between FAZ-D and D-A. A combined microvascular structure-metabolic function approach enhances our understanding of inherited retinal diseases. The presence of macular edema in RP seems to be a result of more altered microvascular-metabolic function. Macular edema should thus be taken into consideration when evaluating microvascular and/or metabolic changes in RP.


Rapamycin regulates the balance between cardiomyocyte apoptosis and autophagy in chronic heart failure by inhibiting mTOR signaling.
The progressive loss of cardiomyocytes caused by cell death leads to cardiac dysfunction and heart failure (HF). Rapamycin has been shown to be cardioprotective in pressure‑overloaded and ischemic heart diseases by regulating the mechanistic target of rapamycin (mTOR) signaling network. However, the impact of rapamycin on cardiomyocyte death in chronic HF remains undetermined. Therefore, in the current study we addressed this issue using a rat myocardial infarction (MI)‑induced chronic HF model induced by ligating the coronary artery. Following surgery, rats were randomly divided into six groups, including the sham‑, vehicle‑ and rapamycin‑operated groups, at 8 or 12 weeks post‑MI. A period of 4 weeks after MI induction, the rats were treated with rapamycin (1.4 mg‑kg‑day) or vehicle for 4 weeks. Cardiac function was determined using echocardiography, the rats were subsequently euthanized and myocardial tissues were harvested for histological and biochemical analyses. In the cell culture experiments with H9c2 rat cardiomyocytes, apoptosis was induced using angiotensin II (100 nM; 24 h). Cardiomyocyte apoptosis and autophagy were assessed via measuring apoptosis‑ and autophagy‑associated proteins. The activities of mTOR complex 1 (mTORC1) and mTORC2 were evaluated using the phosphorylation states of ribosomal S6 protein and Akt, respectively. The activity of the endoplasmic reticulum (ER) stress pathway was determined using the levels of GRP78, caspase‑12, phospho‑JNK and DDIT3. Echocardiographic and histological measurements indicated that rapamycin treatment improved cardiac function and inhibited cardiac remodeling at 8 weeks post‑MI. Additionally, rapamycin prevented cardiomyocyte apoptosis and promoted autophagy at 8 weeks post‑MI. Rapamycin treatment for 4 weeks inhibited the mTOR and ER stress pathways. Furthermore, rapamycin prevented angiotensin II‑induced H9c2 cell apoptosis and promoted autophagy by inhibiting the mTORC1 and ER stress pathways. These results demonstrated that rapamycin reduced cardiomyocyte apoptosis and promoted cardiomyocyte autophagy, by regulating the crosstalk between the mTOR and ER stress pathways in chronic HF.


C-reactive protein as an early predictor for anastomotic leakage in elective abdominal surgery.
Anastomotic leakage (AL) represents a serious complication after abdominal surgery. Therefore, it is important to detect it early before it becomes clinically apparent. The predictive value of C-reactive protein (CRP) as a marker of infective postoperative complications, particularly in the form of anastomotic leakage, has been investigated by several authors with promising results. The aim of this study was to evaluate the diagnostic accuracy of C-reactive protein in predicting anastomotic leakage. The serum CRP level, white blood cell (WBC) count, and body temperature (BT) of 156 patients who underwent elective abdominal surgery with primary anastomosis were monitored daily until postoperative day (POD) 7. We recorded all postoperative complications and analyzed the data. Diagnostic accuracy of CRP with regard to development of AL was assessed by receiver operating characteristic curve analysis. Fifteen patients (9.6 %) developed anastomotic leakage. CRP was significantly higher every day during the first 7 postoperative days in patients who developed AL compared with those patients who did not develop complications, whereas the WBC count and BT were not. A CRP cutoff value of 135 mg/l on POD 3 yielded a sensitivity of 73 %, a specificity of 73 %, and a negative predictive value of 95.4 % for the detection of AL. According to our results, values of CRP less than 135 mg/l on POD 3 may contribute to a safe discharge from hospital. Patients with CRP values higher than 135 mg/l on POD 3 require prolonged hospitalization and an intensive search for infective complications, particularly AL.


Effect of thromboxane synthetase inhibitors on platelet function: enhancement by inhibition of phosphodiesterase.
The effects of several selective thromboxane synthetase inhibitors, alone and in combination with inhibitors of cyclic AMP phosphodiesterase, on the aggregation of human platelets in response to collagen, ADP, 1-0-alkyl-2-acetyl-sn-glycerophosphocholine (1-alkyl-2-acetyl-GPC), 9,11-azo-PGH2 and sodium arachidonate were studied in vitro. The thromboxane synthetase inhibitors caused little or no inhibition of aggregation at the concentrations used, while the phosphodiesterase inhibitors caused partial to complete inhibition of aggregation induced by all of the aggregating agents, with anagrelide being the most potent inhibitor and sodium arachidonate the agent most susceptible to inhibition. Combination of inhibitors of thromboxane synthetase with inhibitors of cyclic AMP phosphodiesterase, at concentrations of each which caused little or no effect when used alone, produced marked inhibition of platelet aggregation induced by collagen or arachidonic acid but not by the other aggregating agents studied. This interaction between the two classes of inhibitors appears to be due to the accumulation of cyclic AMP as it can be reversed by 9-(tetrahydro-2-furyl) adenine, an inhibitor of adenylate cyclase. Furthermore, as no synergistic inhibition was found using aggregating agents that are poor inducers of thromboxane formation, or using collagen after the ingestion of aspirin, it is most likely that activation of adenylate cyclase occurs because of diversion of thromboxanes into prostaglandins particularly PGD2. The present results suggest that combined use of inhibitors of thromboxane synthetase and inhibitors of cyclic AMP phosphodiesterase may provide a new approach to antithrombotic therapy.


Zika Virus and Pregnancy.
Recent outbreaks of Zika virus and reports linking infection in pregnant women with microcephaly in newborns have caused concern worldwide. Information has been evolving rapidly. Nurses and other clinicians, especially those who work with women of childbearing age, play a pivotal role in disseminating accurate information and identifying potential cases of Zika virus infection.


Prognostic value of Ki-67 for prostate cancer death in a conservatively managed cohort.
Standard clinical parameters cannot accurately differentiate indolent from aggressive prostate cancer. Our previous work showed that immunohistochemical (IHC) Ki-67 improved prediction of prostate cancer death in a cohort of conservatively treated clinically localised prostate cancers diagnosed by transurethral resection of the prostate (TURP). Here, we present results in a more clinically relevant needle biopsy cohort. Biopsy specimens were microarrayed. The percentage of Ki-67 positively stained malignant cells per core was measured and the maximum score per individual used in analysis of time to death from prostate cancer using a Cox proportional hazards model. In univariate analysis (n=293), the hazard ratio (HR) (95% confidence intervals) for dichotomous Ki-67 (≤ 10%, >10%) was 3.42 (1.76, 6.62) χ(2) (1 df)=9.8, P=0.002. In multivariate analysis, Ki-67 added significant predictive information to that provided by Gleason score and prostate-specific antigen (HR=2.78 (1.42, 5.46), χ(2) (1 df)=7.0, P=0.008). The IHC Ki-67 scoring on prostate needle biopsies is practicable and yielded significant prognostic information. It was less informative than in the previous TURP cohort where tumour samples were larger and more comprehensive, but in more contemporary cohorts with larger numbers of biopsies per patient, Ki-67 may prove a more powerful biomarker.


[Carcinoid tumor--diagnostic and therapeutic problems].
This paper presents a patient with diarrhoeic syndrome, who was finally diagnosed to have carcinoid tumor of the heart. Symptomatic remission has been achieved with Somatostatin therapy. It seems to be treatment of choice in non-operable carcinoid tumours.


Magnetic resonance imaging measurement of left ventricular blood flow and coronary flow reserve in patients with chronic heart failure due to coronary artery disease.
Coronary sinus flow reflects global cardiac perfusion and has been used for the assessment of myocardial flow reserve, which is reduced in chronic heart failure(CHF). Coronary flow reserve (CFR) can be measured by using phase-contrast (PC)velocity-encoded cine (VEC) magnetic resonance imaging (MRI). To quantify and compare global left ventricular (LV) perfusion and CFR inpatients with CHF and in a healthy control group by measuring coronary sinus flow with PC VEC MRI, and to correlate this with global LV perfusion, segmental first-pass perfusion, and viability in the same patients. Cardiac MRI was performed in 20 patients with CHF of ischemic origin and in a control group of healthy subjects (n=11) at rest and after pharmacological stress induced by i.v. dipyridamole. The MRI protocol included cine MRI, VEC MRI, first-pass perfusion, and delayed contrast-enhanced MRI for viability.Global LV perfusion was quantified by measuring coronary sinus flow on VEC MRI at rest in all subjects. CFR was determined as the ratio of global LV perfusion before and after pharmacologic stress. At rest, global LV perfusion was not significantly different in patients with CHF and the control group. After administration of dipyridamole, global LV perfusion and CFR were significantly lower in patients with CHF compared to the control group(P<0.001). An inverse correlation was observed between CFR and the number of infarcted and/or ischemic segments (P=0.083, P=0.037). A combined cardiac MRI protocol including function and perfusion techniques together with VEC MRI can be used to evaluate global LV perfusion and CFR in patients with CHF. Global LV perfusion and CFR measurements may have potential in the monitoring of CHF. Impaired CFR may contribute to progressive decline in LV function in patients with CHF.


Identification and clustering of dairy propionibacteria by RAPD-PCR and CGE-REA methods.
A total of 67 classical propionic acid bacteria (PAB) strains, 10 of which were from type culture collections and 57 from milk, typical Italian cheeses, acid whey and feed flour of different regions, were analysed by Randomly Amplified Polymorphic DNA (RAPD-PCR) and by Conventional Gel Electrophoresis Restriction Endonuclease Analysis (CGE-REA). The genotypic traits achieved using RAPD-PCR with three primers (OPL-01, OPL-02 and OPL-05) and SmaI CGE-REA patterns were compared by numerical analysis and allowed a clear distinction of four clusters corresponding to the currently described species of classical propionibacteria according to type and reference strains positions. No discrepancies exist in species recognition between the two methods; 36 isolates were identified as Propionibacterium freudenreichii, 15 as P. jensenii, four as P. acidipropionici and two as P. thoenii. Many differences, however, were observed in intraspecific clustering. Numerical comparison of RAPD-PCR profiles appeared to be a suitable method for highlighting the presence of particular phenotypic characters, while intraspecific differentiation obtained by CGE-REA analysis allowed association of strains at high similarity levels on the basis of their geographical origin.


Occult infection with hepatitis C virus: friend or foe?
Hepatitis C virus (HCV) infection is a global pandemic associated with a growing disease burden due to cirrhosis and the consequent morbidity and mortality. Transmission is largely via blood-to-blood contact. Following primary infection, a minority of individuals clear the infection predominantly via cellular immune mechanisms, whereas the majority become chronically infected. Recent data suggest that a third outcome may also be possible, termed 'occult' infection in which subjects who are known, or suspected to have previously been infected with HCV, no longer have viral RNA in their serum at levels detectable by sensitive commercial assays, but do have virus detected by ultra-sensitive techniques. Occult infection has also been detected in peripheral blood mononuclear cells, which may indicate an extra-hepatic reservoir of the virus. Although the clinical significance of occult infection remains unknown, most authors have raised concerns of recrudescent infection. Here we critically review the published literature, suggest further avenues of investigation and propose that occult infection may be beneficial to the host by maintaining immunological memory to protect against reinfection.