Reversible translocation of cytidylyltransferase between cytosol and endoplasmic reticulum occurs within minutes in whole cells.
Addition of oleic acid to Krebs II cells induced a rapid incorporation of [3H]choline into phosphatidylcholine, since 500 microM of the fatty acid stimulated choline incorporation by 5-fold over the control after 5 min of incubation. In fact, a noticeable increase in phosphatidylcholine labelling could be monitored immediately after 1 min of cell incubation with [3H]choline, at which time 50% of cytosolic cytidylyltransferase activity (EC 188.8.131.52), the regulatory enzyme of phosphatidylcholine synthesis, was translocated on to membranes. Non-esterified [3H]oleic acid content was also increased in the same range of time in the particulate fraction. Subcellular fractionation indicated that endoplasmic reticulum was the unique binding site for cytidylyltransferase even after 1 min of incubation. Also, [3H]oleic acid accumulated mainly in the same internal membrane. Addition of exogenous albumin to cells prelabelled with [3H]oleic acid induced the release of 50% of membrane-bound cytidylyltransferase activity within 1 min, together with a decrease in unesterified oleic acid in the same membrane. Although total depletion of oleic acid was obtained, total release of membrane-bound cytidylyltransferase was not. The remaining minor pool of membrane-bound cytidylyltransferase was not affected by cell incubation with dibutyryl cyclic AMP, suggesting that this pool was neither regulated by fatty acid nor modulated by cyclic-AMP-dependent protein phosphorylation. Addition of [3H]oleic acid directly to an homogenate led to a less specific accumulation of the fatty acid in the endoplasmic reticulum, but cytidylyltransferase remained exclusively associated with this membrane. We concluded that in vivo translocation of cytidylyltransferase provoked by oleic acid concerns one specific pool of the enzyme distinct from the enzyme firmly bound to endoplasmic reticulum, but other factor(s) than fatty acid seem to be required to explain the specificity of endoplasmic reticulum for cytidylyltransferase binding.


Dynamics of phytoplankton blooms in turbulent vortex cells.
Turbulence and coherent circulation structures, such as submesoscale and mesoscale eddies, convective plumes and Langmuir cells, play a critical role in shaping phytoplankton spatial distribution and population dynamics. We use a framework of advection-reaction-diffusion equations to investigate the effects of turbulent transport on the phytoplankton population growth and its spatial structure in a vertical two-dimensional vortex flow field. In particular, we focus on how turbulent flow velocities and sinking influence phytoplankton growth and biomass aggregation. Our results indicate that conditions in mixing and growth of phytoplankton can drive different vertical spatial structures in the mixed layer, with the depth of the mixed layer being a critical factor to allow coexistence of populations with different sinking speed. With increasing mixed layer depth, positive growth for sinking phytoplankton can be maintained with increasing turbulent flow velocities, allowing the apparently counter-intuitive persistence of fast sinking phytoplankton populations in highly turbulent and deep mixed layers. These dynamics demonstrate the role of considering advective transport within a turbulent vortex and can help to explain observed phytoplankton biomass during winter in the North Atlantic, where the overturn of deep convection has been suggested to play a critical role in phytoplankton survival.


Distribution of deep-water scleractinian and stylasterid corals across abiotic environmental gradients on three seamounts in the Anegada Passage.
In the Caribbean Basin the distribution and diversity patterns of deep-sea scleractinian corals and stylasterid hydrocorals are poorly known compared to their shallow-water relatives. In this study, we examined species distribution and community assembly patterns of scleractinian and stylasterid corals on three high-profile seamounts within the Anegada Passage, a deep-water throughway linking the Caribbean Sea and western North Atlantic. Using remotely operated vehicle surveys conducted on the E/V Nautilus by the ROV Hercules in 2014, we characterized coral assemblages and seawater environmental variables between 162 and 2,157 m on Dog Seamount, Conrad Seamount, and Noroît Seamount. In all, 13 morphospecies of scleractinian and stylasterid corals were identified from video with stylasterids being numerically more abundant than both colonial and solitary scleractinians. Cosmopolitan framework-forming species including Madrepora oculata and Solenosmilia variabilis were present but occurred in patchy distributions among the three seamounts. Framework-forming species occurred at or above the depth of the aragonite saturation horizon with stylasterid hydrocorals being the only coral taxon observed below Ωarag values of 1. Coral assemblage variation was found to be strongly associated with depth and aragonite saturation state, while other environmental variables exerted less influence. This study enhances our understanding of the factors that regulate scleractinian and stylasterid coral distribution in an underreported marginal sea and establishes a baseline for monitoring future environmental changes due to ocean acidification and deoxygenation in the tropical western Atlantic.


Heat Wave Vulnerability Mapping for India.
Assessing geographic variability in heat wave vulnerability forms the basis for planning appropriate targeted adaptation strategies. Given several recent deadly heatwaves in India, heat is increasingly being recognized as a public health problem. However, to date there has not been a country-wide assessment of heat vulnerability in India. We evaluated demographic, socioeconomic, and environmental vulnerability factors and combined district level data from several sources including the most recent census, health reports, and satellite remote sensing data. We then applied principal component analysis (PCA) on 17 normalized variables for each of the 640 districts to create a composite Heat Vulnerability Index (HVI) for India. Of the total 640 districts, our analysis identified 10 and 97 districts in the very high and high risk categories (> 2SD and 2-1SD HVI) respectively. Mapping showed that the districts with higher heat vulnerability are located in the central parts of the country. On examination, these are less urbanized and have low rates of literacy, access to water and sanitation, and presence of household amenities. Therefore, we concluded that creating and mapping a heat vulnerability index is a useful first step in protecting the public from the health burden of heat. Future work should incorporate heat exposure and health outcome data to validate the index, as well as examine sub-district levels of vulnerability.


Effectiveness of xylitol and polyol chewing gum on salivary streptococcus mutans in children: A randomized controlled trial.
Dental caries is a multi-factorial, infectious disease, the prevention of which is based on multifaceted approaches. Chewing sugar-free gum has potential beneficial effects on dental health. The aim of this study is to assess and compare the effectiveness of xylitol and polyol chewing gums on salivary Streptococcus mutans in 12-15 years old schoolchildren residing in hostels in Belgaum city. The acceptability of the two chewing gums was also assessed. Sixty children of 12-15 year age groups from three hostels, who fulfilled all the inclusion criteria, were included in this triple blind randomized controlled field trial. They were then randomly allocated into one of the three groups using lottery method. Xylitol chewing gum, polyol chewing gum and control group (no chewing gum). Patients were instructed to chew one pellet two times a day after meals for 5 min each for 30 days. Salivary samples were collected at baseline, 30 days after chewing gum use and 30 days after discontinuation, for microbiological analysis. The data were subjected to statistical analysis using SPSS software version 18. Chewing 100% xylitol chewing gum 2 times a day for 5 min for 30 days can successfully reduce salivary S. mutans counts. The xylitol gum has shown a maximum benefit against salivary S. mutans when compared to polyol gum and control group. Xylitol-containing chewing gums can be used as an adjunct to regular home care preventive procedures to prevent dental caries.


What is the evidence for chronic concussion-related changes in retired athletes: behavioural, pathological and clinical outcomes?
The purpose of this paper was to review the current state of evidence for chronic traumatic encephalopathy (CTE) in retired athletes and to consider the potential differential diagnoses that require consideration when retired athletes present with cognitive and psychiatric problems. MEDLINE, CINAHL, EMBASE, Mosby's Index, PsycEXTRA, PsycINFO and Scopus. Key words included CTE, dementia pugilistica, punch drunk syndrome, traumatic encephalopathy, CTE, repetitive head injury, sports concussion, multiple concussions, chronic concussions, subconcussive blow and sports-related traumatic brain injury. At present, there are no published epidemiological, cross-sectional or prospective studies relating to modern CTE. Owing to the nature of the published studies, being case reports or pathological case series, it is not possible to determine the causality or risk factors with any certainty. As such, the speculation that repeated concussion or subconcussive impacts cause CTE remains unproven. The extent to which age-related changes, psychiatric or mental health illness, alcohol/drug use or coexisting dementing illnesses contribute to this process is largely unaccounted for in the published literature. At present, the interpretation of causation in the modern CTE case studies should proceed cautiously. The causal assumptions require further prospective or longitudinal studies on the topic.


The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its evolutionary implications.
In 1992 we started assembling an ordered library of cosmid clones from chromosome XIV of the yeast Saccharomyces cerevisiae. At that time, only 49 genes were known to be located on this chromosome and we estimated that 80% to 90% of its genes were yet to be discovered. In 1993, a team of 20 European laboratories began the systematic sequence analysis of chromosome XIV. The completed and intensively checked final sequence of 784,328 base pairs was released in April, 1996. Substantial parts had been published before or had previously been made available on request. The sequence contained 419 known or presumptive protein-coding genes, including two pseudogenes and three retrotransposons, 14 tRNA genes, and three small nuclear RNA genes. For 116 (30%) protein-coding sequences, one or more structural homologues were identified elsewhere in the yeast genome. Half of them belong to duplicated groups of 6-14 loosely linked genes, in most cases with conserved gene order and orientation (relaxed interchromosomal synteny). We have considered the possible evolutionary origins of this unexpected feature of yeast genome organization.


Permutationally invariant part of a density matrix and nonseparability of N-qubit states.
We consider the concept of "the permutationally invariant (PI) part of a density matrix," which has proven very useful for both efficient quantum state estimation and entanglement characterization of N-qubit systems. We show here that the concept is, in fact, basis dependent but that this basis dependence makes it an even more powerful concept than has been appreciated so far. By considering the PI part ρ(PI) of a general (mixed) N-qubit state ρ, we obtain (i) strong bounds on quantitative nonseparability measures, (ii) a whole hierarchy of multipartite separability criteria (one of which entails a sufficient criterion for genuine N-partite entanglement) that can be experimentally determined by just 2N+1 measurement settings, (iii) a definition of an efficiently measurable degree of separability, which can be used for quantifying a novel aspect of decoherence of N qubits, and (iv) an explicit example that shows there are, for increasing N, genuinely N-partite entangled states lying closer and closer to the maximally mixed state. Moreover, we show that if the PI part of a state is k nonseparable, then so is the actual state. We further argue to add as requirement on any multipartite entanglement measure E that it satisfy E(ρ)≥E(ρ(PI)), even though the operation that maps ρ→ρ(PI) is not local.


Effect of intracrevicular restoration margins on peri-implant health: clinical, biochemical, and microbiologic findings around esthetic implants up to 9 years.
The aim of the present study was to evaluate longitudinally the stability of a cohort of esthetic implants that had been in function for at least 1 year prior to the baseline examination. Sixty-one maxillary anterior ITI implants in 45 systemically healthy patients, supporting single crown restorations, were randomly selected and examined. Clinical, microbiologic, and biochemical parameters were recorded at baseline and again after 3 years. Clinical examination included Plaque Index, Gingival Index, bleeding on probing, probing pocket depth (PPD), distance between implant shoulder and mucosal margin (DIM), and mobility. Dark-field microscopy and immunofluorescence were used to evaluate the bacteria morphotypes and the presence of 5 specific pathogenic bacteria, respectively. Peri-implant crevicular fluid (PICF) was collected at the mesial and distal sites of each implant, and total amounts of 3 biochemical markers were assessed: alkaline phosphatase was measured by using p-nitrophenyl-phosphate as substrate, elastase activity was measured by the use of a low-molecular-weight fluorogenic substrate, and the inhibitor alpha2-macroglobulin (alpha2M) was measured by enzyme-linked immunosorbent assay. The only statistically significant differences between baseline and follow-up examination concerned PPD and DIM measurements, which increased slightly. The remainder of the clinical measurements and almost all of the microbiologic and biochemical parameters did not change significantly. Furthermore, no associations were observed between the above results and the number of years that implants had been in function. Based on an observation period of 4 to 9 years (mean 6.8 years at the time of the follow-up examination), it can be concluded that in patients with appropriate oral hygiene, the intracrevicular position of the restoration margin does not appear to adversely affect peri-implant health and stability.


A crossover trial of high and low sucrose-carbohydrate diets in type II diabetics with hypertriglyceridemia.
Earlier work shows that hyperlipemic type II diabetics tolerate wide ranges of sucrose and carbohydrate intake without effects on glycemic control, but a rise of fasting serum triglycerides sometimes occurs. To address further the issue of individual susceptibility to carbohydrate, the current study was designed to use each patient as his own control when given diets widely varying in sucrose content. After a stabilization period in the hospital on a normal sucrose content diet, each subject was given either a very low sucrose (less than 3 gm/day)-low carbohydrate (38 +/- 2%) diet or a high sucrose (220 gm)-high carbohydrate (63 +/- 3%) diet for 4 weeks. On a separate admission the opposite diet was assessed, again after an initial normal sucrose content diet. No consistent differences occurred in serum glucose levels or in 24-hr urinary glycosuria. High sucrose-carbohydrate intake raised fasting hypertriglyceridemia after 2 weeks but less thereafter. Severe sucrose-carbohydrate restriction did not significantly decrease fasting serum triglycerides; postprandial triglycerides changed in a trend opposite to fasting levels. No differences occurred in fasting serum insulin or serum cholesterol levels, but postprandial insulin levels were higher in high sucrose-carbohydrate diets. A diet with low sucrose and low total carbohydrate appears to offer no improvement in glycemic control over at least 70-fold higher dietary sucrose levels. However, high sucrose and carbohydrate diets increase fasting triglyceride levels in hypertriglyceridemic type II diabetics.


Hemiarthroplasty for Femoral Neck Fracture.
Hemiarthroplasty is a common treatment for femoral neck fractures in the elderly population. The main complications are periprosthetic dislocation and infection, which potentially impact morbidity and quality of life and may contribute to mortality. This procedure can be technically demanding, and adequate closure of the capsule and soft tissue cannot be emphasized enough. One advantage of a bipolar prosthesis is that it can be easily converted to a total hip arthroplasty without replacing the femoral component and with approximately the same complication rates as a revision total hip arthroplasty. Cement should be used when the patient is osteoporotic or has a Dorr type-C canal because there is a significant reduction in risk of fracture. The addition of a collared stem is helpful if there is a crack in the calcar extending from the fracture. The procedure is as follows. (1) The patient is placed in the lateral decubitus position. (2) The surgical site is prepared and draped to above the iliac crest and mid-sacrum. (3) A posterior approach is utilized. (4) The hip is dislocated. (5) A cut is made at the femoral neck. (6) The implant is templated with the femoral head. (7) The femur is broached. (8) The trial implant is placed. (9) The femur is cemented. (10) Trial implants are removed and cement is placed. (11) The final stem implant is placed in 5° to 10° of anteversion. (12) The final head and neck implants are trialed and then placed. (13) Implant position and range of motion are tested. (14) The surgical wound is irrigated. (15) Short external rotators are repaired. The posterior approach, which is often used, is known for increased rates of dislocation. The rate of dislocation can be minimized with repair of the posterior capsule and posterior soft tissue. Proper placement of the implants is of the utmost importance to minimize complications. Other contributing factors that lead to dislocation are implant malpositioning and patient factors.


Differential niche dynamics among major marine invertebrate clades.
The degree to which organisms retain their environmental preferences is of utmost importance in predicting their fate in a world of rapid climate change. Notably, marine invertebrates frequently show strong affinities for either carbonate or terrigenous clastic environments. This affinity is due to characteristics of the sediments as well as correlated environmental factors. We assessed the conservatism of substrate affinities of marine invertebrates over geological timescales, and found that niche conservatism is prevalent in the oceans, and largely determined by the strength of initial habitat preference. There is substantial variation in niche conservatism among major clades with corals and sponges being among the most conservative. Time-series analysis suggests that niche conservatism is enhanced during times of elevated nutrient flux, whereas niche evolution tends to occur after mass extinctions. Niche evolution is not necessarily elevated in genera exhibiting higher turnover in species composition.


Test-enhanced learning improves learner attendance during a laparoscopic box trainer simulation program.
Laparoscopy is the gold standard approach for many surgical procedures, but it is a complex skill to learn. Laparoscopic simulation training may help, but it is unclear how to best engage trainees in these programs. Test-enhanced learning (TEL) uses regular, well-defined assessments of performance throughout the training phase of learning. The aim of this study was to assess the effects of TEL on a laparoscopic simulation program involving a cohort of medical student volunteers. A prospective cohort study was performed with a convenience sample of 40 medical students. Students were recruited to participate in a ten-week laparoscopic simulation program. Twenty students participated in a laparoscopic surgical program with TEL ('TEL group'), and 20 students participated in a standard laparoscopic simulation program ('control group'). Attendance in the TEL group was significantly higher than in the standard group (71 vs 51.5%, P = 0.03). There was no difference between groups in mean time scores. Four themes were identified in qualitative data drawn from student surveys - personal traits and motivators, training context, clear goals and feedback enabling understanding of one's own performance. Testing laparoscopic skills throughout a learning program, in conjunction with individualised feedback and tracking of learning trajectory, increases trainee attendance. Laparoscopic simulation training programs are encouraged to reflect on the pedagogic framework in which their procedural skills training operates.


Montelukast treatment does not affect peripheral blood neutrophil functions in asthma patients.
Leukotriene receptor antagonists have become an integral part of asthma treatment as an add-on therapy for patients with moderate disease activity. To determine whether in vivo treatment with montelukast, a leukotriene receptor antagonist, at the recommended therapeutic dose affects neutrophil functions which are essential for host defense. Twenty nonsmoking patients between the ages of 18 and 70 with moderate asthma were recruited to the study. All of them were receiving inhaled corticosteroids for at least 6 months and beta2-agonist as needed. After the 2-week run-in period, in addition to the regular medication, each patient was treated with 10 mg of montelukast for a 6-week period. Pulmonary function test was performed and blood was tested for neutrophil activity twice during the run-in period and twice during the treatment period. Each assay was performed in parallel to a matched control. The 6-week treatment period with montelukast did not significantly affect neutrophil chemotaxis or phagocytosis nor the elevated superoxide production. However, at 2 weeks of treatment some of the patients showed a reduction in neutrophil function. The study demonstrated that the recommended dose of montelukast has no significant effect on peripheral blood neutrophil activities, indicating that montelukast treatment does not induce an inflammatory process and does not interfere with the first line of host defense.


Risk management of onco-hematological drugs: how and how fast can we improve?
Medication errors in oncology may cause severe damage to patients, professionals, and the environment. The Italian Ministry of Health issued Raccomandazione 14 to provide guidelines for prevention of errors while using antineoplastic drugs. This work aimed at analyzing Raccomandazione 14 through the different viewpoints of the hospital pharmacist, the nurse, the oncologist, and the hospital director. Twenty-seven Italian healthcare organizations participated in a self-assessment survey evaluating compliance with Raccomandazione 14 within the oncology, hematology, and pharmacy departments. The self-assessment results showed a general acknowledgement of the need for centralized management of anticancer agents. The specific responsibility of the pharmacist on the centralized management of anticancer drugs from preparation to disposal emerged as a critical point. The nurse, beyond the skills in drug administration and prevention of extravasation, also plays a fundamental role in educating and supporting the patient. The physicians, who are attentive to scientific, clinical, and regulatory criteria in prescribing and monitoring the therapies, are called upon to improve awareness on the importance of sharing standardized procedures with other professionals, to minimize medication error occurrence. The implementation of a complete computerized management from prescribing to drug administration and follow-up was highlighted. Multidisciplinary groups were constituted across the nation by professionals dedicated to the implementation of electronic health records and drug history and medical reconciliation processes. Our analysis of the Ministerial Raccomandazione 14 urges implementation of the resources for ensuring quality and safety during prescription, preparation, and administration of anticancer drugs.


Transition state analogues in quorum sensing and SAM recycling.
Transition state structures can be derived from kinetic isotope effects and computational chemistry. Molecular electrostatic potential maps of transition states serve as blueprints to guide synthesis of transition state analogue inhibitors of target enzymes. 5'- Methylthioadenosine phosphorylase (MTAP) functions in the polyamine pathway by recycling methylthioadenosine (MTA) and maintaining cellular S-adenosylmethionine (SAM). Its transition state structure was used to guide synthesis of MT-DADMe-ImmA, a picomolar inhibitor that shows anticancer effects against solid tumors. Biochemical and genomic analysis suggests that MTAP inhibition acts by altered DNA methylation and gene expression patterns. A related bacterial enzyme, 5'-methylthioadenosine nucleosidase (MTAN), functions in pathways of quorum sensing involving AI-1 and AI-2 molecules. Transition states have been solved for several bacterial MTANs and used to guide synthesis of powerful inhibitors with dissociation constants in the femtomolar to picomolar range. BuT-DADMe-ImmA blocks quorum sensing in Vibrio cholerae without changing bacterial growth rates. Transition state analogue inhibitors show promise as anticancer and antibacterial agents.


[Mycotic aneurysm of the abdominal aortic due to Salmonella enterica serotype enteritidis: a case report].
Bacteraemia due to non Typhi Salmonella is frequent in human immunodeficiency virus (HIV infected patients). Focal vascular complications especially in patients with artheriosclerosis are rarely reported. We report the case of patient who presented a mycotic aneurysm of the abdominal aortic due to Salmonella enterica serotype enteritidis. Despite the chirurgical treatment associated with antibiotherapy, the patient evolution was fatal.


Career opportunities for infectious diseases subspecialists.
Few data are available regarding trends in career opportunities for subspecialty physicians. A review of advertisements for infectious diseases physicians in the 1990, 1993, and 1995 issues of the New England Journal of Medicine revealed a significant decline in the number of openings between 1990 and 1995. In each year the number of private practice advertisements exceeded those in all other categories combined, and this ratio increased over time. Both private practice and academic advertisements commonly listed opportunities or requirements for teaching or research. Expertise in internal medicine, rarely mentioned in advertisements for academic infectious diseases physicians, became the most frequently cited private practice subclassification in 1995. Both private practice and academic settings offered numerous positions related to the care of patients with human immunodeficiency virus infection. The demand for expertise in epidemiology, intravenous therapy, travel medicine, transplantation, or sexually transmitted diseases remained low. Most positions were in heavily populated states or geographic areas.


Prospects for gene therapy of haemophilia.
That gene therapy offers the promise of a cure for haemophilia was apparent more than a decade ago. After years of failure, substantial progress in the efficiency of gene transfer technology has recently resulted in impressive success in animal models with haemophilia. However, fears of the risks intrinsic to such therapy have been raised by the fate of two children cured of immune deficiency by gene transfer who have, however, subsequently developed leukaemia as a result of insertional mutagenesis. The purpose of this review is to outline the current status of gene therapy in light of recent successes and tragedies and to consider the prospects for curing haemophilia in the short-to-medium term.


Computed vibrational frequencies of actinide oxides AnO(0/+/2+) and AnO2(0/+/2+) (An = Th, Pa, U, Np, Pu, Am, Cm).
The vibrational frequencies of the actinide oxides AnO and AnO(2) (An = Th, Pa, U, Np, Pu, Am, Cm) and of their mono- and dications have been calculated using advanced quantum chemical techniques. The stretching fundamental frequencies of the monoxides have been determined by fitting the potential function to single-point energies obtained by relativistic CASPT2 calculations along the stretching coordinate and on this basis solving numerically the ro-vibrational Schrödinger equation. To obtain reliable fundamental frequencies of the dioxides, we developed an empirical approach. In this approach the harmonic vibrational frequencies of the AnO(2)(0/+/2+) species were calculated using eight different exchange-correlation DFT functionals. On the basis of the good correlation found between the vibrational frequencies and computed bond distances, the final frequency values were derived for the CASPT2 reference bond distances from linear regression equations fitted to the DFT data of each species. As a test, the approach provided excellent agreement with accurate experimental data of ThO, ThO(+), UO, and UO(+). The joint analysis of literature experimental and our computed data facilitated the prediction of reliable gas-phase molecular properties for some oxides. They include the stretching frequencies of PuO, ThO(2), UO(2), and UO(2)(+) and the bond distance of PuO (1.818 Å, being likely within 0.002 Å of the real value). Also the derived equilibrium bond distances of ThO(2), UO(2), and UO(2)(+) (1.896, 1.790, and 1.758 Å, respectively) should approximate closely the (yet unknown) experimental values. On the basis of the present results, we suggest that the ground electronic state of PuO(2) in Ar and Kr matrices is probably different from that in the gaseous phase, similarly to UO(2) observed previously.


Evidence for asymmetric electron transfer in cyanobacterial photosystem I: analysis of a methionine-to-leucine mutation of the ligand to the primary electron acceptor A0.
The X-ray crystal structure of photosystem I (PS I) depicts six chlorophyll a molecules (in three pairs), two phylloquinones, and a [4Fe-4S] cluster arranged in two pseudo C2-symmetric branches that diverge at the P700 special pair and reconverge at the interpolypeptide FX cluster. At present, there is agreement that light-induced electron transfer proceeds via the PsaA branch, but there is conflicting evidence whether, and to what extent, the PsaB branch is active. This problem is addressed in cyanobacterial PS I by changing Met688(PsaA) and Met668(PsaB), which provide the axial ligands to the Mg2+ of the eC-A3 and eC-B3-chlorophylls, to Leu. The premise of the experiment is that alteration or removal of the ligand should alter the midpoint potential of the A0-/A0 redox pair and thereby result in a change in the forward electron-transfer kinetics from A0- to A1. In comparison with the wild type, the PsaA-branch mutant shows: (i) slower growth rates, higher light sensitivity, and reduced amounts of PS I; (ii) a reduced yield of electron transfer from P700 to the FA/FB iron-sulfur clusters at room temperature; (iii) an increased formation of the 3P700 triplet state due to P700(+)A0- recombination; and (iv) a change in the intensity and shape of the polarization patterns of the consecutive radical pair states P700(+)A1- and P700(+)FX-. The latter changes are temperature dependent and most pronounced at 298 K. These results are interpreted as being due to disorder in the A0 binding site, which leads to a distribution of lifetimes for A0- in the PsaA branch of cofactors. This allows a greater degree of singlet-triplet mixing during the lifetime of the radical pair P700(+)A0-, which changes the polarization patterns of P700(+)A1- and P700(+)FX-. The lower quantum yield of electron transfer is also the likely cause of the physiological changes in this mutant. In contrast, the PsaB-branch mutant showed only minor changes in its physiological and spectroscopic properties. Because the environments of eC-A3 and eC-B3 are nearly identical, these results provide evidence for asymmetric electron-transfer activity primarily along the PsaA branch in cyanobacterial PS I.


Optimal staffing for Acute Care of the Elderly (ACE) units.
Acute Care of the Elderly (ACE) units have been shown to improve outcomes for hospitalized elders. Because the literature offers little to describe the appropriate staffing of such units, we surveyed ACE units about their size, configuration, staffing, patient selection, training, and outcomes data. Although we had anticipated speaking with staff from 30 to 40 units, we were able to poll key personnel on only 18 ACE units. This article describes staffing and continuous quality improvement data for these sites.


Postoperative Complications and Outcomes Associated With a Transition to 24/7 Intensivist Management of Cardiac Surgery Patients.
Nighttime intensivist staffing does not improve patient outcomes in general ICUs. Few studies have examined the association between dedicated in-house 24/7 intensivist coverage on outcomes in specialized cardiac surgical ICUs. We sought to evaluate the association between 24/7 in-house intensivist-only management of cardiac surgical patients on postoperative complications and health resource utilization. Before-and-after propensity matched cohort study. Tertiary care cardiac surgical ICU. Patients greater than 18 years old who underwent cardiac surgery between January 1, 2006, and April 30, 2013 (nighttime resident model), were propensity-matched (1:1) to patients from August 1, 2013, to December 31, 2014 (24/7 in-house intensivist model). Cardiac surgical ICU coverage change from a nighttime resident physician coverage model to a 24/7 in-house intensivist staffing model. The primary outcome of interest was a composite of postoperative major complications. Secondary outcomes included duration of mechanical ventilation, all-cause cardiac surgical ICU readmissions, and surgical postponements attributed to lack of cardiac surgical ICU bed availability. A total of 1,509 patients during the nighttime resident model were matched to 1,509 patients during the intensivist model. The adjusted risk of major complications (26.3% vs 19.3%; odds ratio, 0.73; 95% CI, 0.36-0.85; p < 0.01), mean mechanical ventilation time (25.2 vs 19.4 hr; p < 0.01), cardiac surgical ICU readmissions (5.3% vs 1.6%; odds ratio, 0.31; 95% CI, 0.19-0.48; p < 0.01), and surgical postponements (3.4 vs 0.3 per mo; p < 0.01) were lower with the intensivist model. A transition to a 24/7 in-house intensivist care model was associated with a reduction in postoperative major complications, duration of mechanical ventilation, cardiac surgical ICU readmissions, and surgical postponements. These findings suggest that 24/7 intensivist physician care models may improve patient outcomes and health resource utilization in specialized cardiac surgical ICUs.


Exciplex formation in bimolecular photoinduced electron-transfer investigated by ultrafast time-resolved infrared spectroscopy.
The dynamics of bimolecular photoinduced electron-transfer reactions has been investigated with three donor/acceptor (D/A) pairs in tetrahydrofuran (THF) and acetonitrile (ACN) using a combination of ultrafast spectroscopic techniques, including time-resolved infrared absorption. For the D/A pairs with the highest driving force of electron transfer, all transient spectroscopic features can be unambiguously assigned to the excited reactant and the ionic products. For the pair with the lowest driving force, three additional transient infrared bands, more intense in THF than in ACN, with a time dependence that differs from those of the other bands are observed. From their frequency and solvent dependence, these bands can be assigned to an exciplex. Moreover, polarization-resolved measurements point to a relatively well-defined mutual orientation of the constituents and to a slower reorientational time compared to those of the individual reactants. Thanks to the minimal overlap of the infrared signature of all transient species in THF, a detailed reaction scheme including the relevant kinetic and thermodynamic parameters could be deduced for this pair. This analysis reveals that the formation and recombination of the ion pair occur almost exclusively via the exciplex.


Factors affecting selectivity of brilliant green-phenol red agar for salmonellae.
Commercial brilliant green (BG)-sulfa agar was found to be nonselective toward a test series of Enterobacteriaceae. Various formulations of BG were prepared by using Trypticase soy agar (BBL) as a base. Results were more reproducible when BG dye was added after sterilization than before. Sulfonamides improved selectivity as compared with brilliant green alone. Sulfanilamide (SN) was slightly more selective for salmonellae than other sulfonamides tested. Bile salts and sodium dodecyl sulfate markedly reduced the toxicity of BG to all the test bacteria. Enterobacter strains were most difficult to inhibit. A combination of 5 mg of BG and 1 g of SN/liter prevented growth of Proteus mirabilis and Escherichia coli and retarded growth of Enterobacter strains. The BG-SN agars were superior in selectivity to a series of commercial agars tested, and numbers of salmonellae recovered on BG-SN agar and Trypticase soy agar (BBL) were the same. Brilliant green agars with various degrees of selectivity are described.


Stimulus Context and Reward Contingency Induce Behavioral Adaptation in a Rodent Tactile Detection Task.
Behavioral adaptation is a prerequisite for survival in a constantly changing sensory environment, but the underlying strategies and relevant variables driving adaptive behavior are not well understood. Many learning models and neural theories consider probabilistic computations as an efficient way to solve a variety of tasks, especially if uncertainty is involved. Although this suggests a possible role for probabilistic inference and expectation in adaptive behaviors, there is little if any evidence of this relationship experimentally. Here, we investigated adaptive behavior in the rat model by using a well controlled behavioral paradigm within a psychophysical framework to predict and quantify changes in performance of animals trained on a simple whisker-based detection task. The sensory environment of the task was changed by transforming the probabilistic distribution of whisker deflection amplitudes systematically while measuring the animal's detection performance and corresponding rate of accumulated reward. We show that the psychometric function deviates significantly and reversibly depending on the probabilistic distribution of stimuli. This change in performance relates to accumulating a constant reward count across trials, yet it is exempt from changes in reward volume. Our simple model of reward accumulation captures the observed change in psychometric sensitivity and predicts a strategy seeking to maintain reward expectation across trials in the face of the changing stimulus distribution. We conclude that rats are able maintain a constant payoff under changing sensory conditions by flexibly adjusting their behavioral strategy. Our findings suggest the existence of an internal probabilistic model that facilitates behavioral adaptation when sensory demands change.SIGNIFICANCE STATEMENT The strategy animals use to deal with a complex and ever-changing world is a key to understanding natural behavior. This study provides evidence that rodent behavioral performance is highly flexible in the face of a changing stimulus distribution, consistent with a strategy to maintain a desired accumulation of reward.


The development of map-reading skills.
The present study investigated the development of map-reading skills in kindergartners and second graders. The maps were read either inside or outside the space shown on the map, and they were either aligned with the space or rotated 90 degree or 180 degree. The current maps had only 1 landmark to establish the correspondence to the space. These impoverished maps allowed the examination of 2 variables not previously studied: the proximity of the target to the landmark (near vs. far) and the type of landmark (movable vs. fixed). Consistent with previous research, at both grades subjects were able to extract information from the maps to guide search. When the maps were rotated, the younger subjects made "egocentric" errors on the inside reading trials but not on the outside trials. At both grades, most errors preserved the near/far relation to the landmark. Thus, children extracted critical (near/far) information from the maps instead of creating a mental map which was then mentally projected in space.


Global lactylome reveals lactylation-dependent mechanisms underlying TH17 differentiation in experimental autoimmune uveitis.
Dysregulation of CD4+ T cell differentiation is linked to autoimmune diseases. Metabolic reprogramming from oxidative phosphorylation to glycolysis and accumulation of lactate are involved in this process. However, the underlying mechanisms remain unclear. Our study showed that lactate-derived lactylation regulated CD4+ T cell differentiation. Lactylation levels in CD4+ T cells increased with the progression of experimental autoimmune uveitis (EAU). Inhibition of lactylation suppressed TH17 differentiation and attenuated EAU inflammation. The global lactylome revealed the landscape of lactylated sites and proteins in the CD4+ T cells of normal and EAU mice. Specifically, hyperlactylation of Ikzf1 at Lys164 promoted TH17 differentiation by directly modulating the expression of TH17-related genes, including Runx1, Tlr4, interleukin-2 (IL-2), and IL-4. Delactylation of Ikzf1 at Lys164 impaired TH17 differentiation. These findings exemplify how glycolysis regulates the site specificity of protein lactylation to promote TH17 differentiation and implicate Ikzf1 lactylation as a potential therapeutic target for autoimmune diseases.


[Evaluation of therapy effectiveness in patients with hypertension using graded physical load].
J. W. Franz graded exercise test (GET) was employed to examine healthy subjects, untreated patients with stage I and II essential hypertension and hypertensive subjects treated with hydrochlorthiazide, alpha-methyldopa, prazosine, dilthiazem resultant in normal resting values of blood pressure. Hydrochlorthiazide did not protect the patients from a pathological hypertensive response to GET, whereas alpha-methyldopa and prazosine furnish a physiological hypertensive response in much less number of patients and dilthiazem made possible normal response in the majority of treated patients. GET is suggested for assessing effectiveness of hypertension treatment and individual choice of antihypertensive drugs.


An early Australopithecus afarensis postcranium from Woranso-Mille, Ethiopia.
Only one partial skeleton that includes both forelimb and hindlimb elements has been reported for Australopithecus afarensis. The diminutive size of this specimen (A.L. 288-1 ["Lucy"]) has hampered our understanding of the paleobiology of this species absent the potential impact of allometry. Here we describe a large-bodied (i.e., well within the range of living Homo) specimen that, at 3.58 Ma, also substantially antedates A.L. 288-1. It provides fundamental evidence of limb proportions, thoracic form, and locomotor heritage in Australopithecus afarensis. Together, these characteristics further establish that bipedality in Australopithecus was highly evolved and that thoracic form differed substantially from that of either extant African ape.


Evaluation of ABC Bleeding Score and SAMe-TT2R2 Score on the Risk of Bleeding after Anticoagulation in Patients with Nonvalvular Atrial Fibrillation Complicated with Coronary Heart Disease.
To explore the predictive value of ABC bleeding score and SAMe-TT2R2 score on the risk of bleeding in patients with nonvalvular atrial fibrillation (NVAF) complicated with coronary heart disease (CHD) after anticoagulation. 149 patients with NVAF complicated with CHD were followed up in our hospital for one year. The bleeding events during the follow-up period were observed, the ABC bleeding score and SAMe-TT2R2 score were calculated, the predictive value of the two scoring methods for the main bleeding risk was analyzed by the ROC curve, and the AUC area under the ROC curve of the two scoring methods was compared by the Delong test. There were 32 bleeding events during the follow-up period. The AUC of ABC bleeding score and SAMe-TT2R2 score were 0.775 (P < 0.01) and 0.624 (P < 0.05), respectively. The Delong test showed that the AUC of ABC bleeding score was significantly higher than that of SAMe-TT2R2 score (d = 2.177, P < 0.05). Both the ABC bleeding score and SAMe-TT2R2 score can predict the risk of bleeding after anticoagulation in patients with NVAF and CHD. The critical value of the SAMe-TT2R2 score for predicting bleeding events in patients with NVAF and CHD may need to be increased to 4 or 5, and the prediction ability of ABC bleeding score is significantly better than that of the SAMe-TT2R2 score.


Chondromesenchymal Hamartoma With Nasopharyngeal Involvement: Two Unusual Cases of an Extremely Rare Lesion.
Chondromesenchymal hamartoma (CMH) is a rare, benign lesion of the nasal cavity, paranasal sinuses, and skull base, composed of islands of hyaline cartilage in a myxoid background. The vast majority of CMH cases are infants and young children. According to the world literature, nasopharyngeal involvement of CMH is extremely rare. In all cases, the lesions were masses protruding from the nasal cavity or paranasal sinuses to the nasopharynx. We hereby report 2 adult male patients with masses completely situated in the nasopharyngeal space. In the first patient, the tumor originated from the posterior edge of the nasal septum and in the second one, from the posterolateral wall of the nasopharynx, adjacent to the pharyngeal orifice of the Eustachian tube. In both patients, the lesion was excised endoscopically, and histopathological analyses were consistent with a diagnosis of CMH. To our knowledge, those are the only cases of CMH completely situated in the nasopharynx.


Diet and dermatology: the role of dietary intervention in skin disease.
For decades, it was thought that many common dermatological conditions had no relationship to diet. Studies from recent years, however, have made it clear that diet may influence outcome. In this review, the authors focus on conditions for which the role of diet has traditionally been an underappreciated aspect of therapy. In some cases, dietary interventions may influence the course of the skin disease, as in acne. In others, dietary change may serve as one aspect of prevention, such as in skin cancer and aging of the skin. In others, dermatological disease may be linked to systemic disease, and dietary changes may affect health outcomes, as in psoriasis. Lastly, systemic medications prescribed for dermatological disease, such as steroids, are known to raise the risk of other diseases, and dietary change may reduce this risk.


The distribution of choline acetyltransferase in the rat amygdaloid complex and adjacent cortical areas, as determined by quantitative micro-assay and immunohistochemistry.
The distribution of choline acetyltransferase (ChAT) within the amygdaloid complex has been studied to evaluate what should primarily represent the terminal field of the cholinergic projection from the basal forebrain. Two currently available methods have been combined for the comparison: immunohistochemistry with a monoclonal antibody against ChAT, by a double peroxidase-antiperoxidase procedure, and quantitative histochemistry involving micro-assay of the ChAT activity of contiguous microdissected samples. Both methods indicate prominent ChAT activity in the basolateral amygdaloid nucleus (especially rostrally), the nucleus of the lateral olfactory tract (especially layer II), and the amygdalohippocampal area. Regions of lower ChAT activity were not accurately represented by the immunohistochemistry, but could be discriminated by the quantitative assays. Lowest activity was found in the medial nucleus of the amygdala. Most other regions had activities at least as high as average brain or neocortex. Gradients of enzyme activity were found within several regions, including the basolateral and lateral amygdaloid nuclei and the nearby posterior piriform cortex. In the piriform cortex, a region of particularly high ChAT activity was found at its medial edge near the nucleus of the lateral olfactory tract. The immunohistochemical method shows a few intensely reactive somata in layer III within this zone. Comparison of the results seen with immunohistochemistry and quantitative histochemistry suggests an advantage in using them together, since their respective strengths and weaknesses tend to complement each other.


Probenecid, a gout remedy, inhibits pannexin 1 channels.
Probenecid is a well-established drug for the treatment of gout and is thought to act on an organic anion transporter, thereby affecting uric acid excretion in the kidney by blocking urate reuptake. Probenecid also has been shown to affect ATP release, leading to the suggestion that ATP release involves an organic anion transporter. Other pharmacological evidence and the observation of dye uptake, however, suggest that the nonvesicular release of ATP is mediated by large membrane channels, with pannexin 1 being a prominent candidate. In the present study we show that probenecid inhibited currents mediated by pannexin 1 channels in the same concentration range as observed for inhibition of transport processes. Probenecid did not affect channels formed by connexins. Thus probenecid allows for discrimination between channels formed by connexins and pannexins.


Iodine status remains critical in mother and infant in Central Anatolia (Kayseri) of Turkey.
Severe iodine deficiency disorders have been eradicated in many parts of the world, but milder forms still exist and may escape detection. Turkey has long been known to be a mild to moderate iodine deficiency area. The aim of this study was to assess the iodine nutritional status and the thyroid function of pregnant women and their neonates in the region of Kayseri (central Anatolia of Turkey) that appeared to be iodine deficient in previous studies performed before the introduction of mandatory salt iodization. A cross-sectional voluntary screening study was performed in the Maternity Unit of a university hospital. A total of 70 mothers and their healthy full-term neonates were included in this study. Urinary iodine concentration was estimated in spot urine samples obtained from mothers and their neonates on day 5. All the neonates were breastfed. The iodine content was determined in the breast milk of all mothers on day 5. Serum concentrations of TSH, thyroglobulin (Tg), free triiodothyronine (FT3) and free thyroxine (FT4) were investigated in the cord serum of neonates and compared to those of mothers immediately after parturition The median urinary iodine on day 5 in mothers and their babies were 30.20 and 23.80 microg/l, respectively. These figures are much lower than normal for these age groups (150-200 microg/l). The median iodine content of breast-milk was 73 microg/l. It is again much lower than in iodine sufficient areas, indicating that the status of iodine nutrition of pregnant and lactating women is clearly insufficient. The median concentrations (and ranges) of neonatal TSH, Tg, FT3 and FT4 were 7.44 mU/l, 71.62 ng/ml, 1.30 pg/ml and 1.34 ng/dl respectively. The corresponding levels for the mothers during labor were 2.19 mU/l, 25.65 ng/ml, 1.31 pg/ml and 1.23 ng/dl respectively. The median neonatal serum concentrations of TSH and Tg were significantly higher than the corresponding maternal levels (P < 0.0001, P < 0.0001, respectively) and 27.1% of the neonates had serum TSH concentrations above 10 mU/l and 57.1 % had cord blood serum Tg concentrations above 54 ng/ml. None of the mothers showed TSH concentrations above 5 mU/l and 41.4% had serum Tg concentrations above 30 ng/ml. Iodine deficiency with low urinary iodine excretion and high serum Tg and TSH concentrations were recognized among pregnant women and their babies in Kayseri in spite of the program of salt iodization. National measures are urgently required for improving the correction of iodine deficiency in Turkey. This includes regular supplementation with iodine, starting at preconception or in early pregnancy and continuing during the period of nursing in this region.


Cancer, fatigue and the return of patients to work-a prospective cohort study.
Fatigue is a highly prevalent and debilitating symptom in cancer survivors. The aim of this study was to assess the impact of fatigue and other cancer-related symptoms on the return to work of cancer survivors. A prospective inception cohort study with 12 months of follow-up was initiated. At 6 months following the first day of sick leave, levels of fatigue, depression, sleep problems, physical complaints, cognitive dysfunction and psychological distress were assessed, in addition to clinical, sociodemographic and work-related factors. Data were obtained from one academic hospital and two general hospitals in the Netherlands. 235 patients who had a primary diagnosis of cancer and underwent treatment with curative intent were included. The rate of return to work was measured at 6, 12 and 18 months. Hazard ratios (HRs) for the duration of sick leave up to 18 months following the first day of sick leave were calculated. The rate of return to work increased from 24% at 6 months to 64% at 18 months following the first day of sick leave. Fatigue, diagnosis, treatment type, age, gender, depression, physical complaints and workload were all related to the time taken to return to work. Fatigue scores were also strongly related to diagnosis, physical complaints, and depression scores. Fatigue at 6 months predicted a longer sick leave with a hazard ratio of 0.71 (95% Confidence Interval (C.I.) 0.59-0.85), adjusted for diagnosis, treatment type, age and gender. In a multivariate Cox regression analysis, diagnosis, treatment, age, physical complaints and workload remained the only significant predictors of duration of the sick leave. 64% of cancer survivors returned to work within 18 months. Fatigue levels predicted the return to work. This was independent of the diagnosis and treatment, but not of other cancer-related symptoms. Better management of cancer-related symptoms is therefore needed to facilitate the return to work of cancer patients.


The Study of Dried Ginger and Linggan Wuwei Jiangxin Decoction Treatment of Cold Asthma Rats Using GC-MS Based Metabolomics.
Dried ginger is the monarch drug in Linggan Wuwei Jiangxin (LGWWJX) decoction, which is used to treat cold asthma. The purpose of this study was to investigate and compare the effects of dried ginger and LGWWJX decoction for treatment of cold asthma rats at the metabolomics level using gas chromatography-mass spectrometry (GC-MS). OVA and ice water-induced cold asthma were induced in SD rats. The effects of dried ginger and LGWWJX decoction were evaluated by general morphological observation, hematoxylin and eosin staining, inflammatory cell count, IgE, IL-4, IFN-γ quantitation, and visceral index. GC-MS-based metabolomics was performed and analyzed using multivariate statistical analysis. Biomarker identification, pathway analysis, correlations between identified biomarker, and efficacy indices were performed. The results showed that dried ginger and LGWWJX decoction had obvious effects on cold asthma rats. Thirty-seven metabolites (15 in serum and 22 in urine) associated with cold asthma were identified. These metabolites were mainly carbohydrates, fatty acids and their products, organic acids, and others. Seven pathways were identified by MetaboAnalyst 4.0 metabolic pathway analysis. After intervention with dried ginger and LGWWJX decoction, the majority of altered metabolites and metabolic pathways returned to control levels. LGWWJX decoction regulated more metabolites of carbohydrates and fatty acids, which contribute to energy metabolism and oxidative stress in cold asthma, than dried ginger. We concluded that dried ginger and LGWWJX decoction both were effective for treatment of cold asthma. LGWWJX decoction was more effective than dried ginger for treatment of cold asthma. This study evaluated the effects of dried ginger and LGWWJX decoction on cold asthma at the metabolomics level. It provides a reference for the research on the compatibility of Chinese Medicine.


[Significance of subjective symptoms in the diagnosis of hyperviscosity syndrome].
A questionnaire including 9 main signs: headache, vertigo, vision and hearing derangement, fatigue, hemorrhage, somnolescence, loss of appetite has been elaborated and introduced into the clinical practice. It was revealed that patients with Sjögren's syndrome had an elevated viscosity of the serum in 30% of the cases. These patients complained of headache and vision derangement more often than those with normal indices, though in the first group it did not reach critical values corresponding to an extended clinical picture of the hyperviscous syndrome. The mentioned questionnaire can be used for early diagnosis of the rheological properties of the blood.


Comparison of accumulated allele loss between primary tumor and lymph node metastasis in stage II non-small cell lung carcinoma: implications for the timing of lymph node metastasis and prognostic value.
Although the Tumor-Node-Metastasis staging of non-small cell lung carcinoma (NSCLC) is the most effective predictor of survival, the clinical outcome of patients at each stage is variable on an individual case basis. We tested the value of incorporating information about the tumor heterogeneity of NSCLC into microsatellite allelotyping in a cohort of 48 node-positive stage II patients (T1N1M0 and T2N1M0). Microsatellite allelotyping involved microdissection of the invasive component of primary tumor and lymph node metastasis at multiple target sites followed by loss of heterozygosity (LOH) analysis at specific regions on chromosomes 1p, 3p, 5q, 7q, 8q, 9p, 10q, 17p, and 18q using 16 markers. All microsatellites manifested LOH ranging from 44 to 76% in primary tumor and showed various degree of heterogeneity between primary tumor and lymph node metastasis. LOH on 3p and 5q in the lymph node metastases was associated significantly with shortened survival of the patients (P = 0.033 and 0.004, respectively), whereas no single LOH in the primary tumors showed association with prognosis. For the analysis of the accumulated load of allele loss, fractional allele loss (FAL) was calculated for each sample. The maximal FAL of lymph node metastasis was significantly lower than that of primary tumor (P = 0.0015), possibly reflecting the early lymphatic spread. High maximal FAL of lymph node metastasis was significantly correlated with an adverse outcome (P = 0.012), whereas maximal FAL of primary tumor did not show any prognostic significance (P = 0.552). A composite mutational profile for each patient based on the allelotyping of the primary tumor and lymph node deposits may make a significant contribution to a more accurate prognosis of stage II NSCLC.


Lymphangiomas of the head and neck in adults.
Lymphangiomas are considered to be congenital malformations of lymphatic channels. Fifty percent to 60% of these lesions are present at birth, with 80% to 90% detected by the second year of life. These lesions are rare in adults but may occur as late as the fifth decade of life. Primary lymphangiomas of the hypopharynx and upper aerodigestive tract are exceedingly rare in adults. The clinical courses of three adults with lymphangiomas of the head and neck are presented. In one case the lesion was confined to the hypopharynx. The literature contains considerable discussion about congenital lymphangiomas; few studies, however, have addressed this problem specifically in the adult population. The clinical appearance, difficulties of diagnosis, and guidelines of treatment are discussed.


[Diabetes and cancer: an injurious association].
A clear relationship between diabetes and cancer has been demonstrated. An increased incidence of several cancers is observed in diabetic patients, notably pancreatic, hepatic, colo-rectal, breast, urinary tract and endometrial cancer. By contrast a decreased incidence of prostate cancer is observed in diabetes patients implying a protective effect. Multiple potential mechanisms have been proposed but they remain hypothetical.


Assortative mating and the maintenance of population structure in a natural hybrid zone.
Understanding the factors that give rise to natural hybrid zones and govern their dynamics and structure is important to predicting the evolutionary consequences of hybridization. Here we use a combination of multigenerational population genetic data, mating patterns from a natural population, behavioral assays, and mark-recapture data within clinal hybrid zones of the genus Xiphophorus to test the role of assortative mating in maintaining population structure and the potential for ongoing genetic exchange between heterospecifics. Our data demonstrate that population structure is temporally robust and driven largely by assortative mating stemming from precopulatory isolation between pure species. Furthermore, mark-recapture data revealed that rates of migration within the same stream reach are far below the level needed to support population structure. In contrast to many empirical studies of natural hybrid zones, there appeared to be no hybrid male dysfunction or discrimination against hybrid males by pure parental females, and hybrid females mated and associated with pure species and hybrid males at random. Despite strong isolation between pure parentals, hybrids therefore can act as a conduit for genetic exchange between heterospecifics, which has been shown to increase the tempo of evolutionary change. Additionally, our findings highlight the complexity of natural hybrid zone dynamics, demonstrating that sexual and ecological selection together can give rise to patterns that do not fit classical models of hybrid zone evolution.


Lats2 phosphorylates p21/CDKN1A after UV irradiation and regulates apoptosis.
LATS2 (Large tumor suppressor 2), a member of the conserved AGC Ser/Thr (S/T) kinase family, is a human tumor suppressor gene. Here, we show that in response to ultraviolet radiation, Lats2 is phosphorylated by Chk1 at Ser835 (S835), which is located in the kinase domain of Lats2. This phosphorylation enhances Lats2 kinase activity. Subsequently, Lats2 phosphorylates p21 at S146. p21 (CDKN1A) is a cyclin-dependent kinase (CDK) inhibitor, which not only regulates the cell cycle by inhibition of CDK, but also inhibits apoptosis by binding to procaspase-3 in the cytoplasm. Phosphorylation by Lats2 induces degradation of p21 and promotes apoptosis. Accordingly, Lats2 overexpression induces p21 degradation, activation of caspase-3 and caspase-9, and apoptosis. These findings describe a novel Lats2-dependent mechanism for induction of cell death in response to severe DNA damage.


[Bronchopulmonary and laryngeal symptoms of gastroesophageal reflux disease: diagnosis and treatment].
The article discloses the results of the examination and treatment of patients with gastroesophageal reflux disease, the course of which was complicated with extraesophageal (bronchopulmonary and laryngeal) symptoms. The authors managed to establish the connection between gastric reflux and pulmonary and laryngeal symptoms with a high degree of reliability, based on the results of functional methods of research (24-hour pH-measurement in the esophagus). The obtained results of the treatment testify to the efficiency of active surgical tactics in this group of patients.


Inhalation of budesonide/formoterol increases diaphragm muscle contractility.
Although budesonide/formoterol (BUD/FORM) is used clinically as a steroid/β(2)-agonist single inhaler, it has not yet been clarified whether BUD/FORM has inotropic effects on diaphragm muscles after inhalation. We examined the effects of BUD/FORM inhalation, endotoxin injection, and BUD/FORM inhalation plus endotoxin injection on diaphragm contractile properties and nitric oxide (NO) production. After these three treatments, the diaphragm muscle was dissected, and its contractile properties were measured. Histochemistry for the reduced form of nicotinamide adenine dinucleotide phosphate diaphorase was performed for each muscle to assess NO production. The force-frequency curves showed an upward shift 1 h after inhalation (p < 0.05) in the BUD/FORM inhalation only group. The force-frequency curves showed a downward shift 4 h after injection (p < 0.001) in the endotoxin injection groups. In the BUD/FORM inhalation plus endotoxin injection groups, a downward shift in the force-frequency curves at 4 h after endotoxin injection was prevented. NO production was inhibited in the BUD/FORM inhalation plus endotoxin injection group compared with that of the endotoxin injection only groups. BUD/FORM inhalation has an inotropic effect on diaphragm muscle, protects diaphragm muscle deterioration after endotoxin injection, and inhibits NO production. Increments in muscle contractility with BUD/FORM inhalation are induced through a synergistic effect of an anti-inflammatory agent and β(2)-agonist.


[The legal possibilities for action in the health inspection of public eating establishments].
This study, based upon the Spanish legal framework and upon the experience of the authors, is intended to establish the legal procedures for action when a sanitary inspector finds himself in the situation where he observes that a public establishment is infringing some hygiene or sanitary regulation which may carry a health risk of varying seriousness. Possibilities for action are outlined, depending on the urgency and seriousness of the situation, as well as indicating who is responsible for the application of the law in each case. The legal possibilities for action are: the closure of the establishment, a warning, and institution of penal proceedings. Finally some suggestions are made as to the method of carrying out such inspections.


Evidence supporting a late Golgi location for lactosylceramide to ganglioside GM3 conversion.
Ganglioside GM2 synthase and other enzymes required for complex ganglioside synthesis were localized recently to the trans Golgi network (TGN). However, there are conflicting reports as to the location of GM3 synthase; originally this enzyme was detected in the early Golgi of rat liver but a recent report localized it to the late Golgi. We have used chimeric forms of ganglioside GM2 synthase to determine if the location of lactosylceramide (LacCer) to GM3 conversion in Chinese hamster ovary (CHO) cells was the early or late Golgi. Our approach tested whether GM3 could be utilized as a substrate by GM2 synthase chimeras which were targeted to compartments earlier than the trans Golgi, i.e., GM3 produced in the cis Golgi should be utilized by GM2 synthase located anywhere in the Golgi whereas GM3 produced in the trans Golgi should only be used by GM2 synthase located in the trans Golgi or TGN. Comparison of cell lines stably expressing these chimeras revealed that the in vivo functional activity of GM2 synthase decreased progressively as the enzyme was targeted to earlier compartments; specifically, the percentage of GM3 converted to GM2 was 83-86% for wild type enzyme, 70% for the medial Golgi targeted enzyme, 13% for the ER and cis Golgi targeted enzyme, and only 1.7% for the ER targeted enzyme. Thus, these data are consistent with a late Golgi location for LacCer to GM3 conversion in these cells.


Excellent survivorship of the Morscher monoblock cup with a 28-mm Metasul-on-Metasul bearing at a mean of 5-year follow-up.
The Morscher monoblock cup is designed for optimal osteointegration and holds the potential for excellent long-term survival. The Metasul-on-Metasul bearing was introduced to eliminate wear-induced periprosthetic osteolysis. This study reviews 137 Morscher cups with a 28-mm Metasul-on-Metasul bearing used in primary THA at 5.1years (3.2-6.6) after implantation. One hundred thirty-seven cups were implanted in 119 patients. Three patients (2.2%) had died of unrelated causes, and 10 patients (8.0%) were lost to follow-up. The mean Harris Hip score was 89.8 and the mean WOMAC sum score was 18.5. No cases of acetabular osteolysis were found. The 5-year cup survival rate was 98.5%. The Morscher cup with a 28-mm Metasul-on-Metasul bearing used in uncemented THA showed no acetabular osteolysis and promising survivorship at intermediate-term follow-up.


Perspectives on neonatal hypoxia/ischemia-induced edema formation.
Neonatal hypoxia/ischemia (HI) is the most common cause of developmental neurological, cognitive and behavioral deficits in children, with hyperoxia (HHI) treatment being a clinical therapy for newborn resuscitation. Although cerebral edema is a common outcome after HI, the mechanisms leading to excessive fluid accumulation in the brain are poorly understood. Given the rigid nature of the bone-encased brain matter, knowledge of edema formation in the brain as a consequence of any injury, as well as the importance of water clearance mechanisms and water and ion homeostasis is important to our understanding of its detrimental effects. Knowledge of the pathological process underlying the appearance of dysfunctional outcomes after development of cerebral edema after neonatal HI in the developing brain and the molecular events triggered will allow a rational assessment of HHI therapy for neonatal HI and determine whether this treatment is beneficial or harmful to the developing infant.


Non-contact electrical detection of intrinsic local charge and internal electric field at nanointerfaces.
A nanoscale non-contact electrical measurement has been developed based on Auger electron spectroscopy. This approach used the specialty of an Auger electron, which is self-generated and free from external influences, to overcome the technical limitations of conventional measurements. The detection of the intrinsic local charge and internal electric field for nanostructured materials was achieved with a resolution below 10 nm. As an example, the electrical properties at the GaN/AlGaN/GaN nanointerfaces were characterized. The concentration of the intrinsic polarization sheet charges embedded in GaN/AlGaN nanointerfacial layers were accurately detected to be -4.4 e nm(-2). The mapping of the internal electric field across the nanointerface revealed the actual energy-band configuration at the early stage of the formation of a two-dimensional electron gas.


Preparation of an (inorganic/organic) hybrid hydrogel from a peptide oligomer and a tubular aluminosilicate nanofiber.
'Imogolite', a tubular inorganic nanotube surface, was modified with a peptide oligomer to prepare a hybrid hydrogel. The formation of the gels was confirmed by conducting a vial inversion test and rheological measurements. The surface modification of imogolite with the peptide oligomer was verified by performing thermogravimetric analysis and circular dichroism measurements. Furthermore, the formation of the network-like morphology of the prepared hydrogel was confirmed by scanning force microscopy.


Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS.
Elevated levels of neurofilament light (NfL) and heavy (NfH) chain in amyotrophic lateral sclerosis (ALS) cerebrospinal fluid (CSF) and serum reflect neuro-axonal degeneration and are used as diagnostic biomarkers. However, studies comparing the differential diagnostic potential for ALS of all four parameters are missing. Here, we measured serum NfL/NfH and CSF NfL/NfH in a large cohort of ALS and other neurological disorders and analysed the differential diagnostic potential. In total CSF and serum of 294 patients were analysed. The diagnostic groups comprised: ALS (n=75), frontotemporal lobar degeneration (FTLD) (n=33), Alzheimer's disease (n=20), Parkinson's disease (dementia) (n=18), Creutzfeldt-Jakob disease (n=11), non-neurodegenerative controls (n=77) (Con) and 60 patients who were seen under the direct differential diagnosis of a patient with ALS (Con.DD). CSF and serum NfL and NfH showed significantly increased levels in ALS (p<0.0001) compared with Con and Con.DD. The difference between ALS and FTLD was markedly stronger for NfH than for NfL. CSF and serum NfL demonstrated a stronger correlation (r=0.84 (95% CI 0.80 to 0.87), p<0.001) than CSF and serum NfH (r=0.68 (95% CI 0.61 to 0.75), p<0.0001). Comparing ALS and Con.DD, receiver operating characteristic analysis revealed the best area under the curve (AUC) value for CSF NfL (AUC=0.94, 95% CI 0.91 to 0.98), followed by CSF NfH (0.93, 95% CI 0.88 to 0.98), serum NfL (0.93, 95% CI 0.89 to 0.97) and serum NfH (0.88, 95% CI 0.82 to 0.94). Our results demonstrate that CSF NfL and NfH as well as serum NfL are equally suited for the differential diagnosis of ALS, whereas serum NfH appears to be slightly less potent.


[Serum haptoglobin in lung cancer patients].
Changes in the concentration of haptoglobin-glycoprotein-globulin fraction of blood serum were studied in patients with lung cancer. It was found, that haptoglobin concentration increased in accordance to a disease stage. Formation of haptoglobin hemoglobin (Hp-Hb) complex in the sera of patients may be of great importance for neutralization of superoxidative products.


Classification of fish-pathogenic vibrios based on comparative 16S rRNA analysis.
No systematic classification of fish-pathogenic vibrios has been accomplished previously despite the use of serological, physiological, and genetical classification systems. In this study, a comparative 16S rRNA analysis of 34 strains (representing seven species) of fish-pathogenic vibrios was performed. The 16S rRNA sequences were obtained by using reverse transcriptase. Nearly complete sequences were obtained for nine strains. On the basis of the results of this analysis, the remaining strains were investigated by analyzing selected stretches containing a total of 560 nucleotides. With the exception of a few strains, including ATCC 43313 (serovar O9), our comparative 16S rRNA analysis confirmed that strains preliminarily identified as Vibrio anguillarum were phylogenetically closely related. Strains of V. anguillarum could be divided into groups, with the main group containing serotype O1 and O2 strains isolated from Atlantic salmon, rainbow trout, turbot, cod, and saithe. The other distinctive group was represented by type strain NCMB 6. This strain was nearly indistinguishable from the type strains of Vibrio ordalii and Vibrio damsela on the basis of the 16S rRNA stretches compared. The results of a comparative 16S rRNA analysis justified the status of Vibrio salmonicida as a distinct species. Originally, this species was characterized biochemically as a very homogeneous species. However, two strains, which were isolated from diseased halibut and from the intestines of healthy cod, could not be distinguished from V. salmonicida strains phylogenetically, although they differed from the original species description in several phenotypic traits. Our results indicate that V. salmonicida and Vibrio fischeri form a cluster that is clearly separated from the cluster that includes V. anguillarum.


Nanocellulose: a bioadsorbent for chemical contaminant remediation.
Chemical contaminants such as heavy metals, dyes, and organic oils seriously affect the environment and threaten human health. About 2 million tons of waste is released every day into the water system. Heavy metals are the largest contributor which cover about 31% of the total composition of water contaminants. Every day, approximately 14 000 people die due to environmental exposure to selected chemicals. Removal of these contaminants down to safe levels is expensive, high energy and unsustainable by current approaches such as oxidation, biodegradation, photocatalysis, precipitation, reverse osmosis and adsorption. A combination of biosorption and nanotechnology offers a new way to remediate these chemical contaminants. Nanostructured materials are proven to have higher adsorption capacities than the same material in its larger-scale form. Nanocellulose is very promising as a high-performance bioadsorbent due to its interesting characteristics of high adsorption capacity, high mechanical strength, hydrophilic surface chemistry, renewability and biodegradability. It has been proven to have higher adsorption capacity and better binding affinity than other similar materials at the macroscale. The high specific surface area and abundance of hydroxyl groups within lead to the possible functionalization of this material for decontamination purposes. Several research papers have shown the effectiveness of nanocellulose in the remediation of chemical contaminants. This review aims to provide an overview of the most recent developments regarding nanocellulose as an adsorbent for chemical contamination remediation. Recent advancements regarding the modification of nanocellulose to enhance its adsorption efficiency towards heavy metals, dyes and organic oils were highlighted. Moreover, the desorption capability and environmental issue related to every developed nanocellulose-based adsorbent were also tackled.


Projective imaging of pulsatile flow with magnetic resonance.
Noninvasive angiography with magnetic resonance is demonstrated. Signal arising in all structures except vessels that carry pulsatile flow is eliminated by means of velocity-dependent phase contrast, electrocardiographic gating, and image subtraction. Background structures become in effect transparent, enabling the three-dimensional vascular tree to be imaged by projection to a two-dimensional image plane. Image acquisition and processing are accomplished with entirely conventional two-dimensional Fourier transform magnetic resonance imaging techniques. When imaged at 0.6 tesla, vessels 1 to 2 millimeters in diameter are routinely detected in a 50-centimeter field of view with data acquisition times less than 15 minutes. Studies of normal and pathologic anatomy are illustrated in human subjects.


Million hearts: prevalence of leading cardiovascular disease risk factors--United States, 2005-2012.
Each year, approximately 1.5 million U.S. adults have a heart attack or stroke, resulting in approximately 30 deaths every hour and, for nonfatal events, often leading to long-term disability. Overall, an estimated 14 million survivors of heart attacks and strokes are living in the United States. In 2011, the U.S. Department of Health and Human Services, in collaboration with nonprofit and private organizations, launched Million Hearts (http://www.millionhearts.hhs.gov), an initiative focused on implementing clinical and community-level evidence-based strategies to reduce cardiovascular disease (CVD) risk factors and prevent a total of 1 million heart attacks and strokes during the 5-year period 2012-2016. From 2005-2006 to the period with the most current data, analysis of the Million Hearts four "ABCS" clinical measures (for aspirin, blood pressure, cholesterol, and smoking) showed 1) no statistically significant change in the prevalence of aspirin use for secondary prevention (53.8% in 2009-2010), 2) an increase to 51.9% in the prevalence of blood pressure control (in 2011-2012), 3) an increase to 42.8% in the prevalence of cholesterol management (in 2011-2012), and 4) no statistically significant change in the prevalence of smoking assessment and treatment (22.2% in 2009-2010). In addition, analysis of two community-level indicators found 1) a decrease in current tobacco product smoking (including cigarette, cigar, or pipe use) prevalence to 25.1% in 2011-2012 and 2) minimal change in mean daily sodium intake (3,594 mg/day in 2009-2010). Although trends in some measures are encouraging, further reductions of CVD risk factors will be needed to meet Million Hearts goals by 2017.


Self-control of task difficulty during training enhances motor learning of a complex coincidence-anticipation task.
The aim of the present work was to analyze the influence of self-controlled task difficulty on motor learning. Participants had to intercept three targets falling at different velocities by displacing a stylus above a digitizer Task difficulty corresponded to racquet width. Half the participants (self-control condition) could choose the racquet width at the beginning of each trial. Each was paired with a participant from the yoked group. The self-control condition resulted in better performances and accuracy during immediate and delayed retention tests. These results confirm the advantage of a self-control condition on motor learning. They are discussed with reference to the challenge point hypothesis (Guadagnoli & Lee, 2004).


to assess specificities of course of the long-QT syndrome in children before and after implantation of cardioverter-defibrillator (ICD), and optimization of indications to ICD-therapy. We included in this study 48 children with long-QT syndrome from 44 unrelated families (28 boys and 20 girls), who underwent ICD implantation at the mean age 11.8±3.8 years. Mean duration of follow-up after implantation was 5.2±2.8 years. Data from these children were compared with those from 59 children of comparable age and gender with long-QT syndrome from 46 unrelated families receiving antiarrhythmic therapy (β-adrenoblockers). We assessed clinical and electrocardiographic characteristics of the disease obtained at initial visit and their dynamics thereafter. Children with long-QT syndrome and ICD were mainly probands with interval QT longer than 500 ms, recurrent syncope and often history of sudden cardiac arrest requiring high doses of β-adrenoblockers for control of ventricular tachyarrhythmias. ICD implantation is an effective and safe method both of primary and secondary prevention of sudden cardiac death in children with long-QT syndrome.


[Predictors of the efficacy of psychorelaxation therapy in hypertension].
Results of clinical, psychological and psychophysiological examinations of 136 patients with mild essential hypertension indicate that psychorelaxation therapy is more effective in patients with a higher level of BP response to emotional stress and a shorter period of BP recovery after stress. Those patients had a moderate level of anxiety and interpersonal conflicts. Predictors of the efficacy of autogenic training, breathing relaxation training and biofeedback differed. The antihypertensive effect of those methods was associated with various personality traits.


When is it socially acceptable to feel sick?
Disease is a ubiquitous and powerful evolutionary force. Hosts have evolved behavioural and physiological responses to disease that are associated with increased survival. Behavioural modifications, known as 'sickness behaviours', frequently involve symptoms such as lethargy, somnolence and anorexia. Current research has demonstrated that the social environment is a potent modulator of these behaviours: when conflicting social opportunities arise, animals can decrease or entirely forgo experiencing sickness symptoms. Here, I review how different social contexts, such as the presence of mates, caring for offspring, competing for territories or maintaining social status, affect the expression of sickness behaviours. Exploiting the circumstances that promote this behavioural plasticity will provide new insights into the evolutionary ecology of social behaviours. A deeper understanding of when and how this modulation takes place may lead to better tools to treat symptoms of infection and be relevant for the development of more efficient disease control programmes.


Two types of static gamma-axon in cat muscle spindles.
The action of single static gamma-axons in 'single fibre' ventral root filaments was tested on the responses of from two to eight spindles in the same tenuissimus muscle in anaesthetized cats. The type of intrafusal fibre activated in each spindle by a particular axon was diagnosed from its effect on the discharge of primary and secondary sensory endings, frequently in the same spindle. One or two spindles were subsequently isolated in most experiments and the type of intrafusal fibre activated by the axon was observed directly. Except in the case of a few weak actions which could not be interpreted, the diagnosis made from the afferent recordings was always correct. Twenty-four static gamma-axons activated the chain fibres in every spindle they supplied on which their action was tested; the static bag2 fibre was also involved in about 20% of the spindles though its contraction was quite often weak. Eleven static gamma-axons activated the static bag2 fibre in every spindle they supplied on which their action was tested; some chain fibres were activated as well in about 20% of the spindles. There were only two possible exceptions to the general rule that a static gamma-axon activates either the chain fibres or the static bag2 fibre in every spindle it supplies and never activates only the chain fibres in one spindle, and only the static bag2 fibre in another spindle. Direct observation of isolated spindles provided preliminary evidence that some non-selective connexions of static gamma-axons have a pronounced physiological action by way of their terminals on one type of intrafusal fibre while the terminal(s) on the other type of fibre produce such a weak contraction that the sensory endings are not affected. Other non-selective connexions do, however, have a significant physiological effect by way of their terminals on both the static bag2 fibre and the chain fibres. It is proposed that there are two types of static gamma-motoneurone. 'Static bag gamma-motoneurones', through their terminals on the static bag2 fibre in every spindle, bias the discharge from primary endings (and to a lesser extent from some secondary endings) but leave their length sensitivity largely unaltered; connexions to chain fibres in some spindles have a weak action on primary endings but may greatly increase the length sensitivity of secondary endings.(ABSTRACT TRUNCATED AT 400 WORDS)


Acute mastoiditis in infancy: the Soroka experience: 1990-2000.
Acute mastoiditis (AM) is an uncommon but serious complication of acute otitis media (AOM). In the pre-antibiotic era, AM was seen more frequently than it is today, but it was rare in infants. However, in the last two decades an increase in the incidence of AM in infancy has been reported in the literature. During the years 1990-2002, we treated 113 patients with 128 episodes of AM; of them, 24 were infants (median age 6 months; 18 males) who suffered from 26 episodes of AM. Twenty developed AM as a complication of their first episode of AOM. One of the four infants with a prior history of AOM suffered from common variable immunodeficiency. A significant increase in the incidence of AM in infants was recorded during the study period (P = 0.01). The most common presenting clinical signs were post-auricular swelling and fever >38 degrees C (77% and 77%, respectively, of all patients). Seventeen episodes of AM were not treated with prior antibiotics. Tympanocentesis was performed in all episodes of AM. Middle ear fluid culture was positive in 17 (65%) of the 26 AM episodes. The most common pathogens cultured were Streptococcus pneumoniae (10 infants, 58% of all pathogens, 3/10 intermediately susceptible to penicillin) followed by Streptococcus pyogenes (4, 23%), non-typable H. influenzae (2, 12%) and S. aureus (1, 6%). Temporal bone CT showed bone destruction in 14 patients; 3 infants had subperiosteal abscesses and 3 lateral sinus thrombosis. Ten infants underwent mastoid surgery due to non-resolution of symptoms and signs with antibiotic therapy. Eight underwent cortical mastoidectomy with two patients undergoing ventilation tube introduction only. The remainder of the infants healed with conservative treatment. (1) A significant increase in the incidence of AM in infants was recorded over the last decade, though a specific reason for this trend remains uncertain; (2) Most of the cases of AM followed the infant's initial AOM episode, and most of the infants had not received prior antibiotic therapy; (3) The clinical signs and symptoms of AM were more severe in infants than in older patients; (4) While S. pneumonia was the most common pathogen isolated in middle ear fluid cultures, the involvement of S. pyogenes in AM was higher than that reported in AOM.


Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis.
Sympathetic tone is one of the main determinants of blood pressure (BP) variability and treatment-resistant hypertension. The aim of our study was to assess changes in BP variability after renal denervation (RDN). In addition, on an exploratory basis, we investigated whether baseline BP variability predicted the BP changes after RDN. We analyzed 24-h BP recordings obtained at baseline and 6 months after RDN in 167 treatment-resistant hypertension patients (40% women; age, 56.7 years; mean 24-h BP, 152/90 mmHg) recruited at 11 expert centers. BP variability was assessed by weighted SD [SD over time weighted for the time interval between consecutive readings (SDiw)], average real variability (ARV), coefficient of variation, and variability independent of the mean (VIM). Mean office and 24-h BP fell by 15.4/6.6 and 5.5/3.7 mmHg, respectively (P < 0.001). In multivariable-adjusted analyses, systolic/diastolic SDiw and VIM for 24-h SBP/DBP decreased by 1.18/0.63 mmHg (P ≤ 0.01) and 0.86/0.42 mmHg (P ≤ 0.05), respectively, whereas no significant changes in ARV or coefficient of variation occurred. Furthermore, baseline SDiw (P = 0.0006), ARV (P = 0.01), and VIM (P = 0.04) predicted the decrease in 24-h DBP but not 24-h SBP after RDN. RDN was associated with a decrease in BP variability independent of the BP level, suggesting that responders may derive benefits from the reduction in BP variability as well. Furthermore, baseline DBP variability estimates significantly correlated with mean DBP decrease after RDN. If confirmed in younger patients with less arterial damage, in the absence of the confounding effect of drugs and drug adherence, baseline BP variability may prove a good predictor of BP response to RDN.


Preliminary results of a phase II study of weekly paclitaxel (PTX) and carboplatin (CBDCA) administered concurrently with thoracic radiation therapy (TRT) followed by consolidation chemotherapy with PTX/CBDCA for stage III unresectable non-small-cell lung cancer (NSCLC).
Concurrent chemoradiotherapy plays an important role in the treatment of unresectable NSCLC. This phase II study was conducted to evaluate the efficacy and toxicity of paclitaxel (PTX) and carboplatin (CBDCA) at a recommended dose, based on other previous phase I studies. Twenty-two unresectable stage III NSCLC patients participated in this trial. Of those 22 patients, 19 were evaluable, with a median age of 57 (with ages ranging between 42 and 74), in stages IIIA/IIIB: 6/13. Every patient displayed adequate organ functions. Treatment consisted of a 1-hour i.v. infusion of 50 mg/m2 of PTX followed by a half-hour infusion of CBDCA AUC 2 administered weekly concurrently with radiation treatment, every first day of those weeks in which the patient underwent radiotherapy. Concurrent thoracic radiation therapy was performed in daily doses of 2 Gy to a total dose of 66 Gy over a period of 6.5 weeks. After completion of chemoradiotherapy, consolidation chemotherapy was administered via a 3-hour i.v. infusion of 175 mg/2 PTX on days 1 and 22, in combination with a 1-hour i.v. infusion of CBDCA AUC 6 on days 1 and 22, q 4 weeks for 4 cycles. The overall response rate was 78.9% (95% CI: 62-87.7) with 5 CR (26.3%), 10 PR (52.6%), 2 SD (15.8%), and 1 PD (5.3%). The median survival rate of the patients was 13.9 months, and the 1-year survival rate was 65.1%. Toxicity was moderate: grade 2 neutropenia was seen in 8, and grade 3 neutropenia in 5 patients. Grade 2 thrombocytopenia was seen in 3 patients, and grade 3 thrombocytopenia was not observed. Nonhematologic toxicities were moderate: esophagitis was the most common, and significant toxicity was noted in this study (89.4%). Grade 1 asthenia/fatigue was observed in 5, and grade 2 asthenia/fatigue in 3 patients; furthermore, grade 1 peripheral neuropathy was seen in 4 of the cases and grade 2 peripheral neuropathy in 3 of the cases. Concurrent chemoradiotherapy with weekly PTX/CBDCA, followed by consolidation chemotherapy with the same regimen in patients with stage III unresectable NSCLC is feasible and well tolerated.


[Treatment of children with diffuse polyposis of the colon].
In 1971-1990 the authors treated 41 children 3 to 15 years of age with diffuse familial polyposis of the colon (juvenile form). Forty-four operations were carried out (3 patients underwent the second operation. The authors conducted several variants of colon resection with due account for the sites of greatest accumulation of the polyps--resection of the sigmoid colon, hemicolectomy, combined resection. Progressive growth of polyps was encountered in the remaining areas in the late-term periods. In view of this, the authors recommend total colectomy with the creation of an ileorectal or ileoanal anastomosis as the method of choice. The article describes an original operative method suggested by the authors. Twenty-eight similar operations were performed with good results.


Different injection sites of radionuclide for sentinel lymph node detection in breast cancer: single institution experience.
The sentinel node is defined as the first lymph node in a regional basin that receives lymph flow from the primary tumor. There is still a controversy over deep versus superficial injection administration in the breast. From June 2006 to June 2008, 133 patients with biopsy proven breast carcinoma and clinically negative axilla have been treated with conservative surgery and a study of their axillary sentinel lymph nodes (SLN) has been conducted. The median number of SLN detected was significantly higher in the periareolarly injected (PA) group (2.43) than in the intratumorally injected (IT) group (1.92) (p=0.008). The incidence of positive SLN in the PA group was not significantly different from the incidence observed in the IT group (p=0.22). Both techniques seem to reliably identify the true SLN in the axilla. Although intradermal as compared with intratumoral injection has numerous advantages, including ease of injection, shorter time between injection and sentinel node identification, and increased radiotracer nodal uptake, nevertheless, intradermal injection allows almost exclusive identification of axillary nodes, and only on rare occasions, of non-axillary nodes. We therefore think that intratumoral injection must be preferred to intradermal when possible to identify the node that is the first draining step of the tumoral tissue.


Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: implications in type 2 diabetic nephropathy.
Molecular mechanisms underlying renal complications of diabetes remain unclear. We tested whether renal NADPH oxidase (Nox) 4 contributes to increased reactive oxygen species (ROS) generation and hyperactivation of redox-sensitive signaling pathways in diabetic nephropathy. Diabetic mice (db/db) (20 wk) and cultured mouse proximal tubule (MPT) cells exposed to high glucose (25 mmol/l, D-glucose) were studied. Expression (gene and protein) of Nox4, p22(phox), and p47(phox), but not Nox1 or Nox2, was increased in kidney cortex, but not medulla, from db/db vs. control mice (db/m) (P < 0.05). ROS generation, p38 mitogen-activated protein (MAP) kinase phosphorylation, and content of fibronectin and transforming growth factor (TGF)-β1/2 were increased in db/db vs. db/m (P < 0.01). High glucose increased expression of Nox4, but not other Noxes vs. normal glucose (P < 0.05). This was associated with increased NADPH oxidase activation and enhanced ROS production. Nox4 downregulation by small-interfering RNA and inhibition of Nox4 activity by GK-136901 (Nox1/4 inhibitor) attenuated d-glucose-induced NADPH oxidase-derived ROS generation. High d-glucose, but not l-glucose, stimulated phosphorylation of p38MAP kinase and increased expression of TGF-β1/2 and fibronectin, effects that were inhibited by SB-203580 (p38MAP kinase inhibitor). GK-136901 inhibited d-glucose-induced actions. Our data indicate that, in diabetic conditions: 1) renal Nox4 is upregulated in a cortex-specific manner, 2) MPT cells possess functionally active Nox4-based NADPH, 3) Nox4 is a major source of renal ROS, and 4) activation of profibrotic processes is mediated via Nox4-sensitive, p38MAP kinase-dependent pathways. These findings implicate Nox4-based NADPH oxidase in molecular mechanisms underlying fibrosis in type 2 diabetic nephropathy.


What's in the Literature?
For this issue of Journal, a few recent publications that discuss disorders of motor unit (motor neuron, nerve, neuromuscular junction, and muscle) are selected. Articles about amyotrophic lateral sclerosis, Guillain-Barré syndrome, hereditary neuropathies, myasthenia gravis, and myopathies that convey a salient clinical lesson are discussed. There have been many other excellent publications in the past few months, but the space constrains do not allow to include them all.