Opsonic and antibody responses to pneumococcal polysaccharide types 6A, 19F and 23F after vaccination of immunocompromised patients.
Opsonic and antibody responses to pneumococcal polysaccharide types 6A, 19F and 23F were evaluated before and after vaccination with a 14-valent pneumococcal vaccine in 25 patients splenectomized due to trauma, non-malignant or malignant disease and in 8 non-splenectomized patients with malignant disease. In approximately 50% of the tests, a 2-fold or greater increase in antibody concentrations and a significantly enhanced opsonization of pneumococci was found. A close correlation between antibody increase an enhancement of opsonization was demonstrated. 93% of paired samples with postimmunization antibody increase above 150 ELISA units showed significantly enhanced opsonization. Increased postvaccination opsonic activity and antibody levels were infrequently accompanied by increased granulocyte chemotactic activity of the serum. No significant difference in antibody and opsonic response to vaccination was found between the groups of patients, except for patients with Hodgkin's disease receiving chemotherapy, who had a reduced immunization response. Prevaccination antibody concentration, type of antigen or age of the patients did not influence the outcome of vaccination.


A comparison of in vivo and in vitro human airway reactivity to histamine.
To examine for a relationship between in vivo nonspecific bronchial reactivity to histamine and in vitro smooth muscle response to histamine, we performed inhalation dose-response curves prior to lung surgery in 12 patients and compared this with their bronchial smooth muscle response in vitro. In vivo reactivity was assessed by the provocative concentration of histamine resulting in a 20% fall in forced expiratory volume in one second (PC20), and in vitro reactivity was measured by the negative log of the molar concentration of histamine producing 50% maximal contraction (pD2) as well as maximal tension generated (Tmax). In addition, morphometric analysis was performed on the in vitro tissue to quantitate the amount of smooth muscle present. A wide range of in vivo responses was found in the 12 subjects (PC20-0.065 lead to 16). There was less in vitro variability and no correlation between PC20 and in vitro reactivity assessed by pD20 or Tmax or between PC20 and the percent of smooth muscle.


Forced exercise attenuates neuropathic pain in chronic constriction injury of male rat: an investigation of oxidative stress and inflammation.
Initial peripheral/central nerve injuries, such as chronic constriction injury (CCI)/spinal cord injury, are often compounded by secondary mechanisms, including inflammation and oxidative stress, which may lead to chronic neuropathic pain characterized by hyperalgesia or allodynia. On the other hand, exercise as a behavioral and non-pharmacological treatment has been shown to alleviate chronic neuropathic pain. Therefore, this study was conducted to examine whether or not exercise reduces neuropathic pain through modifying oxidative stress and inflammation in chronic constriction injury of the sciatic nerve. Wistar male rats weighing 200±20 g were randomly divided into five groups (normal, sham, CCI, pre-CCI exercise, and post-CCI exercise group). Sciatic nerve of anesthetized rats was loosely ligated to induce CCI, and they were then housed in separate cages. The rats ran on treadmill at a moderate speed for 3 weeks. Mechanical allodynia and thermal hyperalgesia were determined using von Frey filament and plantar test, respectively. Tumor necrosis factor-alpha (TNF-α) assayed in the cerebrospinal fluid, malondialdehyde, and total antioxidant capacity were measured in the serum using Western blot test, thiobarbituric acid, and ferric reducing ability of plasma (FRAP), respectively. The mechanical allodynia (P=0.024) and thermal hyperalgesia (P=0.002) in the CCI group were higher than those in the sham group. Exercise after CCI reduced (P=0.004) mechanical allodynia and thermal hyperalgesia (P=0.025) compared with the CCI group. Moreover, the level of FRAP in the CCI group was (P=0.001) lower than that in the sham group, and post-CCI exercise reversed FRAP amount toward the control level (P=0.019). The amount of malondialdehyde did not differ between groups. Level of TNF-α increased in the CCI group (P=0.0002) compared with sham group and post-CCI exercise could reverse it toward the level of control (P=0.005). Post CCI-exercise but not pre CCI-exercise reduces CCI-induced neuropathic pain. One of the possible involved mechanisms is increasing the total antioxidant capacity and reducing the amount of TNF-α.


Multi-dimensional co-separation analysis reveals protein-protein interactions defining plasma lipoprotein subspecies.
The distribution of circulating lipoprotein particles affects the risk for cardiovascular disease (CVD) in humans. Lipoproteins are historically defined by their density, with low-density lipoproteins positively and high-density lipoproteins (HDLs) negatively associated with CVD risk in large populations. However, these broad definitions tend to obscure the remarkable heterogeneity within each class. Evidence indicates that each class is composed of physically (size, density, charge) and compositionally (protein and lipid) distinct subclasses exhibiting unique functionalities and differing effects on disease. HDLs in particular contain upward of 85 proteins of widely varying function that are differentially distributed across a broad range of particle diameters. We hypothesized that the plasma lipoproteins, particularly HDL, represent a continuum of phospholipid platforms that facilitate specific protein-protein interactions. To test this idea, we separated normal human plasma using three techniques that exploit different lipoprotein physicochemical properties (gel filtration chromatography, ionic exchange chromatography, and preparative isoelectric focusing). We then tracked the co-separation of 76 lipid-associated proteins via mass spectrometry and applied a summed correlation analysis to identify protein pairs that may co-reside on individual lipoproteins. The analysis produced 2701 pairing scores, with the top hits representing previously known protein-protein interactions as well as numerous unknown pairings. A network analysis revealed clusters of proteins with related functions, particularly lipid transport and complement regulation. The specific co-separation of protein pairs or clusters suggests the existence of stable lipoprotein subspecies that may carry out distinct functions. Further characterization of the composition and function of these subspecies may point to better targeted therapeutics aimed at CVD or other diseases.


Analysis of maternal mortality in a tertiary care hospital to determine causes and preventable factors.
All pregnant women are at risk of obstetrical complications and most of these occur during labour and delivery that lead to maternal death. In our setup maternal mortality is seriously under estimated. Safe motherhood as a priority for action can not be identified with out properly assessing maternal mortality. The objectives of this study were to determine causes and preventable factors responsible for maternal mortality. This study was conducted in Gynaecology 'C' unit of Ayub Teaching Hospital, Abbottabad, from January 2000 to December 2001. Patients were admitted through emergency obstetrics care unit and Gynaecology out patient department. Patients' demographic record including age, parity, education, socio-economic status along with antenatal care record, level of care and distance from hospital were noted. Causative factors leading to maternal death and contribution factors evaluated. All this information was collected from patients' records. Twenty-six maternal deaths were recorded during study period. The major causative factors were haemorrhage 9 (34.6%), eclampsia 8 (30%), sepsis 5 (19.2%), anaesthetic complications 3 (11.5%) and hepatic encephalopathy 1 (3.8%). Maternal mortality ratio was 12.7/1000 live births (26/2040). The age range was between 18-42 years. There were 16 (61.5%) patients in > 30 years age group. Most of them (69%) were grand multiparas (Parity > 5). Education, antenatal booking and socio-economic status were poor. The distance from hospital was between 10 and 100 KM. The level of care available at nearest health facility was estimated, 40% were attended by traditional birth attendants, 33% by lady health visitors, 10% by doctors and to 17% no level of care was available. Obstetrical haemorrhage and hypertensive disorders are still major causes of maternal deaths. Most maternal deaths are preventable. The provision of skilled care and timely management of complications can lower maternal mortality in our setup.


Non-heme iron(II) complexes containing tripodal tetradentate nitrogen ligands and their application in alkane oxidation catalysis.
A series of iron(II) bis(triflate) complexes containing tripodal tetradentate nitrogen ligands with pyridine and dimethylamine donors of the type [N(CH(2)Pyr)(3-n)()(CH(2)CH(2)NMe(2))(n)] [n = 0 (tpa, 1), n = 1 (iso-bpmen, 3), n = 2 (Me(4)-benpa, 4), n = 3 (Me(6)-tren, 5)] and the linear tetradentate ligand [(CH(2)Pyr)MeN(CH(2)CH(2))NMe(CH(2)Pyr), (bpmen, 2)] has been prepared. The preferred coordination geometry of these complexes in the solid state and in CH(2)Cl(2) solution changes from six- to five-coordinate in the order from 1 to 5. In acetonitrile, the triflate ligands of all complexes are readily displaced by acetonitrile ligands. The complex [Fe(1)(CH(3)CN)(2)](2+) is essentially low spin at room temperature, whereas ligands with fewer pyridine donors increase the preference for high-spin Fe(II). Both the number of pyridine donors and the spin state of the metal center strongly affect the intensity of a characteristic MLCT band around 400 nm. The catalytic properties of the complexes for the oxidation of alkanes have been evaluated, using cyclohexane as the substrate. Complexes containing ligands 1-3 are more active and selective catalysts, possibly operating via a metal-based oxidation mechanism, whereas complexes containing ligands 4 and 5 give rise to Fenton-type chemistry.


Optimization of a two-stage recombinant fermentation process: the dilution rate effect.
The effects of dilution rates on the performance of a two-stage fermentation system for a recombinant Escherichia coli culture were studied. Dilution rate determines the apparent or averaged specific growth rate of a heterogeneous population of cells in the recombinant culture. The specific growth rate affects the genetic parameters involved in product formation in the second stage, such as plasmid stability, plasmid content, and specific gene expression rate. Kinetic models and correlations were developed for these parameters based on experimental data. Simulations of plasmid stability in the first stage showed that for longer fermentation periods, plasmid stability is better at higher dilution rates. However, the plasmid content is lower at these dilution rates. The optimal apparent specific growth rate for maximum productivity in the second stage was determined using two methods: (1) direct search for a constant specific growth rate, and (2) dynamic optimization using the maximum principle for a time-dependent specific growth rate profile. The results of the calculations showed that the optimum constant apparent specific growth rate for maximum over-all productivity is 0.40 h(-1). This coincides with the optimal specific growth rate for maximum plasmid content in the expressed stage. A 3.5% increase in overall productivity can be obtained by using a linear time dependent apparent specific growth rate control, micro(2)(t) = 0.0007t, in the course of the fermentation time.


Identification of restriction fragment length polymorphism and random amplified polymorphic DNA markers linked to downy mildew resistance genes in lettuce, using near-isogenic lines.
Near-isogenic lines were used to identify restriction fragment length polymorphism (RFLP) and random amplified polymorphic DNA (RAPD) markers linked to genes for resistance to downy mildew (Dm) in lettuce. Two pairs of near-isogenic lines that differed for Dm1 plus Dm3 and one pair of near-isogenic lines that differed for Dm11 were used as sources of DNA. Over 500 cDNAs and 212 arbitrary 10-mer oligonucleotide primers were screened for their ability to detect polymorphism between the near-isogenic lines. Four RFLP markers and four RAPD markers were identified as linked to the Dm1 and Dm3 region. Dm1 and Dm3 are members of a cluster of seven Dm genes. Marker CL922 was absolutely linked to Dm15 and Dm16, which are part of this cluster. Six RAPD markers were identified as linked to the Dm11 region. The use of RAPD markers allowed us to increase the density of markers in the two Dm regions in a short time. These regions were previously only sparsely populated with RFLP markers. The rapid screening and identification of tightly linked markers to the target genes demonstrated the potential of RAPD markers for saturating genetic maps.


[Erickson's hypnosis].
Milton H. Erickson (1901-1980) renovated the study and practice of therapeutic hypnosis. The author first presents a synthetic overview of Erickson's original work and its spread. He then illustrates this with excerpts from observations of six of his own patients which correspond to the progressive integration of an ericksonian approach into a classical psychiatric practice in a general hospital setting.


Multicanonical basin hopping: a new global optimization method for complex systems.
We introduce a new optimization algorithm that combines the basin-hopping method, which can be used to efficiently map out an energy landscape associated with minima, with the multicanonical Monte Carlo method, which encourages the system to move out of energy traps during the computation. As an example of implementing the algorithm for the global minimization of a multivariable system, we consider the Lennard-Jones systems containing 150-185 particles, and find that the new algorithm is more efficient than the original basin-hopping method.


HLA alleles associated with asparaginase hypersensitivity in childhood ALL: a report from the DFCI Consortium.
Aim: To evaluate the association between human leukocyte antigen (HLA) alleles and native Escherichia coli asparaginase hypersensitivity (AH) in children with acute lymphoblastic leukemia (ALL) who received Dana-Farber Cancer Institute treatment protocols. Patients & methods:HLA-DQA1, HLA-DRB1 and HLA-DQB1 alleles were retrieved from available whole exome sequencing data of a subset of childhood ALL patients from Quebec ALL cohort and analyzed for an association with AH. PCR assay was developed to analyze associated alleles in the entire discovery and replication cohorts. Results: Two alleles in linkage disequilibrium (HLA-DRB1*07:01 and DQA1*02:01) were associated with AH. Additional analyses, performed to distinguish between HLA-DRB1*07:01 haplotypes with and without DQB1*02:02 allele, showed that the association was dependent on the presence of DQB1*02:02. Conclusion: This study confirms the implication of HLA-DRB1*07:01, DQA1*02:01 and DQB1*02:02 alleles in developing AH in childhood ALL.


[Distribution and mechanism of the carcinogenic action of 1,2-dimethylhydrazine in rats].
The radioactivity of blood, bile, urine and contents of isolated intestinal segments was measured at various periods after 3H-1,2-dimethylhydrazine (3H-DMH) and 3H-1,2-diethylhydrazine (3H-DEH) subcutaneous administration. These experiments have revealed that DMH metabolites entered the intestine both with bile and directly through the intestinal wall. The DMH metabolites entering the bowel as glucuronides are cleaved with beta-glucuronidase of bacterial origin, and as a result of this the alkylation of enterocytes nucleic acids and protein takes place. In totally hepatectomized animals no methylation of enterocyte macromolecules was noted. DEH fails to penetrate the intestinal wall and to alkylate biomolecules of enterocytes, when administered parenterally or per os. Some possible DMH metabolic pathways are discussed, and the dynamics of DNA and protein methylation is analysed in the light of these proposed pathways.


Effect of rare Earth ions on the properties of composites composed of ethylene vinyl acetate copolymer and layered double hydroxides.
The study on the rare earth (RE)-doped layered double hydroxides (LDHs) has received considerable attention due to their potential applications in catalysts. However, the use of RE-doped LDHs as polymer halogen-free flame retardants was seldom investigated. Furthermore, the effect of rare earth elements on the hydrophobicity of LDHs materials and the compatibility of LDHs/polymer composite has seldom been reported. The stearate sodium surface modified Ni-containing LDHs and RE-doped Ni-containing LDHs were rapidly synthesized by a coprecipitation method coupled with the microwave hydrothermal treatment. The influences of trace amounts of rare earth ions La, Ce and Nd on the amount of water molecules, the crystallinity, the morphology, the hydrophobicity of modified Ni-containing LDHs and the adsorption of modifier in the surface of LDHs were investigated by TGA, XRD, TEM, contact angle and IR, respectively. Moreover, the effects of the rare earth ions on the interfacial compatibility, the flame retardancy and the mechanical properties of ethylene vinyl acetate copolymer (EVA)/LDHs composites were also explored in detail. S-Ni₀.₁MgAl-La displayed more uniform dispersion and better interfacial compatibility in EVA matrix compared with other LDHs. Furthermore, the S-Ni₀.₁MgAl-La/EVA composite showed the best fire retardancy and mechanical properties in all composites.


Application of Micropore Filter Technology: Exploring the Blood Flow Path in Arterial-Line Filters and Its Effect on Bubble Trapping Functions.
Conventional arterial-line filters commonly use a large volume circular shaped housing, a wetted micropore screen, and a purge port to trap, separate, and remove gas bubbles from extracorporeal blood flow. Focusing on the bubble trapping function, this work attempts to explore how the filter housing shape and its resulting blood flow path affect the clinical application of arterial-line filters in terms of gross air handling. A video camera was used in a wet-lab setting to record observations made during gross air-bolus injections in three different radially designed filters using a 30-70% glycerol-saline mixture flowing at 4.5 L/min. Two of the filters both had inlet ports attached near the filter-housing top with bottom oriented outlet ports at the bottom, whereas the third filter had its inlet and outlet ports both located at the bottom of the filter housing. The two filters with top-in bottom-out fluid paths were shown to direct the incoming flow downward as it passed through the filter, placing the forces of buoyancy and viscous drag in opposition to each other. This contrasted with the third filter's bottom-in bottom-out fluid path, which was shown to direct the incoming flow upward so that the forces of buoyancy and viscous drag work together. The direction of the blood flow path through a filter may be important to the application of arterial-line filter technology as it helps determine how the forces of buoyancy and flow are aligned with one another.


Supplemental effect of different levels of taurine in Modena on boar semen quality during liquid preservation at 17°C.
Peroxidation damage induces sublethal injury to boar sperm during the storage process. Taurine has already been demonstrated to protect cells effectively from oxidant-induced injury. This study was aimed to evaluate the effect of different concentrations of taurine (0.5, 1, 5 and 10 mmol/L) in Modena diluent on boar sperm quality during liquid storage at 17°C. Ejaculates from sexually mature Duroc pigs were collected, pooled and preserved in the Modena containing different concentrations of taurine. Sperm motility, plasma membrane integrity, acrosome integrity, total antioxidative capacity (T-AOC) activity and malondialdehyde content (MDA) were examined every 24 h. Modena diluent containing taurine suppressed the reduction in sperm qualities during the process of liquid preservation compared with those of the control group. After 5 days of liquid preservation, the addition of taurine at 5 mmol/L had the optimal effect on survival time as well as maintenance of motility, plasma membrane integrity, acrosomal integrity, T-AOC activity and MDA content. These results may suggest the possibility that the proper addition of taurine to the semen extender improves the swine production system using artificial insemination by the suppressing of sperm damage and subsequent dysfunction during liquid preservation.


Review of the prevalence and incidence of eating disorders.
To review the literature on the incidence and prevalence of eating disorders. We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases. An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s. Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.


Geriatrics Curricula for Internal and Family Medicine Residents: Assessing Study Quality and Learning Outcomes.
Prior reviews of geriatrics curricula for internal medicine (IM) and family medicine (FM) residents have not evaluated study quality or assessed learning objectives or specific IM or FM competencies. This review of geriatrics curricula for IM and FM residents seeks to answer 3 questions: (1) What types of learning outcomes were measured? (2) How were learning outcomes measured? and (3) What was the quality of the studies? We evaluated geriatrics curricula that reported learning objectives or competencies, teaching methods, and learning outcomes, and those that used a comparative design. We searched PubMed and 4 other data sets from 2003-2015, and assessed learning outcomes, outcome measures, and the quality of studies using the Medical Education Research Study Quality Instrument (MERSQI) and Best Evidence Medical Education (BEME) methods. Fourteen studies met inclusion criteria. Most curricula were intended for IM residents in the inpatient setting; only 1 was solely dedicated to FM residents. Median duration was 1 month, and minimum geriatrics competencies covered were 4. Learning outcomes ranged from Kirkpatrick levels 1 to 3. Studies that reported effect size showed a considerable impact on attitudes and knowledge, mainly via pretests and posttests. The mean MERSQI score was 10.5 (range, 8.5-13) on a scale of 5 (lowest quality) to 18 (highest quality). Few geriatrics curricula for IM and FM residents that included learning outcome assessments were published recently. Overall, changes in attitudes and knowledge were sizeable, but reporting was limited to low to moderate Kirkpatrick levels. Study quality was moderate.


Interatomic methods for the dispersion energy derived from the adiabatic connection fluctuation-dissipation theorem.
Interatomic pairwise methods are currently among the most popular and accurate ways to include dispersion energy in density functional theory calculations. However, when applied to more than two atoms, these methods are still frequently perceived to be based on ad hoc assumptions, rather than a rigorous derivation from quantum mechanics. Starting from the adiabatic connection fluctuation-dissipation (ACFD) theorem, an exact expression for the electronic exchange-correlation energy, we demonstrate that the pairwise interatomic dispersion energy for an arbitrary collection of isotropic polarizable dipoles emerges from the second-order expansion of the ACFD formula upon invoking the random-phase approximation (RPA) or the full-potential approximation. Moreover, for a system of quantum harmonic oscillators coupled through a dipole-dipole potential, we prove the equivalence between the full interaction energy obtained from the Hamiltonian diagonalization and the ACFD-RPA correlation energy. This property makes the Hamiltonian diagonalization an efficient method for the calculation of the many-body dispersion energy. In addition, we show that the switching function used to damp the dispersion interaction at short distances arises from a short-range screened Coulomb potential, whose role is to account for the spatial spread of the individual atomic dipole moments. By using the ACFD formula, we gain a deeper understanding of the approximations made in the interatomic pairwise approaches, providing a powerful formalism for further development of accurate and efficient methods for the calculation of the dispersion energy.


Drug Repurposing to Fight Colistin and Carbapenem-Resistant Bacteria.
The emergence of new resistance mechanisms, the failure of classical antibiotics in clinic, the decrease in the development of antibiotics in the industry are all challenges that lead us to consider new strategies for the treatment of infectious diseases. Indeed, in recent years controversy has intensified over strains resistant to carbapenem and/or colistin. Various therapeutic solutions are used to overcome administration of last line antibiotics. In this context, drug repurposing, which consists of using a non-antibiotic compound to treat multi-drug resistant bacteria (MDR), is encouraged. In this review, we first report what may have led to drug repurposing. Main definitions, advantages and drawbacks are summarized. Three major methods are described: phenotypic, computational and serendipity. In a second time we will focus on the current knowledge in drug repurposing for carbapenem and colistin-resistant bacteria with different studies describing repurposed compounds tested on Gram-negative bacteria. Furthermore, we show that drug combination therapies can increase successful by drug repurposing strategy. In conclusion, we discuss the pharmaceutical industries that have little interest in reprofiling drugs due to lack of profits. We also consider what a clinician might think of the indications of these uncommon biologists to treat MDR bacterial infections and avoid therapeutic impasses.


Veterans Health Administration Transitional work experience vs. job placement in veterans with co-morbid substance use and non-psychotic psychiatric disorders.
This study seeks to compare the effectiveness of Veterans Health Administration's (VHA) transitional work experience (TWE) services and a minimal but common intervention-job placement (JP) services, for veterans with co-morbid substance and psychiatric disorders. We conducted a random clinical trial comparing work outcomes for 89 veterans with co-morbid psychiatric and substance use disorders (SUD) who were randomly assigned to participate in VHA TWE services with those assigned to simple JP services provided by state vocational rehabilitation professionals. Participants were enrolled at the time of application to VHA TWE services and then randomly assigned to the two treatment groups and followed for 12 months. VHA TWE participants were more likely to engage in paid activity, to work more total hours, to work more weeks and to earn more in total wages. The groups were not significantly different with respect to competitive employment, in terms of the percentage acquiring competitive jobs, the number of hours worked, or wages earned. These data suggest that the primary benefit of VHA TWE services is in rapidly engaging participants in paid activity and that these services are not effective at helping dually diagnosed veterans obtain competitive employment.


Integrated socio-hydrogeological approach to tackle nitrate contamination in groundwater resources. The case of Grombalia Basin (Tunisia).
Nitrate contamination still remains one of the main groundwater quality issues in several aquifers worldwide, despite the perduring efforts of the international scientific community to effectively tackle this problem. The classical hydrogeological and isotopic investigations are obviously of paramount importance for the characterization of contaminant sources, but are clearly not sufficient for the correct and long-term protection of groundwater resources. This paper aims at demonstrating the effectiveness of the socio-hydrogeological approach as the best tool to tackle groundwater quality issues, while contributing bridging the gap between science and society. An integrated survey, including land use, hydrochemical (physicochemical parameters and major ions) and isotopic (δ15NNO3 and δ18ONO3) analyses, coupled to capacity building and participatory activities was carried out to correctly attribute the nitrate origin in groundwater from the Grombalia Basin (North Tunisia), a region where only synthetic fertilizers have been generally identified as the main source of such pollution. Results demonstrates that the basin is characterized by high nitrate concentrations, often exceeding the statutory limits for drinking water, in both the shallow and deep aquifers, whereas sources are associated to both agricultural and urban activities. The public participation of local actors proved to be a fundamental element for the development of the hydrogeological investigation, as it permitted to obtain relevant information to support data interpretation, and eventually guaranteed the correct assessment of contaminant sources in the studied area. In addition, such activity, if adequately transferred to regulators, will ensure the effective adoption of management practices based on the research outcomes and tailored on the real needs of the local population, proving the added value to include it in any integrated investigation.


Synthesis, crystal chemistry, and magnetic properties of RE7Li8Ge10 and RE11Li12Ge16 (RE = La-Nd, Sm): new members of the [REGe2](n)[RELi2Ge](m) homologous series.
Eight new rare-earth metal-lithium-germanides belonging to the [REGe(2)](n)[RELi(2)Ge](m) homologous series have been synthesized and structurally characterized by single-crystal X-ray diffraction. The structures of the title compounds can be rationalized as linear intergrowths of imaginary RELi(2)Ge (MgAl(2)Cu structure type) and REGe(2) (AlB(2) structure type) slabs. The compounds with general formula RE(7)Li(8)Ge(10) (RE = La-Nd, Sm), i.e., [REGe(2)](3)[RELi(2)Ge](4), crystallize in the orthorhombic space group Cmmm (No. 65) with a new structure type. Similarly, the compounds with general formula RE(11)Li(12)Ge(16) (RE = Ce-Nd), i.e., [REGe(2)](5)[RELi(2)Ge](6), crystallize in the orthorhombic space group Immm (No. 71) also with its own structure type. Temperature-dependent DC magnetization measurements indicate Curie-Weiss paramagnetism in the high-temperature regime and hint at complex magnetic ordering at low temperatures. The measured effective moments are consistent with RE(3+) ground states in all cases. The experimental results have been complemented by tight-binding linear muffin-tin orbital (TB-LMTO) electronic structure calculations.


Use of the dye-guided sentinel lymph node biopsy method alone for breast cancer metastasis to avoid unnecessary axillary lymph node dissection.
For sentinel lymph node biopsy (SLNB), a combination of dye-guided and γ-probe-guided methods is the most commonly used technique. However, the number of institutes in which the γ-probe-guided method is able to be performed is limited, since special equipment is required for the method. In this study, SLNB with the dye-guided method alone was evaluated, and the clinicopathological characteristics were analyzed to identify any factors that were predictive of whether the follow-up axillary lymph node dissection (ALND) was able to be omitted. A total of 374 patients who underwent SLNB between 1999 and 2009 were studied. The SLN identification rate was analyzed, in addition to the false-positive and false-negative rates and the correlation between the clinicopathological characteristics and axillary lymph node metastases. The SLN was identified in 96.8% of cases, and, out of the patients who had SLN metastasis, 63.0% did not exhibit metastasis elsewhere. The sensitivity was 96.4% and the specificity was 100%. The false-negative rate was 3.6%. Univariate analyses revealed significant differences in the lymph vessel invasion (ly) status, nuclear grade (NG), maximum tumor size and the percentage of the area occupied by the tumor cells in the SLN (SLN occupation ratio) between the patients with and without non-SLN metastasis, indicating that these factors may be predictive of axillary lymph node metastasis. Multivariate analysis revealed that ly status was an independent risk factor for non-SLN metastasis. In conclusion, SLN with the dye-guided method alone provided a high detection rate. The study identified a predictive factor for axillary lymph node metastasis that may improve the patients' quality of life.


Outcomes of Kidney Transplant Recipients With Percutaneous Ureteral Interventions: A Single-Center Study.
Long-term outcomes of kidney transplantation recipients with percutaneous ureteral management of transplant ureteral complications are not well characterized. Electronic records of 1753 recipients of kidney-alone transplant between January 2000 and December 2008 were reviewed. One hundred thirty-one patients were identified to have undergone percutaneous ureteral management, with placement of percutaneous nephrostomy tube or additional intervention (nephroureteral stenting and/or balloon dilation). Indications for intervention included transplant ureteral stricture or ureteral leak. Kaplan-Meier survival curves and multivariable regression modeling were performed to determine survival outcomes. Kaplan- Meier graft survival (P = 0.04) was lower in patients with percutaneous ureteral intervention for transplant ureteral complication. Graft survival at 1, 5, and 10 years was 94.3% 78.3%, and 59.1% for no intervention and 97.2%, 72.1%, and 36.2% for intervention cohort. Patient survival (P = 0.69) was similar between cohorts. Multivariate analysis demonstrated no association with graft failure (hazard ratio, 1.21; 95% confidence interval, 0.67-2.19; P = 0.53) or patient death (hazard ratio, 0.56; 95% confidence interval, 0.22-1.41; P = 0.22) in intervention group. The major cause of graft failure was infection for percutaneous ureteral intervention group (20.4%) and chronic rejection for those without intervention (17.3%). Kidney transplant recipients with percutaneous ureteral interventions for ureteral complications do not have a significant difference in graft and patient survival outcomes. Therefore, aggressive nonoperative management can be confidently pursued in the appropriate clinical setting.


Human T-lymphotropic virus type II and neurological disease.
Human T-lymphotropic virus type I (HTLV-I) and type II (HTLV-II) are closely related retroviruses with similar biological properties and common modes of transmission. HTLV-I infection is endemic in well-defined geographic regions, and it is estimated that some 20 million individuals are infected worldwide. Although most infected individuals are asymptomatic carriers, some 2 to 5% will develop a chronic encephalomyelopathy, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In contrast with HTLV-I, the role of HTLV-II in the development of neurological disorders is much less clear. HTLV-II is endemic in many native Amerindian groups and epidemic in injecting drug users (IDUs) worldwide. To evaluate the role of HTLV-II in neurological disease, we have critically reviewed all reported cases of HTLV-II-associated disorders. This has confirmed that although rare infection is associated with a disorder clinically similar or identical to HAM/TSP. However, most reports that have attributed infection to a range of other neurological disorders are difficult to evaluate in that in many cases either the association appears to be fortuitous or the presentations were confounded by a background of concomitant human immunodeficiency virus-1 infection and/or active IDU. In view of the many HTLV-II-infected individuals in urban areas of North America and Europe, neurologists should be aware of the potential clinical consequences of this infection.


Patch tests with house dust mite antigens in atopic dermatitis patients: methodological problems.
Patch tests with house dust mite allergens were performed in 21 atopic dermatitis patients with a positive prick test and RAST for house dust mite. Variables in methodology of patch testing, i.e. allergen concentration, application time, and intensity of tape stripping, were studied. Tests were performed with Dermatophagoides pteronyssinus solutions containing 20X, 100X and 500X the prick test concentration and purified HDM antigen: 10 and 50 micrograms/ml P1Ag solution. The series was applied on 8X or 15X tape-stripped and clinically normal skin on the back during 24 and 48 h. Non-specific reactions due to tape stripping, fixation tape or patch test occlusion were frequently observed: after 15X tape-stripping in 3/7 (24-h application) and 6/7 (48-h application) patients, after 8X tape-stripping in 2/19 (24-h application) and 8/19 (48-h application) patients. Reactions clinically assessed as specific occurred in 6/21 (29%) atopic dermatitis patients, 4/6 occurring in the 10 patients with a serum IgE greater than 1000 kU/l. High allergen concentrations and 48 h of application increased the number of patients with specific reactions. If 15X tape-stripping had been omitted, 2/3 patients tested in this manner and showing specific test reactions would have been negative. Further conclusions regarding the value and the preferable method of patch testing with atopic allergens require an in vitro control test.


Immunomodulatory effects of human umbilical cord Wharton's jelly-derived mesenchymal stem cells on differentiation, maturation and endocytosis of monocyte-derived dendritic cells.
The Wharton's jelly of the umbilical cord is believed to be a source of mesenchymal stem cells (MSCs) which can be therapeutically applied in degenerative diseases.In this study, we investigated the immunomodulatory effect of umbilical cord derived-mesenchymal stem cells (UC-MSCs) and bone marrow-derived-mesenchymal stem cells (BM-MSCs) on differentiation, maturation, and endocytosis of monocyte-derived dendritic cells in a transwell culture system under laboratory conditions. Monocytes were differentiated into immature dendritic cells (iDCs) in the presence of GM-CSF and IL-4 for 6 days and then differentiated into mature dendritic cells (mDCs) in the presence of TNF-α for 2 days. In every stage of differentiation, immature and mature dendritic cells were separately co-cultured with UC-MSCs and BM-MSCs. The findings showed that UC-MSCs and BM-MSCs inhibited strongly differentiation and maturation of dendritic cells at higher dilution ratios (1:1). The BM-MSCs and UC-MSCs showed more inhibitory effect on CD1a, CD83, CD86 expression, and dendritic cell endocytic activity, respectively. On the other hand, these cells severely up-regulated CD14 marker expression. We concluded that UC-MSCs and BM-MSCs could inhibit differentiation, maturation and endocytosis in monocyte-derived DCs through the secreted factors and free of any cell-cell contacts under laboratory conditions. As DCs are believed to be the main antigen presenting cells for naïve T cells in triggering immune responses, it would be logical that their inhibitory effect on differentiation, maturation and function can decrease or modulate immune and inflammatory responses.


Carbonic Anhydrase Inhibitors Induce Developmental Toxicity During Zebrafish Embryogenesis, Especially in the Inner Ear.
In vertebrates, carbonic anhydrases (CAs) play important roles in ion transport and pH regulation in many organs, including the eyes, kidneys, central nervous system, and inner ear. In aquatic organisms, the enzyme is inhibited by various chemicals present in the environment, such as heavy metals, pesticides, and pharmaceuticals. In this study, the effects of CA inhibitors, i.e., sulfonamides [ethoxyzolamide (EZA), acetazolamide (AZA), and dorzolamide (DZA)], on zebrafish embryogenesis were investigated. In embryos treated with the sulfonamides, abnormal development, such as smaller otoliths, an enlarged heart, an irregular pectoral fin, and aberrant swimming behavior, was observed. Especially, the development of otoliths and locomotor activity was severely affected by all the sulfonamides, and EZA was a consistently stronger inhibitor than AZA or DZA. In the embryos treated with EZA, inner ear hair cells containing several CA isoforms, which provide HCO3- to the endolymph for otolith calcification and maintain an appropriate pH there, were affected. Acridine orange/ethidium bromide staining indicated that the hair cell damage in the inner ear and pectral fin is due to apoptosis. Moreover, RNA measurement demonstrated that altered gene expression of cell cycle arrest- and apoptosis-related proteins p53, p21, p27, and Bcl-2 occurred even at 0.08 ppm with which normal development was observed. This finding suggests that a low concentration of EZA may affect embryogenesis via the apoptosis pathway. Thus, our findings demonstrated the importance of potential risk assessment of CA inhibition, especially regarding the formation of otoliths as a one of the most sensitive organs in embryogenesis.


DNA double-strand breaks and Aurora B mislocalization induced by exposure of early mitotic cells to H2O2 appear to increase chromatin bridges and resultant cytokinesis failure.
Aneuploidy, an abnormal number of chromosomes that is a hallmark of cancer cells, can arise from tetraploid/binucleated cells through a failure of cytokinesis. Reactive oxygen species (ROS) have been implicated in various diseases, including cancer. However, the nature and role of ROS in cytokinesis progression and related mechanisms has not been clearly elucidated. Here, using time-lapse analysis of asynchronously growing cells and immunocytochemical analyses of synchronized cells, we found that hydrogen peroxide (H2O2) treatment at early mitosis (primarily prometaphase) significantly induced cytokinesis failure. Cytokinesis failure and the resultant formation of binucleated cells containing nucleoplasmic bridges (NPBs) seemed to be caused by increases in DNA double-strand breaks (DSBs) and subsequent unresolved chromatin bridges. We further found that H2O2 induced mislocalization of Aurora B during mitosis. All of these effects were attenuated by pretreatment with N-acetyl-L-cysteine (NAC) or overexpression of Catalase. Surprisingly, the PARP inhibitor PJ34 also reduced H2O2-induced Aurora B mislocalization and binucleated cell formation. Results of parallel experiments with etoposide, a topoisomerase IIα inhibitor that triggers DNA DSBs, suggested that both DNA DSBs and Aurora B mislocalization contribute to chromatin bridge formation. Aurora B mislocalization also appeared to weaken the "abscission checkpoint". Finally, we showed that KRAS-induced binucleated cell formation appeared to be also H2O2-dependent. In conclusion, we propose that a ROS, mainly H2O2 increases binucleation through unresolved chromatin bridges caused by DNA damage and mislocalization of Aurora B, the latter of which appears to augment the effect of DNA damage on chromatin bridge formation.


Motivating medical students to learn teamwork skills.
This study examined teaching teamwork skills to first-year medical students. Teamwork skills focused on verbal communication in PBL-tutorial sessions and in healthcare teams. The aim was to find out how to teach teamwork skills to first-year medical students and how to motivate them to learn these skills. Three consecutive classes of first-year medical students (N = 342) participated in teamwork skills module in the years 2006, 2007 and 2008. After the first year, the introduction to the topic was revised in order to be more motivating to medical students. After each module data were collected with a feedback questionnaire containing numerical and open questions. By analyzing the students' numerical answers and the content of students' open answers regarding the module, we examined how the revised introduction affected students' perceptions of the usefulness of the module. Medical students' feedback in the years 1 (n = 81), 2 (n = 99) and 3 (n = 95) showed that the students found the module in the second and third years significantly more useful than in the first year. These results support earlier findings that clearly stated clinical relevance motivates medical students. When introducing multidisciplinary subjects to medical students, it is important to think through the clinical relevance of the topic and how it is introduced to medical students.


JNK signalling in human and experimental renal ischaemia/reperfusion injury.
Ischaemia/reperfusion (I/R) is an important factor in delayed graft function in renal transplantation and is a determinant of long-term graft outcome. This study examined the role of c-Jun N-terminal kinase (JNK) signalling in human and experimental renal I/R injury. Biopsies obtained 15-20 min after reperfusion of human renal allografts were examined for JNK signalling by immunostaining for phospho-c-Jun. To examine the pathologic role of JNK signalling, a selective JNK inhibitor (CC-401) was administered to rats before or after the induction of a 30-min period of bilateral renal ischaemia followed by reperfusion. Renal function and tubular damage were analysed. Substantial JNK activation was evident in tubular epithelial cells in kidneys from deceased donors (n = 30) which was less prominent in kidneys from live donors (n = 7) (44.6 +/- 24.8% vs 29.1 +/- 20% p-c-Jun+, respectively; P < 0.05), whereas biopsies of thin basement membrane disease exhibited little, or no, p-c-Jun staining. The degree of p-c-Jun staining correlated with ischaemic time in deceased donor allografts, but not with graft function. Administration of CC-401 to rats prior to bilateral renal I/R prevented acute renal failure and largely prevented tubular damage, leucocyte infiltration and upregulation of pro-inflammatory molecules. However, delaying CC-401 treatment until 1 h after reperfusion (after the peak of JNK activation) had no protective effect. We have identified acute activation of the JNK signalling pathway following I/R in human kidney allografts. Experimental studies indicate that blockade of JNK signalling, commenced prior to this activation, can prevent acute tubular necrosis and renal dysfunction secondary to I/R injury.


National health expenditures: a global analysis.
As part of the background research to the World development report 1993: investing in health, an effort was made to estimate public, private and total expenditures on health for all countries of the world. Estimates could be found for public spending for most countries, but for private expenditure in many fewer countries. Regressions were used to predict the missing values of regional and global estimates. These econometric exercises were also used to relate expenditure to measures of health status. In 1990 the world spent an estimated US$ 1.7 trillion (1.7 x 10(12) on health, or $1.9 trillion (1.9 x 10(12)) in dollars adjusted for higher purchasing power in poorer countries. This amount was about 60% public and 40% private in origin. However, as incomes rise, public health expenditure tends to displace private spending and to account for the increasing share of incomes devoted to health.


Rapid identification of Penicillium marneffei by PCR-based detection of specific sequences on the rRNA gene.
An emerging pathogenic dimorphic fungus, Penicillium marneffei, is one of the major causes of morbidity in patients with human immunodeficiency virus infection in Southeast Asia. A PCR-hybridization assay has been developed to identify this pathogen. This study describes the use of single and nested PCR methods for the rapid identification of P. marneffei. Two sets of oligonucleotide primers were derived from the sequence of 18S rRNA genes of P. marneffei. The outer primers (RRF1 and RRH1) were fungus specific. The inner primers (Pm1 and Pm2) were specific for P. marneffei and were used in nested or single PCR. The specific fragment of approximately 400-bp was amplified from both mold and yeast forms of 13 P. marneffei human isolates, 12 bamboo rat isolates, and 1 soil isolate, but not from other fungi, bacteria, and human DNA. The amplified products were analyzed by agarose gel electrophoresis followed by ethidium bromide staining. The sensitivities of the single PCR and nested PCR were 1.0 pg/microl and 1.8 fg/microl, respectively. The assay is useful for rapid identification of P. marneffei cultures. Very young culture of P. marneffei (2-day-old filamentous colony, 2 mm in diameter) could be performed by this assay. The species was identified within 7 h (single PCR) or 10 h (nested PCR), compared to 4 to 7 days for confirmation of dimorphism. The application of these PCR methods for early diagnosis of the disease needs to be studied further.


LIFE-HISTORY VARIATION WITHIN A POPULATION OF THE COLONIAL ASCIDIAN BOTRYLLUS SCHLOSSERI. I. THE GENETIC AND ENVIRONMENTAL CONTROL OF SEASONAL VARIATION.
Many empirical analyses of life-history tactics are based on the assumption that demographic variation ought to be greatest among populations or species living in different environments. However, in a single population of the sessile colonial sea squirt Botryllus schlosseri, there are two discrete life-history morphs. Semelparous colonies are characterized by a) death immediately following the production of a single clutch, b) early age at first reproduction, c) rapid growth to first reproduction, and d) high reproductive effort. In contrast, iteroparous colonies a) produce at least three clutches before dying, b) postpone sexual reproduction until they are nearly twice the age of semelparous colonies, c) grow at about half the rate of semelparous colonies, and d) invest roughly 75% less in reproductive effort than semelparous colonies. Semelparous colonies numerically dominate the population through midsummer; later in the summer, iteroparous colonies are most numerous. Field and laboratory common-garden experiments, along with breeding studies, indicate that the demographic differences between the morphs are genetically determined. Consequently, the seasonal switch from dominance by semelparous colonies to dominance by iteroparous colonies may be an evolved response to a seasonally changing environment. On theoretical grounds, temporal variation in selection is thought to play a relatively unimportant role in maintaining genetic polymorphism; nonetheless, the seasonally recurrent life-history polymorphism shown in this study indicates that temporal variation in selection can lead to the maintenance of genetic polymorphism for traits strongly affecting fitness.


Using transrectal sonography to teach patients with spinal cord injuries to retrain their bladders.
When patients who have spinal cord injuries perform the Crede maneuver, the bladder neck tends to close. We suggest that these patients watch a video monitor during transrectal sonography and learn to tap the bladder appropriately, which allows voiding to occur with little increase in bladder pressure.


Elevated expression of notch1 is associated with metastasis of human malignancies.
The expression level of Notch1 has been studied in many primary tumor types, but has not been widely investigated in metastatic lesions from human malignancies. Using immunohistochemistry (IHC), the expression level of Notch1 was evaluated and compared between primary and metastatic tumors in 12 different cancers. The mean IHC score of Notch1 was significantly increased in metastatic hepatocellular carcinoma (HCC; 5.4 ± 0.7) and in metastatic renal cell carcinoma (RCC; 5.0 ± 2.3) compared with primary HCC (3.1 ± 0.7, P = .035) and RCC (1.3 ± 0.6, P = .049), respectively. Similarly, the expression level of Notch1 showed an increasing trend in the metastatic malignancies in the larynx, prostate, and stomach compared with corresponding primary malignancies (P values are .055, .072, and .074, respectively). The results demonstrate elevated expression of Notch1 in some metastatic tumors, suggesting that Notch1 may play an important role in the development or maintenance of metastatic lesions, and targeting of Notch1 might be a therapeutic approach against tumor metastasis.


The significance of socio-economic characteristics for adult seasonal body-weight fluctuations: a study in north-western Benin.
Large variations in seasonal body-weight fluctuations have been described for individuals from different households living and working under comparable circumstances. In the present study the relationship between socio-economic household characteristics and seasonal body-weight fluctuations of individual members of rural Beninese households were studied. No significant correlation was found for body-weight fluctuation between the two study years, nor for body-weight fluctuation of men and women belonging to the same household. When comparing dichotomized socio-economic classes for relative body-weight fluctuation of men and women in both study years, no consistent trends were observed for both years nor for both sexes. The distribution of subjects with a consistent high weight fluctuation over the two study years did not differ between socio-economic groups. In conclusion it may be stated that there were no indications that socio-economic characteristics play a determining role in the magnitude of body-weight fluctuation of this study population, despite the large variations observed in the latter. Therefore it is most likely that other factors decide the weight fluctuations of individuals, health and sanitation being the most likely candidates.


Magnetic activated charcoal/Fe2O3 nanocomposite for the adsorptive removal of 2,4-Dichlorophenoxyacetic acid (2,4-D) from aqueous solutions: Synthesis, characterization, optimization, kinetic and isotherm studies.
Magnetic activated charcoal/Fe2O3 nanocomposite (AC/Fe2O3NC) was fabricated using Spondias dulcis leaf extract by a facile method and used for the adsorptive removal of 2,4-Dichlorophenoxyacetic acid (2,4-D) from aqueous solutions for the first time. The nanocomposite was characterized by methods such as FE-SEM, EDS, XRD, FTIR, TGA, VSM, and BET to identify and confirm the surface morphology, elemental composition, crystalline nature, functional groups, thermal stability, magnetic behavior, and surface area respectively. Box-Behnken Design (BBD) - an optimization method, which belongs to the Response surface methodology (RSM) and a modeling tool - Artificial Neural Network (ANN) were employed to design, optimize and predict the relationship between the input parameters (pH, initial concentration of 2,4-D, time and agitation speed) versus the output parameter (adsorption efficiency of 2,4-D). Adsorption efficiency of 98.12% was obtained at optimum conditions (pH: 2.05, initial concentration: 32 ppm, contact time: 100 min, agitation speed: 130 rpm, temperature: 30 °C, and dosage: 0.2 g/L). The predictive ability of the ANN was superior (R2 = 0.99) than the quadratic model, given by the RSM (R2 = 0.93). The equilibrium data were best-fitted to Langmuir isotherm (R2 = 0.9944) and the kinetics obeyed pseudo-second-order model (R2 = 0.9993) satisfactorily. Thermodynamic studies revealed the spontaneity and exothermic nature of adsorption. The maximum adsorption capacity, qm was found to be 255.10 mg/g, substantially larger than the reported values for 2,4-D adsorption by other magnetic nanoadsorbents. Therefore, this nanoadsorbent may be utilized as an excellent alternative for the elimination of 2,4-D from the waterbodies.


Spatial regulation of ARAF controls the MST2-Hippo pathway.
The RAF-MAPK signaling pathway regulates several very diverse cellular processes such as proliferation, differentiation, apoptosis, and transformation. While the canonical function of RAF kinases within the MAPK pathway is the activation of MEK, our group could demonstrate an important crosstalk between RAF signaling and the pro-apoptotic mammalian sterile 20-like kinase (MST2) tumor suppressor pathway in several cancer entities, including head and neck, colon, and breast. Here, the RAF kinases CRAF and ARAF sequester and inhibit the pro-apoptotic kinase MST2 independently of their own kinase activity. In our recent study, we showed that the ARAF-MST2 complex is regulated by subcellular compartmentalization during epithelial differentiation. Proliferating cells of the basal cell layer in squamous epithelia and tumor cells express ARAF at the mitochondria thus allowing for efficient sequestration of MST2. In contrast, non-malignant squamous epithelia have ARAF localized at the plasma membrane, where the control of MST2-mediated apoptosis is compromised. This re-distribution is regulated by the scaffold protein kinase suppressor of Ras 2 (KSR2). Here, we summarize how spatial and temporal regulation of RAF signaling complexes affect cellular signaling and functions.


Screening of venlafaxine hydrochloride for transdermal delivery: passive diffusion and iontophoresis.
The objective of the study was to investigate in vitro transdermal delivery of venlafaxine hydrochloride across the pigskin by passive diffusion and iontophoresis. For passive diffusion, experiments were carried out in Franz diffusion cell whereas for iontophoretic permeation, the diffusion cell was modified to contain both the donor and return electrode on the same side of skin. Anodal iontophoresis was carried out using a current density of 0.5 mA/cm(2). Donor concentrations used were 585.5 mg/ml (saturated solution) and 100 mg/ml. Experiments initially performed to determine the transport efficiency of venlafaxine ions showed promising results. Iontophoresis increased the permeation rate at both concentration levels over their passive counterparts (P < 0.01), but surprisingly higher steady-state flux was obtained from lower donor drug load (P < 0.01). The favorable pH of the unsaturated solutions is suggested to be the cause for this effect. Mild synergistic effect was observed when iontophoresis was carried out incorporating peppermint oil in the donor but the same was not found in passive diffusion. Highest steady-state flux obtained in the experiment was 3.279 mumol/cm(2)/h when peppermint oil (0.1%) was included in the donor. As the maintenance requirement of venlafaxine hydrochloride is approximately 9.956 mumol/h, the results suggested that the drug is a promising candidate for iontophoretic delivery.


Predictors of permanent pacemaker implantation in aortic valve diseases after TAVI with vitaFlow liberty system.
Permanent pacemaker implantation (PPI) is a known complication in patients with aortic stenosis following transcatheter aortic valve implantation (TAVI). However, there is limited research on TAVI for pure aortic regurgitation (PAR), and more investigation is needed to determine the occurrence of postoperative cardiac conduction block and the need for PPI in this population. Therefore, this retrospective analysis aimed to evaluate the incidence of cardiac conduction block and the necessity of PPI after TAVI in patients with different types of aortic valve disease, including pure aortic stenosis (PAS), aortic stenosis with regurgitation (ASR), and PAR. Clinical data of 100 patients who TAVI were analyzed retrospectively. The incidence of conduction block was assessed, and clinical factors were examined to predict the necessity of PPI. Cardiac conduction block was found to be a common complication following TAVI, particularly in patients with PAR. PAR was identified as an independent risk factor for requiring PPI. Additionally, first-degree atrioventricular block emerged as a sensitive predictor for PPI in patients with PAR. These findings provide valuable insights into the safety and effectiveness of TAVI, which can help enhance patient management and reduce complications.


Low density lipoprotein apolipoprotein B metabolism in treatment-naive HIV patients and patients on antiretroviral therapy.
Dyslipidaemia and lipodystrophy have been described in treated HIV patients and in a small percentage of untreated HIV patients. Lipodystrophy in these patients has been shown to be associated with a lower expression of low density lipoprotein (LDL) receptors. We have investigated the effect of antiretroviral treatment with either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) on body fat distribution and LDL apolipoprotein B (apoB) kinetics in 12 HIV-negative controls and 52 HIV-infected patients, including antiretroviral treatment-naive (TN) patients (n=13) and patients taking two nucleoside analogues plus either a PI (n=15) or an NNRTI (n=24). LDL cholesterol was not different between groups. Compared with the controls, LDL apoB absolute synthetic rate (ASR) and fractional catabolic rate (FCR) were lower and residence time (RT) was higher in the PI and NNRTI groups (P<0.05). In the TN patients, LDL ASR was lower (P<0.05) and there was a trend for a lower FCR and higher RT compared with the controls (P=0.07). LDL apoB pool size was greater in the PI group compared with the controls (P<0.05). In the PI group, patients on ritonavir (RTV)-containing regimens had a lower LDL apoB ASR (P=0.009) and a trend to a lower LDL apoB FCR and increased RT compared with non-RTV-containing PI regimens (P=0.05). There was a positive correlation between LDL apoB FCR and limb fat/lean body mass (P=0.004) in all subjects. Decreased LDL FCR, despite unchanged LDL cholesterol, was demonstrated in both treated and untreated HIV patients. It was more marked with RTV-containing regimens and was associated with reduced limb fat. The increased LDL RT may lead to an increased risk of atherogenesis thus contributing to the risk for cardiovascular disease in these patients.


Genetic variation of fish parasite populations in historically connected habitats: undetected habitat fragmentation effect on populations of the nematode Procamallanus fulvidraconis in the catfish Pelteobagrus fulvidraco.
Habitat fragmentation may have some significant effects on population genetic structure because geographic distance and physical barriers may impede gene flow between populations. In this study, we investigated whether recent habitat fragmentation affected genetic structure and diversity of populations of the nematode Procamallanus fulvidraconis in the yellowhead catfish, Pelteobagrus fulvidraco. The nematode was collected from 12 localities in 7 floodplain lakes of the Yangtze River. Using 11 intersimple sequence repeat markers, analysis of molecular variance showed that genetic diversity occurred mainly within populations (70.26%). Expected heterozygosity (He) of P. fulvidraconis was barely different between connected (0.2105) and unconnected lakes (0.2083). Population subdivision (Fst) between connected lakes (0.2177) was higher than in unconnected lakes (0.1676). However, the connected and unconnected lakes did not cluster into 2 clades. A Mantel test revealed significant positive correlation between genetic and geographic distances (R = 0.5335, P < 0.01). These results suggest that habitat fragmentation did not cause genetic differentiation among populations or a reduction of diversity in isolated populations of P. fulvidraconis. At least 2 factors may increase the dispersal range of the nematode, i.e., flash flooding in summer and other species of fish that may serve as the definitive hosts. Moreover, lake fragmentation is probably a recent process; population size of the nematode in these lakes is large enough to maintain population structure.


Treatment Options for Colistin Resistant Klebsiella pneumoniae: Present and Future.
Multidrug-resistant (MDR) Klebsiella pneumoniae represents an increasing threat to human health, causing difficult-to-treat infections with a high mortality rate. Since colistin is one of the few treatment options for carbapenem-resistant K. pneumoniae infections, colistin resistance represents a challenge due to the limited range of potentially available effective antimicrobials, including tigecycline, gentamicin, fosfomycin and ceftazidime/avibactam. Moreover, the choice of these antimicrobials depends on their pharmacokinetics/pharmacodynamics properties, the site of infection and the susceptibility profile of the isolated strain, and is sometimes hampered by side effects. This review describes the features of colistin resistance in K. pneumoniae and the characteristics of the currently available antimicrobials for colistin-resistant MDR K. pneumoniae, as well as the characteristics of novel antimicrobial options, such as the soon-to-be commercially available plazomicin and cefiderocol. Finally, we consider the future use of innovative therapeutic strategies in development, including bacteriophages therapy and monoclonal antibodies.


Microorganisms Isolated from Blood Cultures of Febrile Neutropenic Patients in ‹bn-i Sina Hospital.
Patients with profound neutropenia have increased risk of septicemia associated with significant morbidity. To provide the appropriate broad-spectrum antimicrobial cover, documentation of causative agents and their antimicrobial susceptibilities should be established in each hospital. During 2001 in Ibn-i Sina Hospital Hematology unit, among 125 isolates from blood cultures of febrile neutropenic patients, gram-negative bacteria was prevalent (56.8%). Among the gram-positives (34.4% of isolates) coagulase-negative staphylococci (CNS) were the predominant bacteria (15/43) followed by Staphylococcus aureus (12/43). Escherichia coli (23/71) and Klebsiella spp. (15/71) were the most common species among 71 gram-negative bacteria. Nonfermentative gram-negative bacilli were 21.6% of the isolates. Increase in the isolation rate of Acinetobacter baumannii (7 strains) and Stenotrophomonas maltophilia (6 strains) was noticed.


N- and O- ligand doped mesoporous silica-chitosan hybrid beads for the efficient, sustainable and selective recovery of rare earth elements (REE) from acid mine drainage (AMD): Understanding the significance of physical modification and conditioning of the polymer.
Silica-chitosan hybrid beads were synthesized via three different methods to investigate the selective recovery of REE from AMD. The influence of amino/non-amino silanes, high molecular weight/high viscous chitosan and N-/O- based ligands were studied and their effects on REE removal efficiencies were analyzed. The adsorption efficiencies of three various groups of modified beads were inspected with respect to feed pH, in a single and a multi-component system, and their affinities towards the light and heavy rare earth elements (LREE/ HREEs) were interpreted to understand the intra-series REE separation behavior. The focus of the study was mainly directed towards utilizing these fabricated beads for the recovery of valuable REEs from the real AMD obtained at three different sampling depths which was found rich in iron, sulfur and aluminum. Moreover, the selectivity of the beads towards REEs improved with silanized and ligand immobilized gels and their impacts on REE recovery in the presence of competing ions were successfully presented in this paper. Also, the synthesized beads showed rapid REE adsorption and recovery within a process time of 5 min. Group II adsorbents, synthesized by forming silica-chitosan hybrid beads followed by PAN/acac modifications, showed superiority over the other groups of adsorbents.


Development of a drug-in-adhesive patch combining ion pair and chemical enhancer strategy for transdermal delivery of zaltoprofen: pharmacokinetic, pharmacodynamic and in vitro/in vivo correlation evaluation.
The aim of the study was to develop a drug-in-adhesive patch system for transdermal delivery of zaltoprofen (ZAL). The formulation was designed in combination with the ion pair and chemical enhancer strategy. Seven organic amines were chosen as counter ions, and the prepared ion pairs were characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The in vivo pharmacokinetic performance of ZAL was studied on rabbits following transdermal and intravenous administration. A deconvolution method was applied to determine the correlation between the in vitro permeation and the in vivo absorption. Acetic acid-induced writhing response was conducted on mice to evaluate the analgesic effect. In vitro permeation results showed that both ion pairs and chemical enhancers were effective in modulating ZAL skin permeation from patches. The enhancement ratio was negatively correlated to the polar surface area (PSA) of counter ions, and was positively correlated to the octanol-water partition coefficient (log Ko/w) of chemical enhancers, respectively. The optimized formulation contained 10% (w/w) ZAL-triethylamine and 10% (w/w) isopropyl myristate, with DURO-TAK® 87-4098 as the pressure sensitive adhesive matrix. Furthermore, the in vitro permeation data were well correlated with the in vivo absorption data. The analgesic effect of the optimized patch was comparable to the commercial indometacin plasters. In conclusion, it was feasible for transdermal delivery of ZAL by the synergistic action of ion pair and chemical enhancer, and the in vitro permeation data were indicative of the in vivo performance for the developed patches.


[Results of therapy in different groups of risk for superficial bladder cancer].
Approximately 10.0% of tumors occurs in the lower urinary tract and morbidity and lethality are constantly on the rise. Over 90% of such tumors registered in Europe and the USA is transitional cell carcinoma. Primary bladder cancer morbidity in Russian males rose by 4.0-4.6% in 1990-1997 while the share of patients with superficial bladder cancer (SBC) went up by 1.5% for the same period. According to the National Bladder Cancer Group, the rising incidence of relapsing SBC is associated with urothelial dysplasia, positive test for urinary sediment after therapy and occurrence of four or more tumors larger than 5 cm. Prevention of muscular invasion is vital in management of SBC. Sometimes, such aggressive modalities as early cystectomy or radiotherapy are recommended in cases of high risk for this pathology. Conversely, certain palliative measures, short of transurethral resection of the bladder and adjuvant intravesical therapy, are regarded as sufficient.


What is the potential role of transcutaneous carbon dioxide in guiding acute noninvasive ventilation?
Transcutaneous carbon dioxide (PtcCO2 ) monitoring is rarely used in the acute hospital setting, where serial samples of arterial blood are instead taken to measure carbon dioxide tension (PaCO2 ). In this pilot observational study, we assessed the potential of PtcCO2 monitoring to calculate pH and guide management of acute noninvasive ventilation (NIV). Ten subjects with acute hypercapnic respiratory failure were recruited. All had arterial lines placed to guide acute NIV. PtcCO2 was monitored for 12 h (TOSCA TCM4) and compared with PaCO2 . Noninvasive transcutaneous pH was determined from PtcCO2 and calculated bicarbonate and then compared with true arterial pH. Agreements between PCO2 and pH methods were assessed using Bland-Altman analysis of limits of agreement and Pearson correlation coefficients. Hypothetical adjustments to acute NIV settings were based on transcutaneous data alone and evaluated in comparison with true management. Pain scores for each method were compared using the Wilcoxon signed-rank test. PCO2 time trends were concordant. Mean PCO2 bias was -2.33 (95% limits of agreement of -9.60 to 5.03) mm Hg, and r = 0.89 (P < .001). Mean pH bias was 0.012 (95% limits of agreement of -0.070 to 0.094), and r = 0.84 (P < .001). Hypothetical clinical decisions based on transcutaneous data alone matched true management on 85% of 34 occasions. Initiation of transcutaneous monitoring was less painful than the arterial equivalent (P = .008). This pilot study demonstrates that PtcCO2 monitoring provides a continuous and reliable trend and also allows pH prediction. This patient-friendly approach is a promising alternative to repeated arterial blood gas sampling in patients requiring NIV for acute hypercapnic respiratory failure.


Application of Artificial Intelligence to Cardiovascular Computed Tomography.
Cardiovascular computed tomography (CT) is among the most active fields with ongoing technical innovation related to image acquisition and analysis. Artificial intelligence can be incorporated into various clinical applications of cardiovascular CT, including imaging of the heart valves and coronary arteries, as well as imaging to evaluate myocardial function and congenital heart disease. This review summarizes the latest research on the application of deep learning to cardiovascular CT. The areas covered range from image quality improvement to automatic analysis of CT images, including methods such as calcium scoring, image segmentation, and coronary artery evaluation.


Determination of dexamethasone and corticosterone half-lives in male broilers.
Normal broiler males were used in a series of experiments to determine the rate of disappearance of dexamethasone, a synthetic corticoid, and corticosterone, the quantitatively most important glucocorticoid in the bird. Determination of the half-life (T1/2) of these compounds following an intravenous bolus injection was by high performance liquid chromatography. Half-lives for dexamethasone and corticosterone were found to be 36 and 22 min, respectively. The slower rate of disappearance from the blood may help to explain the ability of dexamethasone to overcome some of the problems associated with hyperthermic stress in birds. This method of quantitating exogenously administered steroids is applicable not only to basic research but also to analyses by inspection and regulatory agencies.


[Adenocarcinoma of the ampulla of Vater revealed by prurigo].
Chronic prurigo may reveal several internal diseases. Its association with a solid neoplasia is rare. We report an exceptional case of chronic prurigo revealing surgically curable adenocarcinoma of the ampulla of Vater. Our study involved a 70-year old patient, with no particular previous history, who was hospitalized for etiological assessment of prurigo lasting for 06 months associated with non-documented weight loss. The lesions were isolated and involved the trunk and the limbs (A); initial assessment was strictly normal. Given the lack of patient's improvement with symptomatic treatment, additional exams were performed, including thoracoabdominopelvic CT scan, which objectified a tumor of the biliopancreatic junction measuring 2 cm, suggesting the diagnosis of ampulloma (B). The patient underwent surgical excision of this adenocarcinoma of the ampulla of Vater followed by regression of the skin lesions without further treatment. At 1-year follow-up, there was no evidence of recurrence of the skin lesions and the patient achieved complete remission of adenocarcinoma.


Patient characteristics and hospital quality for colorectal cancer surgery.
To assess associations of patient characteristics with quality-related characteristics of the hospitals where they were treated for colorectal cancer and the role of these associations in disparities in treatment quality affecting vulnerable patient groups or variations across health plans. Population-based cancer registry in California. A total of 38 237 patients diagnosed with stage I-III (non-metastatic) colorectal cancer in California between 1994 and 1998. Registry data were linked with hospital discharge abstracts, US census data, and Medicare enrollment data. The associations of patients' sociodemographic, clinical, and geographic covariates with treatment at high-volume institutions were assessed with logistic regression. The associations of patients' covariates with the risk-adjusted 30-day mortality rates of the hospitals where they received surgery were tested with linear regression. Patients with more advanced tumor stage or more extensive comorbidity, those of Hispanic or Asian race/ethnicity, and those from less affluent communities were less likely to undergo surgery at high-volume institutions and were treated at hospitals with higher risk-adjusted 30-day postoperative mortality rates than those who were less severely ill, white, or more affluent, respectively (all P < 0.05). Black patients also received surgery at hospitals with above-average mortality. Among patients 65 years and older, Medicare managed-care enrollees underwent surgery in higher-volume hospitals than Medicare fee-for-service enrollees, and there was substantial variation in hospital volume and adjusted hospital mortality among Medicare managed-care plans. Improving access of sicker, poorer, and minority patients to high-quality hospitals for cancer surgery may improve their outcomes. Further study of processes affecting hospital referral is warranted.


Computer-Based Auditory Training Programs for Children with Hearing Impairment - A Scoping Review.
Introduction Communication breakdown, a consequence of hearing impairment (HI), is being fought by fitting amplification devices and providing auditory training since the inception of audiology. The advances in both audiology and rehabilitation programs have led to the advent of computer-based auditory training programs (CBATPs). Objective To review the existing literature documenting the evidence-based CBATPs for children with HIs. Since there was only one such article, we also chose to review the commercially available CBATPs for children with HI. The strengths and weaknesses of the existing literature were reviewed in order to improve further researches. Data Synthesis Google Scholar and PubMed databases were searched using various combinations of keywords. The participant, intervention, control, outcome and study design (PICOS) criteria were used for the inclusion of articles. Out of 124 article abstracts reviewed, 5 studies were shortlisted for detailed reading. One among them satisfied all the criteria, and was taken for review. The commercially available programs were chosen based on an extensive search in Google. The reviewed article was well-structured, with appropriate outcomes. The commercially available programs cover many aspects of the auditory training through a wide range of stimuli and activities. Conclusions There is a dire need for extensive research to be performed in the field of CBATPs to establish their efficacy, also to establish them as evidence-based practices.


The CYP1A1 Ile462Val polymorphism and platinum resistance of epithelial ovarian neoplasms.
The role of estrogens in ovarian carcinogenesis and progression of ovarian cancer is unclear. Cytochrome P450 is involved in estrogen metabolism, and polymorphisms have been associated with functional changes and risk for ovarian cancer. In this study, we investigated the impact of the CYP1A1 Ile462Val polymorphism upon tumor risk and disease progression in ovarian cancer patients. One hundred and eleven ovarian cancer patients who had been treated at the University Hospital of Essen between 1999 and 2007 and 119 age-matched healthy female controls were enrolled in this study. Genotyping was performed using PCR-RFLP. The distribution of genotypes was statistically significant different between ovarian cancer patients and healthy controls. We observed a significant association of the Ile allele with ovarian cancer (OR 2.6, 95% CI 1.5-4.7, p = 0.001). Clinical parameters such as overall survival, FIGO stage, grading, and age at diagnosis did not differ significantly. We observed a statistically significant association between the 462Val allele and platinum resistance, which was defined as a time interval < 6 months to disease progression after administration of a platinum-based primary chemotherapy (OR 5.9, 95% CI 1.5-23.2, p = 0.005). We observed a significant association between the presence of the 462Ile allele with ovarian cancer. While there is uncertainty about the potential involvement of CYP1A1 in the metabolism of platinum-containing agents, our findings suggest an association between the 462Val allele and the development of platinum resistance in ovarian tumors. If confirmed in a larger, independent collective, our findings would have important relevance with respect to the clinical consequences for the primary chemotherapy of ovarian cancer patients.


Patient factors and haemodialysis arteriovenous fistula outcomes.
Arteriovenous fistulas (AVF) improve survival and morbidity for most haemodialysis (HD) patients. Are they better for all patients? In the enthusiastic pursuit of AVFs for all, concerns have been raised regarding high primary AVF failure rates, continued high incident central venous catheter (CVC) use in some countries, and the limited life expectancy of some HD patients. "Fistula first" is changing to "catheter last". The focus must be on decreasing AVF failure to mature and decreasing incident CVC use. An optimal outcome should be sought for each individual patient, and multiple failed attempts at AVF creation avoided.


[Percutaneous transluminal angioplasty via dorsalis pedis artery for chronic total occlusion of superficial femoral artery: a case report].
A 60-year-old woman with intermittent claudication underwent angiography, which showed total occlusion of the left superficial femoral artery and no distal flow. Computed tomography with contrast medium revealed that the occlusion extended to the popliteal artery but distal flow was maintained to the dorsalis pedis artery. Percutaneous transluminal angioplasty was attempted via the right femoral artery, but the guidewire could not be advanced. Therefore, a 4F sheath was inserted into the dorsalis pedis artery and the guidewire was passed through the occluded lesion. After pre-dilation, the guidewire was re-crossed from the right femoral artery and two stents were successfully implanted. Finally sufficient antegrade blood flow was achieved after the procedure. The trans-dorsalis pedis artery approach is a valuable option for the percutaneous transluminal angioplasty of long superficial femoral artery occlusion if the antegrade approach is impossible.


Polyelectrolyte complexes from polysaccharides: formation and stoichiometry monitoring.
Colloids were obtained from non-stoichiometric polyelectrolyte complexes with two polysaccharides of opposite charge: chitosan and dextran sulfate (DS) as the polycation and polyanion, respectively. The complexes were elaborated by a one-shot addition of the polymer in default to the one in excess. The colloids were positively or negatively charged according to the nature of the polymer in excess. Dynamic light scattering (DLS) demonstrated that particles were formed at a very early stage in the complexation process. The consumption of the excess polyelectrolyte was monitored with a dye assay specific for dextran sulfate (toluidine blue) or chitosan (orange II). From these experiments, two different mechanisms of colloidal PEC formation were evidenced, according to the nature of the polymer in excess. On adding chitosan to DS in excess, regular consumption of the polyanion was observed at a constant stoichiometry, in the 1.5 to 1.85 range (sulfate residues for one glucosamine group), according to the molar mass of the polycation. When DS was added to chitosan in excess, the overall stoichiometry varied from ca. 6 (glucosamine residues for one sulfate group) down to 1 as the charge molar mixing ratio R=n+/n- decreased from 20 to 1. The existence of various mechanisms, according to the nature of the polymer in excess, could be attributed to the differences in chemical reactivity (strong vs low) of the ion in excess and the conformation and flexibility of the macromolecular chains related to their electrostatic potential.


Near-field laser ablation inductively coupled plasma mass spectrometry: a novel elemental analytical technique at the nanometer scale.
An analytical technique utilizing a near-field effect (to enhance the incident light energy on the thin tip of an Ag needle) in a laser ablation inductively coupled plasma mass spectrometry (NF-LA-ICP-MS) procedure was developed. To produce the thin needles with a tip diameter in the hundreds of nm range a robust needle etching procedure was established. The 'sample-to-tip' distance was controlled via the measurement of a tunnel current between the needle and sample surface. The NF-LA-ICP-MS technique thus developed was applied for the analysis of copper isotopic standard reference material NIST SRM 976 and tungsten-molybdenum alloy NIST SRM 480 in the nm resolution range. The observed craters ranged from 200 nm to about 2 microm in diameter and were dependent on the needle used as well as on the 'sample-to-tip' distance. The mass spectrometric measurements of (63)Cu(+) ion intensity on NIST SRM 976 showed that using near-field enhancement in laser ablation allowed a roughly 6-fold increase in the ion intensity of the analyte when the needle was about 100 nm (and below) from the surface, in contrast to when it was far away (e.g. 10 microm) from the sample. The relative standard deviation (RSD) of the (65)Cu(+)/(63)Cu(+) isotopic ratio measurements by NF-LA-ICP-MS was 3.9% (n = 9). The detection efficiencies obtained for the compared LA-ICP-MS and NF-LA-ICP-MS methods were found to be 4.6 x 10(-3) counts per second (cps)/ablated atom and 2.7 x 10(-5) cps/ablated atom, respectively.


Generation and mapping of SCAR and CAPS markers linked to the seed coat color gene in Brassica napus using a genome-walking technique.
The yellow seed coat trait in No. 2127-17, a resynthesized purely yellow Brassica napus line, is controlled by a single partially dominant gene, Y. A double-haploid population derived from the F1 of No. 2127-17 x 'ZY821' was used to map the seed coat color phenotype. A combination of AFLP analysis and bulked segregant analysis identified 18 AFLP markers linked to the seed coat color trait. The 18 AFLP markers were mapped to a chromosomal region of 37.0 cM with an average of 2.0 cM between adjacent markers. Two markers, AFLP-K and AFLP-H, bracketed the Y locus in an interval of 1.0 cM, such that each was 0.5 cM away from the Y locus. Two other markers, AFLP-A and AFLP-B, co-segregated with the seed color gene. For ease of use in breeding programs, these 4 most tightly linked AFLP markers were converted into reliable PCR-based markers. SCAR-K, which was derived from AFLP-K, was assigned to linkage group 9 (N9) of a B. napus reference map consisting of 150 commonly used SSR (simple sequence repeat) markers. Furthermore, 2 SSR markers (Na14-E08 and Na10-B07) linked to SCAR-K on the reference map were reversely mapped to the linkage map constructed in this study, and also showed linkage to the Y locus. These linked markers would be useful for the transfer of the dominant allele Y from No. 2127-17 to elite cultivars using a marker-assisted selection strategy and would accelerate the cloning of the seed coat color gene.


Involvement of IMA in tuberculosis control.
Tuberculosis has been declared to be a global emergency and the HIV/AIDS is fuelling the epidemic. To contain the disease for its re-emergence a massive funding was earmarked. Widespread implementation of the DOTS strategy specially in countries of high TB burden is a major progress in global TB control. As a sizeable section of TB patients contact a private health provider, so the policy makers of health envisaged the idea for Public-Private Partnership mix model to contain the disease and hence the role of IMA with its two lacs members has definite role to play to stop the menace. The Stop TB strategy is designed to achieve the targets set for the period 2006-2015. Members of IMA have got a life time chance to prove to the people and to the power that they are not lagging behind in providing a service to the nation and there lies the strength of the IMA.


Primary neuroendocrine tumor of the pineal gland: a case report.
Primary intracranial neuroendocrine tumors are exceedingly rare, with few cases in the literature. We present a case of a primary neuroendocrine carcinoma of the pineal gland, which is the second that has ever been reported. A 53-year-old male patient presented with vomiting, weakness, and headaches. Imaging revealed a lesion in the pineal region, which was surgically resected. This mass was characterized by histology as a neuroendocrine carcinoma, given the presence of neuroendocrine markers and cytokeratin markers with absence of a primary lesion elsewhere on imaging. There are currently no guidelines on the management of primary intracranial neuroendocrine tumors. In this case, the patient underwent surgical resection and craniospinal radiotherapy. He subsequently received one cycle of chemotherapy with temozolomide, an alkylating agent, but he unfortunately did not tolerate treatment. A multidisciplinary decision was made along with the patient and his family to focus on palliative care. Eighteen months after the initial presentation, disease recurred in the patient's neck. The patient underwent resection to control the metastases, with a plan to follow with radiotherapy and chemotherapy. Unfortunately, the patient became unwell and died at 21 months after initial diagnosis. This demonstrates a need for continued research and reporting on this uncommon disease entity.


Evaluation of blood urea nitrogen concentration and anorexia as predictors of nonsurvival in client-owned rabbits evaluated at a veterinary referral center.
OBJECTIVE To determine the prognostic relevance of BUN concentration in client-owned rabbits evaluated at a veterinary referral center. ANIMALS 246 healthy or clinically ill client-owned rabbits with BUN concentrations measured at a veterinary referral center. PROCEDURES In a retrospective cohort study design, medical records of rabbits were retrieved, and data were collected on BUN concentration (exposure variable of interest) and other variables, including outcome (survival status at 15 days after BUN concentration measurement). Univariate, multivariate, and subgroup analyses were performed to identify variables associated with outcome. RESULTS BUN concentrations ranged from 6.5 to 251.1 mg/dL (median, 18.7 mg/dL). Univariate analysis revealed that the risk of nonsurvival over the 15-day period for rabbits with a high BUN concentration (≥ 23.3 mg/dL) was 33% higher (relative risk, 1.33; 95% confidence interval [CI], 1.06 to 1.69) than that for rabbits with unremarkable BUN values. Subgroup analysis revealed that for rabbits with anorexia, a high (vs unremarkable) BUN concentration was associated with an increased risk of nonsurvival (relative risk, 1.69; 95% CI, 1.05 to 2.71). In the final multivariate model that controlled for age, sex, and appetite (anorexia vs no anorexia), the odds of nonsurvival for rabbits with BUN values > 24.74 mg/dL were 3 times that for rabbits with BUN values < 14.00 mg/dL (OR, 2.92; 95% CI, 1.29 to 6.58). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that a high BUN concentration increased the risk of nonsurvival over a 15-day period for client-owned rabbits, particularly those with anorexia. Blood urea nitrogen concentration should be used together with other clinical indicators to provide prognostic information for rabbits receiving veterinary care.


Recent Advances in Rhodium-Catalyzed Electrochemical C-H Activation.
Rhodium-catalyzed C-H activation has emerged as a powerful tool for forging C-C and C-heteroatom bonds. Nevertheless, the requirement of stoichiometric chemical oxidants for oxidative transformations significantly hampered the overall sustainability of the C-H activation transformations. The emergence of merging transition metal catalysis and electrochemistry, called metalla-electrocatalysis provides an excellent opportunity to construct organic molecules efficiently and sustainably. This review highlights the recent developments of rhodium-catalyzed electrochemical C-H activation transformations, challenges and opportunities for future developments.


Role of hyaluronic acid in periodontal therapy (Review).
Hyaluronic acid (HA) is essential for the function of extracellular matrices in both hard and soft periodontal components. HA plays an important role in the mechanisms underlying inflammation and wound healing. HA is located in periodontal tissues in differing amounts, including non-mineralized tissues, such as gingiva and periodontal ligament, and lower levels located in mineralized tissues, such as cementum and alveolar bone. According to preliminary findings, HA exhibits potential in the regulation of periodontal tissue regeneration and in the treatment of periodontal disease. HA promotes symptomatic relief in both marginal gingiva and deeper periodontal tissues. The present review aimed to examine the role of HA in periodontal therapy, and investigate the current literature supporting its use in periodontal regeneration.


Social and neural modulation of sexual plasticity in teleost fish.
Teleost fishes are the 'champions' of sexual plasticity among vertebrates. Several species have two male reproductive morphs with distinct suites of behavioral, somatic, neuronal, endocrinological, and life history traits. Here, we consider recent studies of the social and neural modulation of sexual plasticity for such species with a focus on two neuropeptides, gonadotropin releasing hormone (GnRH) and arginine vasotocin (AVT, teleostean analogue of mammalian arginine vasopressin). The major premise of this review is that phenotypic changes in GnRH and AVT expression in the brain can orchestrate events leading to changes in either sexual status or the expression of morph specific display behaviors important in reproduction.


[Electrocardiographic manifestations of severe accidental hypothermia: report of one case].
We report a 77-year-old female patient who was admitted to the Emergency Department with impairment of consciousness, hypotension, bradycardia and hypothermia. She required endotracheal intubation and transfer to Intensive Care Unit (ICU). Computed tomography of the brain showed no lesions. Electrocardiogram showed abnormalities suggestive of severe hypothermia (bradycardia, marked elevation of J point associated with ST depression, a negative T wave in V2 to V6 and prolongation of QTc), which was confirmed with a pulmonary artery catheter. Myxedema coma, infections and neurological diseases were discarded. The cause of severe hypothermia was unclear, and the probable source was suspected to be accidental. After intensive treatment the patient improved, achieving normalization of electrocardiographic changes, recovery of organic functions and she was discharged home after 22 days.


The curious case of vanishing mitochondria.
Due to their involvement in the energy metabolism, mitochondria are essential for most eukaryotic cells. Microbial eukaryotes living in low oxygen environments possess reduced forms of mitochondria, namely mitochondrion-related organelles (MROs). These do not produce ATP by oxidative phosphorylation on their membranes and some do not produce ATP at all. Still, they are indispensable because of other essential functions such as iron-sulphur (Fe-S) cluster assembly. Recently, the first microbial eukaryote with neither mitochondrion nor MRO was characterized - Monocercomonoides sp. Genome and transcriptome sequencing of Monocercomonoides revealed that it lacks all hallmark mitochondrial proteins. Crucially, the essential mitochondrial pathway for the Fe-S cluster assembly (ISC) was replaced by a bacterial sulphur mobilization (SUF) system. The discovery of such bona fide amitochondriate eukaryote broadens our knowledge about the diversity and plasticity of eukaryotic cells and provides a substantial contribution to our understanding of eukaryotic cell evolution.


Variable efficacy of glucocorticoids in congenital adrenal hyperplasia.
We have examined the suppression of urinary pregnanetriol and 17-ketosteroids during treatment with cortisol, cortisone, prednisone, and dexamethasone in eight patients with congenital adrenal hyperplasia. A large individual variation in response to each agent was observed. In some individuals, cortisone is less effective than its generally accepted potency would indicate. At equivalent glucocorticoid dosage, dexamethasone was twice as effective as the other steroids in suppressing urinary 17-ketosteroids and pregnanetriol. The potency of dexamethasone in suppressing adrenal function was 80 times that of cortisol, about twice its generally accepted potency as a glucocorticoid or anti-inflammatory agent.


Stereoisomeric pattern of lilac aldehyde in Silene latifolia, a plant involved in a nursery pollination system.
The monoterpene lilac aldehyde is found in floral scent of several plants species, among them Silene latifolia. This plant is involved in a nursery pollination system, because a noctuid moth, Hadena bicruris, is not only pollinator but also seed predator. Lilac aldehyde is the key floral scent compound of S. latifolia for attracting Hadena. This monoterpene has three stereogenic centers, and eight different isomers are possible. Here, we analysed the ratio of lilac aldehyde isomers from plants originating from 18 different populations of S. latifolia using enantioselective multidimensional GC-MS (enantio-MDGC-MS), and compared resulting variability with variability found in total scent emitted by specimen under study. Though variability in total emitted scent was high, ratio of lilac aldehyde isomers was a more conservative trait. There was no correlation between the ratio of lilac aldehyde isomers and the total emitted floral scent pattern. Both, ratio of stereoisomers and total emitted scent were independent from the geographic origin of the plants. In conclusion, the ratio of lilac aldehyde stereoisomers in S. latifolia is a reliable trait, and may used by the nursery pollinator H. bicruris for host-plant detection.