Retrospective analysis of operative ankle fractures

A seroprevalence survey to recently proposed adenovirus (AV) serotypes AV 48 and AV 49, isolated primarily from AIDS patients, was conducted among the San Francisco Men's Health Study cohort. This cohort of homosexual, heterosexual, or bisexual HIV-seronegative and -seropositive men from selected San Francisco census tracts has been studied since 1984. The presence or absence of type-specific antibody in 628 serum specimens from 1989 was determined by microneutralization. Thirty of these subjects (26 positive and four negative) were studied longitudinally. Serum specimens taken at 6-month intervals from 1984 to 1993 were tested to characterize antibody response and to document the advent of these new serotypes. Eight subjects were tested against five other AV serotypes for comparison. AV 48 and AV 49 seroprevalence rates were significantly higher in HIV-seropositives, but infection was not limited to the immunocompromised. Sexual preference was not a significant determinant for AV seroprevalence in HIV-seronegatives. However, the extent and duration of the neutralizing antibody response was strikingly different between homosexuals and heterosexuals: an endemic pattern of continuous reexposure over the 9-year period was seen in 90% of 19 homosexuals, while five of six heterosexuals (83%) had an episodic pattern of exposure with antibody decline to undetectable levels. These data suggest that these viruses may be endemic in some part of the homosexual population and that sexual transmission may be the primary source of continuous reexposure.     

Identification of a putative histidine kinase two-component phosphorelay gene (CaHK1) in Candida albicans

We have cloned and analysed the sequence of a putative histidine kinase, two-component gene (CaHK1) from Candida albicans. This gene encodes a 2471 amino acid protein (Cahk1p) with an estimated molecular mass of 281·8 kDa. A homology search of Cahk1p with other proteins in the databases showed that Cahk1p exhibits the greatest homology at its C-terminus with both the sensor and regulator components of prokaryotic and eukaryotic two-component histidine kinases. A further analysis of this homology showed that the Cahk1p possessed both sensor and regulator domains in the same polypeptide. Also, Cahk1p is likely to be a soluble protein. The sensor kinase domain of Cahk1p contains conserved motifs that are characteristic of all histidine kinase proteins, including the putative histidine which is believed to be autophosphorylated during activation, ATP binding motifs and others (F- and N-motifs), with unknown function. The Cahk1p regulator domain also contains conserved aspartate and lysine residues and the putative aspartate, which is secondarily phosphorylated by the autophosphorylated histidine. Finally, according to the codon usage frequency of the CaHK1 gene in comparison with other genes from C. albicans, there would appear to be a low level of expression of the gene. The accession number for the described sequence is AF013273, as filed in the EMBL/GenBank/DDBJ database. © 1998 John Wiley & Sons, Ltd.     

Identification of a putative response regulator two‐component phosphorelay gene ( CaSSK1) from Candida albicans

We have identified and analysed a putative response regulator two‐component gene (CaSSK1) from Candida albicans and its encoding protein (CaSsk1p). CaSSK1 has an open reading frame of 2022 bp. In the promotor region of CaSSK1 a short sequence is found that matches the consensus sequence of the stress response elements (STRE) from Saccharomyces cerevisiae. CaSSK1 is located on chromosome 1 and is expressed in either yeast or mycelial phases of C. albicans. CaSSK1 encodes a 674 amino acid protein (CaSsk1p) with an estimated molecular mass of 73·5 kDa and a basic isoelectric point (pI 9·5). It has a tripeptide (NKA) located in its C‐terminus, which resembles the peroxisomal signalling target type 1 sequence (PST1) of most of the peroxisomal matrix proteins. A homology search of CaSsk1p with other proteins in databases showed that the C‐terminus of CaSsk1p exhibits the greatest similarity with the C‐terminus of Ssk1p and Mcs4 from Saccharomyces cerevisiae and Schizosaccharomyces pombe, respectively. The response regulator domain of CaSsk1p contains the motifs that are characteristic of all response regulators, including the conserved aspartate and lysine residues as well as the putative aspartate, which is phosphorylated by a phosphohistidine residue. Finally, in spite of the structural similarities among CaSsk1p, Ssk1p and Mcs4, CaSsk1p does not seem to exhibit functional homology with these proteins. The Accession No. for the described sequence is AF084608, as filed in the EMBL/GenBank/DDBJ database. Copyright © 1999 John Wiley & Sons, Ltd.     

Inhibitors of Mitochondrial Human Carbonic Anhydrases VA and VB as a Therapeutic Strategy against Paclitaxel-Induced Neuropathic Pain in Mice

Neuropathy development is a major dose-limiting side effect of anticancer treatments that significantly reduces patient’s quality of life. The inadequate pharmacological approaches for neuropathic pain management warrant the identification of novel therapeutic targets. Mitochondrial dysfunctions that lead to reactive oxygen species (ROS) increase, cytosolic Ca²⁺ imbalance, and lactate acidosis are implicated in neuropathic pain pathogenesis. It has been observed that in these deregulations, a pivotal role is played by the mitochondrial carbonic anhydrases (CA) VA and VB isoforms. Hence, preclinical studies should be conducted to assess the efficacy of two novel selenides bearing benzenesulfonamide moieties, named 5b and 5d, and able to inhibit CA VA and VB against paclitaxel-induced neurotoxicity in mice. Acute treatment with 5b and 5d (30–100 mg/kg, per os – p.o.) determined a dose-dependent and long-lasting anti-hyperalgesic effect in the Cold plate test. Further, repeated daily treatment for 15 days with 100 mg/kg of both compounds (starting the first day of paclitaxel injection) significantly prevented neuropathic pain development without the onset of tolerance to the anti-hyperalgesic effect. In both experiments, acetazolamide (AAZ, 100 mg/kg, p.o.) used as the reference drug was partially active. Moreover, ex vivo analysis demonstrated the efficacy of 5b and 5d repeated treatments in reducing the maladaptive plasticity that occurs to glia cells in the lumbar portion of the spinal cord and in improving mitochondrial functions in the brain and spinal cord that were strongly impaired by paclitaxel-repeated treatment. In this regard, 5b and 5d ameliorated the metabolic activity, as observed by the increase in citrate synthase activity, and preserved an optimal mitochondrial membrane potential (ΔΨ) value, which appeared depolarized in brains from paclitaxel-treated animals. In conclusion, 5b and 5d have therapeutic and protective effects against paclitaxel-induced neuropathy without tolerance development. Moreover, 5b and 5d reduced glial cell activation and mitochondrial dysfunction in the central nervous system, being a promising candidate for the management of neuropathic pain and neurotoxicity evoked by chemotherapeutic drugs.     

Computer construction of test banks and tests

Chronic infection of the gastroduodenal mucosae by the gram-negative spiral bacterium Helicobacter pylori is responsible for chronic active gastritis, peptic ulcers, and gastric cancers such as adenocarcinoma and low-grade B-cell lymphoma. The success of eradication by antibiotic therapy is being rapidly hampered by the increasing occurrence of antibiotic-resistant strains. An attractive alternative approach to combat this infection is represented by the therapeutic use of vaccines. In the present work, we have exploited the mouse model of persistent infection by mouse-adapted H. pylori strains that we have developed to assess the feasibility of the therapeutic use of vaccines against infection. We report that an otherwise chronic H. pylori infection in mice can be successfully eradicated by intragastric vaccination with H. pylori antigens such as recombinant VacA and CagA, which were administered together with a genetically detoxified mutant of the heat-labile exterotoxin of Escherichia coli (referred to as LTK63), in which the serine in position 63 was replaced by a lysine. Moreover, we show that therapeutic vaccination confers efficacious protection against reinfection. These results represent strong evidence of the feasibility of therapeutic use of VacA- or CagA-based vaccine formulations against H. pylori infection in an animal model and give substantial preclinical support to the application of this kind of approach in human clinical trials.     

The Tarasoff raid: a new extension of the duty to protect

The authors discuss the general outlines of the Tarasoff duty of psychotherapists to protect potential victims of their violent patients. They describe the flexible range of clinical responses that therapists have utilized, as well as their professional concerns about preserving patient confidentiality (or at least strictly circumscribing the scope of disclosure when confidentiality must be breached). A recent case is reported that illustrates a striking new extension of Tarasoff, involving a police search and seizure of a psychotherapist's confidential treatment records and tapes, in response to a third-party complaint that the records contained evidence of his patients' violent acts and propensities. The implications of this case are that the therapist's discretion in the assessment of his duty to protect, the selection of a proper course of action, and the implementation of specific responses may be taken out of his hands, for all intents and purposes, and expropriated by law and order officials. Moreover, regardless of whatever clinical approach he adopts and whether or not he issues a warning, his attempts to preserve patient confidentiality are bound to prove unsuccessful in any future legal proceedings. Patient communications are likely to lose their confidential status on the grounds that they caused or triggered the Tarasoff warning (or that they should have triggered it). If the patient directed serious threats against the therapist himself, the court may find that, as a consequence, a "genuine therapeutic relationship" ceased to exist and thereafter all patient disclosures were no longer confidential on that basis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrospun PHBV/PEO co-solution blends: Microstructure,thermal and mechanical properties

Blending allows to tailor and modulate the properties of selected polymers. Blends of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and polyethylene oxide (PEO) were fabricated by electrospinning in different weight ratios i.e. 100:0, 80:20, 70:30, 50:50, 0:100.In order to evaluate the influence of PEO addition on the final properties of PHBV, a complete microstructural, thermal and mechanical characterization of PHBV/PEO blends has been performed. The two neat polymeric membranes were also considered for the sake of comparison. The following characterization techniques were employed: scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy, simultaneous thermogravimetric and differential analyses (TG-DTA), differential scanning calorimetry (DSC), and uniaxial tensile tests.All electrospun mats consisted of randomly oriented and uniform fibers. It has been observed that the microstructure of PHBV/PEO was remarkably affected by blend composition. The average fiber size ranged between 0.5 μm and 2.6 μm. It resulted that the electrospun polymeric blends consisted of separate crystalline domains associated to an amorphous interdisperse phase. PHBV/PEO blends presented intermediate mechanical properties, in terms of tensile modulus and ultimate tensile stress, with respect to the two neat components.     

Analysis of isotopic ratios for the detection of illegal watering of beverages

The applications of the stable isotope ratio analyses (D/H, ¹³C and ¹⁸O) in the assessment of watering in beverages such as wine and fruit juices are discussed in this study. The measurement of ¹⁸O/¹⁶O ratio in combination with D/H and ¹³C/¹²C ratio is mainly focused and the international official methods implementing stable isotope techniques will be mentioned. Furthermore, the ongoing study on a possible use of ¹³C/¹²C ratio of CO₂ to detect the addition of technical produced CO₂ in mineral sparkling waters is also presented.