Rapid detection of urinary tract infections using isotachophoresis and molecular beacons.

We present a novel assay for rapid detection and identification of bacterial urinary tract infections using isotachophoresis (ITP) and molecular beacons. We applied on-chip ITP to extract and focus 16S rRNA directly from bacterial lysate and used molecular beacons to achieve detection of bacteria specific sequences. We demonstrated detection of E. coli in bacteria cultures as well as in patient urine samples in the clinically relevant range 1E6-1E8 cfu/mL. For bacterial cultures we further demonstrate quantification in this range. The assay requires minimal sample preparation (a single centrifugation and dilution), and can be completed, from beginning of lysing to detection, in under 15 min. We believe that the principles presented here can be used for design of other rapid diagnostics or detection methods for pathogenic diseases.

Climate change adaptation in conflict-affected countries: A systematic assessment of evidence.

People affected by conflict are particularly vulnerable to climate shocks and climate change, yet little is known about climate change adaptation in fragile contexts. While climate events are one of the many contributing drivers of conflict, feedback from conflict increases vulnerability, thereby creating conditions for a vicious cycle of conflict. In this study, we carry out a systematic review of peer-reviewed literature, taking from the Global Adaptation Mapping Initiative (GAMI) dataset to documenting climate change adaptation occurring in 15 conflict-affected countries and compare the findings with records of climate adaptation finance flows and climate-related disasters in each country. Academic literature is sparse for most conflict-affected countries, and available studies tend to have a narrow focus, particularly on agriculture-related adaptation in rural contexts and adaptation by low-income actors. In contrast, multilateral and bilateral funding for climate change adaptation addresses a greater diversity of adaptation needs, including water systems, humanitarian programming, and urban areas. Even among the conflict-affected countries selected, we find disparity, with several countries being the focus of substantial research and funding, and others seeing little to none. Results indicate that people in conflict-affected contexts are adapting to climate change, but there is a pressing need for diverse scholarship across various sectors that documents a broader range of adaptation types and their results.

A novel suppressor of ras1 in fission yeast, byr4, is a dosage-dependent inhibitor of cytokinesis.

A novel gene, designated byr4, was identified in Schizosaccharomyces pombe that affects the mitotic cell cycle and shows genetic interactions with the ras1 signaling pathways. Null alleles of byr4 cause cell cycle arrest in late mitosis and permit multiple rounds of septation. The multiple septa typically divide two nuclei, but the nuclei frequently do not stain equally with 4',6-diamidino-2-phenylindole (DAPI), suggesting that byr4 is required for proper karyokinesis. Overexpression of byr4 inhibits cytokinesis, but cell cycle progression continues leading to multinucleate cells. When byr4 is overexpressed, the early steps in the cytokinesis pathway, including formation of the medial F-actin ring, occur normally; however, the later steps in the pathway, including contraction of the F-actin ring, septation, and rearrangement of the medial F-actin following mitosis, rarely occur, byr4 shows two genetic interactions with ras1. The inhibition of cytokinesis by byr4 overexpression was exacerbated by null alleles of ras1 and scd1, suggesting a link between pathways needed for cell polarity and cytokinesis. Overexpression of byr4 also partially bypasses the need for ras1 for sporulation. The electrophoretic mobility of the byr4 protein varied in response to mutants that perturb cytokinesis and karyokinesis, suggesting interactions between byr4 and these gene products. A more rapidly migrating byr4 protein was found in cells with mutations in cdc16, which undergo repeated septation, and in cdc15, which fail to form a medial F-actin ring in mitosis. A slower migrating byr4 protein was found in cells with a mutation in the beta-tubulin gene, which arrests cells at the metaphase-anaphase transition.

Loss of Rhb1, a Rheb-related GTPase in fission yeast, causes growth arrest with a terminal phenotype similar to that caused by nitrogen starvation.

The Rheb GTPase is most similar in primary sequence to the Ras, Rap, R-Ras, and Ral GTPases, which regulate cell growth and differentiation in many cell types. A likely fission yeast homologue of mammalian Rheb, which we designated Rhb1, was identified by genome sequencing. Our investigation of rhb1 showed that rhb1(-) cells arrested cell growth and division with a terminal phenotype similar to that of nitrogen-starved cells. In particular, cells depleted of Rhb1 arrested as small, round cells with 1N DNA content, arrested more quickly in low-nitrogen medium, and induced expression of fnx1 and mei2 mRNA, two mRNAs that were normally induced by nitrogen starvation. Since mammalian Rheb binds and may regulate Raf-1, a Ras effector, we tested for functional overlap between Ras1 and Rhb1 in fission yeast. This analysis showed that Ras1 overexpression did not suppress rhb1(-) mutant phenotypes, Rhb1 overexpression did not suppress ras1(-) mutant phenotypes, and ras1(-) rhb1(-) double mutants had phenotypes equal to the sum of the corresponding single-mutant phenotypes. Hence, there is no evidence for overlapping functions between Ras1 and Rhb1. On the basis of this study, we hypothesize that Rhb1 negatively regulates entry into stationary phase when extracellular nitrogen levels are adequate for growth. If this hypothesis is correct, then Rhb1 and Ras1 regulate alternative responses to limiting nutrients.

Reduction of bis

The reduction of symmetric, fully-substituted titanocene dichlorides bearing two pendant omega-alkenyl groups, [TiCl2(eta5-C5Me4R)2], R = CH(Me)CH= CH2 (1a). (CH2)2CH=CH2 (1b) and (CH2)3CH=CH2 (1c), by magnesium in tetrahydrofuran affords bis(cyclopentadienyl)titanacyclopentanes [Ti(IV)[eta1:eta1: eta5:eta5-C5Me4CH(Me)CH(Ti)CH2CH(CH2(Ti))CH(Me)C5Me4]] (2a), [Ti(IV)[eta1:eta1:eta5: eta5-C5Me4(CH2)2CH(Ti)(CH2)2CH(Ti)(CH2)2C5Me4]] (2b) and [Ti(IV)[eta1:eta1:eta5:eta5-C5Me4(CH2)2CH(Ti)CH(Me)CH(Me)CH(Ti)(CH2)2C5Me4]](2c), respectively, as the products of oxidative coupling of the double bonds across a titanocene intermediate. For the case of complex 1c, a product of a double bond isomerisation is obtained owing to a preferred formation of five-membered titanacycles. The reaction of the titanacyclopentanes with PbCl2 recovers starting materials 1a from 2a and 1b from 2b, but complex 2c affords, under the same conditions, an isomer of 1c with a shifted carbon - carbon double bond, [TiCl[eta5-C5Me4(CH2CH2CH=CHMe)]2] (1c'). The titanacycles 2a-c can be opened by HCl to give ansa-titanocene dichlorides ansa-[[eta5:eta5-C5Me4CH(Me)CH2CH2CH(Me)CH(Me)C5Me4]TiCl2] (3a), ansa-[[eta5:eta5-C5Me4(CH2)8C5Me4]TiCl2] (3b), along with a minor product ansa-[[eta5:eta5-C5Me4CH2CH=CH(CH2)5C5Me4]TiCl2] (3b'), and ansa-[[eta5:eta5-CsMe4(CH2)3CH(Me)CH(Me)CH=CHCH2C5Me4]TiCl2] (3c), respectively, with the bridging aliphatic chain consisting of five (3a) and eight (3b, 3b' and 3c) carbon atoms. The course of the acidolysis changes with the nature of the pendant group; while the cyclopentadienyl ring-linking carbon chains in 3a and 3b are fully saturated, compounds 3c and 3b' contain one asymetrically placed carbon-carbon double bond, which evidently arises from the beta-hydrogen elimination that follows the HCl addition.

Phase I/II trial of dexverapamil, epirubicin and granulocyte/macrophage-colony-stimulating factor in patients with advanced pancreatic adenocarcinoma.

A group of 28 previously untreated patients with locally advanced or metastatic adenocarcinoma of the pancreas were entered in this phase I/II study. Treatment consisted of oral dexverapamil 1000-1200 mg/day for 3 days, epirubicin given as an intravenous bolus injection on day 2 with a starting dose of 90 mg/m2, and 400 micrograms granulocyte/macrophage-colony-stimulating factor (GM-CSF) administered subcutaneously from day 5 through 14. Epirubicin dose escalation levels were 90, 105, 120 and 135 mg/m2. Consecutive cohorts of 4-8 patients were planned at each dose level. Treatment cycles were repeated every 3 weeks. Haematological toxicity, specifically granulocytopenia constituted the dose-limiting toxicity with a maximum tolerated dose of 120 mg/m2 for epirubicin. Despite routine supportive therapy with GM-CSF, 4, 2, and 5 patients experienced grade 4 granulocytopenia during their first two treatment courses at levels of 105, 120, and 135 mg/m2 respectively. Non-haematological toxicity was uncommon, generally modest, and did not demonstrate a clear relationship with the anthracycline dose. Dexverapamil-related cardiovascular symptoms occurred frequently, but they never resulted in serious toxicity requiring active medical intervention or permanent discontinuation of therapy. Of the 28 patients, 9 achieved partial reponses to this therapy. The recommended dose of epirubicin for this regimen with dexverapamil and GM-CSF is 120 mg/m2 every 3 weeks. Therapeutic results suggest this regimen to be an effective and tolerable treatment strategy in pancreatic cancer, which should be evaluated further.

Post-transcriptional action of ACTH in the control of P450c17 expression in rabbit adrenal glands.

Stimulation of transcription of the CYP17 gene by ACTH has been demonstrated previously by others using cultures of adrenal tissue from several species. In the present investigations we have demonstrated from measurements in pooled rabbit adrenal glands that after 4 or 6 days of ACTH injections no difference in amounts of CYP17 mRNA per microgram of total adrenal RNA was observed between ACTH and control animals. While the total amount of CYP17 mRNA per adrenal increased 1.4- to 1.7-fold over the injected and non-injected controls due to an increase in total RNA in the ACTH-stimulated adrenals, Western analysis of adrenal microsomal protein demonstrated that the amount of adrenal P450c17 protein, the product of the CYP17 gene, increased over 50-fold. The data show that ACTH is acting at both transcriptional and post-transcriptional loci to increase the amount of rabbit adrenal P450c17 and that the greater effect is post-transcriptional.

[Balloon dilatation of benign esophageal stenoses]. / Ballondilatation von benignen Osophagusstenosen.

Benign stenoses of the oesophagus have been conventionally treated by endoscopic bougienage and were operated on in case of failure. Now that balloon catheters with large balloon diameters are available, interventional radiological dilatation of enteric strictures can be easily performed. In case of eccentric high-grade stenosis with or without blind loop, stenosis is often easier to manage and associated with less risk with an angiographic guide wire and catheter than by endoscopy. 53.3% of the patients were referred to balloon dilatation after failed endoscopic bougienage. The indications for balloon dilatation were anastomotic stenosis (66.2%), peptic stenosis (16.9%), achalasia (7%), pylorospasm (5.6%) and stenosis due to pemphigus vulgaris, acid ingestion and (in one case) a Schatzki ring. The complication rate was low at 1%. The experience collected with 297 dilatations in 71 patients with benign oesophageal stenosis, is reported.

[Repeat mass screening for fecal occult blood for the diagnosis of colorectal neoplasms in a rural district. Results of an informational campaign]. / Wiederholte Massenscreeninguntersuchung auf okkultes Blut im Stuhl zur Erfassung kolorektaler Neoplasien in einem ländlichen Bezirk. Ergebnisse einer Informationskampagne.

In 1987/88 and 1988/89 we tested the population (aged greater than or equal to 40) of the district of Oberpullendorf in 2 series for faecal occult blood by means of the Hemdetect Test. In the first test series the test was offered to 18,233 persons and 8235 (45%) persons completed the test; 187 (2.3%) were positive. In the second series 6512 (36%) out of 18,241 completed the test and 472 (7.2%) persons were positive. The persons with positive results were examined by colonoscopy, gastroscopy, and abdominal sonography, in combination with routine investigations. Secondary compliance in these investigations was 92%. The screening method revealed 34 colorectal cancers with the favourable pathological staging: Dukes A 18 (53%), Dukes B 6 (18%), Dukes C 10 (29%), Dukes D 0. 11 polyps showing carcinoma in situ and 174 polyps (70% of which were adenomas) in 124 patients were treated by colonoscopy. In the meantime we have detected 14 "interval" cancers among people with a false negative test result, also at a favourable staging: Dukes A 6 (43%), Dukes B 4 (29%), Dukes C 4 (29%), Dukes D 0. In the non-responders we found 30 colorectal cancers at a much worse staging: Dukes A 7 (23%), Dukes B 10 (33%), Dukes C 8 (27%), and Dukes D 5 (17%). Screening for faecal occult blood in combination with the necessary investigations of the positive persons by colonoscopy is able to detect symptomless colorectal cancers at a less advanced pathological stage and enables the treatment of precancerous adenomatous polyps. An improvement in cumulative sensitivity is expected on annual repetition of screening for faecal occult blood.

[Results of thoracoscopic sympathectomy in hyperhidrosis of the upper extremities (author's transl)]. / Ergebnisse der thorakoskopischen Sympathektomie bei Hyperhidrosis der oberen Extremität

Thoracoscopic sympathectomy bei Kux's method was undertaken on 256 occasions for the treatment of 168 patients suffering from hyperhidrosis of the upper extremities. There were no operative fatalities. Thoracotomy was required in only 2 cases, the indication being intraoperative bleeding. 2 further patients developed a tension pneumothorax postoperatively necessitating drainage. The operation was successful in all but 2 cases. Division of the sympathetic chain between T1 and T2 suffices to achieve dryness of the hands; if underarm perspiration is to equally influenced then division of the sympathetic trunk must be extended caudally to the level of T5. On follow-up examination of 104 patients 2 and 10 years after the operation, a successful result was noted in 94% of cases. Unwanted side effects were vicarious and gustatory perspiration, which arose in 39% and 56% of cases respectively, but did not affect the successful outcome of the operation.

[Acne vulgaris--principles and results of treatment with retinoic acid and tetracyclines (author's transl)]. / Akne vulgaris--Grundlagen und Ergebnisse der Behandlung mit Vitamin-A-Säure und Tetrazyklinen

According to the results obtained in a recent clinical trial over a four-year period retinoic acid represents the most effective single agent available for the topical management of acne vulgaris. Retinoic acid yields impressive therapeutic results not only in patients with manifest acne, but, provided it is applied early enough, it is also effective in preventing the severe inflammatory manifestations of this disease. In medium to severe cases of inflammatory acne, topical retinoic acid therapy should be combined with a low-dose, long-term systemic tetracycline regimen. The course of treatment may extend over months or years, depending on the severity of the condition. Particularly patients in the acne-prone age group are candidates for long-term therapy. Retinoic acid therapy, alone or in combination with tetracyclines, proved far superior to conventional regimens with respect to the effective treatment and prophylaxis of acne.

[Treatment of Amanita phalloides poisoning with silybin in combination with penicillin and cortisone]. / Therapie der Knollenblätterpilzvergiftung mit Silibinin in Kombination mit Penicillin und Cortison.

A report is presented of Amanita phalloides poisoning in a family of 3 members admitted with acute gastrointestinal symptoms after eating a meal of various self-picked mushrooms. A latent period of 11 hours preceded the onset of symptoms, a typical feature of this form of poisoning. There was an enormous increase in liver-specific enzymes in two of the cases. The clinical picture was markedly mitigated by the early initiation of silybin therapy, in combination with penicillin and cortisone. The patients made a rapid symptomatic recovery and the liver parameters were sufficiently improved by the 12th day so that the patients could be discharged.

[Treatment of metastatic malignant melanoma (author's transl)]. / Klinische Erfahrungen mit DTIC beim metastasierenden Melanom.

24 patients with metastatic malignant melanoma were treated with DTIC applied alone or in combination with other cytotoxic agents (Oncovin, Bleomycin, Adriblastin). Treatment resulted in objective improvement (3 patients), subjective improvement (2 patients), stable state (5 patients). The other patients showed further progression of their disease.

A ferrocenyl-substituted pseudotitanocene complex

The title compound, (eta(5)-cyclopentadienyl)[(1,2,3,4, 5-eta)-4-ferrocenyl-1,2,5,6-tetrakis(trimethylsilyl)cyclohexa-2, 4-dien-1-yl]titanium(II), [TiFe(C(5)H(5))(2)(C(23)H(42)Si(4))] or [Tieta(5)-C(6)H(2)Fe(eta(5)-C(5)H(4))(eta(5)-C(5)H(5))Si(CH(3))(3 )(4)(eta(5)-C(5)H(5))], possesses two directly linked metallocene units that subtend an angle of 52.9 (1) degrees (defined by the least-squares planes of the directly connected pi-ligands) associated with the steric requirements of the bulky trimethylsilyl substituents. The cyclohexadienyl ligand adopts an envelope conformation; the perpendicular distance of its eta(5)-plane to the Ti atom is 1.512 (1) A.