Structure-Activity Relationships and Target Selectivity of Phenylsulfonylamino-Benzanilide Inhibitors Based on S1647 at the SLC10 Carriers ASBT, NTCP, and SOAT.

The intestinal bile acid carrier ASBT (), the hepatic bile acid carrier NTCP (), and the steroid sulfate carrier SOAT (), all members of the solute carrier family SLC10, are established drug targets. The ASBT inhibitors odevixibat, maralixibat, and elobixibat are used to treat intrahepatic cholestasis, cholestatic pruritus, and obstipation. The peptide drug bulevirtide blocks binding of the hepatitis B and D viruses to NTCP and thereby inhibits the virus's entry into hepatocytes.

100 ancient genomes show repeated population turnovers in Neolithic Denmark.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (C and N content), mobility (Sr/Sr ratio) and vegetation cover (pollen).

Arabidopsis pavement cell shape formation involves spatially confined ROPGAP regulators.

In many plant species, pavement cell development relies on the coordinated formation of interdigitating lobes and indentations. Polarity signaling via the activity of antagonistic Rho-related GTPases from plants (ROPs) was implicated in pavement cell development, but the spatiotemporal regulation remained unclear. Here, we report on the role of the PLECKSTRIN HOMOLOGY GTPase ACTIVATING PROTEINS (PHGAPS) during multipolar growth in pavement cell shape establishment.

Quantifying the economic benefit of the personal alarm and emergency response system in Australia: a cost analysis of the reduction in ambulance attendances.

Objectives MePACS is a triage and support-based personal alarm emergency response system designed to assist older and/or disabled people to live safely in their homes. The aim of this study was to estimate avoidable ambulance attendances and transports to emergency departments and quantify the cost savings attributed to MePACS compared with a comparison cohort without a personal alarm system. Methods Alarm activation and demographic data for clients registered in the program from June 2016 to May 2017 and funded through the Personal Alert Victoria program were extracted from routinely collected MePACS electronic data.

Identification of tetragametic human chimerism by routine DNA profiling.

Chimerism in humans is defined as the presence of two genetically different cell lines within the same organism. It is usually an acquired condition that is restricted to certain tissues and can be explained by therapeutic interventions such as blood transfusion or the transplantation of allogenic hematopoietic cells. Implications of such patients for forensic DNA testing have been described in the literature.

Ionizing radiation in secret services' conspirative actions.

Introduction: The death of Litvinenko has been reported by the media. It has raised the question whether this case had been unique. The fall of the wall has allowed a glimpse in the planning and comporting of a secret service.

Demand as a driving force in medical innovation.

On the basis of two case histories of medical device innovation, two aspects of demand are identified: (a) the prospect of new markets and (b) information about user needs. Conditions for direct interaction between the user and producer in the innovation process are identified. The article concludes with some normative implications for the publicly designed generation of new medical technology.

Photodynamic therapy with haematoporphyrin derivative on mice with solid Ehrlich carcinomas.

The tumor-toxic effect of the photosensitizer HpD/Halle activated by laser radiation was demonstrated. Solid Ehrlich carcinoma was used as model. Investigations into the tumor growth, the HpD-distribution after different kinds of drug administration by means of fluorescence measurements, the phototoxicity and the reduction of tumor masses after HpD application and laser irradiation were carried out.

Dazoxiben-induced changes in the thromboxane/prostacyclin balance in the lateral cochlear wall of the guinea pig.

Dazoxiben, a thromboxane synthetase inhibitor, was infused i.v. in a first group of guinea pigs.

Continuous positive airway pressure effect on functional residual capacity, vital capacity and its subdivisions.

Thirty-four otherwise healthy patients having to undergo elective upper abdominal surgery were randomly assigned to two equal groups. In the treatment group, constant positive airway pressure (CPAP) with an expiratory pressure of 12 cm H2O was applied at one hour following extubation, and at daily intervals for the first five days following surgery for a continuous period of three hours. The control group received no CPAP treatment.

Subcortical arteriosclerotic encephalopathy: CT spectrum and pathologic correlation.

Because of recent papers suggesting that subcortical arteriosclerotic encephalopathy (SAE) (Binswanger's disease) is more common than historically assumed, this investigation was initiated to assess the frequency of SAE, to gauge the reliability of CT in making this diagnosis, and to assess the strength of the correlation between SAE and arterial hypertension. Of 202 autopsied patients in a 17-month period, 82 had undergone antemortem CT. Of these, 20 had CT findings thought to represent varying degrees of the disease spectrum of SAE.

The metabolic reaction of the cochlea to unphysiological noise exposure.

Guinea pigs were exposed to continuous white noise of 120 dB SPL. The performance included a recording of CM, pO2, and metabolites in the perfusate of the perilymphatic spaces. The metabolic reactions observed following the exposure are limited.

[Aortofemoral bifurcation bypass. Effect of the anesthesia procedure (NLA, thoracic continuous catheter peridural anesthesia) on circulation, respiration and metabolism. Homeostasis and oxygen transport].

50 patients were investigated during induction of anaesthesia and infrarenal aortic bypass surgery. 26 were operated on under neuroleptanaesthesia (NA group) and 24 under continuous epidural combined with a light general anaesthesia (epidural group). Blood losses were replaced with 5 per cent human albumin, red cell concentrates, and fresh frozen plasma.

Neurologic disorders: the many new uses of CT.

Every patient being evaluated for dementia deserves at least one CT study in the hope of discovering a treatable cause. Although many treatable causes of dementia are not necessarily diagnosable by CT, a careful observer may detect suggestions of such disorders in the CT findings. Presentations that prompt CT is rule out neoplasm in the brain include progressive neurologic deficits of insidious onset, new onset of seizures, and increased intracranial pressure.

Hemorrhagic nerve sheath tumors (plexiform neurofibromas) of the scalp: CT findings.

Three cases of hemorrhagic nerve sheath tumors of the scalp are presented with emphasis on CT findings. Each mass produced a mixed pattern of CT density due to the combination of tumor and hemorrhage within it. The CT findings were remarkably similar in the three patients and included a calvarial abnormality underlying the mass in each.

[Sodium bicarbonate administration in cardiopulmonary resuscitation. Results of an animal experimental study].

One minute following electrically induced ventricular fibrillation, 12 anaesthetized pigs (hybrids between German and Belgian pedigree swine of 29 kg average body weight) were resuscitated for 30 min with a mechanical thorax compressor and ventilator. Six animals were given 1 mval sodium bicarbonate per kilogram body weight via a central venous line during the first ten minutes of resuscitation, and then 0.5 mval/kg body weight during both of the remaining ten minute intervals.

[Postoperative pulmonary function following abdominal surgery. Comparison of continuous, segmental thoracic peridural anesthesia and intramuscular piritramide injections].

Respiratory function was studied in 35 patients after upper abdominal surgery, who had been randomized into two groups. 15 patients (median age: 59 years) were operated on using neuroleptanalgesia and received intramuscular piritramide as postoperative analgesic. A continuous thoracic epidural was placed prior to surgery in 20 patients (median age 52 years).