Scientists at Washington University School of Medicine in St. Louis have found new clues to why some urinary tract infections recur persistently after multiple rounds of treatment.
Their research, conducted in mice, suggests that the bacteria that cause urinary tract infections take advantage of a cellular waste disposal system that normally helps fight invaders. In a counterintuitive finding, they learned that when the disposal system was disabled, the mice cleared urinary tract infections much more quickly and thoroughly.
‘This could be the beginning of a paradigm shift in how we think about the relationship between this waste disposal system, known as autophagy, and disease-causing organisms,’ says senior author Indira Mysorekar, PhD, assistant professor of obstetrics and gynaecology and of pathology and immunology. ‘There may be other persistent pathogens that have found ways to exploit autophagy, and that information will be very useful for identifying new treatments.’
Urinary tract infections are very common, particularly in women. In the United States alone, annual treatment costs are estimated to run as high as $1.6 billion. Scientists believe 80 percent to 90 percent of these infections are caused by the bacterium Escherichia coli (E. coli).
Data from the new study and earlier results have led Mysorekar and her colleagues to speculate that E. coli that cause recurrent urinary tract infections may hide in garbage-bin-like compartments within the cells that line the urinary tract.
These compartments, found in nearly all cells, are called autophagosomes. They sweep up debris within the cell, including harmful bacteria and worn-out cell parts. Then, they merge with other compartments in the cell that are filled with enzymes that break down the contents of autophagosomes.
‘We think, but can

Researchers have created a new type of miniature pump activated by body heat that could be used in drug-delivery patches powered by fermentation.
The micropump contains Baker’s yeast and sugar in a small chamber. When water is added and the patch is placed on the skin, the body heat and the added water causes the yeast and sugar to ferment, generating a small amount of carbon dioxide gas. The gas pushes against a membrane and has been shown to continually pump for several hours, said Babak Ziaie, a Purdue University professor of electrical and computer engineering and biomedical engineering.
Such miniature pumps could make possible drug-delivery patches that use arrays of ‘microneedles’ to deliver a wider range of medications than now possible with conventional patches. Unlike many other micropumps under development or in commercial use, the new technology requires no batteries, said Ziaie, who is working with doctoral student Manuel Ochoa.
‘This just needs yeast, sugar, water and your own body heat,’ Ziaie said.
The robustness of yeast allows for long shelf life, and the design is ideal for mass production, Ochoa said.
‘It would be easy to fabricate because it’s just a few layers of polymers sandwiched together and bonded,’ he said.
The paper was written by Ochoa and Ziaie, and the research is based at Purdue’s Birck Nanotechnology Center in the university’s Discovery Park.
The ‘the microorganism-powered thermopneumatic pump’ is made out of layers of a rubberlike polymer, called polydimethylsiloxane, which is used commercially for diaphragms in pumps. The prototype is 1.5 centimeters long.
Current ‘transdermal’ patches are limited to delivering drugs that, like nicotine, are made of small hydrophobic molecules that can be absorbed through the skin, Ziaie said.
‘Many drugs, including those for treating cancer and autoimmune disorders cannot be delivered with patches because they are large molecules that won’t go through the skin,’ he said. ‘Although transdermal drug delivery via microneedle arrays has long been identified as a viable and promising method for delivering large hydrophilic molecules across the skin, a suitable pump has been hard to develop.’
Patches that used arrays of tiny microneedles could deliver a multitude of drugs, and the needles do not cause pain because they barely penetrate the skin, Ziaie said. The patches require a pump to push the drugs through the narrow needles, which have a diameter of about 20 microns, or roughly one-fourth as wide as a human hair.
Most pumps proposed for drug-delivery applications rely on an on-board power source, which is bulky, costly and requires complex power-management circuits to conserve battery life.
‘Our approach is much more simple,’ Ziaie said. ‘It could be a disposable transdermal pump. You just inject water into the patch and place it on your skin. After it’s used up, you would throw it away.’ Purdue University

A new study by Weill Cornell Medical College researchers provides compelling evidence that electronic health records (EHRs) enhance the quality of patient care in a community-based setting with multiple players, which is representative of how medicine is generally practiced across the United States.

The use of EHRs is on the rise, in part because the federal government has invested up to $29 billion in incentives promoting the meaningful use of these systems, with the aim of tracking and improving patient outcomes. Previous studies have provided conflicting evidence about the impact of EHRs, and until now it had been not clear whether they improved the quality of patient care, particularly in typical communities that use commercially available systems.

‘The previous studies on the effects of electronic health records in the outpatient setting have been mixed,’ says the study’s lead investigator, Dr. Lisa M. Kern, associate professor of public health and medicine at Weill Cornell Medical College. ‘This is one of the first studies to find a positive association between the use of EHRs and quality of care in a typical community-based setting, using an off-the-shelf electronic health record that has not been extensively tailored and refined. This increases the generalisability of these findings.’

‘This study starts to grow the evidence that the use of these systems can systematically improve the quality of care, although their maximum value likely lies in their ability to support new health care delivery models,’ says the study’s senior investigator Dr. Rainu Kaushal, director of the Center for Healthcare Informatics and Policy and the Frances and John L. Loeb Professor of Medical Informatics at Weill Cornell Medical College. ‘The findings of this study lend support to the very significant investments in health information technology that are being made by the federal government, states, and health care providers.’

This study was conducted with the Health Information Technology Evaluation Collaborative (HITEC)

What makes laparoscopic surgery ‘minimally invasive’

UC Davis cancer researchers have discovered significant differences in radiation-therapy response among patients with oropharyngeal cancer depending on whether they carry the human papillomavirus (HPV), a common sexually transmitted virus. The findings could lead to more individualised radiation treatment regimens, which for many patients with HPV could be shorter and potentially less toxic.
HPV-related cancers of the oropharynx (the region of the throat between the soft palate and the epiglottis, including the tonsils, base of tongue and uvula) have steadily increased in recent years, according to the National Cancer Institute, especially among men. At the same time, the incidence of oropharyngeal cancers related to other causes, such as smoking or alcohol consumption, is declining. HPV is the most common sexually transmitted infection in the United States; it can spread through direct skin-to-skin contact during vaginal, anal and oral sex.
The UC Davis study, conducted by Allen Chen, associate professor in the UC Davis Department of Radiation Oncology, examined patterns of tumour reduction during radiation treatment in two otherwise similar groups of patients with oropharyngeal cancer: those who tested positive for HPV and those who tested negative for the virus. None of the HPV patients in the study was a smoker, a leading risk factor for the disease.
Chen used CT scans acquired during image-guided radiation therapy (IGRT) and endoscopy (a tube with a small camera) to capture 3D images of the patients’ tumours and monitor their treatment progress. He found that within the first two weeks after starting radiation, the gross tumour volume decreased by 33 percent in HPV-positive patients, while the volume decreased by only 10 percent in HPV-negative patients.
Chen said the results demonstrate that HPV-positive patients have a more rapid and robust response to radiation treatments, confirming what clinicians have suspected for years.
‘These HPV-related tumours literally melt before your eyes,’ he said. ‘It is very gratifying to tell patients early on during treatment that their tumours are responding so quickly. Most of them are pleasantly relieved to hear such news.’
The rapid rate of tumour regression did not continue, however, after the second week of radiation treatment, and by the end of the seven-week regimen, the total tumour shrinkage in both groups of patients was nearly the same.
However, ‘the dramatic early response observed in the HPV-positive patients strongly implies that these tumours behave distinctly from a biological standpoint and could be approached as a separate disease process,’ Chen said.
For example, the findings suggest that treatment for HPV-positive cancer may not need to be as intensive for it to be effective, Chen said, adding that a shorter, abbreviated treatment regimen would potentially lessen the side effects from radiation, which include sore throat, dry mouth, taste loss and swallowing difficulties.
‘It is likely that treatment in the future will be individualised based on biomarkers present in the tumour, and HPV has the potential to do just that,’ said Chen.
Chen said there is increasing evidence that HPV-positive patients who receive radiation treatments live longer and have higher cure rates. According to the NCI, 88 percent of the HPV-positive patients are still alive two years after their treatments, compared with 66 percent of the HPV-negative patients.
‘Given the impressive outcomes for patients with HPV-positive cancer using currently aggressive treatments, how to de-intensify therapy while maintaining cure rates is definitely a hot topic right now,’ said Chen. UC Davis Comprehensive Cancer Center