Development of Predictive Models to Inform a Novel Risk Categorization Framework for Antibiotic Resistance in E. coli-Causing Uncomplicated Urinary Tract Infection.

BACKGROUND: In clinical practice, challenges in identifying patients with uncomplicated urinary tract infections (uUTIs) at risk of antibiotic non-susceptibility may lead to inappropriate prescribing and contribute to antibiotic resistance. We developed predictive models to quantify risk of non-susceptibility to four commonly prescribed antibiotic classes for uUTI, identify predictors of non-susceptibility to each class, and construct a corresponding risk categorization framework for non-susceptibility. METHODS: Eligible females aged ≥12 years with E. coli-caused uUTI were identified from Optum's de-identified Electronic Health Record dataset (10/1/2015‒2/29/2020). Four predictive models were developed to predict non-susceptibility to each antibiotic class and a risk categorization framework was developed to classify patients' isolates as low, moderate, and high risk of non-susceptibility to each antibiotic class. RESULTS: Predictive models were developed among 87487 patients. Key predictors of having a non-susceptible isolate to ≥3 antibiotic classes included number of previous UTI episodes, prior ß-lactam non-susceptibility, prior fluoroquinolone treatment, census bureau region, and race. The risk categorization framework classified 8.1%, 14.4%, 17.4%, and 6.3% of patients as having isolates at high risk of non-susceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, ß-lactams, and fluoroquinolones, respectively. Across classes, the proportion of patients categorized as having high-risk isolates was 3-12 folds higher among patients with non-susceptible isolates versus susceptible isolates. CONCLUSIONS: Our predictive models highlight factors that increase risk of non-susceptibility to antibiotics for uUTIs, while the risk categorization framework contextualizes risk of non-susceptibility to these treatments. Our findings provide valuable insight to clinicians treating uUTIs and may help inform empiric prescribing in this population.

Combining conventional QTL analysis and whole-exome capture-based bulk-segregant analysis provides new genetic insights into tuber sprout elongation and dormancy release in a diploid potato population.

Tuber dormancy and sprouting are commercially important potato traits as long-term tuber storage is necessary to ensure year-round availability. Premature dormancy release and sprout growth in tubers during storage can result in a significant deterioration in product quality. In addition, the main chemical sprout suppressant chlorpropham has been withdrawn in Europe, necessitating alternative approaches for controlling sprouting. Breeding potato cultivars with longer dormancy and slower sprout growth is a desirable goal, although this must be tempered by the needs of the seed potato industry, where dormancy break and sprout vigour are required for rapid emergence. We have performed a detailed genetic analysis of tuber sprout growth using a diploid potato population derived from two highly heterozygous parents. A dual approach employing conventional QTL analysis allied to a combined bulk-segregant analysis (BSA) using a novel potato whole-exome capture (WEC) platform was evaluated. Tubers were assessed for sprout growth in storage at six time-points over two consecutive growing seasons. Genetic analysis revealed the presence of main QTL on five chromosomes, several of which were consistent across two growing seasons. In addition, phenotypic bulks displaying extreme sprout growth phenotypes were subjected to WEC sequencing for performing BSA. The combined BSA and WEC approach corroborated QTL locations and served to narrow the associated genomic regions, while also identifying new QTL for further investigation. Overall, our findings reveal a very complex genetic architecture for tuber sprouting and sprout growth, which has implications both for potato and other root, bulb and tuber crops where long-term storage is essential.

Asymptomatic Bacteriuria.

Asymptomatic bacteriuria, defined as the presence of bacteria in the urine in the absence of urinary symptoms, is a common clinical finding that often warrants a decision about whether to initiate antimicrobial therapy. There are few indications to treat asymptomatic bacteriuria, and inappropriate treatment contributes to the development of antimicrobial resistance. In 2019, the Infectious Diseases Society of America revised its 2005 guidelines on asymptomatic bacteriuria, incorporating new evidence. The updated guidelines recommend screening and appropriate treatment for asymptomatic bacteriuria in pregnant women and in individuals undergoing endourological procedures associated with mucosal trauma. The guidelines recommend against screening and treatment in infants and children; healthy adults, including nonpregnant pre- and postmenopausal women; and patients with diabetes mellitus, long-term indwelling catheters, or spinal cord injuries. The guidelines also recommend against screening and treatment in patients undergoing nonurological surgery, patients who have had a kidney transplant more than one month prior, recipients of other solid organ transplants, or those with impaired voiding following spinal cord injury. Although delirium in older adults can be caused by a urinary tract infection, the guidelines recommend that patients with delirium and no urinary or systemic symptoms be assessed for other causes of delirium, rather than initiating treatment for asymptomatic bacteriuria, because treatment has not been shown to have any beneficial effect on clinical outcomes.

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America.

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America.

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.

The use of ozone to extend the shelf-life and maintain quality of fresh produce.

Fresh produce has been recognised as a healthy food, thus there is increasing consumer demand for fresh fruit and vegetables. The shelf-life of fresh produce, however, is relatively short and is limited by microbial contamination or visual, textural and nutritional quality loss. There are many methods to reduce/eliminate microorganisms present in food and ozone treatment is one of them. The use of ozone by the fresh produce industry is a good alternative to chemical treatments, e.g. the use of chlorine. The effectiveness of ozone as an antimicrobial agent has previously been reviewed and has been updated here, with the latest findings. The main focus of this review is on the effects of ozone on the fresh produce quality, defined by maintenance of texture, visual quality, taste and aroma, and nutritional content. Furthermore, ozone has been found to be efficient in reducing pesticide residues from the produce. The treatments that have the ability to reduce microbial contamination of the product without having an adverse effect on its visual, textural and nutritional quality can be recommended and subsequently incorporated into the supply chain. A good understanding of all the benefits and limitations related to the use of ozone is needed, and relevant information has been reviewed in this paper.

I remember...it was December.

William Osler is quoted as saying, "Nothing will sustain you more potently than the power to recognize in your humdrum routine, as perhaps it may be thought, the true poetry of life-the poetry of the commonplace, of the plain, toil-worn woman, with their loves and their joys, their sorrows and their griefs."(1) A family physician reflects how he continues to derive sustenance from having cared for a dying woman and her family over several home visits in his earliest years of private practice. The author's memory of these house calls continues to reinforce his love for medicine. Today, when physicians are overburdened with countless numbers of interruptions, requirements, and measures we are reminded that one of the things which can maintain our passion for medicine is in realizing that caring for others is the focus of our sacred vocation. By appreciating the impact we have on the lives of those less fortunate, we may find meaning in our own lives.

Recombinant monoclonal antibody yield in transgenic tobacco plants is affected by the wounding response via an ethylene dependent mechanism.

Variability in recombinant IgG yield in transgenic tobacco plants has previously been observed in relation to leaf position, and is interpreted as a function of ageing and the senescence process, leading to increasing protein degradation. Here, similar findings are demonstrated in plants of different ages, expressing IgG but not IgG-HDEL, an antibody form that accumulates within the endoplasmic reticulum. Antibody yields declined following wounding in young transgenic plants expressing IgG but not in those expressing IgG-HDEL. However, in mature IgG plants, the opposite was demonstrated, with significant boosts in yield, while mature IgG-HDEL plants could not be boosted. The lack of response in IgG-HDEL plants suggests that the changes induced by wounding occur post-translationally, and the findings might be explained by wounding responses that differ in plants according to their developmental stages. Plant mechanisms involved in senescence and wounding overlap to a significant degree and compounds such as ethylene, jasmonic acid and salicylic acid are important for mediating downstream effects. Treatment of transgenic plants with ethylene also resulted in a decrease in recombinant IgG yield, which was consistent with the finding that wounded plants could induce lower IgG yields in neighbouring non-wounded plants. Treatment with 1-MCP, an ethylene antagonist, abrogated the IgG yield drop that resulted from wounding, but had no effect on the more gradual IgG yield loss associated with increasing plant age.

International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases.

A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the 1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include the American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases-Canada, and the Society for Academic Emergency Medicine. The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment choices and thus are reflected in the rankings of recommendations.

Diagnosis and treatment of acute uncomplicated cystitis.

Urinary tract infections are the most common bacterial infections in women. Most urinary tract infections are acute uncomplicated cystitis. Identifiers of acute uncomplicated cystitis are frequency and dysuria in an immunocompetent woman of childbearing age who has no comorbidities or urologic abnormalities. Physical examination is typically normal or positive for suprapubic tenderness. A urinalysis, but not urine culture, is recommended in making the diagnosis. Guidelines recommend three options for first-line treatment of acute uncomplicated cystitis: fosfomycin, nitrofurantoin, and trimethoprim/sulfamethoxazole (in regions where the prevalence of Escherichia coli resistance does not exceed 20 percent). Beta-lactam antibiotics, amoxicillin/clavulanate, cefaclor, cefdinir, and cefpodoxime are not recommended for initial treatment because of concerns about resistance. Urine cultures are recommended in women with suspected pyelonephritis, women with symptoms that do not resolve or that recur within two to four weeks after completing treatment, and women who present with atypical symptoms.

Diagnosis and treatment of acute pyelonephritis in women.

Acute pyelonephritis is a common bacterial infection of the renal pelvis and kidney most often seen in young adult women. History and physical examination are the most useful tools for diagnosis. Most patients have fever, although it may be absent early in the illness. Flank pain is nearly universal, and its absence should raise suspicion of an alternative diagnosis. A positive urinalysis confirms the diagnosis in patients with a compatible history and physical examination. Urine culture should be obtained in all patients to guide antibiotic therapy if the patient does not respond to initial empiric antibiotic regimens. Escherichia coli is the most common pathogen in acute pyelonephritis, and in the past decade, there has been an increasing rate of E. coli resistance to extended-spectrum beta-lactam antibiotics. Imaging, usually with contrast-enhanced computed tomography, is not necessary unless there is no improvement in the patient's symptoms or if there is symptom recurrence after initial improvement. Outpatient treatment is appropriate for most patients. Inpatient therapy is recommended for patients who have severe illness or in whom a complication is suspected. Practice guidelines recommend oral fluoroquinolones as initial outpatient therapy if the rate of fluoroquinolone resistance in the community is 10 percent or less. If the resistance rate exceeds 10 percent, an initial intravenous dose of ceftriaxone or gentamicin should be given, followed by an oral fluoroquinolone regimen. Oral beta-lactam antibiotics and trimethoprim/sulfamethoxazole are generally inappropriate for outpatient therapy because of high resistance rates. Several antibiotic regimens can be used for inpatient treatment, including fluoroquinolones, aminoglycosides, and cephalosporins.

University of Maryland School of Medicine increases medical student education in primary care.

In August 2012 the University of Maryland School of Medicine will start a new Primary Care Track for incoming first year medical students as a collaborative program of the departments of Family and Community Medicine, Internal Medicine, and Pediatrics. Its focus will be to introduce all students to primary care role models early in medical school, and to offer a longitudinal experience in primary care in rural and urban underserved communities to interested students, with the intention of increasing the number of UMD medical students who choose primary care careers in these communities.

De novo sequencing and analysis of the transcriptome of two highbush blueberry (Vaccinium corymbosum L.) cultivars 'Bluecrop' and 'Legacy' at harvest and following post-harvest storage.

Fruit firmness and in particular the individual components of texture and moisture loss, are considered the key quality traits when describing blueberry fruit quality, and whilst these traits are genetically regulated, the mechanisms governing their control are not clearly understood. In this investigation, RNAseq was performed on fruits of two blueberry cultivars with very different storage properties, 'Bluecrop' and 'Legacy', at harvest, three weeks storage in a non-modified environment at 4 °C and after three weeks storage at 4 °C followed by three days at 21 °C, with the aim of understanding the transcriptional changes that occur during storage in cultivars with very different post-harvest fruit quality. De novo assemblies of the transcriptomes of the two cultivars were performed separately and a total of 39,335 and 41,896 unigenes for 'Bluecrop' and 'Legacy' respectively were resolved. Differential gene expression analyses were grouped into four cluster profiles based on changes in transcript abundance between harvest and 24 days post-harvest. A total of 290 unigenes were up-regulated in 'Legacy' only, 685 were up-regulated in 'Bluecrop', 252 were up-regulated in both cultivars and 948 were down-regulated in both cultivars between harvest and 24 days post-harvest. Unigenes showing significant differential expression between harvest and following post-harvest cold-storage were grouped into classes of biological processes including stress responses, cell wall metabolism, wax metabolism, calcium metabolism, cellular components, and biological processes. In total 21 differentially expressed unigenes with a putative role in regulating the response to post-harvest cold-storage in the two cultivars were identified from the de novo transcriptome assemblies performed. The results presented provide a stable foundation from which to perform further analyses with which to functionally validate the candidate genes identified, and to begin to understand the genetic mechanisms controlling changes in firmness in blueberry fruits post-harvest.

Mini-Medical school empowers community members to advocate for their and others health.

PURPOSE: Over the past three decades, the term Mini-Medical School (MMS) has been used to describe programs offered by schools of medicine, which provide health education to the lay public and health career exposure to youth. The University of Maryland School of Medicine has operated an MMS program since 2001. The purpose of this study was to assess the sociodemographic characteristics of MMS participants and the impacts of this program on their health. METHODS: We analyzed anonymous post-completion program evaluation survey responses and we conducted focus groups with some of the participants who had attended the program for ≥10 years. RESULTS: Most of the MMS participants were women (84%, n = 72), ≥55 years of age (88%), and well-educated (58% with college degree and higher); and 59% had attended the program for ≥5 years. The focus group discussions revealed acquisition of medical knowledge and community outreach as recurring themes; the former leading to empowerment of the participants for better self-care and care for others, while the latter driving them to health education and advocacy. Most of the participants showed interest in becoming "ambassadors" in their respective communities. CONCLUSION: The health information provided by the MMS program is well-received and even anticipated by its participants. It has empowered them to care for themselves and for others by making them educated consumers and health advocates in their community. The MMS program should work with the School's community partners to make this resource more widely accessible, particularly to populations experiencing the most health disparities.

Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America.

Guidelines for the diagnosis, prevention, and management of persons with catheter-associated urinary tract infection (CA-UTI), both symptomatic and asymptomatic, were prepared by an Expert Panel of the Infectious Diseases Society of America. The evidence-based guidelines encompass diagnostic criteria, strategies to reduce the risk of CA-UTIs, strategies that have not been found to reduce the incidence of urinary infections, and management strategies for patients with catheter-associated asymptomatic bacteriuria or symptomatic urinary tract infection. These guidelines are intended for use by physicians in all medical specialties who perform direct patient care, with an emphasis on the care of patients in hospitals and long-term care facilities.

Optimisation of contained Nicotiana tabacum cultivation for the production of recombinant protein pharmaceuticals.

Nicotiana tabacum is emerging as a crop of choice for production of recombinant protein pharmaceuticals. Although there is significant commercial expertise in tobacco farming, different cultivation practices are likely to be needed when the objective is to optimise protein expression, yield and extraction, rather than the traditional focus on biomass and alkaloid production. Moreover, pharmaceutical transgenic tobacco plants are likely to be grown initially within a controlled environment, the parameters for which have yet to be established. Here, the growth characteristics and functional recombinant protein yields for two separate transgenic tobacco plant lines were investigated. The impacts of temperature, day-length, compost nitrogen content, radiation and plant density were examined. Temperature was the only environmental variable to affect IgG concentration in the plants, with higher yields observed in plants grown at lower temperature. In contrast, temperature, supplementary radiation and plant density all affected the total soluble protein yield in the same plants. Transgenic plants expressing a second recombinant protein (cyanovirin-N) responded differently to IgG transgenic plants to elevated temperature, with an increase in cyanovirin-N concentration, although the effect of the environmental variables on total soluble protein yields was the same as the IgG plants. Planting density and radiation levels were important factors affecting variability of the two recombinant protein yields in transgenic plants. Phenotypic differences were observed between the two transgenic plant lines and non-transformed N. tabacum, but the effect of different growing conditions was consistent between the three lines. Temperature, day length, radiation intensity and planting density all had a significant impact on biomass production. Taken together, the data suggest that recombinant protein yield is not affected substantially by environmental factors other than growth temperature. Overall productivity is therefore correlated to biomass production, although other factors such as purification burden, extractability protein stability and quality also need to be considered in the optimal design of cultivation conditions.

Increasing student interest in family medicine and urban health care: the family care tract.

Throughout the last decade, general interest in primary care has drastically decreased. While medical students collectively show a high awareness for the significance of primary care during their first two years of medical school, this enthusiasm wanes for many as they complete their clinical years. As a result, fewer students enter into this concentration each year. In an attempt to mediate this changing interest, the University of Maryland School of Medicine Department of Family and Community Medicine has implemented the Family Care Track. This longitudinal experience spans the first two years of medical school and allows for mentorship by family medicine faculty, while also providing students with the opportunity to learn via the formation of long-term relationships with patients.