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.

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.

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.

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.

Beneath the surface: derm clues to underlying disorders.

When evaluating patients with suspected cutaneous lupus erythematosus, use multiple criteria--including histologic and immunofluorescent biopsy findings and American College of Rheumatology criteria--to rule out systemic disease.

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.

Risk factors for trimethoprim-sulfamethoxazole resistance in patients with acute uncomplicated cystitis.

Emerging antimicrobial resistance among uropathogens makes the management of acute uncomplicated cystitis increasingly challenging. Few prospective data are available on the risk factors for resistance to trimethoprim-sulfamethoxazole (TMP-SMX), the drug of choice in most settings. In order to evaluate this, we prospectively enrolled women 18 to 50 years of age presenting to an urban primary care practice with symptoms of cystitis. Potentially eligible women provided a urine sample for culture and completed a questionnaire regarding putative risk factors for TMP-SMX resistance. Escherichia coli isolates were tested for clonal group A (CGA) membership by a fumC-specific PCR. Of 165 women with cystitis symptoms, 103 had a positive urine culture and were eligible for participation. E. coli was the predominant uropathogen (86%). Fifteen (14.6%) women had a TMP-SMX-resistant (TMP-SMX r) organism (all of which were E. coli). Compared with the women who had a TMP-SMX-susceptible organism, women in the TMP-SMX r group were more likely to have traveled (odds ratio [OR], 15.4; 95% confidence interval [CI], 4.4 to 54.3; P < 0.001) and to be Asian (OR, 6.1; 95% CI, 1.0 to 36.4; P = 0.048). CGA was also independently associated with TMP-SMX resistance (OR, 105; 95% CI, 6.3 to 1,777.6; P = 0.001). No association with TMP-SMX resistance was demonstrated for the use of either TMP-SMX or another antibiotic in the past 3 months or with having a child in day care. Among these women with acute uncomplicated cystitis, Asian race and recent travel were independently associated with TMP-SMX resistance. TMP-SMX r isolates were more likely to belong to CGA. Knowledge of these risk factors for TMP-SMX resistance could facilitate the accurate selection of empirical therapy.

Effect of down-regulation of ethylene biosynthesis on fruit flavor complex in apple fruit.

The role of ethylene in regulating sugar, acid, texture and volatile components of fruit quality was investigated in transgenic apple fruit modified in their capacity to synthesize endogenous ethylene. Fruit obtained from plants silenced for either ACS (ACC synthase; ACC-1-aminocyclopropane-1-carboxylic acid) or ACO (ACC oxidase), key enzymes responsible for ethylene biosynthesis, expectedly showed reduced autocatalytic ethylene production. Ethylene suppressed fruits were significantly firmer than controls and displayed an increased shelf-life. No significant difference was observed in sugar or acid accumulation suggesting that sugar and acid composition and accumulation is not directly under ethylene control. Interestingly, a significant and dramatic suppression of the synthesis of volatile esters was observed in fruit silenced for ethylene. However, no significant suppression was observed for the aldehyde and alcohol precursors of these esters. Our results indicate that ethylene differentially regulates fruit quality components and the availability of these transgenic apple trees provides a unique resource to define the role of ethylene and other factors that regulate fruit development.

A 'gap' between physician and patient assessment of symptom severity in acute cystitis?: a multicenter trial of women treated with extended-release ciprofloxacin.

The current trial assessed differences in physician and patient symptom-severity perceptions in ambulatory outpatient females with uncomplicated urinary tract infections (uUTIs). We also investigated the efficacy and safety profile of once-daily ciprofloxacin in a 500-mg PO extended-release formulation for 3 days to treat acute cystitis. This prospective, open-label, multicenter (1,972 sites), phase 4 clinical trial enrolled 7,614 adult women with a clinical diagnosis of an acute uUTI. After assessing the patient's cystitis symptoms, physicians rated each cystitis-related symptom on a 4-point severity scale. Patients independently completed a pretreatment survey including a self-assessment of these same symptoms. Clinical outcomes were assessed at the end-of-study visit (2 to 7 days post-therapy). Exact agreement on symptom severity between physician and patient was between 54% and 57% for symptoms. The discrepancies between assessments were significant in the marginal homogeneity tests (P less than 0.00001). Clinical cure following this regimen was 91.3% of efficacy-valid women. Women who had 2 or more UTI episodes in the previous 12 months tended to have lower rates of clinical cure than those who had 1 or no episodes in that time.