Clofarabine monotherapy in aggressive, relapsed and refractory Langerhans cell histiocytosis.

Over 50% of patients with systemic LCH are not cured with front-line therapies, and data to guide salvage options are limited. We describe 58 patients with LCH who were treated with clofarabine. Clofarabine monotherapy was active against LCH in this cohort, including heavily pretreated patients with a systemic objective response rate of 92.6%, higher in children (93.8%) than adults (83.3%). BRAFV600E+ variant allele frequency in peripheral blood is correlated with clinical responses. Prospective multicentre trials are warranted to determine optimal dosing, long-term efficacy, late toxicities, relative cost and patient-reported outcomes of clofarabine compared to alternative LCH salvage therapy strategies.

Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: a role for gut microbiota?

Many epidemiological studies have shown the beneficial effects of a largely plant-based diet, and the strong association between the consumption of a Mediterranean-type diet with healthy aging including a lower risk of cognitive decline. The Mediterranean diet is characterized by a high intake of olive oil, fruits and vegetables and is rich in dietary fiber and polyphenols - both of which have been postulated to act as important mediators of these benefits. Polyphenols are large molecules produced by plants to protect them from environmental threats and injury. When ingested by humans, as little as 5% of these molecules are absorbed in the small intestine with the majority metabolized by the gut microbiota into absorbable simple phenolic compounds. Flavan-3-ols, a type of flavonoid, contained in grapes, berries, pome fruits, tea, and cocoa have been associated with many beneficial effects on several risk factors for cardiovascular disease, cognitive function and brain regions involved in memory formation. Both preclinical and clinical studies suggest that these brain and heart benefits can be attributed to endothelial vascular effects and anti-inflammatory properties among others. More recently the gut microbiota has emerged as a potential modulator of the aging brain and intriguingly polyphenols have been shown to alter microbiota composition and be metabolized by different microbial species. However, there is a need for well controlled studies in large populations to identify predictors of response, particularly given the vast inter-individual variation of human gut microbiota.

Mixed Phenotype Acute Leukemia, B/Myeloid (Bilineal and Biphenotypic), With t(2;22)(q35;q12);EWSR1-FEV.

BACKGROUND: Ewing sarcoma breakpoint region 1 gene (EWSR1) rearrangements are largely associated with the Ewing sarcoma family of tumors. OBSERVATIONS: We report the first case of infantile, mixed phenotype acute leukemia, B/myeloid (bilineal and biphenotypic [B-lymphoid and B-lymphoid/myeloid]), with a t(2;22)(q35;q12). The EWSR1-fifth Ewing variant gene fusion and nonsense mutation in STAG2 were detected by next-generation sequencing and markedly high expression of fifth Ewing sarcoma variant mRNA detected by quantitative reverse transcription polymerase chain reaction. The patient was treated with a combined myeloid/lymphoid leukemia regimen followed by allogeneic stem cell transplant and was in complete remission at 3.8-year follow-up. CONCLUSIONS: Our case study underscores the importance of a comprehensive evaluation of acute leukemia and provides insights into the phenotype of EWSR1 rearranged neoplasms in the context of partner genes and cell type.

Histamine and cholesterol lowering abilities of lactic acid bacteria isolated from artisanal Pico cheese.

AIMS: This study was designed to select lactic acid bacteria with histamine- and cholesterol-reducing abilities to be used as potential probiotics. METHODS AND RESULTS: Thirty strains of lactic acid bacteria isolated from an artisanal raw milk cheese were screened for their abilities to degrade histamine, reduce cholesterol and hydrolyse bile salts. Strains were also screened for safety and probiotic traits, such as resistance to gastrointestinal conditions, adhesion to Caco-2 cells, resistance to antibiotics and presence of virulence genes. Two Lactobacillus paracasei strains presented high cholesterol- and histamine-lowering abilities, tested negative for the presence of virulence genes and showed susceptibility to most important antibiotics. These strains were also shown to possess desirable in vitro probiotic properties, revealed by tolerance to gastrointestinal conditions and high adhesion to intestinal cells. CONCLUSIONS: Among the screened strains, Lb. paracasei L3C21M6 revealed the best cholesterol and histamine reducing abilities together with desirable probiotic and safety features to be used in food applications. SIGNIFICANCE AND IMPACT OF THE STUDY: The strain L3C21M6 is a good candidate for use as a probiotic with histamine-degrading activity and cholesterol lowering effect. In addition, this strain could be use in dairy foods to prevent histamine food poisoning.

Multicenter Investigation of Fungal Infections of Inflatable Penile Prostheses.

BACKGROUND: Fungal infections of inflatable penile prostheses (IPPs) are inadequately understood in the literature. AIM: To review a multi-institution database of IPP infections to examine for common patient and surgical factors related to IPP fungal infections. METHODS: This is a retrospective Institutional Review Board-approved analysis of 217 patients at 26 institutions who underwent salvage or device explant between 2001 and 2018. Patient data were compiled after an extensive record review. OUTCOMES: 26 patients (12%) with fungal infections were identified. RESULTS: 23 of 26 patients (83%) with a fungal IPP infection were either diabetic or overweight. 15 patients had undergone primary IPP implantation, and the other 11 had previously undergone an average of 1.7 IPP-related surgeries (range 1-3; median 2). The average age at implantation was 63 years (range 31-92; median 63). 18 of the 26 patients with fungal infection had diabetes (69%), with a mean hemoglobin A1c (HbA1c) value of 8.4 (range 5.8-13.3; median 7.5). Twenty-two patients (85%) were overweight or obese. The mean body mass index for all patients was 30.1 kg/m2 (range 23.7-45 kg/m2; median 28.4 kg/m2), and that for diabetic patients was 30.8 kg/m2 (range 24.1-45 kg/m2, median 29.7 kg/m2). Ninety-one percent of implants were placed with intravenous antibiotics, consistent with current American Urological Association guidelines: an aminoglycoside plus first- or second-generation cephalosporin or vancomycin or ampicillin/sulbactam or piperacillin/tazobactam. 65% (17 of 26) of infected IPPs had only fungal growth in culture. No patient had concomitant immunosuppressive disease or recent antibiotic exposure before IPP implantation. CLINICAL IMPLICATIONS: More than two-thirds of the fungal infections occurred in diabetic patients and 85% occurred in overweight or obese patients, suggesting that antifungal prophylaxis may be appropriate in these patients. STRENGTHS & LIMITATIONS: This is the largest series of fungal infections reported to date in the penile prosthesis literature. The overall number of such cases, however, remains small. CONCLUSION: Fungal infections represent 12% of all penile prosthesis infections in our series and were seen mostly in diabetic or overweight patients, who may benefit from antifungal prophylaxis. Gross MS, Reinstatler L, Henry GD, et al. Multicenter Investigation of Fungal Infections of Inflatable Penile Prostheses. J Sex Med 2019;16:1100-1105.

Meta-analysis of suicide rates among people discharged from non-psychiatric settings after presentation with suicidal thoughts or behaviours.

OBJECTIVE: To quantify the suicide rate among people discharged from non-psychiatric settings after presentations with suicidal thoughts or behaviours. METHOD: Meta-analysis of studies reporting suicide deaths among people with suicidal thoughts or behaviours after discharge from emergency departments or the medical or surgical wards of general hospitals. RESULTS: A total of 115 studies reported 167 cohorts and 3747 suicide deaths among 248 005 patients during 1 263 727 person-years. The pooled suicide rate postdischarge was 483 suicide deaths per 100 000 person-years (95% confidence interval (CI) 445-520, prediction interval (PI) 200-770) with high between-sample heterogeneity (I2  = 92). The suicide rate was highest in the first year postdischarge (851 per 100 000 person-years) but remained elevated in the long term. Suicide rates were elevated among samples of men (716 per 100 000 person-years) and older people (799 per 100 000 person-years) but were lower in samples of younger people (107 per 100 000 person-years) and among studies published between 2010 and 2018 (329 per 100 000 person-years). CONCLUSIONS: People with suicidal thoughts or behaviours who are discharged from non-psychiatric settings have highly elevated rates of suicide despite a clinically meaningful decline in these suicide rates in recent decades.

Genitourinary Complications of Gender-Affirming Surgery.

PURPOSE OF REVIEW: Gender-affirming surgery has become a more common procedure in the last 5 years. Feminizing genitoplasty typically involves inversion of penile skin as a neovagina, urethral shortening, and glans reduction to create a neoclitoris. Masculinizing genitoplasty is more complex, typically is performed in multiple stages, and has more inherent urologic risks. RECENT FINDINGS: The most common urologic complications involve voiding dysfunction, specifically meatal stenosis or fistula to the urinary tract. Urethral stricture, fistula, urinary retention, and voiding dysfunction are very common and require early recognition and intervention. This includes placement of catheter drainage, if necessary with the appropriate urologic instrumentation. Genital risks relating to phallus health are rare, but risks associated with placement of penile prosthesis for sexual function are common and require immediate attention. Urological complications after gender-affirming surgery are common, and the general urologist and urogynecologist should be able to identify and treat problems in this population after review of this chapter.

Trend differences in men and women in rural and urban U.S. settings.

BACKGROUND: Smoking prevalence is declining at a slower rate in rural than urban settings in the United States (U.S.), and known predictors of smoking do not readily account for this trend difference. Given that socioeconomic and psychosocial determinants of health disparities accumulate in rural settings and that life-course disadvantages are often greater in women than men, we examined whether smoking trends are different for rural and urban men and women. METHOD: We used yearly cross-sectional data (n = 303,311) from the U.S. National Survey on Drug Use and Health (NSDUH) from 2007 through 2014 to compare cigarette smoking trends in men and women across rural and urban areas. Current smoking status was modelled using logistic regression controlling for confounding risk factors. RESULTS: Regression derived graphs predicting unadjusted prevalence estimates and 95% confidence bands revealed that whereas the smoking trends of rural men, urban men, and urban women significantly declined from 2007 to 2014, the trend for rural women was flat. Controlling for demographic, socioeconomic and psychosocial predictors of smoking did not explain rural women's significantly different trend from those of the other three groups. CONCLUSION: Rural women lag behind rural men, urban men and urban women in decreasing smoking, a health disparity finding that supports the need for tobacco control and regulatory policies and interventions that are more effective in reducing smoking among rural women.

The intestinal protist Blastocystis is not a common member of the healthy infant gut microbiota in a Westernized country (Ireland).

Research into the gut microbiota of human infants is necessary in order to better understand how inter-species interactions and ecological succession shape the diversity of the gut microbiota, and in turn, how the specific composition of the gut microbiota impacts on host health both during infancy and in later years. Blastocystis is a ubiquitous intestinal protist that has been linked to a number of intestinal and extra-intestinal diseases. However, emerging data show that asymptomatic carriage is common and that Blastocystis is prevalent in the healthy adult gut microbiota. Nonetheless, little is known about the prevalence and diversity of this microorganism in the healthy infant gut, including when and how individuals become colonized by Blastocystis. Here, we surveyed the prevalence and diversity of Blastocystis in an infant population (n = 59) from an industrialized country (Ireland) using Blastocystis-specific primers at three or more time-points up to 24 months old. Only three infants were positive for Blastocystis (prevalence = 5%) and this was only noted for samples collected at month 24. This rate is comparatively low relative to previously reported prevalence rates in the contemporaneous adult population. These data suggest that infants in Westernized countries that are successfully colonized by Blastocystis most likely acquire this microorganism via horizontal transfer.

Gender-Affirming Surgery: Current Concepts.

Gender-affirming surgeries (GASs), previously known as gender reassignment surgeries, are surgical procedures born from plastic and reconstructive surgery, colorectal surgery, urology, and gynecology. A multidisciplinary approach is essential for the care of transgender patients. The urologist plays a vital role, both in the perioperative period and as part of continued care. This publication will review the current concepts of genital GAS as it pertains to the practicing urologist. The most utilized surgical techniques will be described along with their notable complications and management options.

Isolation and characterization of an exopolysaccharide-producing Leuconostoc citreum strain from artisanal cheese.

High molar mass exopolysaccharides (EPS) produced from sucrose by lactic acid bacteria (LAB) are of great interest as natural additives to use in foods, medical and pharmaceutical industry. This study aimed to identify the EPS produced by Leuconostoc citreum L3C1E7 isolated from Pico cheese and characterize the strain for technological and probiotic potential. Purified EPS was isolated from the culture of L. citreum L3C1E7 by ethanol precipitation, with a yield of 520 mg ml-1 . The EPS-producing strain had a mucoid phenotype and average molecular weight of 5·88 × 106  Da. The structural characterization of the purified EPS was determined by 1 H, 13 C and two-dimensional NMR spectroscopy. EPS was composed of alternating α-(1→6)-linked and α-(1→3)-linked D-glucopyranyl units, suggesting the existence of an alternan. The strain was slow acidifying, produced diacetyl and displayed high esterase/lipase and aminopeptidase activities, which promote the desirable flavours in dairy products. Moreover, L. citreum showed moderate resistance to the adverse conditions of the gastrointestinal (GI) tract and high adhesion to GI cells. This work provides a better understanding of EPS produced by L. citreum and the potential application of EPS-producing strain in food and/or as a probiotic culture. SIGNIFICANCE AND IMPACT OF THE STUDY: Some LAB strains are known to use extracellular glycoside-hydrolase enzymes for synthesizing a diversity of exopolysaccharides (EPS) with potential application as natural additives to foods. Previous studies have identified an EPS-producing Leuconostoc citreum strain with immunomodulatory properties. This work provides a better understanding of EPS produced by this strain and the potential application of the strain in food fermentation and/or as a probiotic culture.

The influence of rosuvastatin on the gastrointestinal microbiota and host gene expression profiles.

Statins are the most widely prescribed medications worldwide for the treatment of hypercholesterolemia. They inhibit the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R), an enzyme involved in cholesterol synthesis in higher organisms and in isoprenoid biosynthesis in some bacteria. We hypothesized that statins may influence the microbial community in the gut through either direct inhibition or indirect mechanisms involving alterations to host responses. We therefore examined the impact of rosuvastatin (RSV) on the community structure of the murine gastrointestinal microbiota. RSV was orally administered to mice and the effects on the gut microbiota, host bile acid profiles, and markers of inflammation were analyzed. RSV significantly influenced the microbial community in both the cecum and feces, causing a significant decrease in α-diversity in the cecum and resulting in a reduction of several physiologically relevant bacterial groups. RSV treatment of mice significantly affected bile acid metabolism and impacted expression of inflammatory markers known to influence microbial community structure (including RegIIIγ and Camp) in the gut. This study suggests that a commonly used statin (RSV) leads to an altered gut microbial composition in normal mice with attendant impacts on local gene expression profiles, a finding that should prompt further studies to investigate the implications of statins for gut microbiota stability and health in humans.NEW & NOTEWORTHY This work demonstrates that rosuvastatin administration in mice affects the gastrointestinal microbiota, influences bile acid metabolism, and alters transcription of genes encoding factors involved in gut homeostasis and immunity in the gastrointestinal tract.

Trends in Testosterone Replacement Therapy Use from 2003 to 2013 among Reproductive-Age Men in the United States.

PURPOSE: Although testosterone replacement therapy use in the United States has increased dramatically in the last decade, to our knowledge trends in testosterone replacement therapy use among reproductive-age men have not been investigated. We assessed changes in testosterone replacement therapy use and practice patterns among 18 to 45-year-old American men from 2003 to 2013 and compared them to older men. MATERIALS AND METHODS: This is a retrospective, cross-sectional analysis of men 18 to 45 and 56 to 64 years old who were enrolled in the Truven Health MarketScan® Commercial Claims Databases throughout each given calendar year from 2003 to 2013, including 5,094,868 men in 2013. Trends in the yearly rates of testosterone replacement therapy use were calculated using Poisson regression. Among testosterone replacement therapy users, the Cochran-Armitage test was used to assess temporal trends in age, formulation type, semen analysis and serum testosterone level testing during the 12 months preceding the documented use of testosterone replacement therapy. RESULTS: Between 2003 and 2013, there was a fourfold increase in the rate of testosterone use among 18 to 45-year-old men from 29.2/10,000 person-years to 118.1/10,000 person-years (p <0.0001). Among testosterone replacement therapy users, topical gel formulations were initially most used. Injection use then doubled between 2009 and 2012 (23.5% and 46.2%, respectively) and surpassed topical gel use in 2013. In men 56 to 64 years old there was a statistically significant threefold increase in testosterone replacement therapy use (p <0.0001), which was significantly smaller than the fourfold increase in younger men (p <0.0001). CONCLUSIONS: In 2003 to 2013, testosterone replacement therapy use increased fourfold in men 18 to 45 years old compared to threefold in older men. This younger age group should be a focus for future studies due to effects on fertility and unknown long-term sequelae.

The altered gut microbiota in adults with cystic fibrosis.

BACKGROUND: Cystic Fibrosis (CF) is an autosomal recessive disease that affects the function of a number of organs, principally the lungs, but also the gastrointestinal tract. The manifestations of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in the gastrointestinal tract, as well as frequent antibiotic exposure, undoubtedly disrupts the gut microbiota. To analyse the effects of CF and its management on the microbiome, we compared the gut microbiota of 43 individuals with CF during a period of stability, to that of 69 non-CF controls using 454-pyrosequencing of the 16S rRNA gene. The impact of clinical parameters, including antibiotic therapy, on the results was also assessed. RESULTS: The CF-associated microbiome had reduced microbial diversity, an increase in Firmicutes and a reduction in Bacteroidetes compared to the non-CF controls. While the greatest number of differences in taxonomic abundances of the intestinal microbiota was observed between individuals with CF and the healthy controls, gut microbiota differences were also reported between people with CF when grouped by clinical parameters including % predicted FEV1 (measure of lung dysfunction) and the number of intravenous (IV) antibiotic courses in the previous 12 months. Notably, CF individuals presenting with severe lung dysfunction (% predicted FEV1 ≤ 40%) had significantly (p < 0.05) reduced gut microbiota diversity relative to those presenting with mild or moderate dysfunction. A significant negative correlation (-0.383, Simpson's Diversity Index) was also observed between the number of IV antibiotic courses and gut microbiota diversity. CONCLUSIONS: This is one of the largest single-centre studies on gut microbiota in stable adults with CF and demonstrates the significantly altered gut microbiota, including reduced microbial diversity seen in CF patients compared to healthy controls. The data show the impact that CF and it's management have on gut microbiota, presenting the opportunity to develop CF specific probiotics to minimise microbiota alterations.

Multicenter Investigation of the Micro-Organisms Involved in Penile Prosthesis Infection: An Analysis of the Efficacy of the AUA and EAU Guidelines for Penile Prosthesis Prophylaxis.

INTRODUCTION: Penile prosthesis infections remain challenging despite advancements in surgical technique, device improvements, and adoption of antibiotic prophylaxis guidelines. AIM: To investigate penile prosthesis infection microbiology to consider which changes in practice could decrease infection rates, to evaluate current antibiotic prophylaxis guidelines, and to develop a proposed algorithm for penile prosthesis infections. METHODS: This retrospective institutional review board-exempt multi-institutional study from 25 centers reviewed intraoperative cultures obtained at explantation or Mulcahy salvage of infected three-piece inflatable penile prostheses (IPPs). Antibiotic usage was recorded at implantation, admission for infection, and explantation or salvage surgery. Cultures were obtained from purulent material in the implant space and from the biofilm on the device. MAIN OUTCOME MEASURES: Intraoperative culture data from infected IPPs. RESULTS: Two hundred twenty-seven intraoperative cultures (2002-2016) were obtained at salvage or explantation. No culture growth occurred in 33% of cases and gram-positive and gram-negative organisms were found in 73% and 39% of positive cultures, respectively. Candida species (11.1%), anaerobes (10.5%) and methicillin-resistant Staphylococcus aureus (9.2%) constituted nearly one third of 153 positive cultures. Multi-organism infections occurred in 25% of positive cultures. Antibiotic regimens at initial implantation were generally consistent with American Urological Association (AUA) and European Association of Urology (EAU) guidelines. However, the micro-organisms identified in this study were covered by these guidelines in only 62% to 86% of cases. Antibiotic selection at admissions for infection and salvage or explantation varied widely compared with those at IPP implantation. CONCLUSION: This study documents a high incidence of anaerobic, Candida, and methicillin-resistant S aureus infections. In addition, approximately one third of infected penile prosthesis cases had negative cultures. Micro-organisms identified in this study were not covered by the AUA and EAU antibiotic guidelines in at least 14% to 38% of cases. These findings suggest broadening antibiotic prophylaxis guidelines and creating a management algorithm for IPP infections might lower infection rates and improve salvage success. Gross MS, Phillips EA, Carrasquillo RJ, et al. Multicenter Investigation of the Micro-Organisms Involved in Penile Prosthesis Infection: An Analysis of the Efficacy of the AUA and EAU Guidelines for Penile Prosthesis Prophylaxis. J Sex Med 2017;14:455-463.

A growing geographic disparity: Rural and urban cigarette smoking trends in the United States.

Rural areas of the United States have a higher smoking prevalence than urban areas. However, no recent studies have rigorously examined potential changes in this disparity over time or whether the disparity can be explained by demographic or psychosocial characteristics associated with smoking. The present study used yearly cross sectional data from the National Survey on Drug Use and Health from 2007 through 2014 to examine cigarette smoking trends in rural versus urban areas of the United States. The analytic sample included 303,311 respondents. Two regression models were built to examine (a) unadjusted rural and urban trends in prevalence of current smoking and (b) whether differences remained after adjusting for demographic and psychosocial characteristics. Results of the unadjusted model showed disparate and diverging cigarette use trends during the 8-year time period. The adjusted model also showed diverging trends, initially with no or small differences that became more pronounced across the 8-year period. We conclude that differences reported in earlier studies may be explained by differences in rural versus urban demographic and psychosocial risk factors, while more recent and growing disparities appear to be related to other factors. These emergent differences may be attributable to policy-level tobacco control and regulatory factors that disproportionately benefit urban areas such as enforcement of regulations around the sale and marketing of tobacco products and treatment availability. Strong federal policies and targeted or tailored interventions may be important to expanding tobacco control and regulatory benefits to vulnerable populations including rural Americans.

Genetic diversity, safety and technological characterization of lactic acid bacteria isolated from artisanal Pico cheese.

A total of 114 lactic acid bacteria were isolated at one and 21 days of ripening from a traditional raw cow's milk cheese without the addition of starter culture, produced by three artisanal cheese-makers in Azores Island (Pico, Portugal). Identification to species and strain level was accomplished by16S rRNA gene and PFGE analysis. Carbohydrate utilization profiles were obtained with the relevant API kits. Isolates were evaluated according to safety and technological criteria. The most frequently observed genus identified by 16S rRNA sequencing analysis was Enterococcus, whereas API system mostly identified Lactobacillus. The highest percentages of antibiotic resistance were to nalidixic acid (95%), and aminoglycosides (64-87%). All isolates were sensitive to several beta-lactam antibiotics and negative for histamine and DNase production. Gelatinase activity was detected in 49.1% of isolates, 43% were able to degrade casein and 93% were α-hemolytic. Most enterococci presented virulence genes, such as gelE, asaI, ace. Diacetyl production was found to be species dependent and one strain (Leu. citreum) produced exopolysaccharides. Selected strains were further studied for technological application and were found to be slow acid producers in milk and experimental cheeses, a desirable trait for adjunct cultures. Two strains were selected on the basis of technological and safety application as adjunct cultures in cheese production and presented the best cheese aroma and flavor in consumer preference tests. This is the first effort to characterize Pico cheese LAB isolates for potential application as adjunct cultures; the results suggest the potential of two strains to improve the quality of this traditional raw milk product.

Transformation of serum-susceptible Escherichia coli O111 with p16Slux plasmid to allow for real-time monitoring of complement-based inactivation of bacterial growth in bovine milk.

Complement activity has only recently been characterized in raw bovine milk. However, the activity of this component of the innate immune system was found to diminish as milk was subjected to heat or partitioning during cream separation. Detection of complement in milk relies on a bactericidal assay. This assay exploits the specific growth susceptibility of Escherichia coli O111 to the presence of complement. Practical application of the assay was demonstrated when a reduction in complement activity was recorded in the case of pasteurized and reduced-fat milks. This presented an opportunity to improve the functionality of the bactericidal assay by incorporating bioluminescence capability into the target organism. Following some adaptation, the strain was transformed by correctly integrating the p16Slux plasmid. Growth properties of the transformed strain of E. coli O111 were unaffected by the modification. The efficacy of the strain adaptation was correlated using the LINEST function analysis [r=0.966; standard error of prediction (SEy)=0.957] bioluminescence with that of bactericidal assay total plate counts within the range of 7.5 to 9.2 log cfu/mL using a combination of raw and processed milk samples. Importantly, the transformed E. coli O111 p16Slux strain could be identified in milk and broth samples using bioluminescence measurement, thus enabling the bactericidal assay-viability test to be monitored in real time throughout incubation.

Electrical manipulation of crystal symmetry for switching transverse acoustic phonons.

We experimentally explore the use of a novel device where lateral electric fields can be applied to break the translational symmetry within the isotropic plane and hence change the selection rules to allow normally forbidden transverse acoustic (TA) phonon generations. The ultrafast screening of the lateral electric field by the photocarriers relieves shear strain in the structure and switches on the propagating TA waves. The amplitude and on-state time of the TA mode can be modulated by the external field strength and size of the laterally biased region. The observed frequency shift with an external bias as well as the strong geometrical dependence confirm the role of the asymmetric potential distribution in electrically manipulating the crystal symmetry to control modal behavior of acoustic phonons.

Analysis of the clinical safety of intralesional injection of collagenase Clostridium histolyticum (CCH) for adults with Peyronie's disease (PD).

OBJECTIVE: To examine the safety of intralesional injection of collagenase Clostridium histolyticum (CCH) for the treatment of Peyronie's disease (PD), using a pooled safety analysis of patients who received at least one dose of CCH in any of six clinical studies. PATIENTS AND METHODS: Patients from six clinical studies, including three randomised, double-blind, placebo-controlled studies and three open-label safety and efficacy studies, were included if they had received at least one dose of 0.58 mg CCH. Adverse events (AEs), including treatment-emergent AEs, treatment-related AEs, and serious AEs (SAEs), were characterised. Potential immunogenicity-related AEs were evaluated through examination of increased anti-AUX-I and anti-AUX-II antibody levels, AEs, and reported terms possibly associated with immunological or hypersensitivity events. RESULTS: Overall, 85.8% of 1 044 pooled patients reported at least one treatment-related AE. The most frequently reported (≥25.0% of patients) treatment-related AEs included penile haematoma (82.7% had the verbatim 'penile bruising'), penile pain, and penile swelling. Most patients (75.2%) had mild- or moderate-severity treatment-related AEs, and 14.2% had no treatment-related AEs. Nine patients (0.9%) had treatment-related SAEs: five with penile haematoma and four with corporal rupture. There was no association between AEs and anti-AUX-I or anti-AUX-II antibody levels across treatment cycles, and no systemic hypersensitivity reactions occurred. CONCLUSIONS: This pooled safety analysis shows that although non-serious and serious treatment-related AEs can occur after CCH treatment for PD, most were non-serious and the SAEs were manageable. Providers should be prepared to manage possible SAEs.