[Opportunity to develop pharmaceutical care for female infertility in community pharmacy: Results from a survey on patients' perceptions and expectations]. / Développement des soins pharmaceutiques de l'infertilité féminine à l'officine : enquête sur la perception et les attentes des patientes.

Infertility is defined as not being able to get pregnant after one year or longer of unprotected sex. The infertility rate is increasing in France and pharmaceutical care should adapt to this issue. The objective of this study was to assess how women undergoing assisted reproductive technology (ART) perceived ART-related pharmaceutical care in community pharmacies and to suggest ways of improving the service. METHOD: We conducted a study with patients undergoing ART at the Institute of Reproductive Medicine in Marseille, using a questionnaire. The questions concerned the perception of care given at the community pharmacy on various aspects related to medication, on a scale of 1 (not at all satisfied) to 10 (very satisfied). The last question was an open-ended question about patient's expectations. RESULTS: In all, 105 patients answered the questionnaire. The average age of women was 34.5±4.8-years-old. The scores obtained concerning the perception of support on the themes explored varied between 2.8±2.8 for the lowest score and 4.2±3.4 out of 10 for the highest. In all, 79.6% of the respondents were in favor of the development of specific support in community pharmacies, especially about administration methods, management of adverse effects and management of waste linked to treatment. CONCLUSION: Women undergoing ART are willing to receive pharmaceutical care in community pharmacies. In order to meet their expectations, it is necessary to develop dedicated training programs.

Pleural and mediastinal effusions after the extracardiac total cavopulmonary connection: Risk factors and impact on outcome.

Background: This study investigated the volume and duration of pleural and mediastinal effusions following extracardiac total cavopulmonary connection, as well as preoperative risk factors and their impact on outcome. Materials and methods: A total of 210 patients who underwent extracardiac total cavopulmonary connection at our center between 2012 and 2020 were included in this study. Postoperative daily amount of pleural and mediastinal drainage were collected and factors influencing duration and amount of effusions were analyzed. The impact of effusions on adverse events was analyzed. Results: Median age at extracardiac total cavopulmonary connection was 2.2 (interquartile range, 1.8-2.7) years with median weight of 11.6 (10.7-13.0) kg. Overall duration of drainage after extracardiac total cavopulmonary connection was 9 (6-17) days. The total volume of mediastinal, right pleural, and left pleural drainage was 18.8 (11.9-36.7), 64.4 (27.4-125.9), and 13.6 (0.0-53.5) mL/kg, respectively. Hypoplastic left heart syndrome (p = 0.004) and end-diastolic pressure (p = 0.044) were associated with high volume of drainages, and hypoplastic left heart syndrome (p = 0.007), presence of aortopulmonary collaterals (p = 0.002), and high end-diastolic pressure (p = 0.023) were associated with long duration of drainages. Dextrocardia was associated with higher volume (p < 0.001) and longer duration (p = 0.006) of left pleural drainage. Duration of drainage was associated with adverse events following extracardiac total cavopulmonary connection (p = 0.015). Conclusion: Volume and duration of pleural and mediastinal effusions following extracardiac total cavopulmonary connection were related with hypoplastic left heart syndrome, aortopulmonary collaterals, and end-diastolic pressure. The duration of drainage for effusions was a risk factor for adverse events after total cavopulmonary connection.

Drug Discovery and Repurposing Inhibits a Major Gut Pathogen-Derived Oncogenic Toxin.

Objective: The human intestinal microbiome plays an important role in inflammatory bowel disease (IBD) and colorectal cancer (CRC) development. One of the first discovered bacterial mediators involves Bacteroides fragilis toxin (BFT, also named as fragilysin), a metalloprotease encoded by enterotoxigenic Bacteroides fragilis (ETBF) that causes barrier disruption and inflammation of the colon, leads to tumorigenesis in susceptible mice, and is enriched in the mucosa of IBD and CRC patients. Thus, targeted inhibition of BFT may benefit ETBF carrying patients. Design: By applying two complementary in silico drug design techniques, drug repositioning and molecular docking, we predicted potential BFT inhibitory compounds. Top candidates were tested in vitro on the CRC epithelial cell line HT29/c1 for their potential to inhibit key aspects of BFT activity, being epithelial morphology changes, E-cadherin cleavage (a marker for barrier function) and increased IL-8 secretion. Results: The primary bile acid and existing drug chenodeoxycholic acid (CDCA), currently used for treating gallstones, cerebrotendinous xanthomatosis, and constipation, was found to significantly inhibit all evaluated cell responses to BFT exposure. The inhibition of BFT resulted from a direct interaction between CDCA and BFT, as confirmed by an increase in the melting temperature of the BFT protein in the presence of CDCA. Conclusion: Together, our results show the potential of in silico drug discovery to combat harmful human and microbiome-derived proteins and more specifically suggests a potential for retargeting CDCA to inhibit the pro-oncogenic toxin BFT.

Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells.

Pro-carcinogenic bacteria have the potential to initiate and/or promote colon cancer, in part via immune mechanisms that are incompletely understood. Using ApcMin mice colonized with the human pathobiont enterotoxigenic Bacteroides fragilis (ETBF) as a model of microbe-induced colon tumorigenesis, we show that the Bacteroides fragilis toxin (BFT) triggers a pro-carcinogenic, multi-step inflammatory cascade requiring IL-17R, NF-κB, and Stat3 signaling in colonic epithelial cells (CECs). Although necessary, Stat3 activation in CECs is not sufficient to trigger ETBF colon tumorigenesis. Notably, IL-17-dependent NF-κB activation in CECs induces a proximal to distal mucosal gradient of C-X-C chemokines, including CXCL1, that mediates the recruitment of CXCR2-expressing polymorphonuclear immature myeloid cells with parallel onset of ETBF-mediated distal colon tumorigenesis. Thus, BFT induces a pro-carcinogenic signaling relay from the CEC to a mucosal Th17 response that results in selective NF-κB activation in distal colon CECs, which collectively triggers myeloid-cell-dependent distal colon tumorigenesis.

Three dimensional computed technology--a new standard of care.

I-Cat Scan Cone Beam CT (CBCT) technology is rapidly replacing two dimensional radiography in the medical world. Virtual patients may be viewed on a screen and multiple sectional views observed in order to obtain more definitive diagnostic and treatment options. The authors give a brief overview of some opportunities available using I-Cat technology as well as multiple actual cases where subjective diagnosis has been reduced substantially through CBCT technology.

Lyme disease in Oregon.

The incidence of Lyme disease in Oregon is calculated from cases reported to the Oregon State Health Division. We reviewed the exposure history of reported cases of Lyme disease and performed field surveys for infected Ixodes pacificus ticks. The incidence of Lyme disease correlated with the distribution of infected I. pacificus ticks.

Study of different off-line sample processing procedures and the measurement of antibiotic and antiviral levels in human serum by high-performance liquid chromatography.

We attempted to devise a preparation method for clinical samples that could be used for all antibiotics and antivirals. We studied thirteen antibiotics, including five penicillins, four cephalosporins, metronidazole, ofloxacin, and sulfamethoxazole and four protease inhibitors including indinavir, retonavir, nelfinavir, and sequinavir. We compared four sample preparation techniques including solvent precipitation, filtration and resin column. We employ HPLC methods based on a minimal number of columns and mobile phases. We were unable to find one sample preparation method that could be used for all antibiotics and antivirals. But, we did develop an algorithm for determining optimal processing procedures for all drugs.

Comparison of in-house polymerase chain reaction method with the Roche Amplicor technique for detection of Mycobacterium tuberculosis in cytological specimens.

Two techniques have been approved by the United States FDA for diagnosis of tuberculosis in smear positive sputa: LCX M. tuberculosis, a ligase chain reaction procedure manufactured by Abbott Laboratories, and Amplicor, a polymerase chain reaction (PCR) procedure manufactured by Roche. However, these commercial methods are expensive and beyond the reach of laboratories in most developing countries. We compared the Roche Amplicor kit with an in-house PCR using a primer set for Mycobacterium tuberculosis/bovis directed at MPB 64 protein gene. It was able to distinguish between M. tuberculosis, M. avium, M. gordonii, M. intracellularae, and M. kansasii. Fifty-seven cytological samples were submitted to the laboratory for molecular diagnosis of M. tuberculosis. Both procedures were run on every sample submitted and the two methods agreed completely. The custom-made method is less expensive than the commercial technique.