G protein βγ subunits have potential as a target for therapeutic treatment of a number of diseases. We performed virtual docking of a small-molecule library to a site on Gβγ subunits that mediates protein interactions. We hypothesized that differential targeting of this surface could allow for selective modulation of Gβγ subunit functions. Several compounds bound to Gβγ subunits with affinities from 0.1 to 60 μM and selectively modulated functional Gβγ-protein-protein interactions in vitro, chemotactic peptide signaling pathways in HL-60 leukocytes, and opioid receptor–dependent analgesia in vivo. These data demonstrate an approach for modulation of G protein–coupled receptor signaling that may represent an important therapeutic strategy.
The main goal of this study was to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), particularly livestock-associated MRSA (LA-MRSA) in pigs and pork. The genotypic relatedness of isolates on the farm, at slaughter, and at the retail level was assessed. Paired nasal and perianal swab samples were collected from 10 cohorts of market-age pigs (24 pigs per cohort) and carcasses at slaughterhouse, and pork samples were collected at retail. Staphylococci were isolated using selective enrichment method. Isolates were tested for antimicrobial resistance by broth microdilution. Duplex PCR was used to confirm MRSA using species-specific (nuc) and methicillin resistance (mecA) genes. The clonal relatedness of isolates was determined using pulsed-field gel electrophoresis (PFGE), Staphylococcus protein A (spa) typing, multilocus sequence typing (MLST), and staphylococcal cassette chromosome mec element (SCCmec) typing. MRSA was detected in 5 of the 10 cohorts (50%), with the prevalence ranging from 0% to 12.5% per cohort. Of all the pigs sampled on the farm before they went to market, 3% (7/240) were MRSA positive. A higher prevalence of MRSA was detected at holding pens at the slaughterhouse (11% [27/240]). MRSA was also detected in 2% (4/235) of the carcasses and 4% (5/135) of the retail pork. While the isolates appear predominantly to be highly clonal, PFGE had a relatively higher discriminatory power (discriminatory index [DI] ؍ 0.624). Four genotypic clusters were identified by PFGE; of the four clusters, clonal type B was predominant across the farm-to-retail continuum. MLST findings revealed that sequence type 5 (ST5) was the most predominant subtype (32/50). The livestock-associated MRSA (clonal complex 398 [CC398] or sequence type 398 [ST398]) was the second common type (12/50) and was detected at all stages from farm to retail. Nine of the 50 (18%) MRSA isolates belonged to spa type 539/t034 that were of ST398 based on MLST. The results of this study confirm that MRSA, including LA-MRSA, is common in herds of swine in Ohio and hereby shown to persist in the farm to processing and retail continuum.
CTX-M extended-spectrum β-lactamases are enzymes produced by bacteria that are capable of inhibiting the antimicrobial effects of cephalosporin drugs. Recently, the first domestically acquired Salmonella in the United States expressing bla(CTX-M) was reported. This is a concern because expanded-spectrum cephalosporins are the treatment of choice for invasive Gram-negative infections, including salmonellosis in children. Because Salmonella transmission is primarily foodborne, there is also concern that resistant enteric bacteria from livestock can be transferred through the food supply chain to consumers. bla(CTX-M) has not been previously identified in bacterial isolates from food animal populations in the United States. We report the recovery of CTX-M-type extended-spectrum β-lactamases from fecal Escherichia coli of sick and healthy dairy cattle in Ohio. Four individual fecal samples yielded E. coli isolates representing three clonal strains that carried bla(CTX-M) on transferable plasmids. Two distinguishable plasmids were identified, each encoding bla(CTX-M-1) or bla(CTX-M-79). Transferrable bla(CTX-M) genes in bovine E. coli have the potential to serve as a reservoir of resistance for pathogens and may represent a public health concern.
Objective. To implement a role-reversal exercise to increase first-year pharmacy students' awareness of communication barriers in the health care setting, especially for deaf and hard-of-hearing patients. Design. Volunteers from the local deaf community conducted Deaf Strong Hospital, a role-reversal exercise in which students were the ''patients.'' Students navigated through a reception area, encounter with a physician, and having a prescription filled at a pharmacy without receiving or using any spoken language. Assessment. A debriefing session was held in which small groups of students had the opportunity to ask questions of a panel of deaf and hard-of-hearing volunteers. On a survey administered to assess students' learning, 97% agreed or strongly agreed that the experience would likely impact their attitudes and behavior in future interactions with patients who did not speak English. Conclusions. The role-reversal exercise was an effective method of teaching students that the delivery of health care is dependent on adequate communication between health care providers and the patient.
Objectives. To examine the impact of a panel discussion on transgender health care on first-year (P1) pharmacy students' knowledge and understanding of transgender experiences in an Introduction to Diversity course. Design. The panel consisted of both transgender males and females. After panelists shared their healthcare experiences, students asked them questions in a moderated setting. Students completed evaluations on the presentation and learning outcomes. They also wrote a self-reflection paper on the experience. Assessment. Ninety-one percent of students agreed that they could describe methods for showing respect to a transgender patient and 91.0% evaluated the usefulness of the presentation to be very good or excellent. Qualitative analysis (phenomenological study) was conducted on the self-reflection papers and revealed 7 major themes. Conclusion. First-year students reported that they found the panel discussion to be eye opening and relevant to their pharmacy career. Our panel may serve as model for other pharmacy schools to implement.Keywords: health disparities, transgender, pharmacy education, panel discussion, reflection, qualitative analysis INTRODUCTIONThe topic of lesbian, gay, bisexual, and transgender (LGBT) health was added to the Healthy People 2020 initiative, indicating that the US Department of Health and Human Services considered it to be an emerging issue. 1 The document states that LGBT individuals encounter several health disparities linked to societal stigma, discrimination, and denial of human and civil rights. It also specifically mentions the need to provide medical students access to and training about LGBT patients to increase culturally competent care. As pharmacists are also an integral part of the healthcare system, this statement can be extrapolated to pharmacy students as well.Although it is undeniable that the lesbian, gay, and bisexual (LGB) populations have significant challenges within the healthcare system, the struggles that transgender individuals face are even more pronounced. A transgender individual can include anyone whose self-identity, behavior, or anatomy falls outside of societal gender norms and expectations (Appendix 1). Transgender individuals have a high prevalence of human immunodeficiency virus/sexually transmitted diseases, mental health issues, and suicide.1 A significant number (28%) of transgender patients have experienced verbal harassment in a medical setting.2 Additionally, transgender individuals are less likely to have health insurance than heterosexual or LGB individuals. Lesbian, gay, and bisexual individuals, if necessary, can choose not to disclose their sexual orientation to their healthcare providers and still receive adequate primary health care. However, transgender patients must disclose their transgender status to receive thorough and appropriate health care. Yet, fear of discrimination by healthcare providers once they do disclose their status may prevent individuals from seeking both urgent and preventative medical treatment.2, 3 Know...
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