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A sample of 700 undergraduate university students throughout the US completed an online survey about their attitudes answering questions about their sex, sexual orientation, and gender identity (SSOGI) on their university admission form. This study examined differences between cisgender and transgender and gender diverse students in attitudes related to answering sex assigned at birth and gender identity questions, and between heterosexual students and students of diverse sexual orientations in attitudes related to answering sexual orientation questions. Overall, students indicated positive attitudes about answering SSOGI questions on their university application form, but attitudes toward sexual orientation questions were less positive. Differences were found in question/answer choice understanding (gender identity and sexual orientation), ease of answering (sex assigned at birth), offensiveness in asking (sex assigned at birth), privacy concerns (sex assigned at birth), comfort in answering (sex assigned at birth and sexual orientation), confidentiality concerns (gender identity), and importance of asking (sex assigned at birth and sexual orientation). Findings demonstrate that most respondents held positive attitudes about answering SSOGI questions and that communicating to LGBTQ+ applicants the importance of and privacy protections associated with answering SSOGI questions on university application forms might be important. [ABSTRACT FROM AUTHOR]

Although parents of sexual and gender minority (SGM) adolescents play a critical role in communicating about sexual health to their children, most parents have reported that they are unknowledgeable and uncomfortable talking about sexual health to their SGM adolescent. Because of the limited availability of sex education programs for parents of SGM adolescents, the study aimed to (1) describe the attitudes toward using and willingness to use a hypothetical online sex communication intervention for parents of SGM adolescents and (2) examine factors associated with willingness to use such an intervention. Parents of SGM adolescents from across the United States (N = 385) completed an online survey from March 10–16, 2023. Most participants were open to participating in a hypothetical online sex communication program and had positive attitudes toward it. Logistic regression results showed that participants who overall agreed a hypothetical online parent-based sex education intervention would be helpful and of interest had higher odds of being overall willing to participate in such a hypothetical intervention. Additionally, participants with higher income levels were also more likely to be willing to participate in a hypothetical program. Results from this exploratory study suggest that most parents of SGM adolescents have positive attitudes toward a hypothetical online parent-based sex education program and are willing to participate in it, highlighting a need to develop sex education programs tailored to the needs and preferences of parents of SGM adolescents. Additionally, equitable access to such programs is necessary especially regarding income level. [ABSTRACT FROM AUTHOR]

In the United States, HIV prevalence is increasing in rural areas, specifically among rural adolescent sexual minority males (ASMM). However, it is unclear what HIV sexual risk behaviors rural ASMM engage in and what HIV preventative services they utilize. This study aimed to (1) document the lifetime HIV sexual risk behaviors and service utilization of rural ASMM and (2) compare rural–urban differences in the prevalence of HIV sexual risk behaviors and service utilization. We analyzed data collected from 1615 ASMM who participated in a baseline survey for an online HIV prevention program from April 2018 to June 2020. We compared the prevalence of lifetime HIV sexual risk behaviors and HIV healthcare utilization among rural and urban participants via descriptive statistics, chi-square tests, linear and logistic regressions, and zero-inflated Poisson regressions. These analyses indicated that rural ASMM were more likely than urban ASMM to engage in condomless sex when they had anal sex. Rural ASMM could benefit from offline and online evidence-based HIV prevention interventions, especially interventions that increase condom use. [ABSTRACT FROM AUTHOR]

Although knowledge is a salient determinant in primary care providers (PCPs) prescribing HIV pre-exposure prophylaxis (PrEP) to adolescents, we know little about what information PCPs want about PrEP. We conducted an online mixed-method study to explore the PrEP information needs of a national sample of 351 PCPs. We analyzed data with deductive content analysis and compared themes between respondents who were aware and not aware of PrEP, knowledgeable and not knowledgeable of the prescribing guidelines, and prescribed and never prescribed PrEP to an adolescent. PCPs who were unknowledgeable about PrEP and never prescribed PrEP to an adolescent mentioned manufacturing information, indications and dosing, and contraindications and adverse reactions more so than PCPs who were aware of and prescribed PrEP. A better understanding of the information needs of PCPs could inform provider education interventions. Future research must examine the facilitators and barriers to integrating PrEP information into medical education and clinical settings. [ABSTRACT FROM AUTHOR]

Primary care providers (PCPs) are critical in prescribing human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) to adolescents at risk of HIV. More research is needed to identify facilitators and barriers PCPs encounter in prescribing PrEP to eligible adolescents post-Food and Drug Administration (FDA) approval. This online cross-sectional survey examined the PrEP implementation facilitators and barriers among a national sample of PCPs in the United States. PCPs (n = 502) specializing in family medicine or pediatrics were recruited from a Qualtrics panel from July 15 to August 9, 2022. We analyzed the collected data using content analysis and applied the Expert Recommendations for Implementing Change (ERIC) to codebook creation and data analysis. We conducted a Fisher's exact chi-square test of independence to compare facilitator and barrier prevalence differences between participants who had and had not prescribed PrEP to an adolescent patient. Results demonstrate that (1) distributing prescriber-focused educational materials, (2) involving parents, (3) changing liability laws, (4) enhancing adolescent PrEP uptake and adherence, (5) changing clinical resources, and (6) using mass/social media to change community norms might be strategies that influence PCPs prescribing PrEP to eligible adolescent patients. Results from this study could facilitate the planning of hybrid implementation-effectiveness trials designed to determine the acceptability, feasibility, and effectiveness of implementation strategies in improving the practices of PCPs prescribing PrEP to at-risk adolescents. [ABSTRACT FROM AUTHOR]

Although parents of sexual and gender minority (SGM) adolescents are key stakeholders in SGM adolescents using HIV pre-exposure prophylaxis (PrEP), there is limited understanding of parental concerns and attitudes about their SGM adolescents taking PrEP. Fifty-four parents in the West South Central region of the U.S. completed an online, mixed-method, cross-sectional questionnaire to explore their concerns and questions about PrEP. Quantitative and qualitative results show that participants were more concerned about side effects, drug interactions, (non)adherence, and eligibility and duration of PrEP. Parents are less worried about picking PrEP from a pharmacy or returning to follow-up lab testing every three months. Most parents reported receiving medication information their adolescent takes from a medical provider and the media. Findings from this study can inform the development of parent-based PrEP interventions. Without further parent-based research and programming, SGM adolescents may continue to be disproportionately affected by HIV. [ABSTRACT FROM AUTHOR]

HIV service providers are the primary implementers of HIV care services, but rural HIV service providers are under researched. We used an interpretative phenomenological analysis to explore rural HIV service providers' lived experiences of working in HIV care, who work in a rural region of a Midwestern state in the United States. From July to August 2019, 15 HIV service providers participated in a one-hour semi-structured telephone interview that elicited their experiences working in the rural HIV care continuum. Participants were tired of constantly educating and working to reduce HIV stigma; however, they received support from family and friends once they educated them about HIV. Participants felt they lacked control over systems and they developed emotional-based coping to address constant occupational stressors. Findings highlight the importance of resiliency and advocacy research and practice across ecological levels. [ABSTRACT FROM AUTHOR]

The article presents a study which examined U.S. men who have sex with men (MSM) and transgender women's behavioral changes and employed exposure mitigation strategies due to the monkeypox outbreak, as of August 26, 2022. Topics discussed include how monkeypox is transmitted, sociodemographic characteristics of the sample, and change in the sexual behaviors of the participants due to the monkeypox outbreak.

Objective: In this study, we estimated the relative contribution of 4 Reasoned Action Approach (RAA) belief determinants in explaining intention to stay home during the COVID-19 pandemic. Methods: Data were obtained from a survey of a nationally representative sample of US adults (N = 942) conducted April 10-20, 2020 (about one-month after initial stay-at-home orders were implemented) using a probability-based Internet household panel (Ipsos KnowledgePanel). Multiple regression analysis tested the association between attitude, injunctive norm, descriptive norm, and self-efficacy and intention to stay home for the next month while controlling for demographic factors. We tested for a moderating effect of worker status on the relationships between the 4 RAA beliefs and intention. Results: Instrumental attitude, injunctive norm, descriptive norm, and self-efficacy demonstrated statistically significant independent associations with intention to stay home. Self-efficacy showed the highest independent association. However, this relation was modified by an interaction between self-efficacy and worker status, revealing that self-efficacy is particularly important for essential workers. Conclusions: These findings suggest that public health strategies to increase individuals' intention to stay home and encourage adherence to stay-at-home policies should focus on enhancing self-efficacy with communication and policy supports. To be most effective, interventions should be targeted based on worker status. [ABSTRACT FROM AUTHOR]

The need for increased testing is pivotal in the response to the coronavirus disease (COVID-19) pandemic. Recently, through the Public Readiness and Emergency Preparedness (PREP) Act, pharmacists were given the ability to order and administer COVID-19 tests, giving them a better opportunity to engage in the pandemic response across the nation as well as in Idaho. This survey sought to determine Idaho pharmacists' willingness to provide different COVID-19 related services, assess needed resources to provide such services, and identify and prioritize other unmet community needs. We conducted a nine-question, cross-sectional survey distributed to pharmacists with addresses located in Idaho. All questions in the survey were optional and focused on pharmacist's willingness to provide services, what resources and additional training they would need, difficulty with 90-day prescriptions, and solicited additional feedback using an open-ended question. A total of 229 responses were received, representing all areas of pharmacy practice, with approximately half from community settings. The majority of respondents (70%) were willing to provide COVID-19 testing. Adequate staffing, changes to workflow, and the need for billing and clear reimbursement mechanisms were most frequently cited as barriers to contributing to the COVID-19 response. In summary, we found that pharmacists are very willing to help during this crisis, but their involvement may be better facilitated with the removal of barriers. [ABSTRACT FROM AUTHOR]

This community-based study explored the lived experiences of being in and going through the rural HIV care continuum among 15 gay and bisexual men (GBM) with HIV who live in a rural area of a Midwestern state. Our analysis adapted a six-step interpretative phenomenological analysis. Five themes emerged that reflected the five continuum stages: 1) Diagnosis means death, 2) Linkage to care means uncertainty, 3) HIV care improves the quality of life lost pre- or peri-diagnosis, 4) ART implies life, and 5) Undetectable addresses the medical but not social aspects of HIV. Participants recalled they faced and continue to face social determinants, stigma, and chronic and mental health conditions. Findings provide future research directions and practical implications to address social determinants of health, promote chronic and mental health, and reduce interpersonal stigma throughout all HIV care continuum stages. [ABSTRACT FROM AUTHOR]

Pre-exposure prophylaxis (PrEP) efficacy in preventing HIV among gay, bisexual, and other men who have sex with men (MSM) is dependent upon adherence. Little is known about the PrEP adherence experiences among MSM who live in rural areas of the US. This qualitative study was informed by a modified version of Straussian Grounded Theory. Thirty-four 34 rural Midwestern MSM participated in telephone interviews that assessed their PrEP adherence factors. Overall, participants adhered to the PrEP regimen, ranging from missing none to a couple of doses per month. Participants had high self-efficacy (competence) and self-reliance (autonomy) in taking PrEP daily. Participants incorporated PrEP into their already existing routines. Participants were motivated to adhere to prevent HIV acquisition and be financially responsible. All participants mentioned their PrEP provider discussed the importance of adherence with PrEP's effectiveness, but future patient-provider PrEP adherence communication varied among participants. Future PrEP adherence interventions should address counseling strategies that leverage these constructs to support pill taking. Future research should explore patient-provider conversations surrounding PrEP adherence to inform provider- and patient-level interventions. [ABSTRACT FROM AUTHOR]

Facilitators and barriers of Pre-exposure Prophylaxis (PrEP) uptake have been established in prior studies; however, most of these studies comprise samples of MSM from metropolitan cities and hypothetical PrEP use. There is a dearth of literature on the uptake factors among rural U.S. MSM who are prescribed PrEP. Thirty-four rural Midwestern MSM who currently take PrEP participated in semi-structured telephone interviews about their barriers and facilitators to their PrEP use. Interviews were analyzed using an inductive thematic analysis approach. There were four barriers: (1) lack of rural dissemination of PrEP information, (2) concern about side and adverse effects of using PrEP, (3) cost of PrEP uptake and engagement, and (4) lack of access to PrEP care and PrEP care quality. Individual and social facilitators that participants utilized to overcome these barriers are discussed. Findings elevate the importance of multilevel interventions that address PrEP adoption from a patient, provider, and healthcare system perspective. [ABSTRACT FROM AUTHOR]

Most pre-exposure prophylaxis (PrEP) research samples men who have sex with men (MSM) who live in metropolitan cities. There is a limited understanding of the PrEP experiences among rural MSM. Thirty-four semi-structured interviews were conducted to explore the PrEP health care experiences among 34 rural Midwestern MSM. Of the 34 participants, 23 obtained PrEP from their non–primary care provider (PCP). Three themes were present: (1) PrEP is unavailable in rural areas, (2) PrEP is inaccessible in rural areas due to PCPs being unwilling to prescribe PrEP, and (3) PrEP services are unamicable in rural areas due to stigmatizing attitudes and behaviors of PCPs. It is important to address PrEP care continuum factors in all settings; however, these factors are often exacerbated in rural areas due to social determinants. Without further research and programming, organizational and social determinants may contribute to lower rates of PrEP outcomes in rural areas. [ABSTRACT FROM AUTHOR]

Abstract: Herbal products are commonly used to treat clinical conditions and are often purchased online without the supervision of a healthcare provider. The use of herbals remains controversial because of widespread exaggerated claims of clinical efficacy and safety. We conducted an online search of 13 common herbals (including black cohosh, echinacea, garlic, ginkgo, ginseng, green tea, kava, saw palmetto, and St John's wort) and reviewed the top 50 Web sites for each using a Google search. We analyzed clinical claims, warnings, and other safety information. A total of 1179 Web sites were examined. Less than 8% of retail sites provided information regarding potential adverse effects, drug interactions, and other safety information; only 10.5% recommended consultation with a healthcare professional. Less than 3% cited scientific literature to accompany their claims. Key safety information is still lacking from many online sources of herbal information. Certain nonretail site types may be more reliable, but physicians and other healthcare professionals should be aware of the variable quality of these sites to help patients make more informed decisions. [Copyright &y& Elsevier]

Despite current consensus guidelines recommending intensive cardiovascular risk factor management for peripheral artery disease (PAD), patients suffering from PAD continue to experience significant morbidity and mortality. This excess morbid burden is at least partially related to impaired vascular function and systemic inflammation. Interventions bridging this gap are critical. Dietary supplementation of n-3 polyunsaturated fatty acids (n-3 PUFA) has been shown to improve endothelial function and reduce inflammation in different cohorts, as well as to decrease cardiovascular events in secondary prevention trials in patients with coronary artery disease. Their effects in the PAD population are, however, less well understood. The OMEGA-PAD trial is a double-blinded, randomized, placebo-controlled trial that examines the impact of a high-dose, short-duration dietary oral supplementation of n-3 PUFA on vascular function and inflammation in patients with established PAD. The purpose of this article is to provide a detailed description of the design and methods of the OMEGA-PAD trial, and a summary of baseline characteristics of the cohort. ClinicalTrials.gov Identifier: NCT01310270 [ABSTRACT FROM AUTHOR]

Context.-Several developments in genitourinary pathology are likely to change our understanding and management of some genitourinary cancers considerably. Objective.-To review 5 stories in genitourinary pathology: (1) fusion in the ETS (E26) gene family in prostatic adenocarcinoma; (2) insulin-like growth factor II messenger RNA-binding protein 3 (IMP3), an important prognostic biomarker for kidney and bladder cancers; (3) translocation renal cell carcinoma; (4) UroVysion fluorescence in situ hybridization test in urine cytology for detection of bladder cancer; and (5) the use of triple immunostaining for diagnosis of prostate cancer. Data Sources.-Literature review and authors' personal experiences. Conclusions.-Many scientific findings have contributed recently to the understanding of the natural pathogenesis and progression of genitourinary cancers. This translational research helps in diagnosing, predicting, and potentially, treating genitourinary cancers. [ABSTRACT FROM AUTHOR]

Abstract: Polyphenolic profiles in the berry samples of 344 European grape (Vitis vinifera) cultivars were evaluated for two consecutive years. These cultivars represent a diverse collection of V. vinifera germplasm maintained at the USDA-Agricultural Research Service Vitis Clonal Repository in Davis of California, USA. A total of 36 polyphenolic compounds, including 16 anthocyanins, 6 flavonols, 6 flavanols, 6 hydroxycinnamic acids and 2 hydroxybenzoic acids, were identified via HPLC–MS and quantified by HPLC–DAD. The mean contents for anthocyanins, flavanols, flavonols, hydroxycinnamic acids and hydroxybenzoic acids were 0.946 (coloured cultivars), 0.147, 0.043, 0.195 and 0.016mgg−1 FW, respectively. On average, wine grapes had higher concentrations than had table grapes for all of these compounds except hydroxycinnamic acids. Berry colours affected the total contents of anthocyanins, but not others. Positive correlations (0.151–0.535) were found among these groups of compounds. As expected, these groups of compounds were all negatively correlated with berry weight. [Copyright &y& Elsevier]

The article presents a study on endothelial dysfunction and arterial stiffness and their possible link to hemodynamic instability during dialysis. Findings showed that every 5% decline in flow-mediated dilation was linked to a 7.5 millimeter of mercury (mmHg) reduction in systolic blood pressure (SBP) after adjusting for phosphorus, body mass index, atherosclerosis, and ultrafiltration. Every 5 meters per second (m/s) increase in pulse wave velocity was linked to an 8 mmHg increase in SBP after adjusting for predialysis SBP and ultrafiltration.

Fine-needle aspiration (FNA) of thyroid bed (TB) lesions is a common diagnostic modality in monitoring patients for recurrent cancer after a thyroidectomy. To elucidate the value of TB FNA, we reviewed our experience at The Johns Hopkins Hospital, Baltimore, MD. We identified 57 TB FNA specimens from 50 patients. Of the patients, 36 were being followed up for papillary carcinoma, 7 for medullary carcinoma, 4 for follicular carcinoma (1 also had papillary carcinoma), and 1 for poorly differentiated neuroendocrine carcinoma; 3 had previous benign diagnoses. TB FNA yielded diagnostic material in 49 of 57 cases. Of 37 malignant or atypical FNA samples, 32 had surgical follow-up; 30 of 32 were confirmed malignant. The FNA result was benign in 12 of 57, including 6 cases of benign thyroid and 1 case of parathyroid tissue. Immunohistochemical staining was contributory in 5 of 57 cases. TB FNA is a highly reliable tool for diagnosing recurrent thyroid carcinoma. Residual benign thyroid and parathyroid tissue are potential pitfalls; awareness of these and judicious use of immunohistochemical staining can prevent misdiagnoses. [ABSTRACT FROM AUTHOR]

The search for effective Hepatitis C antiviral therapies has recently focused on host sterol metabolism and protein prenylation pathways that indirectly affect viral replication. However, inhibition of the sterol pathway with statin drugs has not yielded consistent results in patients. Here, we present a combination chemical genetic study to explore how the sterol and protein prenylation pathways work together to affect hepatitis C viral replication in a replicon assay. In addition to finding novel targets affecting viral replication, our data suggest that the viral replication is strongly affected by sterol pathway regulation. There is a marked transition from antagonistic to synergistic antiviral effects as the combination targets shift downstream along the sterol pathway. We also show how pathway regulation frustrates potential hepatitis C therapies based on the sterol pathway, and reveal novel synergies that selectively inhibit hepatitis C replication over host toxicity. In particular, combinations targeting the downstream sterol pathway enzymes produced robust and selective synergistic inhibition of hepatitis C replication. Our findings show how combination chemical genetics can reveal critical pathway connections relevant to viral replication, and can identify potential treatments with an increased therapeutic window. [ABSTRACT FROM AUTHOR]

Plasma C-reactive protein (CRP) concentration is a biomarker of systemic atherosclerosis and may also be associated with vein graft disease. It remains unclear whether CRP is also an important modulator of biological events in the vessel wall. We hypothesized that CRP influences vein graft healing by stimulating smooth muscle cells (SMCs) to undergo a phenotypic switch. Distribution of CRP was examined by immunohistochemistry in prebypass human saphenous veins (HSVs, n = 21) and failing vein grafts (n = 18, 25-4,400 days postoperatively). Quiescent HSV SMCs were stimulated with human CRP (5-50 µg/ml). SMC migration was assessed in modified Boyden chambers with platelet-derived growth factor (PDGF)-BB (5-10 ng/ml) as the chemoattractant. SMC viability and proliferation were assessed by trypan blue exclusion and reduction of Alamar Blue substrate, respectively. Expression of PDGF ligand and receptor (PDGFR) genes was examined at RNA and protein levels after 24-72 h of CRP exposure. CRP staining was present in 13 of 18 diseased vein grafts, where it localized to the deep media and adventitia, but it was minimally detectable in most prebypass veins. SMCs pretreated with CRP demonstrated a dose-dependent increase in migration to PDGF-BB (P = 0.02), which was inhibited by a PDGF-neutralizing antibody. SMCs treated with CRP showed a dose-dependent increase in PDGFR~3 expression and phosphorylation after 24-48 h. Exogenous CRP had no effect on SMC viability or proliferation. These data suggest that CRP is detectable within the wall of most diseased vein grafts, where it may exert local effects. Clinically relevant levels of CRP can stimulate SMC migration by a mechanism that may involve upregulation and activation of PDGFRβ. [ABSTRACT FROM AUTHOR]

Retrotransposons are retrovirus-related mobile sequences that have the potential to replicate via RNA intermediates and increase the genome size by insertion into new sites. The retroelement, Gret1, has been identified as playing a key role in generating fruit color variation in cultivated grape ( Vitis vinifera L.) due to its insertion into the promoter of VvMybA1. Fruit color variation is an important distinguishing feature of cultivated grapes and virtually no fruit color variation is observed in wild grape species. The presence and relative copy number of Gret1 was assessed using quantitative PCR on 22 different Vitis species, only four of which (plus interspecific hybrids) are known to contain white accessions. Gret1 copy number was observed to vary by species as well as by color within species and was significantly higher in white-fruited accessions across all taxa tested. Additionally, genomic regions surrounding Gret1 insertion were sequenced in white V. vinifera, hybrid, V. labrusca, V. aestivalis, and V. riparia accessions. [ABSTRACT FROM AUTHOR]

Objectives.— To assess migraine prophylactic drug utilization in the Idaho Medicaid population and to evaluate responsiveness of practitioners to an educational intervention from the Idaho Medicaid Drug Utilization Review (DUR) Program. Background.— While established guidelines recommend migraine prophylactic therapies for defined patient populations and several drugs have demonstrated efficacy, their actual utilization is reportedly low. Methods.— Profiles for Idaho Medicaid patients were reviewed retrospectively to identify candidates for migraine prophylactic therapy based on excessive triptan utilization. Use of a prophylactic agent was then characterized for these patients, and an educational mailing was sent to practitioners directly involved in the care of patients who did not appear to be using prophylaxis. Patient profiles were again assessed 6 months following the mailing to determine if a trial of a prophylactic drug had been attempted. Results.— A total of 1909 patients were identified as having at least one claim for a triptan drug in the year studied. Of these patients, 360 appeared to be candidates for prophylaxis, but 154 had no record of prophylactic drug use. In the 6 months following the intervention mailing, 27 of the 91 non-prophylaxis patients (30%) who were still active clients of Idaho Medicaid and who had seen their physician during that time, appeared to have been given a trial of a migraine prophylactic drug. Conclusions.— Following an educational intervention for Idaho Medicaid patients identified through retrospective DUR, a trial of a migraine prophylactic drug was initiated for approximately one-third of potential candidates. [ABSTRACT FROM AUTHOR]

Patients with the most severe manifestations of lower extremity arterial occlusive disease often require peripheral bypass surgery for limb salvage and preservation of function. Although good quality saphenous vein offers the most durable conduit for reconstruction, 5-year failure rates are 30-50% and have remained largely unchanged for the past two decades. The majority of these failures occur within the first year of implantation, which is regarded as the most biologically active time during which the vein graft adapts to the arterial environment. Although intimal hyperplasia is generally regarded as the primary culprit of vein graft failure, geometric remodeling of the healing vein graft has recently emerged as a potentially significant contributing factor. While hemodynamic forces, including an increase in shear stress and wall tension, are undoubtedly central to the magnitude and direction of vein graft remodeling, we have determined that these forces alone cannot account for the extent of variability noted in early remodeling patterns. Therefore, we hypothesize that circulating factors, such as mediators of inflammation, may modulate the vein graft response to mechanical forces. This article reviews the definition and diagnosis of vein graft failure and summarizes our current efforts to understand the mechanisms of normal and abnormal vein graft adaptation to the arterial environment. [ABSTRACT FROM AUTHOR]

Abstract: Background: Carisoprodol is a muscle relaxant indicated as adjunctive therapy in acute, painful musculoskeletal conditions. Case reports of drug-seeking behavior and utilization of carisoprodol in combination with opioids have suggested abuse potential. Objectives: We undertook a retrospective review of claims data to identify and characterize potential indicators of abuse in long-term users of carisoprodol and to determine any continued use of the drug by former long-term users following prior authorization implementation. Methods: The Idaho Medicaid pharmacy and medical claims database was queried from January 1 to December 31, 2005, to identify long-term users of muscle relaxants. Use of concomitant opioids and coded diagnoses relating to past drug abuse were analyzed and compared between patients who used carisoprodol and patients who used other muscle relaxants. Data from 11 of 30 surveys mailed to pharmacies filling prescriptions for long-term users of carisoprodol were also collected to determine the frequency of self-pay-continued use after Medicaid coverage of the drug was discontinued. Results: Long-term users of carisoprodol (n = 340) and other skeletal muscle relaxants (SMRs) (n = 453) were identified from among 130,000 individuals in the Idaho Medicaid pharmacy and medical claims database in calendar year 2005. Patients in both groups were similar in terms of mean age (~47 years) and sex (71.5% female). Patients using carisoprodol used concomitant opioids more frequently (81.5% vs 59.8%; P < 0.01), more commonly had past diagnoses indicating other drug abuse (34.1% vs 21.4%; P < 0.01), and in 80% of reported cases, continued to pay out of pocket for carisoprodol when third-party coverage was discontinued. Taken together, these findings are consistent with published case reports suggesting the abuse potential of carisoprodol. Conclusions: The results from this review suggest that, compared with long-term users of other SMRs, carisoprodol patients utilized concomitant opioids more frequently and concomitant NSAIDs less frequently, more commonly had past diagnoses indicating other drug dependence or abuse, and continued to pay out of pocket for carisoprodol when third-party coverage was discontinued. While none of these issues alone may be direct indicators of abuse, collectively they suggest that patients who used carisoprodol long term displayed abuse potential characteristics more frequently than long-term users of other agents. (Clin Ther. 2007;29:2222-2225) Copyright © 2007 Excerpta Medica, Inc. [Copyright &y& Elsevier]

The article discusses deep fibromatosis or desmoid tumor (DF/DT). It is suggested that studies on DF/DT and fine-needle aspiration (FNA) should be explored more by researchers for a better understanding of its roles and limitations in different scenarios. Also, clinicians are encouraged to implement the appropriate diagnosis of DF/DT or FNA on patients when an open-biopsy is not safe. Also discussed are fibromatosis, cytology, and antibodies.

Context.—Poorly differentiated carcinoma on prostate or colorectal biopsy can occasionally present a diagnostic challenge in determining tumor source especially in locally advanced colorectal carcinoma (CRCa) or prostate carcinoma (PCa). Such determination can affect prognosis and therapy. Objective.—To evaluate the role of morphology and immunohistochemistry in the previously mentioned setting. Design.—Surgical pathology and consultation records. Hematoxylin-eosin sections were reviewed in 16 cases (11 PCa, 5 CRCa). Immunohistochemistry for 9 markers was performed in 15 cases. Results.—Dirty necrosis, seen in 5 (100%) of 5 CRCa and 2 (18%) of 11 PCa cases, and the presence of columnar cells with basal nuclei, seen in 5 (100%) of 5 CRCa and 1 (9%) of 11 PCa cases, appear to be the most useful morphologic parameters. Immunohistochemistry confirmed the value of prostate-specific antigen (PSA), CDX2, cytokeratin (CK) 20, and β-catenin in the differential of CRCa (0% PSA+, 60% CDX2+, 80% CK20+, and 100% β-catenin+) versus PCa (80% PSA+, 0% CDX2+, 10% CK20+, and 0% β-catenin+). P501S had a similar sensitivity as PSA in detecting PCa (80%). Two (20%) of 10 PCa cases were positive for 1 of the 2 markers but not the other. P501S was negative in all 5 cases of CRCa. Conclusions.—P501S is a useful marker in this setting when included together with PSA, CDX2, CK20, and β-catenin. P501S labels a subset of PCa cases that are negative for PSA. Dirty necrosis and/or columnar cells with basal nuclei could also be of help. [ABSTRACT FROM AUTHOR]

The article discusses the controversy over American pharmacists' refusals to fill prescriptions for emergency contraceptives for reasons of conscience. Although some in the medical community assert that pharmacists ought not to dispense emergency contraceptives on the basis of conscience, there are also some who argue that pharmacists are autonomous, moral agents who are accountable for their choices and entitled to decide in which activities they will participate.

Low temperature is one of the most important environmental factors limiting crop plant growth, distribution, and productivity. New cultivars with improved freezing tolerance are a common breeding objective of many temperate fruit breeding programs. Improved freezing tolerance would prevent crop loss due to low temperature and reduce yearly fluctuations in crop quantity and quality. Breeding temperate fruit cultivars for improved freezing tolerance is made difficult by several factors, including complexity of the phenotype, difficulty in accurate measurement of the phenotype, and lack of fundamental knowledge concerning the inheritance and genetic control of this trait. Results from inheritance studies of freezing tolerance in temperate fruit crops as well as recent research in forestry genetics highlight some of the challenges and opportunities for further elucidating the inheritance of freezing tolerance in temperate fruit crops. A tremendous amount of research has been conducted describing the molecular biology and signal transduction of the cold acclimation response in the model plant, Arabidopsis thaliana. These findings have begun the transfer to research in agriculturally important crops and hold great promise for elucidating novel methods for generating new fruit cultivars with improved freezing tolerance. [ABSTRACT FROM AUTHOR]

Abstract: Serious neurodegenerative disorders are increasingly prevalent in our society and excessive oxidative stress may be a key mediator of neuronal cell death in many of these conditions. A variety of metals, such as manganese and zinc, are essential trace elements but can reach localized toxic concentrations through various disease processes or environmental exposures and have been implicated as having a role in neurodegeneration. Both manganese and zinc exist as bivalent cations and are essential cofactors/activators for numerous enzymes. Evidence suggests one action of these metals, when concentrated beyond physiological levels, may be to inhibit cellular energy production, ultimately leading to increased radical formation. Our studies were undertaken to directly investigate the toxic effects of manganese and zinc in an immortalized neuronal-like cell line (SK-N-SH) by testing interactions with the antioxidant, 17β-estradiol, and the neurotoxin, ethanol. Employing undifferentiated SK-N-SH cells, we found that these metals caused biphasic effects, enhancing cell proliferation at low doses and inducing cell death at higher doses. Zinc was both more efficacious and more potent than manganese in enhancing growth and in causing cell death. 17β-Estradiol and ethanol enhanced the proliferative actions of zinc and manganese across a wide concentration range. Furthermore, co-treatment with either 17β-estradiol or ethanol afforded protection against manganese-, but not zinc-induced toxicity. Finally, combined administration of 17β-estradiol and ethanol to SK-N-SH cells resulted in both a loss of growth enhancement and protective properties that were observed when these substances were administered individually. We also noted that the toxic effects occurred more rapidly from zinc than manganese exposure. Taken together, these data suggest that oxidative stress likely has a role in cell death resulting from toxic exposure to either zinc or manganese, but there is a difference in the precise mechanism of their effects. [Copyright &y& Elsevier]

In cells of Old World and some New World monkeys, dominant factors restrict human immunodeficiency virus type 1 (HIV-1) infections after virus entry. The simian immunodeficiency virus SIVmac is less susceptible to these restrictions, a property that is determined largely by the viral capsid protein. For this study, we altered exposed amino acid residues on the surface of the HIV-1 capsid, changing them to the corresponding residues found on the SIVmac capsid. We identified two distinct pathways of escape from early, postentry restriction in monkey cells. One set of mutants that were altered near the base of the cyclophilin A-binding loop of the N-terminal capsid domain or in the interdomain linker exhibited a decreased ability to bind the restricting factor(s). Consistent with the location of this putative factor-binding site, cyclophilin A and the restricting factor(s) cooperated to achieve the postentry block. A second set of mutants that were altered in the ridge formed by helices 3 and 6 of the N-terminal capsid domain efficiently bound the restricting factor(s) but were resistant to the consequences of factor binding. These results imply that binding of the simian restricting factor(s) is not sufficient to mediate the postentry block to HIV-1 and that SIVmac capsids escape the block by decreases in both factor binding and susceptibility to the effects of the factor(s). [ABSTRACT FROM AUTHOR]

Host cell barriers to the early phase of immunodeficiency virus replication explain the current distribution of these viruses among human and non-human primate species. Human immunodeficiency virus type 1 (HIV-1), the cause of acquired immunodeficiency syndrome (AIDS) in humans, efficiently enters the cells of Old World monkeys but encounters a block before reverse transcription. This species-specific restriction acts on the incoming HIV-1 capsid and is mediated by a dominant repressive factor. Here we identify TRIM5a, a component of cytoplasmic bodies, as the blocking factor. HIV-1 infection is restricted more efficiently by rhesus monkey TRIM5a than by human TRIM5a. The simian immunodeficiency virus, which naturally infects Old World monkeys, is less susceptible to the TRIM5a-mediated block than is HIV-1, and this difference in susceptibility is due to the viral capsid. The early block to HIV-1 infection in monkey cells is relieved by interference with TRIM5a expression. Our studies identify TRIM5a as a species-specific mediator of innate cellular resistance to HIV-1 and reveal host cell components that modulate the uncoating of a retroviral capsid. [ABSTRACT FROM AUTHOR]

The cells of most Old World monkey species exhibit early, postentry restrictions on infection by human immunodeficiency virus type 1 (HIV-1) but not by simian immunodeficiency virus of macaques (SIV[sub mac]). Conversely, SIV[sub mac], but not HIV-1, infection is blocked in most New World monkey cells. By using chimeric HIV-1/SIV[sub mac] viruses capable of a single round of infection, we demonstrated that a major viral determinant of this restriction is the capsid (CA) protein. The efficiency of early events following HIV-1 and SIV[sub mac] entry is apparently determined by the interaction of the incoming viral CA and species-specific host factors. [ABSTRACT FROM AUTHOR]

Because most parent-adolescent sex communication studies are from the perspectives of sexual and gender minority (SGM) adolescents rather than their parents, we surveyed 54 parents of SGM adolescents in the Southern region in the U.S. about their HIV-related parent-adolescent sex communication (PASC) practices. We compared topics discussed between the sexual activity and sexual orientation/gender identity of their adolescent. We found significant differences between parents having a sexually-active adolescent or not and parents discussing the importance of using condoms and what their adolescent should do if the adolescent contracts HIV. We provide future directions to further examine and improve PASC between parents and their SGM adolescents. [ABSTRACT FROM AUTHOR]

The author reflects on the medical management of peripheral arterial disease (PAD). He states that PAD affects the adults, nonwhites and women compared with coronary artery disease (CAD). An overview of guidelines for secondary prevention and risk reduction therapy in patients with PAD recommend antiplatelet therapy, lipid-lowering therapy and antihypertensive therapy. The author suggests that cohort studies helps in dealing with the gap between PAD and CAD.

Combined lung cancers containing both small cell and non—small cell carcinoma elements are uncommon but well recognized. Lung tumors with neuroendocrine differentiation form a group of histologically distinct tumors with differing clinical behavior ranging from low-grade tumors with good prognosis (typical carcinoid) to intermediate-grade tumors (atypical carcinoid) to high-grade tumors with poor prognosis (small cell carcinoma and large cell neuroendocrine tumors). The authors report clinical findings and pathologic findings in a case of combined carcinoid tumor and squamous cell carcinoma of lung. To the best of the authors’ knowledge, this is the first report of such a case in the peer reviewed literature, thus broadening the spectrum of combined lung tumors. [ABSTRACT FROM PUBLISHER]

In the more than 15 years since its introduction, quantitative microbial risk assessment (QMRA) has become a widely used technique for assessing population health risk posed by waterborne pathogens. However, the variation in approaches taken for QMRA in relation to drinking water supply is not well understood. This systematic review identifies, categorises, and critically synthesises peer-reviewed and academic case studies of QMRA implementation for existing distributed public drinking water supplies. Thirty-nine English-language, peer-reviewed and academic studies published from 2003 to 2019 were identified. Key findings were synthesised in narrative form. The overall designs of the included studies varied widely, as did the assumptions used in risk calculation, especially in relation to pathogen dose. There was also substantial variation in the degree to which the use of location-specific data weighed with the use of assumptions when performing risk calculation. In general, the included studies' complexity did not appear to be associated with greater result certainty. Factors relating to pathogen dose were commonly influential on risk estimates whereas dose-response parameters tended to be of low relative influence. In two of the included studies, use of the 'susceptible fraction' factor was inconsistent with recognised guidance and potentially led to the underestimation of risk. While approaches and assumptions used in QMRA need not be standardised, improvement in the reporting of QMRA results and uncertainties would be beneficial. It is recommended that future authors consider the water supply QMRA reporting checklist developed for the current review. Consideration of the broad types of uncertainty relevant to QMRA is also recommended. Policy-makers should consider emergent discussion on acute microbial health-based targets when setting normative guidelines. The continued representation of QMRA case studies within peer-reviewed and academic literature would also enhance future implementation. Further research is needed on the optimisation of QMRA resourcing given the application context. Image 1 • First systematic review of QMRA implementation for public drinking water supplies. • Current approaches varied most for deriving dose and varied least for dose-response. • Factors for dose were commonly the most influential determinant of risk. • QMRA study complexity did not indicate greater certainty of risk estimates. • Greater consistency in reporting QMRA assumptions would be beneficial overall. [ABSTRACT FROM AUTHOR]

The presence of an abdominal aortic aneurysm (AAA) can be a contraindication to placement of a HeartMate left ventricular assist device (LVAD) for end-stage heart failure. We describe a 65-year-old patient who underwent endovascular repair of an AAA before placement of a LVAD as destination therapy for end-stage heart failure. This case is the first report of endovascular AAA repair before VAD placement. It not only demonstrates the utility of endovascular AAA repair in patients with undue co-morbidities, but also that the presence of an AAA should not be a contraindication to LVAD placement, if corrected. [Copyright &y& Elsevier]

Although HIV pre-exposure prophylaxis (PrEP) effectively and safely prevents HIV among adolescents, uptake of PrEP is low. Adolescents must have primary care providers (PCPs) prescribe them PrEP, making PCPs critical actors in PrEP delivery. However, research has primarily investigated determinants of PCPs' intention to prescribe adolescents PrEP rather than the determinants of performing the behavior itself. We examined the demographic, clinical practice, and implementation determinants of PCPs previously prescribing PrEP to adolescents. PCPs were recruited from a national Qualtrics panel of licensed medical providers in the United States from July 15-August 19, 2022. The Theoretical Domains Framework informed the implementation determinants measured. A multivariable logistic regression was used. PCPs who were more knowledgeable of the CDC guidelines (aOR 2.97, 95% CI 2.16–4.10), who were assigned male at birth (aOR 1.64, 95% CI 1.03–2.59), and who practiced in the Western region (aOR 1.85, 95% CI 1.04–3.30) had greater odds of prior prescribing adolescents PrEP. Provider-based educational interventions should be designed, implemented, and tested to encourage PCPs to prescribe PrEP to eligible adolescents. [ABSTRACT FROM AUTHOR]

Using data from the 2014 National Survey of Sexual Health and Behavior, a probability survey of Americans aged 14+, we assessed the prevalence and correlates of kissing, cuddling, and massage during 1,493 individuals' most recent sexual event from the past year. Most respondents reported kissing (87%) and cuddling (70%); fewer (23%) reported massage. Each was significantly associated with age, education, and relationship structure. Respondents younger than 30 were significantly more likely to indicate they did not kiss because kissing would have been too intimate with their partner. Only cuddling was significantly associated with event-level emotional intimacy and sexual pleasure. [ABSTRACT FROM AUTHOR]

Purpose - The purpose of this paper is to enhance understanding of shared leadership in a military academy setting. Design/methodology/approach - A qualitative methodology was selected to ask senior cadets about a shared leadership concept at the United States Coast Guard Academy, known as the "corps leading the corps." Cadets responded to, "what does the corps leading the corps mean to you?" via a paper and pencil survey. Cadet responses were coded using content analysis. Findings - Three higher-order dimensions emerged from the data: autonomy and empowerment, developing self and others, and role modeling. Originality/value - The paper provides emerging leaders' commentary to incorporating a shared leadership concept within an educational environment. [ABSTRACT FROM AUTHOR]

Objectives: To explore the implications of cervical conization specimens lacking the targeted high-grade squamous intraepithelial lesions (negative cone).Methods: We studied 540 conization procedures: 400 positive cones and 140 negative cones. Clinicopathologic features and 2-year follow-up results were reported.Results: Negative cones comprised 22% of procedures triggered by CIN2 or higher biopsies. Procedures triggered by cytology produced much higher percentages of negative cones (37% high-grade squamous intraepithelial lesion [HSIL], 46% atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion [ASC-H], and 76% low-grade squamous intraepithelial lesion-cannot exclude high-grade squamous intraepithelial lesion [LSIL-H]). Upon reviewing negative excision-triggering biopsy and cytology, we downgraded 24 (24%) CIN2 biopsies, three (14%) HSIL, five (83%) ASC-H, and 12 (92%) LSIL-H. One-third of our negative cones can be attributed to overdiagnosis either on biopsy or cytology. Patients with negative cones were older and had smaller excisions, negative colposcopic findings, and negative/equivocal high-risk human papillomavirus (HR-HPV). Within 2 years, 35 (25%) women with negative cones experienced ASCUS or LSIL. Only one (0.7%) recurred as CIN3, a significantly lower percentage than women with positive cones (13%).Conclusions: We advocate careful review of all excision-triggering biopsy and cytology, especially in cases of LSIL-H. Patients with negative cones should be surveyed with cytology and HR-HPV testing. [ABSTRACT FROM AUTHOR]