Deficiency in Ever2 does not increase susceptibility of mice to pathogenesis by the mouse papillomavirus, MmuPV1.

Epidermodysplasia verruciformis (EV) is a rare genetic skin disorder that is characterized by the development of papillomavirus-induced skin lesions that can progress to squamous cell carcinoma (SCC). Certain high-risk, cutaneous ß-genus human papillomaviruses (ß-HPVs), in particular HPV5 and HPV8, are associated with inducing EV in individuals who have a homozygous mutation in one of three genes tied to this disease: EVER1, EVER2, or CIB1. EVER1 and EVER2 are also known as TMC6 and TMC8, respectively. Little is known about the biochemical activities of EVER gene products or their roles in facilitating EV in conjunction with ß-HPV infection. To investigate the potential effect of EVER genes on papillomavirus infection, we pursued in vivo infection studies by infecting Ever2-null mice with mouse papillomavirus (MmuPV1). MmuPV1 shares characteristics with ß-HPVs including similar genome organization, shared molecular activities of their early, E6 and E7, oncoproteins, the lack of a viral E5 gene, and the capacity to cause skin lesions that can progress to SCC. MmuPV1 infections were conducted both in the presence and absence of UVB irradiation, which is known to increase the risk of MmuPV1-induced pathogenesis. Infection with MmuPV1 induced skin lesions in both wild-type and Ever2-null mice with and without UVB. Many lesions in both genotypes progressed to malignancy, and the disease severity did not differ between Ever2-null and wild-type mice. However, somewhat surprisingly, lesion growth and viral transcription was decreased, and lesion regression was increased in Ever2-null mice compared with wild-type mice. These studies demonstrate that Ever2-null mice infected with MmuPV1 do not exhibit the same phenotype as human EV patients infected with ß-HPVs.IMPORTANCEHumans with homozygous mutations in the EVER2 gene develop epidermodysplasia verruciformis (EV), a disease characterized by predisposition to persistent ß-genus human papillomavirus (ß-HPV) skin infections, which can progress to skin cancer. To investigate how EVER2 confers protection from papillomaviruses, we infected the skin of homozygous Ever2-null mice with mouse papillomavirus MmuPV1. Like in humans with EV, infected Ever2-null mice developed skin lesions that could progress to cancer. Unlike in humans with EV, lesions in these Ever2-null mice grew more slowly and regressed more frequently than in wild-type mice. MmuPV1 transcription was higher in wild-type mice than in Ever2-null mice, indicating that mouse EVER2 does not confer protection from papillomaviruses. These findings suggest that there are functional differences between MmuPV1 and ß-HPVs and/or between mouse and human EVER2.

A mouse model of gestational glucose intolerance through exposure to a low protein diet during fetal and neonatal development.

KEY POINTS: Pancreatic ß-cell dysfunction is hypothesized to be the significant determinant of gestational diabetes pathogenesis, however pancreatic samples from patients are scarce. This study reports a novel mouse model of gestational glucose intolerance in pregnancy, originating from previous nutrition restriction in utero, in which glucose intolerance was restricted to late gestation as is seen in human gestational diabetes. Glucose intolerance was attributed to reduced ß-cell proliferation, leading to impaired gestational ß-cell mass expansion in maternal endocrine pancreas, in addition to reduced glucose-stimulated insulin secretion. This model reproduces some of the features of gestational diabetes and is suitable for testing safe therapeutic interventions that increase ß-cell mass during pregnancy and prevent or reverse gestational glucose intolerance. ABSTRACT: Gestational diabetes mellitus (GDM) is an increasingly prevalent form of diabetes that appears during pregnancy. Pathological studies link a failure to adaptively increase maternal pancreatic ß-cell mass (BCM) in pregnancy to GDM. Due to the scarcity of pancreatic samples from GDM patients, we sought to develop a novel mouse model for impaired gestational glucose tolerance. Mature female C57Bl/6 mouse offspring (F1) born to dams fed either a control (C) or low-protein (LP) diet during gestation and lactation were randomly allocated into two subsequent study groups: pregnant (CP, LPP) or non-pregnant (CNP, LPNP). Glucose tolerance tests were performed at gestational day (GD) 9, 12 and 18. Subsequently, pancreata were removed for fluorescence immunohistochemistry to assess α-cell mass (ACM), BCM and ß-cell proliferation. An additional group of animals was used to measure insulin secretion from isolated islets at GD18. LPP females displayed glucose intolerance compared to CP females at GD18 (P < 0.001). BCM increased threefold at GD18 in CP females. However, LPP females had reduced BCM expansion (P < 0.01) concurrent with reduced ß-cell proliferation at GD12 (P < 0.05). LPP females also had reduced ACM expansion at GD18 (P < 0.01). LPP islets had impaired glucose-stimulated insulin secretion in vitro compared to CP islets (P < 0.01). Therefore, impaired glucose tolerance during pregnancy is associated with a failure to adequately adapt BCM, as a result of reduced ß-cell proliferation, in addition to lower glucose-stimulated insulin secretion. This model could be used to evaluate novel interventions during pregnancy to increase BCM or function as a strategy to prevent/reverse GDM.

Adherence to Universal Travel Screening in the Emergency Department During Epidemic Ebola Virus Disease.

BACKGROUND: During the 2014 West African Ebola Virus Disease (EVD) outbreak, the U.S. Centers for Disease Control and Prevention recommended that all emergency department (ED) patients undergo travel screening for risk factors of importing EVD. OBJECTIVES: We sought to determine the overall adherence rate to the recommended travel screening protocol and to identify factors associated with nonadherence to the protocol. METHODS: We conducted a multicenter, retrospective analysis of adherence to the travel screening program in an academic hospital and three affiliated community hospitals. A regression model identified patient and hospital factors associated with nonadherence. RESULTS: Of the 147,062 patients included for analysis, 93.7% (n = 137,834) had travel screenings completed. We identified several characteristics of patients that were most likely to be missed by the screening protocol-patients with low English proficiency, patients who arrive via ambulance or helicopter, and patients with more severe illness or injury based on initial triage acuity. CONCLUSIONS: These findings should be used to improve adherence to the travel screening protocol for future emerging infectious disease threats.

The Impact of the 2008 Council of Emergency Residency Directors (CORD) Panel on Emergency Medicine Resident Diversity.

BACKGROUND: In 2008, the Council of Emergency Medicine Residency Directors (CORD) developed a set of recruitment strategies designed to increase the number of under-represented minorities (URMs) in Emergency Medicine (EM) residency. OBJECTIVES: We conducted a survey of United States (US) EM residency program directors to: describe the racial and ethnic composition of residents; ascertain whether each program had instituted CORD recruitment strategies; and identify program characteristics associated with recruitment of a high proportion of URM residents. METHODS: The survey was distributed to accredited, nonmilitary US EM residency programs during 2013. Programs were dichotomized into high URM and low URM by the percentage of URM residents. High- and low-URM programs were compared with respect to size, geography, percentage of URM faculty, importance assigned to common applicant selection criteria, and CORD recruitment strategies utilized. Odds ratios and 95% confidence limits were calculated. RESULTS: Of 154 residency programs, 72% responded. The median percentage of URM residents per program was 9%. Only 46% of EM programs engaged in at least two recruitment strategies. Factors associated with higher resident diversity (high-URM) included: diversity of EM faculty (high-URM) (odds ratio [OR] 5.3; 95% confidence interval [CI] 2.1-13.0); applicant's URM status considered important (OR 4.9; 95% CI 2.1-11.9); engaging in pipeline activities (OR 4.8; 95% CI 1.4-15.7); and extracurricular activities considered important (OR 2.6; 95% CI 1.2-6.0). CONCLUSION: Less than half of EM programs have instituted two or more recruitment strategies from the 2008 CORD diversity panel. EM faculty diversity, active pipeline programs, and attention paid to applicants' URM status and extracurricular activities were associated with higher resident diversity.

Identification of factors integral to designing community-based CPR interventions for high-risk neighborhood residents.

BACKGROUND: High-risk neighborhoods can be identified as census tracts in which cardiac arrest incidence is high and bystander cardiopulmonary resuscitation (CPR) prevalence is low. However, little is known about how best to tailor community CPR training to high-risk neighborhood residents. The objective of this study was to identify factors integral to the design and implementation of community-based CPR intervention programs targeted to these areas. METHODS: Using qualitative methods, six focus groups with 42 participants were conducted in high-risk neighborhoods in Columbus, Ohio during January and February 2011 to elicit resident views on how best to design community-based CPR educational programs for these neighborhoods. Snowball and purposeful sampling by community liaisons was used to recruit participants. Three reviewers analyzed the data in an iterative process to identify recurrent and unifying themes. RESULTS: Focus group participants identified four principal considerations for the design of community-based CPR interventions: 1) identifying lay people to serve as motivated leaders while targeting both senior citizens and school children to increase reach, 2) finding appropriate community-based locations to hold CPR training, 3) providing incentives to encourage more people to participate, and 4) identifying and addressing barriers to participation. CONCLUSION: Out-of-hospital cardiac arrest is a particular risk for minority and low-income communities. By working together with the community key factors integral to designing community-based CPR within these high-risk communities can be identified and implemented.

The Larynx is Protected from Secondary and Vertical Papillomavirus Infection in Immunocompetent Mice.

OBJECTIVE: Mouse papillomavirus MmuPV1 causes both primary and secondary infections of the larynx in immunocompromised mice. Understanding lateral and vertical transmission of papillomavirus to the larynx would benefit patients with recurrent respiratory papillomatosis (RRP). To test the hypothesis that the larynx is uniquely vulnerable to papillomavirus infection, and to further develop a mouse model of RRP, we assessed whether immunocompetent mice were vulnerable to secondary or vertical laryngeal infection with MmuPV1. METHODS: Larynges were collected from 405 immunocompetent adult mice that were infected with MmuPV1 in the oropharynx, oral cavity, or anus, and 31 mouse pups born to immunocompetent females infected in the cervicovaginal tract. Larynges were analyzed via polymerase chain reaction (PCR) of lavage fluid or whole tissues for viral DNA, histopathology, and/or in situ hybridization for MmuPV1 transcripts. RESULTS: Despite some positive laryngeal lavage PCR screens, all laryngeal tissue PCR and histopathology results were negative for MmuPV1 DNA, transcripts, and disease. There was no evidence for lateral spread of MmuPV1 to the larynges of immunocompetent mice that were infected in the oral cavity, oropharynx, or anus. Pups born to infected mothers were negative for laryngeal MmuPV1 infection from birth through weaning age. CONCLUSION: Secondary and vertical laryngeal MmuPV1 infections were not found in immunocompetent mice. Further work is necessary to explore immunologic control of laryngeal papillomavirus infection in a mouse model and to improve preclinical models of RRP. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2322-2330, 2024.

Invasive cancer and spontaneous regression two weeks after papillomavirus infection.

Development of invasive cancer in mammals is thought to require months or years after initial events such as mutation or viral infection. Rarely, invasive cancers regress spontaneously. We show that cancers can develop and regress on a timescale of weeks, not months or years. Invasive squamous cell carcinomas developed in normal adult, immune-competent mice as soon as 2 weeks after infection with mouse papillomavirus MmuPV1. Tumor development, regression or persistence was tissue- and strain-dependent. Cancers in infected mice developed rapidly at sites also prone to papillomavirus-induced tumors and cancers in humans - the throat, anus, and skin - and their frequency was increased in mice constitutively expressing the papillomavirus E5 oncogene, which MmuPV1 lacks. Cancers and dysplasia in the throat and anus regressed completely within 4-8 weeks of infection; however, skin lesions in the ear persisted. T-cell depletion in the mouse showed that regression of throat and anal tumors requires T cells. We conclude that papillomavirus infection suffices for rapid onset of invasive cancer, and persistence of lesions depends on factors including tissue type and host immunity. The speed of these events should promote rapid progress in the study of viral cancer development, persistence, and regression.

JYNNEOS™ effectiveness as post-exposure prophylaxis against mpox: Challenges using real-world outbreak data.

BACKGROUND: JYNNEOSTM vaccine has been used as post-exposure prophylaxis (PEP) during a mpox outbreak in New York City (NYC). Data on effectiveness are limited. METHODS: Effectiveness of a single dose of JYNNEOSTM vaccine administered subcutaneously ≤ 14 days as PEP for preventing mpox disease was assessed among individuals exposed to case-patients from May 22, 2022-August 24, 2022. Individuals were evaluated for mpox through 21 days post-exposure. An observational study was conducted emulating a sequence of nested "target" randomized trials starting each day after exposure. Results were adjusted for exposure risk and race/ethnicity. Analyses were conducted separately based on last (PEPL) and first (PEPF) exposure date. We evaluated the potential to overestimate PEP effectiveness when using conventional analytic methods due to exposed individuals developing illness before they can obtain PEP (immortal time bias) compared to the target trial. RESULTS: Median time from last exposure to symptom onset (incubation period) among cases that did not receive PEPL was 7 days (range 1-16). Time to PEPL receipt was 7 days (range 0-14). Among 549 individuals, adjusted PEPL and PEPF effectiveness was 19 % (95 % Confidence Interval [CI], -54 % to 57 %) and -7% (95 % CI, -144 % to 53 %) using the target trial emulation, respectively, and 78 % (95 % CI, 50 % to 91 %) and 73 % (95 % CI, 31 % to 91 %) using conventional analysis. CONCLUSIONS: Determining PEP effectiveness using real-world data during an outbreak is challenging. Time to PEP in NYC coupled with the observed incubation period resulted in overestimated PEP effectiveness using a conventional method. The target trial emulation, while yielding wide confidence intervals due to small sample size, avoided immortal time bias. While results from these evaluations cannot be used as reliable estimates of PEP effectiveness, we present important methodologic considerations for future evaluations.

Availability and potential impact of international rotations in emergency medicine residency programs.

BACKGROUND: Interest in international emergency medicine (IEM) is growing. With the globalization of medicine, IEM as a field has expanded from disaster relief efforts to opportunities for resident education. Numerous accounts have been published voicing the educational benefits of international rotations (IRs). As such, many residencies now offer opportunity for IRs. OBJECTIVE: To evaluate the availability and utilization of IRs in emergency medicine (EM) residency programs. METHODS: EM residency program directors were surveyed from the 126 Accreditation Council for Graduate Medical Education-accredited programs with ≥2 years of residency graduates. Directors were asked about availability of IR, categorized as: 1) required; 2) elective (with or without pre-designated sites); or 3) not available. RESULTS: One hundred eleven (88%) program directors reported data on 2240 graduates over 2 years. IRs were offered by 101 (91%) programs. No program required an IR. Among programs offering IRs, most (69%) did not have pre-designated sites. Eighty-nine of 101 programs (88%) allowing IRs had at least one resident completing an IR; 23 of 111 programs (21%) had more than 30% resident participation in IRs. Programs offering IRs at pre-designated sites had 210 of 727 (29%) residents complete an IR, compared to 272 of 1469 (19%) in programs without pre-designated sites (p < 0.001). Four-year programs had twice as many IR participants (32%) compared to 3-year programs (17%; p < 0.001). CONCLUSIONS: More residents participated in IRs when a pre-designated site was available compared to programs without. This suggests that programs interested in supporting IRs consider developing pre-designated sites to accommodate residents.

Preclinical Models of Laryngeal Papillomavirus Infection: A Scoping Review.

OBJECTIVE: Laryngeal human papillomavirus (HPV) infection causes recurrent respiratory papillomatosis (RRP) and accounts for up to 25% of laryngeal cancers. Lack of satisfactory preclinical models is one reason that treatments for these diseases are limited. We sought to assess the literature describing preclinical models of laryngeal papillomavirus infection. DATA SOURCES: PubMed, Web of Science, and Scopus were searched from the inception of database through October 2022. REVIEW METHODS: Studies searched were screened by two investigators. Eligible studies were peer-reviewed, published in English, presented original data, and described attempted models of laryngeal papillomavirus infection. Data examined included type of papillomavirus, infection model, and results including success rate, disease phenotype, and viral retention. RESULTS: After screening 440 citations and 138 full-text studies, 77 studies published between 1923 and 2022 were included. Models used low-risk HPV or RRP (n = 51 studies), high-risk HPV or laryngeal cancer (n = 16), both low- and high-risk HPV (n = 1), and animal papillomaviruses (n = 9). For RRP, 2D and 3D cell culture models and xenografts retained disease phenotypes and HPV DNA in the short term. Two laryngeal cancer cell lines were consistently HPV-positive in multiple studies. Animal laryngeal infections with animal papillomaviruses resulted in disease and long-term retention of viral DNA. CONCLUSIONS: Laryngeal papillomavirus infection models have been researched for 100 years and primarily involve low-risk HPV. Most models lose viral DNA after a short duration. Future work is needed to model persistent and recurrent diseases, consistent with RRP and HPV-positive laryngeal cancer. LEVEL OF EVIDENCE: NA Laryngoscope, 133:3256-3268, 2023.

Towards a better understanding between non-Muslim primary care clinicians and Muslim patients: A literature review intended to reduce health care inequities in Muslim patients.

Although Muslims are a growing population within many non-Muslim countries, there are insufficient Muslim clinicians to care for them. Studies have shown that non-Muslim clinicians have limited knowledge and understanding of Islamic practices affecting health, which may lead to disparities in the quality of healthcare delivery and outcomes when caring for Muslim patients. Muslims come from many different cultures and ethnicities and have variations in their beliefs and practices. This literature review provides some insights which may strengthen therapeutic bonds between non-Muslim clinicians and their Muslim patients resulting in improved holistic, patient-centered care in the areas of cancer screening, mental health, nutrition, and pharmacotherapy. Additionally, this review informs clinicians about the Islamic perspective on childbirth, end of life issues, travel for Islamic pilgrimage, and fasting during the month of Ramadan. Literature was sourced by a comprehensive search in PubMed, Scopus, and CINAHL along with hand screening of citations. Title and abstract screening followed by full-text screening excluded studies including less than 30% Muslim participants, protocols, or reporting results deemed irrelevant to primary care. 115 papers were selected for inclusion in the literature review. These were grouped into the themes of general spirituality, which were discussed in the Introduction, and Islam and health, Social etiquette, Cancer screening, Diet, Medications and their alternatives, Ramadan, Hajj, Mental health, Organ donation and transplants, and End of life. Summarizing the findings of the review, we conclude that health inequities affecting Muslim patients can be addressed at least in part by improved cultural competency in non-Muslim clinicians, as well as further research into this area.

Frequency Changes in Terminal Alkynes Provide Strong, Sensitive, and Solvatochromic Raman Probes of Biochemical Environments.

The C≡C stretching frequencies of terminal alkynes appear in the "clear" window of vibrational spectra, so they are attractive and increasingly popular as site-specific probes in complicated biological systems like proteins, cells, and tissues. In this work, we collected infrared (IR) absorption and Raman scattering spectra of model compounds, artificial amino acids, and model proteins that contain terminal alkyne groups, and we used our results to draw conclusions about the signal strength and sensitivity to the local environment of both aliphatic and aromatic terminal alkyne C≡C stretching bands. While the IR bands of alkynyl model compounds displayed surprisingly broad solvatochromism, their absorptions were weak enough that alkynes can be ruled out as effective IR probes. The same solvatochromism was observed in model compounds' Raman spectra, and comparisons to published empirical solvent scales (including a linear regression against four meta-aggregated solvent parameters) suggested that the alkyne C≡C stretching frequency mainly reports on local electronic interactions (i.e., short-range electron donor-acceptor interactions) with solvent molecules and neighboring functional groups. The strong solvatochromism observed here for alkyne stretching bands introduces an important consideration for Raman imaging studies based on these signals. Raman signals for alkynes (especially those that are π-conjugated) can be exceptionally strong and should permit alkynyl Raman signals to function as probes at very low concentrations, as compared to other widely used vibrational probe groups like azides and nitriles. We incorporated homopropargyl glycine into a transmembrane helical peptide via peptide synthesis, and we installed p-ethynylphenylalanine into the interior of the Escherichia coli fatty acid acyl carrier protein using a genetic code expansion technique. The Raman spectra from each of these test systems indicate that alkynyl C≡C bands can act as effective and unique probes of their local biomolecular environments. We provide guidance for the best possible future uses of alkynes as solvatochromic Raman probes, and while empirical explanations of the alkyne solvatochromism are offered, open questions about its physical basis are enunciated.

Voice Handicap Index Changes After Microflap Surgery for Benign Vocal Fold Lesions Are Not Associated With Recommended Absolute Voice Rest Duration.

PURPOSE: Voice rest is frequently prescribed after phonosurgery, but optimal type and duration for voice outcomes have not been demonstrated. Studies to date have been characterized by heterogeneity in surgical procedures and laryngeal diagnoses. We sought to analyze the effect of recommended absolute voice rest duration on outcomes of microflap surgery for benign vocal fold lesions. A secondary purpose was to identify patient factors associated with postoperative voice outcomes. METHOD: Forty-three patients were included in this retrospective review of patients aged 18 years and above who underwent direct microlaryngoscopy with microflap for vocal fold polyp or cyst over a 5-year period at a multidisciplinary voice center. Duration of recommended postoperative absolute voice rest was classified as less than 7 days, 7 days, and more than 7 days. Demographic and vocal hygiene data and voice treatment history were collected. Outcome measures consisted of one pre- and two postoperative Voice Handicap Index (VHI) scores. Effects of recommended voice rest on outcomes were analyzed using mixed models for repeated measures. Effects of patient factors on outcomes were analyzed as exploratory measures. Stroboscopy ratings were analyzed descriptively. RESULTS: Thirteen patients were recommended 7 days of absolute voice rest, 15 were recommended less than 7 days, and 15 were recommended more than 7 days. Postoperatively, VHI scores significantly improved for all patients. Voice rest as a continuous variable was associated with the Functional subscale score in the short term, but there was no effect on VHI total score and no longer term effect of voice rest on any outcome. Age, sex, and preoperative voice therapy were associated with at least one VHI subscale score on at least one time point. CONCLUSION: VHI outcomes of microflap surgery for polyps and cysts do not differ by duration of recommended absolute postoperative voice rest. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.19178459.

Expanded Basal Compartment and Disrupted Barrier in Vocal Fold Epithelium Infected with Mouse Papillomavirus MmuPV1.

Laryngeal infection with low-risk human papillomaviruses can cause recurrent respiratory papillomatosis (RRP), a disease with severe effects on vocal fold epithelium resulting in impaired voice function and communication. RRP research has been stymied by limited preclinical models. We recently reported a murine model of laryngeal MmuPV1 infection and disease in immunodeficient mice. In the current study, we compare quantitative and qualitative measures of epithelial proliferation, apoptosis, differentiation, and barrier between mice with MmuPV1-induced disease of the larynx and surrounding tissues and equal numbers of uninfected controls. Findings supported our hypothesis that laryngeal MmuPV1 infection recapitulates many features of RRP. Like RRP, MmuPV1 increased proliferation in infected vocal fold epithelium, expanded the basal compartment of cells, decreased differentiated cells, and altered cell-cell junctions and basement membrane. Effects of MmuPV1 on apoptosis were equivocal, as with RRP. Barrier markers resembled human neoplastic disease in severe MmuPV1-induced disease. We conclude that MmuPV1 infection of the mouse larynx provides a useful, if imperfect, preclinical model for RRP that will facilitate further study and treatment development for this intractable and devastating disease.

A Novel In Vivo Model of Laryngeal Papillomavirus-Associated Disease Using Mus musculus Papillomavirus.

Recurrent respiratory papillomatosis (RRP), caused by laryngeal infection with low-risk human papillomaviruses, has devastating effects on vocal communication and quality of life. Factors in RRP onset, other than viral presence in the airway, are poorly understood. RRP research has been stalled by limited preclinical models. The only known papillomavirus able to infect laboratory mice, Mus musculus papillomavirus (MmuPV1), induces disease in a variety of tissues. We hypothesized that MmuPV1 could infect the larynx as a foundation for a preclinical model of RRP. We further hypothesized that epithelial injury would enhance the ability of MmuPV1 to cause laryngeal disease, because injury is a potential factor in RRP and promotes MmuPV1 infection in other tissues. In this report, we infected larynges of NOD scid gamma mice with MmuPV1 with and without vocal fold abrasion and measured infection and disease pathogenesis over 12 weeks. Laryngeal disease incidence and severity increased earlier in mice that underwent injury in addition to infection. However, laryngeal disease emerged in all infected mice by week 12, with or without injury. Secondary laryngeal infections and disease arose in nude mice after MmuPV1 skin infections, confirming that experimentally induced injury is dispensable for laryngeal MmuPV1 infection and disease in immunocompromised mice. Unlike RRP, lesions were relatively flat dysplasias and they could progress to cancer. Similar to RRP, MmuPV1 transcript was detected in all laryngeal disease and in clinically normal larynges. MmuPV1 capsid protein was largely absent from the larynx, but productive infection arose in a case of squamous metaplasia at the level of the cricoid cartilage. Similar to RRP, disease spread beyond the larynx to the trachea and bronchi. This first report of laryngeal MmuPV1 infection provides a foundation for a preclinical model of RRP.

Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models.

The artemisinin family of compounds is cytopathic in certain cancer cell lines that are positive for human papillomaviruses (HPV) and can potentially drive the regression of dysplastic lesions. We evaluated the efficacy of topical dihydroartemisinin (DHA) on cervical dysplasia and anal dysplasia in two papillomavirus mouse models: K14E6/E7 transgenic mice, which express HPV16 oncogenes; and immunodeficient NOD/SCID gamma (NSG) mice infected with Mus musculus papillomavirus (MmuPV1). Mice started treatment with DHA at 25 weeks of age (K14E6/E7) or 20 weeks post infection (MmuPV1-infected), when the majority of mice are known to have papillomavirus-induced low- to high-grade dysplasia. Mice were treated with or without topical DHA at the cervix or anus and with or without topical treatment with the chemical carcinogen 7,12 dimethylbenz(a)anthracene (DMBA) at the anus of in transgenic mice to induce neoplastic progression. Mice were monitored for overt tumor growth, and tissue was harvested after 20 weeks of treatment and scored for severity of histological disease. For MmuPV1-infected mice, anogenital lavages were taken to monitor for viral clearance. Tissues were also evaluated for viral gene expression at the RNA and/or protein levels. Treatment with topical DHA did not reduce dysplasia in the anogenital tract in either papillomavirus-induced mouse model and did not prevent progression to anal cancer in the DMBA-treated K14E6/E7 mice.

Assessment of prehospital care and disaster preparedness in a rural Guatemala clinic.

INTRODUCTION: In October 2005, Hurricane Stan impacted Central America, causing severe damage to Guatemala. The main objectives of this study are to report on the effects of Hurricane Stan in rural Guatemala, to assess the responses of a rural clinic during and after the storm, and to identify ways in which the clinic can better prepare for future disasters. The clinic is located in Catarina, San Marcos, Guatemala. Roughly 400-500 patients are attended to each week at the clinic. METHODS: Survey data were obtained during a two-week period using a convenience sample of people at the clinic and in the surrounding community. RESULTS: The major medical problems after the impact of Hurricane Stan included fungal infections, upper respiratory infections, diarrhea, and emotional problems. The most needed supplies included food, electricity, home repair, potable water, communication, and clothing. In the immediate aftermath of event, 61% of the participants could not get to a hospital; however, most did not require medical assistance. CONCLUSIONS: Hurricane Stan had a devastating effect on the San Marcos region of Guatemala. While the clinic could have served as a resource center and a base, it was not prepared to address the community's health needs after the hurricane as there were no previous plans in place for disaster response for the clinic or for the community. Next steps include developing a preparedness plan to utilize the clinic as a local resource center , in the event that the planned national disaster responses are delayed or unable to reach the affected area.

Role of Voice Therapy in Adherence to Voice Rest After Office-Based Vocal Fold Procedures.

Purpose Patients undergoing vocal fold procedures significantly reduce but often do not cease voice use during absolute postprocedure voice rest. We hypothesized that patients who completed preprocedure voice therapy would increase adherence to postprocedure voice rest. Method Eighty-six participants completed this prospective cohort study. Patients scheduled for office-based vocal fold procedures, 1-3 days of absolute postprocedure voice rest, and preprocedure speech-language pathology (SLP) care were recruited. SLP care consisted of either (a) multiple voice therapy sessions, (b) one counseling/therapy session, or (c) voice evaluation only. Participants reported talking and other specific voice behaviors on 100-mm visual analog scales for up to 3 days pre- and postprocedure as well as changes in overall voice use at follow-up at least 1 week postprocedure. Results Talking decreased postprocedure by 63% in the therapy group and 65% in the counseling group, both significantly more than the 35% decrease measured in the evaluation group. There were group differences in talking at baseline but not during voice rest. Coughing and throat clearing were highest in the voice evaluation group and decreased less than talking during voice rest. At follow-up, 84% of participants reported that they completed voice rest for at least as long as recommended and 39.5% reported that they never used their voices during voice rest. Participants estimated a 98% overall reduction in voice use during voice rest at follow-up. Conclusions Voice use before and after vocal fold procedures varies by participation in preprocedure voice therapy. Patients significantly decrease talking during postprocedure voice rest but are not perfectly adherent. Communicative voice use decreases more than noncommunicative voice use during voice rest. Patients may overestimate adherence to voice rest at follow-up. Supplemental Material https://doi.org/10.23641/asha.16589864.

Impact of a pharmacist-administered deprescribing intervention on nursing home residents: a randomized controlled trial.

Background Polypharmacy is prevalent among long-term care residents in Canada, with 48.4% receiving ten or more different medications and 40.7% chronically prescribed potentially inappropriate medications. Objective We implemented a pharmacist-administered deprescribing program in a long-term care facility to determine if the number of medications taken per resident could be reduced. SETTING: A long-term care facility in Newfoundland and Labrador, Canada from February 2017 to February 2018. METHOD: Residents were randomized to receive either a deprescribing-focused medication review by a pharmacist or usual care. Main outcome measure Change in the number of medications at 3 and 6 months. Results Forty-five residents enrolled in the study (n = 22 intervention, n = 23 control). Seventy-eight deprescribing recommendations were made, and 85.1% were successfully implemented. The average number of medications taken by residents in the intervention group was 2.68 less than the control group (p < 0.02; 95% CI - 4.284, - 1.071) at 3 months and 2.88 less (p = 0.02, 95% CI - 4.543, - 1.112) at 6 months. In 14.9% of cases, a medication had to be restarted after deprescribing was attempted because symptoms returned. CONCLUSION: A pharmacist-led deprescribing intervention can reduce the number of unnecessary and potentially harmful medications taken by LTC residents.

Altered pancreas remodeling following glucose intolerance in pregnancy in mice.

Gestational diabetes mellitus increases the risk of dysglycemia postpartum, in part, due to pancreatic ß-cell dysfunction. However, no histological evidence exists comparing endocrine pancreas after healthy and glucose-intolerant pregnancies. This study sought to address this knowledge gap, in addition to exploring the contribution of an inflammatory environment to changes in endocrine pancreas after parturition. We used a previously established mouse model of gestational glucose intolerance induced by dietary low protein insult from conception until weaning. Pancreas and adipose samples were collected at 7, 30 and 90 days postpartum for histomorphometric and cytokine analyses, respectively. Glucose tolerance tests were performed prior to euthanasia and blood was collected via cardiac puncture. Pregnant female mice born to dams fed a low protein diet previously shown to develop glucose intolerance at late gestation relative to controls continued to be glucose intolerant until 1 month postpartum. However, glucose tolerance normalized by 3 months postpartum. Glucose intolerance at 7 days postpartum was associated with lower beta- and alpha-cell fractional areas and higher adipose levels of pro-inflammatory cytokine, interleukin-6. By 3 months postpartum, a compensatory increase in the number of small islets and a higher insulin to glucagon ratio likely enabled euglycemia to be attained in the previously glucose-intolerant mice. The results show that impairments in endocrine pancreas compensation in hyperglycemic pregnancy persist after parturition and contribute to prolonged glucose intolerance. These impairments may increase the susceptibility to development of future type 2 diabetes.