A Preliminary Study of Vallecular Bolus Aggregation in Healthy Swallowing of Solid Food Boluses.

OBJECTIVE: The pharyngeal swallow typically begins within 400 ms following the arrival of a liquid bolus in the pharynx. By contrast, processed food particles aggregate in the valleculae prior to swallow initiation. With solid foods, swallow reaction time (SRT), the interval between bolus passing the ramus of mandible and hyoid burst onset (HYB) can be subdivided into components of vallecular aggregation time (VAT) and the subsequent end of aggregation to hyoid burst interval (EOA-to-HYB). However, expected durations of these timing measures remain unclear. We aimed to study bolus aggregation in healthy swallowing for International Dysphagia Diet Standardisation Initiative Food Levels 5 (minced and moist [MM5]), 6 (soft and bite-sized [SB6]), and 7 (regular [RG7]). Understanding typical patterns and durations of vallecular aggregation with solids in healthy swallowing will inform the identification of impaired swallow timing in patient populations. DESIGN: Twenty healthy adults (10 males, Mage = 28 years, range: 23-55 years) swallowed two boluses each of MM5, SB6, and RG7 foods in videofluoroscopy. Blinded duplicate ratings determined bolus location at swallow onset, SRT, VAT, and EOA-to-HYB. Texture-based differences were measured using Friedman's tests. Bolus location was at/above the valleculae at swallow onset for 85% of boluses, with no differences by texture. SRT, VAT, and EOA-to-HYB did not vary by texture, with overall median values (interquartile range) of 99 ms (-66 to 743 ms) for SRT, 347 ms (66 to 891 ms) for VAT, and -132 ms (-231 to -83 ms) for EOA-to-HYB. CONCLUSIONS: These data corroborate prior evidence that it is not unusual for food particles to aggregate in the valleculae prior to swallow initiation in healthy swallowing. However, durations of vallecular aggregation are typically < 1 s in healthy adults.

Histoplasmosis Around the World: A Global Perspective on Presentation, Virulence Factors, and Treatment of Histoplasmosis.

Histoplasmosis is a systemic infection caused by an endemic dimorphic fungus, Histoplasma capsulatum. Though prevalent in the eastern United States of America, near the Ohio and Mississippi River Valleys, the evidence underlying the global prevalence of histoplasmosis, especially in immunocompromised populations, is underappreciated. This article highlights the global epidemiology, risk factors, microbiology and pathophysiological characteristics, pulmonary and extrapulmonary manifestations, prevention measures, radiographic patterns, diagnostic techniques, and antifungal treatment approaches for Histoplasma capsulatum.

COVID-19 Vaccine Hesitancy Among US Adults: Safety and Effectiveness Perceptions and Messaging to Increase Vaccine Confidence and Intent to Vaccinate.

OBJECTIVE: Public health agencies have a critical role in providing effective messaging about mitigation strategies during a public health emergency. The objectives of this study were (1) to understand perceptions of COVID-19 vaccines, including concerns about side effects, safety, and effectiveness and how these perceptions influence vaccine decision-making among US adults and (2) to learn what messages might motivate vaccine uptake. METHODS: In April and May 2021, we conducted 14 online focus groups with non-Hispanic English-speaking and English- and Spanish-speaking Hispanic adults (N = 99) not vaccinated against COVID-19. We oversampled adults aged 18-39 years and rural residents and systematically assessed 10 test messages. Researchers used a standardized guide and an a priori codebook for focus group discussions, coding transcripts, and thematic analysis. RESULTS: Vaccine hesitancy factors included fear of the unknown; long-term side effects, including infertility; and beliefs that the vaccines were developed too quickly and were not sufficiently effective. Motivating factors for receiving vaccination included the ability to safely socialize and travel. Health care providers were considered important trusted messengers. Participants were critical of most messages tested. Messages that came across as "honest" about what is not yet known about COVID-19 vaccines were perceived more positively than other messages tested. Messages were seen as ineffective if perceived as vague or lacking in data and specificity. CONCLUSIONS: Messages that were simple and transparent about what is unknown about vaccines relative to emerging science were viewed most favorably. Health care providers, friends, and family were considered influential in vaccination decision-making. Findings underscore the benefits of research-informed strategies for developing and disseminating effective messages addressing critical issues in a public health emergency.

Exploring the Efficacy of the Effortful Swallow Maneuver for Improving Swallowing in People With Parkinson Disease-A Pilot Study.

Objectives: To determine the immediate (compensatory) and longer term (rehabilitative) effect of the effortful swallow (ES) maneuver on physiological swallowing parameters in Parkinson disease. Design: Virtual intervention protocol via Microsoft Teams with pre- and post-videofluoroscopic swallowing studies. Setting: Outpatient hospital setting, with intervention performed virtually. Participants: Eight participants (median age 74 years [63-82])with Parkinson disease (years post onset 3-20) with a Hoehn and Yahr scale score between 2 and 4 (N=8). Interventions: ES maneuver, initiated using a maximum effort isometric tongue-to-palate press, with biofeedback provided using the Iowa Oral Performance Instrument. The protocol included 30 minute sessions twice daily, 5 days/week for 4 weeks. Main Outcome Measures: Penetration-Aspiration Scale scores, time-to-laryngeal-vestibule-closure, total pharyngeal residue, and pharyngeal area at maximum constriction as seen on lateral view videofluoroscopy. Results: No consistent, systematic trends were identified in the direction of improvement or deterioration across Penetration-Aspiration Scale scores, time-to-laryngeal-vestibule-closure, pharyngeal area at maximum constriction, or total pharyngeal residue. Conclusions: Heterogeneous response to the ES as both a compensatory and rehabilitative technique. Positive response on the compensatory probe was predictive of positive response after rehabilitation.

The Adverse Effects and Events of Thickened Liquid Use in Adults: A Systematic Review.

PURPOSE: Practice pattern studies suggest that liquid modification is currently a primary strategy used by speech-language pathologists to manage dysphagia; however, the breadth of negative consequences associated with their use is not well understood. The purpose of this review was to summarize the evidence on adverse events and effects of thickened liquid (TL) use in adults. METHOD: Six databases were searched in February 2022: EMBASE, MEDLINE (PubMed), Speechbite, AMED, AgeLine, and CINAHL. Articles were included if they compared adults receiving different TL viscosities and discussed at least one adverse event or effect of consuming TLs. Articles were excluded if they were review articles, rehabilitation studies, rheological analyses, not in English, or not peer reviewed. Screening and data extraction were completed by two independent reviewers. Risk of bias was assessed using Cochrane tools. RESULTS: Thirty-three studies (N = 4,990 participants across all studies) were eligible for inclusion (2,405 unique records screened). Reported adverse events included dehydration (n = 5), pneumonia (n = 4), death (n = 2), urinary tract infection (n = 1), and hospitalization (n = 1); adverse effects included reduced quality of life (n = 18), aspiration (n = 12), reduced intake (n = 8), increased residue (n = 4), and reduced medication bioavailability (n = 2). Results were mapped on to codes and domains of the International Classification of Functioning, Disability and Health. CONCLUSIONS: A range of adverse outcomes associated with TL use were identified. Adverse outcomes should be monitored and reported in dysphagia research. Given current research evidence, it is vital for clinicians to weigh the risks and benefits of TL use to mitigate potential adverse outcomes.

Reminding Peer Reviewers of Reporting Guideline Items to Improve Completeness in Published Articles: Primary Results of 2 Randomized Trials.

Importance: Numerous studies have shown that adherence to reporting guidelines is suboptimal. Objective: To evaluate whether asking peer reviewers to check if specific reporting guideline items were adequately reported would improve adherence to reporting guidelines in published articles. Design, Setting, and Participants: Two parallel-group, superiority randomized trials were performed using manuscripts submitted to 7 biomedical journals (5 from the BMJ Publishing Group and 2 from the Public Library of Science) as the unit of randomization, with peer reviewers allocated to the intervention or control group. Interventions: The first trial (CONSORT-PR) focused on manuscripts that presented randomized clinical trial (RCT) results and reported following the Consolidated Standards of Reporting Trials (CONSORT) guideline, and the second trial (SPIRIT-PR) focused on manuscripts that presented RCT protocols and reported following the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline. The CONSORT-PR trial included manuscripts that described RCT primary results (submitted July 2019 to July 2021). The SPIRIT-PR trial included manuscripts that contained RCT protocols (submitted June 2020 to May 2021). Manuscripts in both trials were randomized (1:1) to the intervention or control group; the control group received usual journal practice. In the intervention group of both trials, peer reviewers received an email from the journal that asked them to check whether the 10 most important and poorly reported CONSORT (for CONSORT-PR) or SPIRIT (for SPIRIT-PR) items were adequately reported in the manuscript. Peer reviewers and authors were not informed of the purpose of the study, and outcome assessors were blinded. Main Outcomes and Measures: The difference in the mean proportion of adequately reported 10 CONSORT or SPIRIT items between the intervention and control groups in published articles. Results: In the CONSORT-PR trial, 510 manuscripts were randomized. Of those, 243 were published (122 in the intervention group and 121 in the control group). A mean proportion of 69.3% (95% CI, 66.0%-72.7%) of the 10 CONSORT items were adequately reported in the intervention group and 66.6% (95% CI, 62.5%-70.7%) in the control group (mean difference, 2.7%; 95% CI, -2.6% to 8.0%). In the SPIRIT-PR trial, of the 244 randomized manuscripts, 178 were published (90 in the intervention group and 88 in the control group). A mean proportion of 46.1% (95% CI, 41.8%-50.4%) of the 10 SPIRIT items were adequately reported in the intervention group and 45.6% (95% CI, 41.7% to 49.4%) in the control group (mean difference, 0.5%; 95% CI, -5.2% to 6.3%). Conclusions and Relevance: These 2 randomized trials found that it was not useful to implement the tested intervention to increase reporting completeness in published articles. Other interventions should be assessed and considered in the future. Trial Registration: ClinicalTrials.gov Identifiers: NCT05820971 (CONSORT-PR) and NCT05820984 (SPIRIT-PR).

Differences in pharyngeal swallow event timing: Healthy aging, Parkinson disease, and amyotrophic lateral sclerosis.

Objective: The pharyngeal phase of swallowing involves a coordinated sequence of events. Event durations may be prolonged in people with Parkinson disease (PwPD), and amyotrophic lateral sclerosis (PwALS); however, the cumulative effect of these changes is unexplored. We compared event latencies relative to hyoid burst (HYB) (time zero) to understand differences in deglutatory event timing. We hypothesized PwPD and PwALS would display similarly prolonged cumulative pharyngeal phase durations compared to healthy controls, with greater prolongations with increasing bolus viscosity. Method: We retrospectively evaluated videofluoroscopic data of healthy adults (n = 78), PwPD (n = 17), and PwALS (n = 20). Participants swallowed 15 boluses of 20% (w/v) barium across five liquid consistencies. Paired raters evaluated nine deglutitive events using the ASPEKT method. Latencies were plotted by consistency relative to HYB and compared across cohorts using Mann-Whitney U tests (p ≤ .05). Cohen's d was calculated for all statistically significant results to determine effect size. Results: In PwPD, significantly prolonged latencies were observed on thin liquid boluses compared to healthy controls. Latencies to all post-HYB events were significantly prolonged except for maximum upper esophageal sphincter distension. In PwALS, significantly prolonged latencies for events preceding and following HYB were noted on all consistencies compared to healthy controls and PwPD. Conclusion: In PwPD, event latencies for multiple components of the swallowing sequence were prolonged culminating in overall prolongation of the pharyngeal phase on thin liquid. A similar pattern, but with significantly greater prolongation, was seen in the PwALS, and extended to swallows of all liquid consistencies.

Bolus Texture Testing as a Clinical Method for Evaluating Food Oral Processing and Choking Risk: A Pilot Study.

PURPOSE: Choking on food is a leading cause of accidental death in several populations, including children, people with intellectual/developmental disability, and older adults in residential care facilities. One contributor to choking risk is incomplete oral processing and failure to convert food to a cohesive, nonsticky bolus with a maximum particle size that will not block the airway. Clinical tests of mastication do not evaluate properties of chewed food boluses. We characterized expectorated boluses, after oral processing, using methods developed by the International Dysphagia Diet Standardisation Initiative (IDDSI). METHOD: Seventeen adults without dysphagia (seven women and 10 men), aged 23-55 years, chewed samples of a cracker, a raw baby carrot, and a circular, dome-shaped gummy candy. Chewing metrics were obtained up to the point when the person indicated that they were ready to swallow. The bolus was then either expectorated or swallowed; IDDSI tests were used to characterize the expectorated boluses. RESULTS: Measures of chewing did not differ between spit and swallow conditions. Expectorated cracker and carrot boluses had maximum particle size consistent with IDDSI Level SB6 Soft & Bite-Sized foods or lower. The gummy candy samples remained at IDDSI Level RG7 Regular food consistency. CONCLUSIONS: This study suggests that expectorated ready-to-swallow boluses are representative of boluses that are swallowed and that oral processing in adults without dysphagia typically results in boluses at IDDSI's Level SB6 or lower. IDDSI's testing methods provide a practical method for evaluating oral processing by characterizing expectorated ready-to-swallow boluses and may guide food texture recommendations for persons who have increased risk of choking.

Comparison of Lingual Pressure Generation Capacity in Parkinson Disease, Amyotrophic Lateral Sclerosis, and Healthy Aging.

PURPOSE: The tongue plays a key role in bolus propulsion during swallowing, with reduced lingual pressure generation representing a risk factor for impaired swallowing safety and efficiency. We compared lingual pressure generation capacity in people with Parkinson disease (PwPD), people with amyotrophic lateral sclerosis (PwALS), and healthy older adults. We hypothesized that both patient cohorts would demonstrate reduced maximum anterior isometric pressure (MAIP) and regular effort saliva swallow (RESS) pressures compared with healthy controls, with the greatest reductions expected in the ALS cohort. METHOD: We enrolled 20 PwPD, 18 PwALS, and 20 healthy adults over 60 years of age. The Iowa Oral Performance Instrument was used to measure MAIP, RESS, and lingual functional reserve (LFR, i.e., MAIP - RESS). Descriptive statistics were calculated; between-groups differences were explored using univariate analyses of variance and post hoc Sidak tests with alpha set at .05. RESULTS: Mean MAIPs for the PD, ALS, and heathy cohorts were 54.7, 33.5, and 47.4 kPa, respectively. Significantly lower MAIP was found in PwALS compared with PwPD and healthy controls. RESS values did not differ significantly across groups. LFR was significantly higher in PwPD versus PwALS and healthy controls. CONCLUSIONS: Lingual pressure generation capacity and functional reserve were reduced in PwALS, but not in PwPD, beyond changes seen with healthy aging. Both patient cohorts displayed preserved lingual pressure during saliva swallows. Future studies exploring longitudinal changes in tongue pressure generation on isometric and saliva swallowing tasks will be needed to confirm whether tongue pressure measures serve as noninvasive clinical biomarkers of swallowing impairment.

Perceptions, knowledge, and communication preferences about indoor mold and its health implications among persons affected by Hurricane Harvey: a focus group analysis.

BACKGROUND: Among people affected by Hurricane Harvey, we assessed experiences and perceptions (e.g., knowledge, attitudes, and practices) regarding mold and its impact on health and elicited participants' opinions about how to improve public health messaging about indoor mold after a large flooding event. METHODS: Houston Health Department conducted four focus groups with 31 Houston metropolitan area residents during January to March 2020, using a semi-structured discussion guide and federal communication materials about indoor mold. Drawing from a theoretical framework analysis, transcripts were grouped into relevant themes using inductive and deductive coding. RESULTS: Hurricane Harvey had a large impact on participants' living standards, and widespread financial barriers to remediation led to long-term mold exposure for many participants. Knowledge about mold's impact on health and proper mold clean-up practices varied, and clean-up behaviors did not commonly align with federal guidance. Participants generally preferred traditional forms of outreach, such as in-person, radio, and television announcements, to communicate public health messaging. CONCLUSIONS: More strategic dissemination of expanded public health educational materials about proper mold clean-up practices and the health risks of mold exposure following flooding events is needed.

Effectiveness of Interventions for Dysphagia in Parkinson Disease: A Systematic Review.

PURPOSE: Dysphagia is a common sequela of Parkinson disease (PD) and is associated with malnutrition, aspiration pneumonia, and mortality. This review article synthesized evidence regarding the effectiveness of interventions for dysphagia in PD. METHOD: Electronic searches were conducted in Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and speechBITE. Of the 2,015 articles identified, 26 met eligibility criteria: interventional or observational studies with at least five or more participants evaluating dysphagia interventions in adults with PD-related dysphagia, with outcomes measured using videofluoroscopic swallowing study (VFSS), fiberoptic endoscopic evaluation of swallowing (FEES), or electromyography (EMG). Risk of bias (RoB) was evaluated using the Evidence Project tool and predetermined criteria regarding the rigor of swallowing outcome measures. RESULTS: Interventions were classified as follows: pharmacological (n = 11), neurostimulation (n = 8), and behavioral (n = 7). Primary outcome measures varied across studies, including swallowing timing, safety, and efficiency, and were measured using VFSS (n = 17), FEES (n = 6), and EMG (n = 4). Critical appraisal of study findings for RoB, methodological rigor, and transparency showed the majority of studies failed to adequately describe contrast media used, signal acquisition settings, and rater blinding to time point. Low certainty evidence generally suggested improved swallow timing with exercises with biofeedback and deep brain stimulation (DBS), improved safety with DBS and expiratory muscle strength training, and improved efficiency with the Lee Silverman Voice Treatment and levodopa. CONCLUSIONS: Studies with lower RoB and greater experimental rigor showed potential benefit in improving swallowing efficiency but not safety. Further research investigating discrete changes in swallowing pathophysiology post-intervention is warranted to guide dysphagia management in PD. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.17132162.

Which Physiological Swallowing Parameters Change with Healthy Aging?

Research suggests there are age-related changes in swallowing that do not constitute impairment ("presbyphagia"). The goal of this study was to explore the influence of age on quantitative measures of healthy swallowing by controlling for the effects of sex and sip volume in order to determine the specific characteristics of presbyphagia. Videofluoroscopy recordings of thin liquid swallows from 76 healthy adults (38 male), aged 21-82 were analysed. Blinded duplicate ratings of swallowing safety, efficiency, kinematics, and timing were made using the ASPEKT method. Hierarchical regression models were used to determine the effects of age, sex, and sip-volume on swallowing. There were no age-related changes in sip volume, number of swallows per bolus, frequency or severity of penetration-aspiration, duration of the hyoid-burst (HYB)-to-upper-esophageal-sphincter (UES) opening interval, time-to-laryngeal-vestibule-closure (LVC), peak hyoid position, hyoid speed, or pharyngeal residue. Significant changes seen with increasing age included: longer swallow reaction time, UES opening duration and LVC duration; larger pharyngeal area at rest and maximum constriction; and wider UES diameter. Male participants had larger sip volume and pharyngeal area at rest. Larger sip volumes were associated with multiple swallows per bolus and shorter hyoid-burst-to-UES opening intervals. These results help to define presbyphagic changes in swallowing that can be expected in healthy older adults up to 80 years of age, and distinguish them from changes that represent impairment. Certain parameters showed changes that were opposite in direction to changes that are usually considered to reflect impairment: longer UES opening, longer LVC duration and wider UES opening. These changes may reflect possible compensations for slower bolus transit. Further research is needed to determine the points along the age continuum where observed age-related changes in swallowing begin to emerge.

The Frequency of Atypical and Extreme Values for Pharyngeal Phase Swallowing Measures in Mild Parkinson Disease Compared to Healthy Aging.

Purpose Dysphagia is thought to be prevalent and a leading cause of morbidity and mortality in people with Parkinson disease (PwPD). The aim of this study was to compare the frequencies of atypical and extreme values for measures of swallowing physiology in PwPD and in an age- and sex-matched cohort of healthy adults. Atypical and extreme values were defined, respectively, as values falling in the 25% and 5% tails of the reference distribution for healthy adults under age 60 years. Method A standard videofluoroscopy (VF) protocol was performed in 17 adults with mild PD and 17 age- and sex-matched healthy adults using 20% w/v liquid barium ranging from thin to extremely thick consistency. Blinded VF analysis was performed according to the Analysis of Swallowing Physiology: Events, Kinematics and Timing Method. Frequencies for atypical and extreme values were tabulated by cohort and compared using odds ratios. Results Increased frequencies of atypical values (> 25%) were seen in the PwPD for prolonged swallow reaction time, prolonged time-to-laryngeal-vestibule-closure (LVC), and poor pharyngeal constriction. However, these findings were also observed in the healthy controls. The PwPD showed significantly higher odds of atypical values for narrow upper esophageal sphincter (UES) diameter on thin liquids, a short hyoid-burst-to-UES-opening interval on extremely thick liquids, and prolonged time-to-LVC, LVC duration, and UES opening duration on multiple consistencies. The frequencies of extreme values failed to show any significant cohort differences for any parameter. Conclusions In this study, a group of people with mild PD did not show clear evidence of swallowing impairments distinct from the changes seen in a healthy age-matched control group when odds ratios were used to compare the frequencies of atypical values between PwPD and the control group; only a few parameters showed significant differences. These were findings of significantly higher frequencies in PwPD of prolonged LVC and UES opening duration. Supplemental Material https://doi.org/10.23641/asha.15032241.

Patient notification about suspected hospital-associated outbreaks of invasive mold infections: Considerations for public health and hospital personnel.

A common type of fungal disease investigation involves hospital-associated clusters of invasive mold infections (IMIs), which typically occur among immunocompromised patients. Responding to IMI clusters can be challenging for public health and hospital personnel for several reasons such as difficulty of confirming the existence of an outbreak, difficulty of determining source. Although many resources exist to guide patient notification about healthcare incidents (eg, bloodborne exposures, disease outbreaks), IMI clusters involve special considerations related to the complex diseases, uncertain exposures, and differential benefits and risks of notification. Early, nuanced communication about hospital-associated IMI clusters is almost always the best course of action to help reduce risks to patients' health and foster trust between patients and hospitals.

A scoping review of interventions for adults with dysarthria following traumatic brain injury.

Primary objective: To review the current literature on interventions for dysarthria following traumatic brain injury (TBI) for their effectiveness and methodological quality, and identify future directions for research in developing guidelines for treating dysarthria in this population.Research design: Scoping review.Methods and procedures: Electronic databases were searched up until July 2018 to find intervention trials for treating dysarthria following TBI. Articles were assessed by three reviewers to meet the following criteria: (1) population (adults with dysarthria following TBI only) and (2) intervention studies. Of the 1481 articles initially identified, 17 were selected based on inclusion criteria. 16 articles were single case designs (SCD) and one was a cohort study. Methodological qualities of eligible articles were examined using the single-case experimental design (SCED) rating scale; the cohort study was qualitatively described.Main outcomes and results: The interventions described fell into six broad categories - behavioral, prosthetic, instrumental, pharmacological, augmentative and alternative communication (AAC), and mixed intervention. Behavioral interventions received the most focus in the literature. The articles rated using the SCED received an average score of 6.8, indicating moderate methodological quality.Conclusions: This field currently lacks high-quality research. Further research is required to determine the best clinical practice.

Undifferentiated spermatogonia regulate Cyp26b1 expression through NOTCH signaling and drive germ cell differentiation.

Cytochrome P450 family 26 subfamily B member 1 (CYP26B1) regulates the concentration of all-trans retinoic acid (RA) and plays a key role in germ cell differentiation by controlling local distribution of RA. The mechanisms regulating Cyp26b1 expression in postnatal Sertoli cells, the main components of the stem cell niche, are so far unknown. During gonad development, expression of Cyp26b1 is maintained by Steroidogenic Factor 1 (SF-1) and Sex-Determining Region Y Box-9 (SOX9), which ensure that RA is degraded and germ cell differentiation is blocked. Here, we show that the NOTCH target Hairy/Enhancer-of-Split Related with YRPW Motif 1 (HEY1), a transcriptional repressor, regulates germ cell differentiation via direct binding to the Cyp26b1 promoter and thus inhibits its expression in Sertoli cells. Further, using in vivo germ cell ablation, we demonstrate that undifferentiated type A spermatogonia are the cells that activate NOTCH signaling in Sertoli cells through their expression of the NOTCH ligand JAGGED-1 (JAG1) at stage VIII of the seminiferous epithelium cycle, therefore mediating germ cell differentiation by a ligand concentration-dependent process. These data therefore provide more insights into the mechanisms of germ cell differentiation after birth and potentially explain the spatiotemporal RA pulses driving the transition between undifferentiated to differentiating spermatogonia.-Parekh, P. A., Garcia, T. X., Waheeb, R., Jain, V., Gandhi, P., Meistrich, M. L., Shetty, G., Hofmann, M.-C. Undifferentiated spermatogonia regulate Cyp26b1 expression through NOTCH signaling and drive germ cell differentiation.

Pharma Collaboration for Transparent Medical Information (phactMI) Benchmark Study: Trends, Drivers, Success Factors, and Value of Globalization in Medical Information.

BACKGROUND: Over the past decade, biopharmaceutical companies have been progressively establishing global frameworks across their capabilities. It is well recognized that the Medical Information (MI) department is a key externally facing function that needs to maintain a consistent focus on optimizing its capabilities of addressing product medical inquiries worldwide. METHODS: In the United States, a consortium named Pharma Collaboration for Transparent Medical Information, phactMI, a collaboration of pharmaceutical company MI departments dedicated to supporting health care professionals in their commitment to provide quality patient care, has provided a forum to benchmark and share best practices across the companies. In May 2017, phactMI conducted a survey inclusive of 25 biopharmaceutical companies to gain insight into the globalization of respective MI departments and relevant trends. RESULTS: We found increased trends in various aspects of globalization across large, mid, and small size companies, and identified key drivers for success. Overall, 16 of the 25 companies had globalized their MI department, 5 had only partially globalized, and the remaining 4 had not globalized. CONCLUSION: The findings of this survey will further help inform the MI community as to globalization approaches for a successful outcome.

The NOTCH Ligand JAG1 Regulates GDNF Expression in Sertoli Cells.

In the seminiferous epithelium of the testis, Sertoli cells are key niche cells directing proliferation and differentiation of spermatogonial stem cells (SSCs) into spermatozoa. Sertoli cells produce glial cell line-derived neurotrophic factor (GDNF), which is essential for SSC self-renewal and progenitor expansion. While the role of GDNF in the testis stem cell niche is established, little is known about how this factor is regulated. Our previous studies on NOTCH activity in Sertoli cells demonstrated a role of this pathway in limiting stem/progenitor cell numbers, thus ultimately downregulating sperm cell output. In this study we demonstrate through a double-mutant mouse model that NOTCH signaling in Sertoli cells functions solely through the canonical pathway. Further, we demonstrate through Dual luciferase assay and chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) analysis that the NOTCH targets HES1 and HEY1, which are transcriptional repressors, directly downregulate GDNF expression by binding to the Gdnf promoter, thus antagonizing the effects of FSH/cAMP. Finally, we demonstrate that testicular stem/progenitors cells are activating NOTCH signaling in Sertoli cells in vivo and in vitro through the NOTCH ligand JAG1 at their surface, indicating that these cells may ensure their own homeostasis through negative feedback regulation.