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Background : African countries experience high rates of infectious diseases that are mostly preventable by vaccination. Despite the risks of infections and other adverse outcomes, vaccination coverage in the African region remains significantly low. Poor vaccination knowledge is a contributory factor, and effective communication is crucial to bridging the vaccination uptake gap. This review summarises vaccination communication strategies adopted across African countries and associated changes in vaccine uptake. Methods: A systematic search was conducted in five bibliographic databases between 2000 and 2023 and supplemented with an additional Google Scholar search. Studies with data on vaccination communication and uptake in the English language were considered. A narrative synthesis was performed, and findings were presented in text and tables. Findings: Forty-one studies from fourteen African countries met the inclusion criteria. Several communication strategies were implemented for 13 different vaccines, mainly childhood vaccines. Mass campaigns and capacity building were the most common strategies for the public and health workers, respectively. Community-based strategies using social mobilisation effectively complemented other communication strategies.Overall, vaccination uptake increased in all countries following vaccination communication interventions. Barriers and facilitators to optimising vaccination communication at systemic and individual levels were also identified. Key barriers included lack of vaccine information, access issues, and high cost, while facilitators included improved vaccine education, reminders, trust-building initiatives, and community involvement. Conclusions: This review highlights effective vaccination communication strategies implemented across Africa as well as systemic and individual barriers and facilitators influencing vaccination uptake. The findings can inform strategies for vaccination communication and campaign planning to improve vaccination coverage in Africa.

Objective: To develop and validate tools for measuring inpatient gastroenterology (GI) consultation quality on oncologic patients., Methods: A total of 145 inpatient GI consults were analyzed using electronic health records in this cross-sectional study. Essential Consult Elements on oncologic-hospitalized patients (EE-COH) and Hospitalized Oncologic Patients Enhanced Quality of Consult Assessment Tool (HOPE-QCAT) were used for grading. Interrater reliability was assessed., Results: Both EE-COH and HOPE-QCAT showed near-perfect interrater reliability across most measures in the validation cohort. On application of these measures for quality assessment, basic evaluation by the requesting hospitalist was partially complete in 24.8%, the request for GI consultation was inappropriate in 18.6%, while the rationale for recommended studies from the GI consultant was provided in 55.7% of cases suggesting key areas for quality improvement., Conclusion: We developed highly reliable quality measures for inpatient GI consults on oncology patients. The EE-COH and HOPE-QCAT tools can be utilized in future studies of inpatient GI consult quality and to form the basis for interventions to improve communication between consultants and hospitalists. Such tools could be adapted for inpatient quality assessment across other specialties and settings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Numerous speculations have continually emerged, trying to explore the association between COVID-19 infection and a varied range of demographic and clinical factors. Frontline healthcare workers have been the primary group exposed to this infection, and there have been limited global research that examine this cohort. However, while there are a few large studies conducted on Indian healthcare professionals to investigate their potential risk and predisposing factors to COVID-19 infection, to our knowledge there are no studies evaluating the development of long COVID in this population. This cross-sectional study systematically utilized the demographic and clinical data of 3329 healthcare workers (HCW) from a tertiary hospital in India to gain significant insights into the associations between disease prevalence, severity of SARS-Cov-2 infection and long COVID. Most of the study population was found to be vaccinated (2,615, 78.5%), while 654 (19.65%) HCWs were found to be SARS-CoV-2 positive at least once. Of the infected HCWs, 75.1% (491) did not require hospitalization, whereas the rest were hospitalized for an average duration of 9 days. A total of 206 (6.19%) individuals were found to be suffering from long COVID. Persistent weakness/tiredness was the most experienced long-COVID symptom, while females (1.79, 1.25-2.57), individuals who consumed alcohol (1.85, 1.3-2.64) or had blood group B (1.9, 1.33-2.7) were at a significantly higher risk for developing long COVID., (© 2024. The Author(s).)

Background: Polypharmacy, particularly among older adults, is gaining recognition as an important risk to health. The harmful effects on health arise from disease-drug and drug-drug interactions, the cumulative burden of side effects from multiple medications and the burden to the patient. Single-disease clinical guidelines fail to consider the complex reality of optimising treatments for patients with multiple morbidities and medications. Efforts have been made to develop and implement interventions to reduce the risk of harmful effects, with some promising results. However, the theoretical basis (or pre-clinical work) that informed the development of these efforts, although likely undertaken, is unclear, difficult to find or inadequately described in publications. It is critical in interpreting effects and achieving effectiveness to understand the theoretical basis for such interventions., Objective: Our objective is to outline the theoretical underpinnings of the development of a new polypharmacy intervention: the Team Approach to Polypharmacy Evaluation and Reduction (TAPER)., Methods: We examined deprescribing barriers at patient, provider, and system levels and mapped them to the chronic care model to understand the behavioural change requirements for a model to address polypharmacy., Results: Using the chronic care model framework for understanding the barriers, we developed a model for addressing polypharmacy., Conclusions: We discuss how TAPER maps to address the specific patient-level, provider-level, and system-level barriers to deprescribing and aligns with three commonly used models and frameworks in medicine (the chronic care model, minimally disruptive medicine, the cumulative complexity model). We also describe how TAPER maps onto primary care principles, ultimately providing a description of the development of TAPER and a conceptualisation of the potential mechanisms by which TAPER reduces polypharmacy and its associated harms., (© 2023. The Author(s).)

Background: Although guidelines from multiple scientific studies decide the general trend in ACLR practice, there is often a variation between scientific guidelines and actual practice., Methods: A 17-member committee comprised of sports surgeons with experience of a minimum of 10 years of arthroscopy surgery finalized a survey questionnaire consisting of concepts in ACL tear management and perioperative trends, intraoperative and post-operative practices regarding single-bundle anatomic ACLR. The survey questionnaire was mailed to 584 registered sports surgeons in six states of south India. A single, non-modifiable response was collected from each member and analyzed., Results: 324 responses were received out of 584 members. A strong consensus was present regarding Hamstring tendons preference for ACLR, graft diameter ≥ 7.5 mm, viewing femoral footprint through the anterolateral portal, drilling femoral tunnel from anteromedial portal guided by ridges and remnants of femoral footprint using a freehand technique, suspensory devices to fix the graft in femur and interference screw in the tibia and post-operative bracing. A broad consensus was achieved in using a brace to minimize symptoms of instability of an ACL tear and antibiotic soaking of graft. There was no consensus regarding the timing of ACLR, preferred graft in athletes, pre-tensioning, extra-articular procedure, and return to sports. There was disagreement over hybrid tibial fixation and suture tapes to augment graft., Conclusion: Diverse practices continue to prevail in the management of ACL injuries. However, some of the consensuses reached in this survey match global practices. Contrasting or inconclusive practices should be explored for potential future research., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states no conflict of interest., (© The Author(s) 2022.)

Objective: Factors that physicians and patients consider when making decisions about using or recommending health apps are not well understood. We explored these factors to better assess how to support such decision making., Methods: We conducted an exploratory cross-sectional study in Ontario using qualitative focus groups and quantitative surveys. 133 physicians and 94 community dwelling adults completed online surveys and we held two focus groups of nine community dwelling participants who had cardiovascular risk factors and an interest in using mHealth apps. Quantitative survey data was analyzed descriptively. Focus groups were audio-recorded and transcribed verbatim prior to inductive thematic content analysis. We integrated the results from the surveys and focus groups to understand factors that influence physicians' and patients' selection and use of such apps., Results: Physicians recommend apps to patients but the level of evidence they prefer to use to guide selection did not align with what they were currently using. Patients trusted recommendations and reviews from medical organizations and healthcare professionals when selecting apps and were motivated to continue using apps when they supported goal setting and tracking, data sharing, decision making, and empowerment., Conclusions: The findings highlight the significance of evaluating mHealth apps based on metrics that patients and physicians value beyond usage and clinical outcome data. Patients engage with apps that support them in confidently managing their health. Increased training and awareness of apps and creating a more rigorous evidence base showing the value of apps to supporting health goals will support greater adoption and acceptance of mHealth apps., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. VB reports honoraria and an educational grant from Pfizer, honoraria from Bayer and loan of devices from Apple for research purposes., (© The Author(s) 2022.)

Vocal courtship is vital to the reproductive success of many vertebrates and is therefore a highly-motivated behavioral state. Catecholamines have been shown to play an essential role in the expression and maintenance of motivated vocal behavior, such as the coordination of vocal-motor output in songbirds. However, it is not well-understood if this relationship applies to anamniote vocal species. Using the plainfin midshipman fish model, we tested whether specific catecholaminergic (i.e., dopaminergic and noradrenergic) nuclei and nodes of the social behavior network (SBN) are differentially activated in vocally courting (humming) versus non-humming males. Herein, we demonstrate that tyrosine hydroxylase immunoreactive (TH-ir) neuron number in the noradrenergic locus coeruleus (LC) and induction of cFos (an immediate early gene product and proxy for neural activation) in the preoptic area differentiated humming from non-humming males. Furthermore, we found relationships between activation of the LC and SBN nuclei with the total amount of time that males spent humming, further reinforcing a role for these specific brain regions in the production of motivated reproductive-related vocalizations. Finally, we found that patterns of functional connectivity between catecholaminergic nuclei and nodes of the SBN differed between humming and non-humming males, supporting the notion that adaptive behaviors (such as the expression of advertisement hums) emerge from the interactions between various catecholaminergic nuclei and the SBN., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In the past decade, there has been increasing guideline development for short-term medical missions (STMMs) traveling from high-income to low- and middle-income countries for the purpose of supporting health care services. The ethics of STMMs is criticized in the literature and there is frequently a lack of host country collaboration. This typically results in guidelines which are developed through the lens of the sending (high-income) countries' staff and organizations. The aim of this paper is to evaluate an existing best practice guideline document from the perspective of host country participants with knowledge of STMMs from Honduras, Malawi, and the Philippines., Methods: The guideline used for the evaluation consisted of nine best practice elements that were discerned based on literature and the experience of those working within the field. Semi-structured interviews were conducted in a cross-sectional study with participants (n = 118) from the host countries. Thematic analysis was conducted by two researchers and the results were assessed by working group members to confirm interpretations of the data., Results: Overall, participants expressed a strong interest in having more structured guidance surrounding STMM practices. There was a positive response to and general acceptance of the proposed STMM guidelines, although participants found the 24-page document onerous to use; a companion checklist was developed. The key themes that emerged from the interviews included collaboration and coordination, care for hard-to-reach communities, capacity building, critical products and essential medical supplies, and opportunity and feasibility., Conclusions: Host input suggests that the guidelines provide structured regulation and coordination of the medical mission process and have the potential to improve the way STMMs are carried out. The guidelines have also proven to be a useful tool for the actual implementation of STMMs and can be a tool to strengthen links and trust between mission teams and local health staff. However, local contexts vary considerably, and guidelines must be adapted for local use. It is recommended that STMM teams work in conjunction with host partners to ensure they meet local needs, increase capacity development of local health workers, and provide continuity of care for patients into the local system., (© 2022. The Author(s).)

Introduction: We propose a possible mechanism of dislocation in a posterior stabilized (PS) total knee arthroplasty (TKA) and suggest that it can be treated like a stable posteriorly dislocated hip replacement if stable throughout the range on examination under anesthesia., Case Report: A 71-year-old female presented with the right posterior knee dislocation following 1 year of TKA. Following the successful relocation, the knee was found to be stable throughout the range of movement and an uneventful recovery at 3 years follow-up., Conclusion: Dislocation can occur in an otherwise stable TKA while squatting and can be successfully treated closed. The patients should be counseled to avoid squatting in a non-high flexion PS knee., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Introduction: Removal of screws from a titanium locking plate is often difficult once the screw has seized and the head is damaged. Such stripped screws are removed with an extraction screw, which can be used manually or on power. We aim to compare the extraction rates using both these methods., Material and Methods: We used 50, 3.5 mm diameter/20 mm long titanium locking screws. Fourth-generation saw bone models (radii) were used and 3.5 mm locking plates were fixed. The screws were deliberately over tightened and heads were damaged using a carbide drill to mimic stripped, seized screws. A left turn conical extraction screw coupled with a power tool was used for the first 25 screws and extraction screws coupled with a T handle for the remaining 25. A high-definition camera with a 60 fps frame rate was used to record the event. The time taken to remove screws from the plate was recorded., Results: When the extraction screw was used manually with T handle, we could remove 23 out of 25 screws (92%). When we used the extraction screw along with a power tool, 15 out of 25 (60%) locking screws were successfully removed., Conclusion: We recommend manual extraction with a T handle, rather than a power tool when removing the stripped locking screws (p-value <0.001). We feel that the haptic feedback provided when using manual extraction allows the surgeon to engage the extraction screws onto the damaged heads, thereby improving the extraction rates., Competing Interests: Declaration of Competing Interest The authors declare that they have no potential conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

The role for PD-1/PD-L1 and CTLA-4 targeted immunotherapy is well outlined in the treatment of metastatic NSCLC. Increased survival benefit supports the use of these medications and the development of next-generation agents with improved efficacy and favorable side-effect profiles. The prevalence of immunotherapy-associated cardiotoxicity (IAC) has grown significantly over the past two years as awareness of this toxicity class has emerged. High-grade conduction disorders comprise a subset of cardiotoxicities with a high case fatality rate. We presented a case of suspected combination ipilimumab-nivolumab associated 3rd degree heart block. The onset of this event was 16 days after immunotherapy initiation. A literature review has suggested that over 75% of cases of cardiotoxicity are observed within the first 6 weeks. We present findings from an interrogation of the FDA Adverse Event Reporting System (FAERS) and provide clinical guidance for the early identification of high-risk patients., Competing Interests: The authors have no competing financial interests to disclose., (© 2021 The Author(s).)

Background: Mobile health (mHealth) interventions can improve health by improving cardiovascular risk factors, but their adoption in care by physicians and patients is untapped. Few mHealth apps have been evaluated in clinical trials, and due to the fast pace of technological development, those previously evaluated are often outdated by the time trial results are available. Given the rapid pace of change in this field, it is not feasible to rigorously evaluate mHealth apps with current methodologies., Objective: The overall aim of this pilot study was to test the feasibility of using a web research platform called Trial My App to conduct efficient and rigorous web-based randomized controlled trials (RCTs) of mHealth apps relevant to patients with cardiovascular risk factors by evaluating an app that targets hypertension., Methods: For this study, 200 participants with suboptimally controlled hypertension will be recruited through advertisements in newsletters, media, and the internet, as well as through referrals from their health care providers. Screening, consent, randomization, and collection of patient-important health confidence and self-management ability outcomes will be conducted online through the Trial My App research platform. Participants will be randomized into 2 groups: 100 that will use an mHealth app for tracking hypertension and 100 that will be considered as an educational control. All participants will complete questionnaires at 0, 1, 3 and 6 months after enrolment. A substudy to validate the method of blood pressure readings and the consistency of data entered through Trial My App will be conducted with 40 participants., Results: The development of the Trial My App web platform has been completed. The creation of survey instruments has been completed in collaboration with our patient partners and advisory board. Recruitment is expected to begin in the first quarter of 2021; data collection and analysis are expected to be completed approximately 1 year after study commencement. Results will be disseminated through conferences and publications. The primary outcomes of this study include the feasibility of conducting an RCT using the Trial My App platform by reporting recruitment, retention, and completion statistics. We will validate app-entered data with a standard 7-day home blood pressure measurement method. Lastly, the pilot, nonblinded RCT will assess the effectiveness of the mHealth app in improving the control of hypertension compared with the control of hypertension in the educational control group., Conclusions: This study will determine if it is feasible to use the Trial My App web-based platform to evaluate the effectiveness of mHealth apps for patients with cardiovascular risk factors. As more mHealth apps are evaluated in RCTs, patients will be able to select apps that meet their needs and physicians will be able to make evidence-based recommendations to their patients for apps aimed at improving cardiovascular health., Trial Registration: ClinicalTrials.gov NCT04528654; https://clinicaltrials.gov/ct2/show/NCT04528654., International Registered Report Identifier (irrid): PRR1-10.2196/26155., (©Cynthia Lokker, Rita Jezrawi, Itzhak Gabizon, Jobin Varughese, Michael Brown, Dan Trottier, Elizabeth Alvarez, Jon-David Schwalm, Michael McGillion, Jinhui Ma, Vinai Bhagirath. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 01.02.2021.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Competing Interests: Declaration of Competing Interest All authors have nothing to disclose.

Positron-emission tomography-magnetic resonance imaging (PET-MRI) is an emerging hybrid imaging modality that utilizes the superior soft tissue resolution of MR with the metabolic data from PET. In this study, we sought to assess the clinical value of fluorodeoxyglucose (FDG) PET-MRI with dedicated pelvic PET-MR in the initial staging of cervical cancer. In this institutional-approved study, we identified 23 adult females who underwent FDG PET-MRI on hybrid camera for staging of primary uterine cervical cancer that included a dedicated PET-MR of the pelvis. A nuclear medicine physician and a radiologist reviewed the PET, MRI, and fusion-body and pelvis images alone and then with consensus read characterizing PET and MR abnormal findings. There were 23 patients who underwent FDG PET-MRI for initial staging of cervical cancer with an average age of 52.2 ± 14.0 years. A total of 23 suspected lymph nodes in eight different patients were detected within the pelvis with increased metabolic activity on PET. Both the dedicated pelvis and whole-body PET imaging detected the same corresponding pelvic lymph nodes, although the pelvic PET imaging had better lymph node uptake delineation due to longer acquisition time. Using a 10-mm short-axis criterion, MRI identified only 43.5% of the FDG avid lymph nodes. The average SUVmax on the pelvis PET sequences was higher with SUV 8.9 ± 5.2 compared to the whole-body PET with SUV 7.8 ± 5.4 but was not statistically significant ( P > 0.05). Primary cervical cancer was identified in 18 patients on both PET imaging and MRI with dedicated MR pelvis providing better characterization. Based on our results of the patients with cervical cancer evaluated for initial staging, combining dedicated pelvic PET-MRI with whole-body PET/MR provides the most complete status of malignant disease in reference to delineation of primary tumor, involvement of surrounding tissues, and regional lymph nodes., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 World Journal of Nuclear Medicine.)

Background: Two identical phase 3 randomized, double-blind, vehicle-controlled, 12-week studies (NCT03168321 and NCT03168334) demonstrated the efficacy and safety of tazarotene 0.045% lotion in participants with moderate-to-severe acne. Data from these studies were pooled and analyzed post hoc to evaluate outcomes by sex. Methods: Patients aged ≥9 years with moderate-to-severe acne (score 3 or 4 on the Evaluator's Global Severity Score [EGSS]) were randomized (1:1) to once-daily tazarotene 0.045% lotion or vehicle lotion for 12 weeks. Outcomes comprised inflammatory/noninflammatory lesion counts, treatment success (proportion of participants achieving ≥2-grade reduction from baseline in EGSS and score of 0 [“clear”] or 1 [“almost clear”]), and treatment-emergent adverse events (TEAEs). Results: A total of 1,064 females and 550 males were included in this analysis. For both sexes, least-squares mean percent changes from baseline to week 12 in lesion counts were significantly greater with tazarotene 0.045% lotion versus vehicle (inflammatory: females, -60.1% vs -52.1%; males, -53.6% vs -39.8%; noninflammatory: females, -57.6% vs -44.9%; males, -52.9% vs -36.5%; P<0.001, all). The percentage of participants achieving treatment success at week 12 was also significantly higher with tazarotene 0.045% lotion versus vehicle in females and males (P<0.001, both). Compared with tazarotene-treated males, tazarotene-treated females had significantly greater changes from baseline in inflammatory and noninflammatory lesions and a greater proportion achieved treatment success at week 12 (P<0.05, all). TEAE rates were similar between tazarotene- and vehicle-treated males; rates were higher for tazarotene-treated females than vehicle-treated females. Conclusions: Tazarotene 0.045% lotion was efficacious and well tolerated in the treatment of moderate-to-severe acne in female and male participants. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5249

Ovarian cancer is one of the most lethal gynecological cancers in women due to late diagnosis. Despite technological advancements, experienced physicians have high sensitivities and specificities in subjective assessments when combining ultrasound findings and clinical history in analyzing adnexal masses. This study aims to demonstrate general obstetricians and gynecologists' (OB/GYN) appropriateness in gynecologic oncologist referrals for malignant ovarian masses based on history and physical (H&P), imaging, and available tumor markers. Three board certified OB/GYNs were given 148 cases and determined whether or not they would refer them to a gynecologic oncologist. Results showed that OB/GYNs were 81-85% accurate in diagnosing patients with a benign or malignant disease. Among the malignant cases, reviewers had a high sensitivity ranging from 74-81% in appropriately referring a malignancy. In our study, OB/GYNs referred between 23-32% of ovarian masses to a gynecologic oncologist with only 9.5% of cases found to be malignant. Despite the high referral rates, generalists showed a high degree of sensitivity in accurately referring malignant diseases based solely on clinical experience and imaging studies, which could improve survival rates with early intervention by gynecologic oncologists.

Uterine torsion is an uncommon entity that is defined as a rotation of greater than 45° around the longitudinal axis of the uterus. Although cases of uterine torsion among pregnant patients have been mentioned in the literature, torsion of a non-gravid uterus is a rare occurrence. A 73-year-old nulliparous woman with a known fibroid uterus underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy with frozen section of a 17-18 cm pelvic mass seen on CT imaging. The source of the pelvic mass was unclear on imaging, and benign and malignant possibilities were discussed. During the procedure, necrosis of the uterine fundus and bilateral adnexa were seen due to the fundus being torsed with the uterine fibroid being the pivot point. Uterine torsion, though rare, can be the cause of acute pelvic pain in a postmenopausal woman., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Multiple health problems have been reported in survivors of Ebola virus disease (EVD). Attribution of these problems to the disease without a control group for analysis is difficult., Methods: We enrolled a cohort of EVD survivors and their close contacts and prospectively collected data on symptoms, physical examination findings, and laboratory results. A subset of participants underwent ophthalmologic examinations. Persistence of Ebola virus (EBOV) RNA in semen samples from survivors was determined., Results: A total of 966 EBOV antibody-positive survivors and 2350 antibody-negative close contacts (controls) were enrolled, and 90% of these participants were followed for 12 months. At enrollment (median time to baseline visit, 358 days after symptom onset), six symptoms were reported significantly more often among survivors than among controls: urinary frequency (14.7% vs. 3.4%), headache (47.6% vs. 35.6%), fatigue (18.4% vs. 6.3%), muscle pain (23.1% vs. 10.1%), memory loss (29.2% vs. 4.8%), and joint pain (47.5% vs. 17.5%). On examination, more survivors than controls had abnormal abdominal, chest, neurologic, and musculoskeletal findings and uveitis. Other than uveitis (prevalence at enrollment, 26.4% vs. 12.1%; at year 1, 33.3% vs. 15.4%), the prevalence of these conditions declined during follow-up in both groups. The incidence of most symptoms, neurologic findings, and uveitis was greater among survivors than among controls. EBOV RNA was detected in semen samples from 30% of the survivors tested, with a maximum time from illness to detection of 40 months., Conclusions: A relatively high burden of symptoms was seen in all participants, but certain symptoms and examination findings were more common among survivors. With the exception of uveitis, these conditions declined in prevalence during follow-up in both groups. Viral RNA in semen persisted for a maximum of 40 months. (Funded by the National Institute of Allergy and Infectious Diseases and the National Eye Institute; PREVAIL III ClinicalTrials.gov number, NCT02431923.)., (Copyright © 2019 Massachusetts Medical Society.)

Vocal species use acoustic signals to facilitate diverse behaviors such as mate attraction and territorial defense. However, little is known regarding the neural substrates that interpret such divergent conspecific signals. Using the plainfin midshipman fish model, we tested whether specific catecholaminergic (i.e., dopaminergic and noradrenergic) nuclei and nodes of the social behavior network (SBN) are differentially responsive following exposure to playbacks of divergent social signals in sneaker males. We chose sneaker (type II) males since they attempt to steal fertilizations from territorial type I males who use an advertisement call (hum) to attract females yet are also subjected to vocal agonistic behavior (grunts) by type I males. We demonstrate that induction of cFos (an immediate early gene product and proxy for neural activation) in two forebrain dopaminergic nuclei is greater in sneaker males exposed to hums but not grunts compared to ambient noise, suggesting hums preferentially activate these nuclei, further asserting dopamine as an important regulator of social-acoustic behaviors. Moreover, acoustic exposure to social signals with divergent salience engendered contrasting shifts in functional connectivity between dopaminergic nuclei and nodes of the SBN, supporting the idea that interactions between these two circuits may underlie adaptive decision-making related to intraspecific male competition., (Copyright © 2018 Elsevier B.V. All rights reserved.)

One year after a Zaire ebolavirus (EBOV) outbreak occurred in the Boende Health Zone of the Democratic Republic of the Congo during 2014, we sought to determine the breadth of immune response against diverse filoviruses including EBOV, Bundibugyo (BDBV), Sudan (SUDV), and Marburg (MARV) viruses. After assessing the 15 survivors, 5 individuals demonstrated some degree of reactivity to multiple ebolavirus species and, in some instances, Marburg virus. All 5 of these survivors had immunoreactivity to EBOV glycoprotein (GP) and EBOV VP40, and 4 had reactivity to EBOV nucleoprotein (NP). Three of these survivors showed serologic responses to the 3 species of ebolavirus GPs tested (EBOV, BDBV, SUDV). All 5 samples also exhibited ability to neutralize EBOV using live virus, in a plaque reduction neutralization test. Remarkably, 3 of these EBOV survivors had plasma antibody responses to MARV GP. In pseudovirus neutralization assays, serum antibodies from a subset of these survivors also neutralized EBOV, BDBV, SUDV, and Taï Forest virus as well as MARV. Collectively, these findings suggest that some survivors of naturally acquired ebolavirus infection mount not only a pan-ebolavirus response, but also in less frequent cases, a pan-filovirus neutralizing response.

Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that accounts for up to 40% of all endometrial cancer-related deaths. Recent whole-exome sequencing studies have revealed HER2/neu amplification in 27-44% of USC patients, supporting HER2 as an attractive pathway for target therapies based on monoclonal antibodies or tyrosine kinase inhibitors. Preclinical studies and a recently published prospective randomized trial with trastuzumab in combination with chemotherapy demonstrated promising results with anti-HER2-targeted therapies in advanced and recurrent USC patients. In contrast, single-agent trastuzumab or tyrosine kinase inhibitors (i.e., lapatinib) were unable to demonstrate significant clinical activity and/or durable tumor growth inhibition. Combinatorial therapies may represent novel, highly effective therapeutic strategies to overcome inborn or acquired resistance to HER2/neu-targeted therapies in HER2-amplified USC patients. This study presents a comprehensive review of the mechanisms of USC resistance to HER2-targeted therapies and potential strategies to overcome it.

Carcinosarcomas (CSs) of the uterus and ovary are rare biologically aggressive tumors with poor prognosis. The development of novel, effective treatment strategies against CSs of the female genital tract remains an unmet medical need. Whole-exome sequencing studies have recently demonstrated mutations or aberrant activation of multiple genes/pathways in CSs including HER2, PI3K/AKT/mTOR, EGFR, MAPK, genes related to histones and chromatin structure, and genes related to cell-cycle regulation. The carcinomatous component of these biphasic tumors is suggested to be the catalyst in CS tumorigenesis. This article reviews the genetic landscapes and explores novel targeted treatment modalities against this deadly gynecologic tumor.