Migraine Symptoms Induced by an Auricular Piercing in a 27-Year-Old Female: A Case Report.

Introduction: Migraines are common and debilitating, and have high direct and indirect costs. They can be difficult to treat, and many patients make use of alternative medicine techniques. One of these is acupuncture applied to locations on the auricle thought to modulate migraine symptoms. Some patients obtain piercings in these locations in hopes of relieving their symptoms; however, the literature does not address the possibility of migraine symptoms being worsened or even induced by such piercings. Case Presentation: We present a case of a 27-year-old female with a history of transient hemiplegia without headaches who developed headaches, visual disturbances, and nausea after a piercing of the inferior crus of her left antihelix (known as a rook piercing). No abnormalities were found on workup, and symptoms were treated with supportive care. After removing the piercing 9 months later, the patient's symptoms resolved. Conclusion: The mechanism linking the piercing with the migraine symptoms is unclear, but may involve modulation of trigeminal or vagal pain pathways, as both of these cranial nerves innervate this area of the auricle. Regardless, in patients presenting with migraine symptoms, history and physical exam should not overlook piercings as potential contributory factors.

Inhibition of Fas ligand in NOD mice unmasks a protective role for IL-10 against insulitis development.

Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by the destruction of pancreatic insulin-producing ß cells by autoreactive T cells early in life. Despite daily insulin injections, patients typically develop cardiovascular and other complications; and intensive efforts are being directed toward identifying therapeutic targets to prevent the disease without directly impinging on the host defense. Fas ligand (FasL) is one potential target. Fas-FasL interactions primarily regulate T-cell homeostasis, not activation. Nevertheless, spontaneous gene mutation of Fas (called lpr mutation) or FasL (called the gld mutation) prevents autoimmune diabetes in nonobese diabetic (NOD) mice, the widely used model for T1D. Furthermore, although homozygous gld mutations cause age-dependent lymphoproliferation, limiting the gld mutation to one allele (NOD-gld/+) or treating NOD-wild-type mice with FasL-neutralizing monoclonal antibody completely prevents the disease development without causing lymphoproliferation or immune suppression. Herein, we show that the heterozygous gld mutation inhibits the accumulation of diabetogenic T cells in the pancreas, without interfering with their proliferation and expansion in the draining pancreatic lymph nodes. Pancreata from NOD-gld/+ mice contained B cells that expressed CD5 and produced IL-10, which was critical for maintenance of the disease resistance because its neutralization with an IL-10 receptor-blocking monoclonal antibody allowed accumulation of CD4 T cells in the pancreas and led to insulitis development. The results provide novel insights into the pathogenesis of T1D that could have important therapeutic implications.

Providing support in a pandemic: A medical student telehealth service for ambulatory patients with COVID-19.

During the early months of the COVID-19 pandemic, when health systems were overwhelmed with surging hospitalizations and a novel virus, many ambulatory patients diagnosed with COVID-19 lacked guidance and support as they convalesced at home. This case report offers insight into the implementation of a telehealth service utilizing third- and fourth-year medical students to provide follow-up to ambulatory patients diagnosed with COVID-19. The service was evaluated using medical student surveys and retrospective chart review to assess the clinical and social needs of patients during the spring of 2020. Students assessed symptoms for 416 patients with COVID-19 from April 8 to May 20 and provided clinical information and resources. Eighteen percent of these patients sought higher levels of medical care, in part from student referrals. Three key implementation lessons from this experience that may be relevant for others include: 1) Vulnerable patient populations face unique stressors exacerbated by the pandemic and may benefit from intensive follow-up after COVID-19 diagnosis to address both medical and social needs; 2) Medical students can play value-added roles in providing patient education to prevent the spread of COVID-19, assisting patients with escalating care or resource connection, and providing emotional support to those who have lost loved ones; 3) Continuous re-assessment of the intervention was important to address evolving patient needs during the COVID-19 outbreak. Future work should focus on identifying high-risk patient populations and tailoring follow-up interventions to meet the unique needs of these patient populations.

Molecular drivers of oral cavity squamous cell carcinoma in non-smoking and non-drinking patients: what do we know so far?

Oral cavity squamous cell carcinoma (OCSCC) is one of the most common head and neck cancers worldwide. It is well known that risk factors for OCSCC include tobacco and excess alcohol consumption. However, in recent years, OCSCC incidence has been increasing in patients without these traditional risk factors. The cause of this increase is unclear and various genetic, environmental, and infectious factors have been hypothesized to play a role. Additionally, there are expert opinions that oral cancer in non-smoking, non-drinking (NSND) patients have a distinct phenotype resulting in more aggressive disease presentation and poorer prognosis. In this review, we summarize the current state of knowledge for oral cavity cancer in patients without traditional risk factors.

Characterizing Lymph Node Burden With Elective Unilateral Neck Irradiation in Human Papillomavirus-Positive Tonsil Squamous Cell Carcinoma: Defining the Upper Limits.

Objectives Elective unilateral neck irradiation in well-lateralized tonsil carcinoma for N2b disease is controversial. Metrics regarding nodal burden beyond the N-stage to define the upper limit of this de-escalation approach remain limited. We investigated the role of nodal number, level, and volume on outcomes in patients with well-lateralized tonsil carcinoma treated with this approach. Methods A total of 37 patients received radiotherapy (RT) with unilateral neck coverage for well-lateralized tonsil cancer. Of patients, 95% had p16+ disease, and 81% were staged with positron emission tomography/computed tomography. The majority of patients received definitive chemoradiation on prospective de-escalation trials. Ten patients had ipsilateral neck dissections and were treated adjuvantly. The median RT dose to the ipsilateral neck (generally II-IV) was 45 Gy. The effects of nodal number, max dimension, volume, and level on recurrence-free survival (RFS) and overall survival (OS) were to be analyzed via Cox proportional hazards (Cox-PH). Results After a median follow-up of 3.9 years, two-year RFS and two-year OS were 100% and 97%, respectively. Given the 0% contralateral recurrence rate, Cox-PH analysis was not performed. Of patients, 70% were American Joint Committee on Cancer (AJCC) 7th edition N2b, with a median number of nodes, number of nodal levels, max dimension, and volume of two, one, 3.4 cm, and 15.6 cc, respectively. There were several patients with low-lying nodes; aggregate nodal volume measured was up to 85.4 cc. Conclusion Unilateral neck irradiation in well-lateralized tonsil carcinoma resulted in no contralateral recurrence. Nodal volume, level, and number do not seem to have a significant impact on outcomes.

Learning at a social distance: A medical student telehealth service for COVID-19 patients.

This article was migrated. The article was marked as recommended. COVID-19 has disrupted traditional forms of clinical practice in both inpatient and outpatient settings. This novel, potentially-fatal infection proliferated to such a degree that many patients with mild disease had to engage in self-care at home. This disruption to clinical services has also upended in-person clerkship education across the country, leading to sustained periods of student furloughing. We developed a telehealth service-learning opportunity for COVID-19 patients who were advised to self-care in their homes. The service was staffed by medical students in their clinical training years, providing triage advice to patients, their families, and co-habitants until their symptoms improved. Callers set patient education around red flag symptoms as their first priority, but also offered counsel on home infection control and self-isolation strategies, composed work letters, offered resources regarding home management issues such as food and sanitation, and attended to the mental health needs of the patients and their families. An attending was on-call daily to assist and educate students about issues relating to clinical decision-making and the social determinants of health. A survey assessed medical students' opinions on the service. Student respondents found the service valuable, with 100% agreeing or strongly agreeing that the service was worth their time and important. Respondents reported learning important telehealth skills such as triage and patient education. Overwhelmingly, students found emotional connections with patients to be the most meaningful aspects of the service. Our telehealth service allowed students to learn from patients in a longitudinal manner, while remaining safely away from clinical settings. This service may prove a useful model for others in the case of another outbreak, particularly when medical students are furloughed. We hope to develop more clinical experiences in telehealth for medical students moving forward.

Cortical mechanisms of talker normalization in fluent sentences.

Adjusting to the vocal characteristics of a new talker is important for speech recognition. Previous research has indicated that adjusting to talker differences is an active cognitive process that depends on attention and working memory (WM). These studies have not examined how talker variability affects perception and neural responses in fluent speech. Here we use source analysis from high-density EEG to show that perceiving fluent speech in which the talker changes recruits early involvement of parietal and temporal cortical areas, suggesting functional involvement of WM and attention in talker normalization. We extend these findings to acoustic source change in general by examining understanding environmental sounds in spoken sentence context. Though there may be differences in cortical recruitment to processing demands for non-speech sounds versus a changing talker, the underlying mechanisms are similar, supporting the view that shared cognitive-general mechanisms assist both talker normalization and speech-to-nonspeech transitions.

Hearing sounds as words: Neural responses to environmental sounds in the context of fluent speech.

Environmental sounds (ES) can be understood easily when substituted for words in sentences, suggesting that linguistic context benefits may be mediated by processes more general than some language-specific theories assert. However, the underlying neural processing is not understood. EEG was recorded for spoken sentences ending in either a spoken word or a corresponding ES. Endings were either congruent or incongruent with the sentence frame, and thus were expected to produce N400 activity. However, if ES and word meanings are combined with language context by different mechanisms, different N400 responses would be expected. Incongruent endings (both words and ES) elicited frontocentral negativities corresponding to the N400 typically observed to incongruent spoken words. Moreover, sentential constraint had similar effects on N400 topographies to ES and words. Comparison of speech and ES responses suggests that understanding meaning in speech context may be mediated by similar neural mechanisms for these two types of stimuli.

A note by any other name: Intonation context rapidly changes absolute note judgments.

Absolute pitch (AP) judgments, by definition, do not require a reference note, and thus might be viewed as context independent. Here, we specifically test whether short-term exposure to particular intonation contexts influences AP categorization on a rapid time scale and whether such context effects can change from moment to moment. In Experiment 1, participants heard duets in which a "lead" instrument always began before a "secondary" instrument. Both instruments independently varied on intonation (flat, in-tune, or sharp). Despite participants being instructed to judge only the intonation of the secondary instrument, we found that participants treated the lead instrument's intonation as "in-tune" and intonation judgments of the secondary instrument were relativized against this standard. In Experiment 2, participants heard a short antecedent context melody (flat, in-tune, or sharp) followed by an isolated target note (flat, in-tune, or sharp). Target note intonation judgments were once again relativized against the context melody's intonation, though only for notes that were experienced in the context or implied by the context key signature. Moreover, maximally contrastive intonation combinations of context and target engendered systematic note misclassifications. For example, a flat melody resulted in a greater likelihood of misclassifying a "sharp F-sharp" as a "G." These results highlight that both intonation and note category judgments among AP possessors are rapidly modified by the listening environment on the order of seconds, arguing against an invariant mental representation of the absolute pitches of notes. Implications for general auditory theories of perception are discussed. (PsycINFO Database Record

Understanding environmental sounds in sentence context.

There is debate about how individuals use context to successfully predict and recognize words. One view argues that context supports neural predictions that make use of the speech motor system, whereas other views argue for a sensory or conceptual level of prediction. While environmental sounds can convey clear referential meaning, they are not linguistic signals, and are thus neither produced with the vocal tract nor typically encountered in sentence context. We compared the effect of spoken sentence context on recognition and comprehension of spoken words versus nonspeech, environmental sounds. In Experiment 1, sentence context decreased the amount of signal needed for recognition of spoken words and environmental sounds in similar fashion. In Experiment 2, listeners judged sentence meaning in both high and low contextually constraining sentence frames, when the final word was present or replaced with a matching environmental sound. Results showed that sentence constraint affected decision time similarly for speech and nonspeech, such that high constraint sentences (i.e., frame plus completion) were processed faster than low constraint sentences for speech and nonspeech. Linguistic context facilitates the recognition and understanding of nonspeech sounds in much the same way as for spoken words. This argues against a simple form of a speech-motor explanation of predictive coding in spoken language understanding, and suggests support for conceptual-level predictions.

The potential of Fas ligand (apoptosis-inducing molecule) as an unconventional therapeutic target in type 1 diabetes.

The development of type 1 diabetes (T1D) is driven by autoreactive T cells that attack and destroy the insulin-producing ß-cells in pancreatic islets, forcing patients to take multiple daily insulin injections. Insulin therapy, however, is not a cure and diabetic patients often develop serious long-term microvascular and cardiovascular complications. Therefore, intensive efforts are being directed toward developing safe immunotherapy for the disease that does not impair host defense and preserves ß-cells, leading to better glycemic control than exogenous insulin therapy. Engineering therapies that differentially cripple or tolerate autoreactive diabetogenic T cells while sparing protective T cells necessary for maintaining a competent immune system has proven challenging. Instead, recent efforts have focused on modulating or resetting the immune system through global but transient deletion of T cells or B cells using anti-CD3 or anti-CD20 mAb, respectively. However, phase III clinical trials have shown promising but modest efficacy so far with these approaches. Therefore, there is a need to identify novel biological targets that do not fit the classic properties of being involved in adaptive immune cell activation. In this prospective, we provide preclinical evidence that targeting Fas ligand (FasL) may provide a unique opportunity to prevent or cure T1D and perhaps other organ-specific autoimmune diseases without causing immune suppression. Unlike conventional targets that are involved in T and B lymphocyte activation (such as CD3 and CD20, respectively), FasL is an apoptosis-inducing surface molecule that triggers cell death by binding to Fas (also known as CD95 Apo-1). Therefore, targeting FasL is not expected to cause immune suppression, the Achilles Heel of conventional approaches. We will discuss the hypothesis that targeting FasL has unique benefits that are not offered by current immunomodulatory approaches.