Citations

Although the autoantigen involved in Graves’ hyperthyroidism is known to be the TSH receptor (TSHr), whether this antigen plays a primary role in the pathogenesis of Graves’ ophthalmopathy (GO) is unclear. We sought to determine whether fibroblasts derived from orbital adipose/connective tissue are capable of differentiating into adipocytes that bear immunoreactive and functional TSHr. In addition, we assessed relative levels of TSHr gene expression in normal and GO orbital adipose/connective tissue specimens.GO and normal orbital preadipocyte fibroblasts, cultured under conditions known to stimulate adipocyte differentiation, showed evidence of adipogenesis and positive immunostaining for TSHr protein. In addition, significantly more cAMP was produced in response to TSH stimulation in the differentiated cultures than in undifferentiated cultures derived from the same individuals’ cells. Other studies demonstrated relatively greater TSHr gene expression in GO than in normal orbital tissue specimens.These results indicate that orbital preadipocyte fibroblasts increase their TSHr expression with differentiation and suggest that these cells play an important role in the pathogenesis of GO. Furthermore, our studies support the concept that TSHr may be an important target antigen in this condition. Factors that stimulate adipocyte differentiation and TSHr expression in the orbit in GO have yet to be defined.

ObjectiveTo examine the magnitude of explicit and implicit weight biases compared to biases against other groups; and identify student factors predicting bias in a large national sample of medical students.MethodsA web‐based survey was completed by 4,732 1st year medical students from 49 medical schools as part of a longitudinal study of medical education. The survey included a validated measure of implicit weight bias, the implicit association test, and 2 measures of explicit bias: a feeling thermometer and the anti‐fat attitudes test.ResultsA majority of students exhibited implicit (74%) and explicit (67%) weight bias. Implicit weight bias scores were comparable to reported bias against racial minorities. Explicit attitudes were more negative toward obese people than toward racial minorities, gays, lesbians, and poor people. In multivariate regression models, implicit and explicit weight bias was predicted by lower BMI, male sex, and non‐Black race. Either implicit or explicit bias was also predicted by age, SES, country of birth, and specialty choice.ConclusionsImplicit and explicit weight bias is common among 1st year medical students, and varies across student factors. Future research should assess implications of biases and test interventions to reduce their impact.

The American Academy of Otolaryngology—Head and Neck Surgery Foundation (AAO‐HNSF) has published a supplement to this issue featuring the new Clinical Practice Guideline: Bell's Palsy. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 11 recommendations developed encourage accurate and efficient diagnosis and treatment and, when applicable, facilitate patient follow‐up to address the management of long‐term sequelae or evaluation of new or worsening symptoms not indicative of Bell's palsy. There are myriad treatment options for Bell's palsy; some controversy exists regarding the effectiveness of several of these options, and there are consequent variations in care. In addition, there are numerous diagnostic tests available that are used in the evaluation of patients with Bell's palsy. Many of these tests are of questionable benefit in Bell's palsy. Furthermore, while patients with Bell's palsy enter the health care system with facial paresis/paralysis as a primary complaint, not all patients with facial paresis/paralysis have Bell's palsy. It is a concern that patients with alternative underlying etiologies may be misdiagnosed or have an unnecessary delay in diagnosis. All of these quality concerns provide an important opportunity for improvement in the diagnosis and management of patients with Bell's palsy.

Objective Bell's palsy, named after the Scottish anatomist, Sir Charles Bell, is the most common acute mono‐neuropathy, or disorder affecting a single nerve, and is the most common diagnosis associated with facial nerve weakness/paralysis. Bell's palsy is a rapid unilateral facial nerve paresis (weakness) or paralysis (complete loss of movement) of unknown cause. The condition leads to the partial or complete inability to voluntarily move facial muscles on the affected side of the face. Although typically self‐limited, the facial paresis/paralysis that occurs in Bell's palsy may cause significant temporary oral incompetence and an inability to close the eyelid, leading to potential eye injury. Additional long‐term poor outcomes do occur and can be devastating to the patient. Treatments are generally designed to improve facial function and facilitate recovery. There are myriad treatment options for Bell's palsy, and some controversy exists regarding the effectiveness of several of these options, and there are consequent variations in care. In addition, numerous diagnostic tests available are used in the evaluation of patients with Bell's palsy. Many of these tests are of questionable benefit in Bell's palsy. Furthermore, while patients with Bell's palsy enter the health care system with facial paresis/paralysis as a primary complaint, not all patients with facial paresis/paralysis have Bell's palsy. It is a concern that patients with alternative underlying etiologies may be misdiagnosed or have unnecessary delay in diagnosis. All of these quality concerns provide an important opportunity for improvement in the diagnosis and management of patients with Bell's palsy. Purpose The primary purpose of this guideline is to improve the accuracy of diagnosis for Bell's palsy, to improve the quality of care and outcomes for patients with Bell's palsy, and to decrease harmful variations in the evaluation and management of Bell's palsy. This guideline addresses these needs by encouraging accurate and efficient diagnosis and treatment and, when applicable, facilitating patient follow‐up to address the management of long‐term sequelae or evaluation of new or worsening symptoms not indicative of Bell's palsy. The guideline is intended for all clinicians in any setting who are likely to diagnose and manage patients with Bell's palsy. The target population is inclusive of both adults and children presenting with Bell's palsy. Action Statements The development group made a strong recommendation that (a) clinicians should assess the patient using history and physical examination to exclude identifiable causes of facial paresis or paralysis in patients presenting with acute‐onset unilateral facial paresis or paralysis, (b) clinicians should prescribe oral steroids within 72 hours of symptom onset for Bell's palsy patients 16 years and older, (c) clinicians should not prescribe oral antiviral therapy alone for patients with new‐onset Bell's palsy, and (d) clinicians should implement eye protection for Bell's palsy patients with impaired eye closure. The panel made recommendations that (a) clinicians should not obtain routine laboratory testing in patients with new‐onset Bell's palsy, (b) clinicians should not routinely perform diagnostic imaging for patients with new‐onset Bell's palsy, (c) clinicians should not perform electrodiagnostic testing in Bell's palsy patients with incomplete facial paralysis, and (d) clinicians should reassess or refer to a facial nerve specialist those Bell's palsy patients with (1) new or worsening neurologic findings at any point, (2) ocular symptoms developing at any point, or (3) incomplete facial recovery 3 months after initial symptom onset. The development group provided the following options : (a) clinicians may offer oral antiviral therapy in addition to oral steroids within 72 hours of symptom onset for patients with Bell's palsy, and (b) clinicians may offer electrodiagnostic testing to Bell's palsy patients with complete facial paralysis. The development group offered the following no recommendations : (a) no recommendation can be made regarding surgical decompression for patients with Bell's palsy, (b) no recommendation can be made regarding the effect of acupuncture in patients with Bell's palsy, and (c) no recommendation can be made regarding the effect of physical therapy in patients with Bell's palsy.

ABSTRACTUnlike human malaria parasites that induce persistent infection, some rodent malaria parasites, likePlasmodium yoeliistrain 17XNL (Py17XNL), induce a transient (self-curing) malaria infection. Cooperation between CD4 T cells and B cells to produce antibodies is thought to be critical for clearance of Py17XNL parasites from the blood, with major histocompatibility complex (MHC) class II molecules being required for activation of CD4 T cells. In order to better understand the correspondence between murine malaria models and human malaria, and in particular the role of MHC (HLA) class II molecules, we studied the ability of humanized mice expressing human HLA class II molecules to clear Py17XNL infection. We showed that humanized mice expressing HLA-DR4 (DR0401) molecules and lacking mouse MHC class II molecules (EA0) have impaired production of specific antibodies to Py17XNL and cannot cure the infection. In contrast, mice expressing HLA-DR4 (DR0402), HLA-DQ6 (DQ0601), HLA-DQ8 (DQ0302), or HLA-DR3 (DR0301) molecules in an EA0background were able to elicit specific antibodies and self-cure the infection. In a series of experiments, we determined that the inability of humanized DR0401.EA0mice to elicit specific antibodies was due to expansion and activation of regulatory CD4+Foxp3+T cells (Tregs) that suppressed B cells to secrete antibodies through cell-cell interactions. Treg depletion allowed the DR0401.EA0mice to elicit specific antibodies and self-cure the infection. Our results demonstrated a differential role of MHC (HLA) class II molecules in supporting antibody responses to Py17XNL malaria and revealed a new mechanism by which malaria parasites stimulate B cell-suppressogenic Tregs that prevent clearance of infection.

Background: Telemedical physician triage (TPT) is a potential application of telemedicine in the emergency department (ED). We report the technical success, patient satisfaction, and effect on ED throughput metrics (length of stay [LOS] and time to physician evaluation [TPE]) of TPT performed on a mobile platform. Materials and Methods: Patients underwent standard nursing triage with or without TPT. Technical success is reported as raw data. Patient satisfaction is reported as raw data±standard deviation on a 5-point (low-to-high) scale. LOS and TPE are reported as mean±SD [95% CI] values. Statistical analyses of LOS and TPE are via two-sample t test. Results: One hundred six patients were registered during intervention periods, and TPT was completed in 36 (34%). One hundred ninety-six patients were registered during control periods. The technical success rate was 95%. Average patient satisfaction was 4.7 on a 5-point scale. The primary analysis (106 patients) showed no change in LOS (266±101 [244–288] min versus 258±172 [234–282] min) but a trend toward improved TPE with TPT (35±28 [29–41] min versus 42±31 [38–46] min) ( p =0.052). A secondary analysis (36 patients) showed no change in LOS (273±125 [231–316] min versus 258±172 [234–282] min) but improved TPE with TPT (16±15 [11–21] min versus 42±31 [38–46] min) ( p <0.0001). Conclusions: TPT in the ED on a mobile platform was technically successful, well accepted by patients, and associated with a decrease in TPE but not LOS.

Context: Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects women of childbearing age and may be related to obesity and insulin resistance. Objective: The purpose of this systematic review was to appraise the evidence of the impact of lifestyle modification (LSM) interventions on outcomes of women with PCOS. Data Sources: Sources included Ovid Medline, OVID Embase, OVID Cochrane Library, Web of Science, Scopus, PsycINFO, and CINAHL (up to January 2011). Study Selection: We included randomized controlled trials that enrolled woman of any age with PCOS who received LSM and compared them against women who received no intervention, minimal intervention, or metformin. Data Extraction: Two authors performed the data extraction independently. Data Synthesis: We included 9 trials enrolling 583 women with a high loss to follow-up rate, lack of blinding, and short follow-up. Compared with minimal intervention, LSM significantly reduced fasting blood glucose (weighted mean difference, −2.3 mg/dL; 95% confidence interval, −4.5 to −0.1, I2 = 72%, P = .04) and fasting blood insulin (weighted mean difference, −2.1 μU/mL, 95% confidence interval, −3.3 to −1.0, I2 = 0%, P &lt; .001). Changes in body mass index were associated with changes in fasting blood glucose (P &lt; .001). Metformin was not significantly better than LSM in improving blood glucose or insulin levels. We found no significant effect of LSM on pregnancy rate, and the effect on hirsutism was unclear. Conclusions: The available evidence suggests that LSM reduces fasting blood glucose and insulin levels in women with PCOS. Metformin has similar effects. Translation of these short-term effects to patient-important outcomes, beyond diabetes prevention, remains uncertain.

AbstractPurposeThe purpose of this study was to evaluate the utility of multimodal analgesia with fascia iliaca blockade and for acute pain control in patients undergoing hip arthroscopy.MethodsThirty consecutive patients undergoing primary hip arthroscopy were prospectively studied. All patients were treated preoperatively with ultrasound‐guided single injection fascia iliaca blockade and multimodal analgesia. Data collected included post‐operative nausea, numeric rating scale (NRS) pain scores during rest and activity, opioid consumption during the first five days (recorded as tablets of 5 mg hydrocodone/500 mg acetaminophen) and overall patient satisfaction with analgesia.ResultsThis study included 23 female and 7 male patients with a median age of 35 years (range 14–58). No patient required medication for post‐operative nausea. The overall NRS scores were an average of 3.9 on day 0, 3.6 on day 1, 3.4 on day 2, 2.9 on day 3, 3.0 on day 4 and 2.7 on day 5. The average tablets of opioid taken were 1.5 on day 0, 1.2 on day 1, 1.3 on day 2, 1.0 on day 3, 1.1 on day 4 and 0.9 on day 5. Overall, 20 patients rated their post‐operative pain control as very satisfied (67 %), and 10 patients as satisfied (33 %). There were no complications or side effects from the fascia iliaca blockade.ConclusionIn this prospective study, multimodal analgesia with fascia iliaca blockade following hip arthroscopy was safe and effective. The quality of early post‐operative analgesia provided by the fascia iliaca blockade was excellent and resulted in low opioid consumption, high quality of pain relief and high overall patient satisfaction.Level of evidenceProspective case series, Level II.