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Little is known about peripheral auditory function in young adults with HIV, who might be expected to show early evidence of hearing loss if HIV infection or treatment does affect peripheral function. The goal of this study was to compare peripheral auditory function in 2 age- and gender-matched groups of young adults with clinically normal hearing with and without HIV.Matched cohort study with repeated measures.Infectious disease center in Dar es Salaam, Tanzania.Participants included HIV-positive (n = 38) and HIV-negative (n = 38) adults aged 20 to 30 years who had clinically normal hearing, defined as type A tympanograms, air conduction thresholds ≤25 dB HL bilaterally from 0.5 to 8 kHz, and distortion product otoacoustic emissions (DPOAEs)6 dB above the noise floor bilaterally from 1.5 to 8 kHz. Participants were tested multiple times over 6-month intervals (average, 2.7 sessions/participant) for a total of 208 observations. Primary outcome measures included tympanograms, air conduction audiograms, DPOAEs, and click-evoked auditory brainstem responses.HIV groups did not significantly differ in age, static immittance, or air conduction thresholds. HIV-positive status was independently associated with approximately 3.7-dB lower DPOAE amplitudes from 2 to 8 kHz (95% CI, 1.01-6.82) in both ears and 0.04-µV lower (95% CI, 0.003-0.076) auditory brainstem response wave I amplitudes in the right ear.Young adults living with HIV have slightly but reliably smaller DPOAEs and auditory brainstem response wave I amplitudes than matched HIV-negative controls. The magnitude of these differences is small, but these results support measuring peripheral auditory function in HIV-positive individuals as they age.

Purpose To investigate the association among widefield swept-source (SS) OCT angiography (OCTA) metrics and systemic parameters and vitreous hemorrhage (VH) occurrence in eyes with proliferative diabetic retinopathy (PDR). Design Prospective, observational study. Participants Fifty-five eyes from 45 adults with PDR, with no history of VH, followed up for at least 3 months. Methods All patients underwent widefield SS OCTA (Montage 15 × 15 mm and high-definition (HD)-51 line scan) imaging. Images were evaluated independently by 2 graders for quantitative and qualitative widefield SS OCTA metrics defined a priori. Systemic and ocular parameters and widefield SS OCTA metrics were screened using least absolute shrinkage and selection operator and logistic or Cox regression for variable selection. Firth’s bias-reduced logistic regression models (outcome, occurrence of VH) and Cox regression models (outcome, time to occurrence of VH) were used to identify parameters associated with VH occurrence. Main Outcome Measures Occurrence of VH. Results Over a median follow-up of 363 days (range, 28–710 days), 13 of 55 PDR eyes (24%) demonstrated VH during the follow-up period. Presence of extensive neovascularizations (odds ratio, 8.05; 95% confidence interval [CI], 1.43–58.56; P = 0.02), defined as neovascularizations with total area of more than 4 disc diameters, and forward neovascularizations (odds ratio, 5.42; 95% CI, 1.26–35.16; P = 0.02) that traversed the posterior hyaloid face into the vitreous were associated with the occurrence of VH. The presence of flat neovascularizations (odds ratio, 0.25; 95% CI, 0.04–1.01; P = 0.05) confined to the posterior hyaloid face was associated with a lower risk of VH with borderline significance. Similarly, presence of extensive neovascularizations (hazard ratio, 18.24; 95% CI, 3.51–119.47; P Conclusions Widefield SS OCTA is useful for evaluating neovascularizations and their relationship with the vitreous. The presence of forward and extensive neovascularizations was associated with the occurrence of VH in patients with PDR. Larger samples and longer follow-up are needed to verify the risk factors and imaging biomarkers for diabetic VH.

Purpose: This work reports a case of left atrial myxoma presenting with cilioretinal artery occlusion. Methods: A case report is discussed. Results: A 57-year-old man was referred for acute vision loss in the left eye after a workup including electrocardiogram, magnetic resonance imaging of the brain without contrast, computed tomography angiography of the head and neck, erythrocyte sedimentation rate, and C-reactive protein had negative results. Examination revealed cilioretinal artery occlusion with visible emboli. Because an echocardiogram was not performed, the patient was referred to the emergency department. Echocardiogram revealed a large left atrial mass prolapsing into the left ventricle. The mass was excised, and pathology showed myxoma. Conclusions: This is the first case to our knowledge of isolated cilioretinal artery occlusion as the initial presentation of an atrial myxoma. Thorough and complete workup was crucial to averting further morbidity and mortality.

Modeling complements surveillance data to inform coronavirus disease 2019 (COVID-19) public health decision making and policy development. This includes the use of modeling to improve situational awareness, assess epidemiological characteristics, and inform the evidence base for prevention strategies. To enhance modeling utility in future public health emergencies, the Centers for Disease Control and Prevention (CDC) launched the Infectious Disease Modeling and Analytics Initiative. The initiative objectives are to: (1) strengthen leadership in infectious disease modeling, epidemic forecasting, and advanced analytic work; (2) build and cultivate a community of skilled modeling and analytics practitioners and consumers across CDC; (3) strengthen and support internal and external applied modeling and analytic work; and (4) working with partners, coordinate government-wide advanced data modeling and analytics for infectious diseases. These efforts are critical to help prepare the CDC, the country, and the world to respond effectively to present and future infectious disease threats.

This study evaluates the correlation between the bone end and soft tissue end of the quadriceps tendon–patellar bone autograft (QPA) size and pre-operative MRI measurements of the quadriceps tendon along sections to be included in the graft harvest in adolescents. We also assessed association between graft diameter and anthropometric measures (height, weight, and BMI), age, and sex. Patients (10–18 years) who underwent QPA ACL reconstruction and had a pre-operative MRI were considered for inclusion. Age, height, and weight, tibial and femoral side graft diameter, and patellar bone block dimensions were collected. Using a pre-operative 2D sagittal plane MRI, we measured the quadriceps at 10-mm increments above the patella, up to 40 mm. We assessed correlation between the bone-end graft diameter and the AP measure at 10 mm above the patella, and correlation between the soft-tissue end graft diameter and the most proximal AP measure. A total of 103 patients were included. A significant correlation between the soft-tissue side graft diameter and most proximal AP measurement was observed (rs = 0.51; p

Bipolar disorder (BD) is highly heritable. Identifying objective biomarkers reflecting pathophysiological processes predisposing to, versus protecting against BD, can help identify BD risk in offspring of BD parents. We recruited 21 BD participants with a first-degree relative with BD, 25 offspring of BD parents, 27 offspring of comparison parents with non-BD psychiatric disorders, and 32 healthy offspring of healthy parents. In at-risk groups, 23 had non-BD diagnoses and 29, no Axis-I diagnoses(healthy). Five at-risk offspring who developed BD post scan(Converters) were included. Diffusion imaging(dMRI) analysis with tract segmentation identified between-group differences in the microstructure of prefrontal tracts supporting emotional regulation relevant to BD: forceps minor, anterior thalamic radiation(ATR), cingulum bundle(CB), and uncinate fasciculus(UF). BD participants showed lower fractional anisotropy (FA) in the right CB (anterior portion) than other groups (q q qs qs qs

Sampling distortion product otoacoustic emissions (DPOAEs) at multiple fA map significance score was developed as a single measure of map change. Significance scores were evaluated before and after exposure to: loud music (LM), controlled noise (CN), and firing range noise (FR) in three separate sets of subjects. Scores were compared to audiometry and standard DPOAE results in the LM study.The LM and CN exposure studies involved 22, and 20 healthy young subjects respectively with normal hearing. Eight Marines were studied before and after FR exposure.After LM exposure, audiometry showed significant changes at 1, 2, 4, and 6 kHz. Standard DPOAE measures were also significantly different at several frequencies. Map significance scores detected changes more effectively and showed the distribution of DPOAE alterations.Map significance scores detected changes after noise exposure more reliably than audiometry and standard DPOAEs. Additionally, maps showed a diffuse response to sound exposure perhaps explaining why individual DP-grams appear less sensitive.

To investigate factors associated with positive postpartum depression (PPD) screen in pregnancies complicated by fetal congenital cardiac anomaly. We reviewed all records of pregnancies complicated by fetal congenital cardiac anomaly receiving prenatal, intrapartum and postpartum care at our single center, October 2016-October 2019. Maternal, obstetric, and neonatal data were compared between women with and without a positive PPD screen at the 6-week postpartum visit. Out of 415 women referred for fetal congenital cardiac anomaly, 86 women had complete inclusion criteria. Twenty-four women (28%) had a positive PPD screen. The frequencies of planned future infant surgery (73.9 vs. 26.2%, p = 0.01) and neonatal death prior to postpartum visit (12.5 vs. 0%, p = 0.02) were significantly higher among women with a positive PPD screen. In pregnancies complicated by fetal congenital cardiac anomaly, mothers of infants with planned future surgery or neonatal death are at significant risk for postpartum depression.

The SARS-Cov-2 (COVID-19) pandemic remains a major worldwide public health issue. Initially, improved supportive and anti-inflammatory intervention, often employing known drugs or technologies, provided measurable improvement in management. We have recently seen advances in specific therapeutic interventions and in vaccines. Nevertheless, it will be months before most of the world’s population can be vaccinated to achieve herd immunity. In the interim, hyperbaric oxygen (HBO2) treatment offers several potentially beneficial therapeutic effects. Three small published series, one with a propensity-score-matched control group, have demonstrated safety and initial efficacy. Additional anecdotal reports are consistent with these publications. HBO2 delivers oxygen in extreme conditions of hypoxemiaand tissue hypoxia, even in the presence of lung pathology. It provides anti-inflammatory and anti-proinflammatory effects likely to ameliorate the overexuberant immune response common to COVID-19. Unlike steroids, it exerts these effects without immune suppression. One study suggests HBO2 may reduce the hypercoagulability seen in COVID patients. Also, hyperbaric oxygen offers a likely successful intervention to address the oxygen debt expected to arise from a prolonged period of hypoxemia and tissue hypoxia. To date, 11 studies designed to investigate the impact of HBO2 on patients infected with SARS-Cov-2 have been posted on clinicaltrials.gov. This paper describes the promising physiologic and biochemical effects of hyperbaric oxygen in COVID-19 and potentially in other disorders with similar pathologic mechanisms.

Objective Examine the relationship between pre-operative competitive status and return to sport expectations post-operatively among adolescents undergoing ACL reconstruction. Assess the association between perceived levels of social support and doubts in returning to sport after ACL reconstruction. Design Cross-sectional. Setting Outpatient sports medicine clinic at a single institution. Participants 12–18 years old with an ACL tear who were planning to undergo ACL reconstruction. Main outcome measures Psychovitality questionnaire responses and Multidimensional Scale of Perceived Social Support (MSPSS) questionnaire scores. Results 86% of participants expected to return to sports in six months or less after surgery; there was no significant difference in expected time to return to sport between competitive vs. recreational athletes. Competitive athletes were less likely to be content returning to a lower activity level after surgery compared to recreational athletes. There were no significant differences in MSPSS scores between those who did and did not report doubts in their ability to return to their previous sports. Conclusion Most of our adolescent athlete population expected to return to sport after ACL reconstruction within six months of surgery. Those with and without doubts in their ability to return to sports did not significantly differ in levels of perceived social support.

Primary cerebral amyloidoma is an exceedingly rare condition that refers to localized tumor-like deposition of amyloid in the brain without evidence of an underlying systemic process such as multiple myeloma. Reported cases of primary cerebral amyloidoma to date have described restricted light-chain deposition (AL amyloid); we report two cases of primary cerebral amyloidoma with additional heavy-chain deposition (ALH amyloid). Overall, when localized disease is present, therapy such as surgery or radiation therapy is considered to limit the risk of progression. However, in part due to the rarity of the condition, defining optimal treatment has been problematic. Here we discuss definitive management of ALH primary cerebral amyloidoma treated with focal radiation therapy.

Overactivity of the sympathetic nervous system and high blood pressure are implicated in the development and progression of chronic kidney disease (CKD) and independently predict cardiovascular events in end-stage renal disease. To assess the role of renal nerves, we determined whether renal denervation (RDN) altered the hypertension and sympathoexcitation associated with a rabbit model of CKD. The model involves glomerular layer lesioning and uninephrectomy, resulting in renal function reduced by one-third and diuresis. After 3-week CKD, blood pressure was 13±2 mm Hg higher than at baseline ( P P =0.01). The depressor response to ganglion blockade was also +8.0±3 mm Hg greater, but total norepinephrine spillover was 8.7±3.7 ng/min lower (both P

Chronic kidney disease (CKD) is associated with greater sympathetic nerve activity but it is unclear if this is a kidney-specific response or due to generalized stimulation of sympathetic nervous system activity. To determine this, we used a rabbit model of CKD in which quantitative comparisons with control rabbits could be made of kidney sympathetic nerve activity and whole-body norepinephrine spillover. Rabbits either had surgery to lesion 5/6th of the cortex of one kidney by electro-lesioning and two weeks later removal of the contralateral kidney, or sham lesioning and sham nephrectomy. After three weeks, the blood pressure was statistically significantly 20% higher in conscious rabbits with CKD compared to rabbits with a sham operation, but their heart rate was similar. Strikingly, kidney nerve activity was 37% greater than in controls, with greater burst height and frequency. Total norepinephrine spillover was statistically significantly lower by 34%, and kidney baroreflex curves were shifted to the right in rabbits with CKD. Plasma creatinine and urine output were elevated by 38% and 131%, respectively, and the glomerular filtration rate was 37% lower than in sham-operated animals (all statistically significant). Kidney gene expression of fibronectin, transforming growth factor-β, monocyte chemotactic protein1, Nox4 and Nox5 was two- to eight-fold greater in rabbits with CKD than in control rabbits. Overall, the glomerular layer lesioning model in conscious rabbits produced a moderate, stable degree of CKD characterized by elevated blood pressure and increased kidney sympathetic nerve activity. Thus, our findings, together with that of a reduction in total norepinephrine spillover, suggest that kidney denervation, rather than generalized sympatholytic treatments, may represent a preferable management for CKD associated hypertension.

Objective To test the hypothesis that human immunodeficiency virus (HIV) affects auditory-neurophysiological functions. Methods A convenience sample of 68 HIV+ and 59 HIV- normal-hearing adults was selected from a study set in Dar es Salaam, Tanzania. The speech-evoked frequency-following response (FFR), an objective measure of auditory function, was collected. Outcome measures were FFRs to the fundamental frequency (F0) and to harmonics corresponding to the first formant (F1), two behaviorally relevant cues for understanding speech. Results The HIV+ group had weaker responses to the F1 than the HIV- group; this effect generalized across multiple stimuli (d = 0.59). Responses to the F0 were similar between groups. Conclusions Auditory-neurophysiological responses differ between HIV+ and HIV- adults despite normal hearing thresholds. Significance The FFR may reflect HIV-associated central nervous system dysfunction that manifests as disrupted auditory processing of speech harmonics corresponding to the first formant.

To compare different scan protocols of wide-field swept-source optical coherence tomography angiography (SS-OCTA) for the detection of diabetic retinopathy (DR) lesions.Comparison of diagnostic approaches.A prospective, observational study was conducted at Massachusetts Eye and Ear from December 2018 to July 2019. Proliferative diabetic retinopathy (PDR), nonproliferative diabetic retinopathy (NPDR), and diabetic patients without DR were included. All patients were imaged using SS-OCTA using the following scan protocol: 3- × 3-mm Angio centered on the fovea; 6- × 6-mm Angio centered on the fovea and the optic disc; 15- × 9-mm Montage; and 12- × 12-mm Angio centered on the fovea and the optic disc. Images were independently evaluated by 2 graders for the presence or absence of DR lesions including microaneurysms, intraretinal microvascular abnormalities, neovascularization, nonperfusion areas, venous looping, and hard exudates. All statistical analyses were performed using commercial software.A total of 176 eyes in 119 participants were included in the study. The detection rate of neovascularization on 6- × 6-mm Angio centered on the fovea was approximately one-half that on 15- × 9-mm Montage (P.05) imaging. Combining 6- × 6-mm Angio imaging centered on the fovea and the optic disc could increase the rate to approximately two-thirds (P.05). The 12- × 12-mm Angio imaging centered on the combination of fovea and optic disc had detection rates comparable to those of 15- × 9-mm Montage imaging for all DR lesions (P.05). For microaneurysms, 6- × 6-mm Angio had better performance than 15- × 9-mm Montage (P.05).Wide-field SS-OCTA images were useful in detecting DR lesions. The 12- × 12-mm Angio imaging centered on the fovea and on the optic disc may be an optimal balance between speed and efficacy for evaluation of DR in clinical practice.

Chlamydia trachomatis infection is a primary cause of reproductive tract diseases including infertility. Previous studies showed that this infection alters physiological activities in mouse oviducts. Whether this occurs in the uterus and cervix has never been investigated. This study characterized the physiological activities of the uterine horn and the cervix in a Chlamydia muridarum ( Cmu)-infected mouse model at three infection time points of 7, 14, and 21 days postinfection (dpi). Cmu infection significantly decreased contractile force of spontaneous contraction in the cervix (7 and 14 dpi; P < 0.001 and P < 0.05, respectively), but this effect was not observed in the uterine horn. The responses of the uterine horn and cervix to oxytocin were significantly altered by Cmu infection at 7 dpi ( P < 0.0001), but such responses were attenuated at 14 and 21 dpi. Cmu infection increased contractile force to prostaglandin (PGF2α) by 53–83% in the uterine horn. This corresponded with the increased messenger ribonucleic acid (mRNA) expression of Ptgfr that encodes for its receptor. However, Cmu infection did not affect contractions of the uterine horn and cervix to PGE2 and histamine. The mRNA expression of Otr and Ptger4 was inversely correlated with the mRNA expression of Il1b, Il6 in the uterine horn of Cmu-inoculated mice ( P < 0.01 to P < 0.001), suggesting that the changes in the Otr and Ptger4 mRNA expression might be linked to the changes in inflammatory cytokines. Lastly, this study also showed a novel physiological finding of the differential response to PGE2 in mouse uterine horn and cervix.

Objective To characterize the microvascular retinal changes after repair of macula-off rhegmatogenous retinal detachment (RRD) using optical coherence tomography angiography (OCT-A). Patients and methods A retrospective review of patients who underwent repair of macula-off RRD. Fellow unaffected eyes were used as controls. Post-operative OCT-A allowed comparison of vessel density (VD) and foveal avascular zone (FAZ) area in the superficial and deep retinal capillary plexus (DCP) as well as VD in the choriocapillaris layer. Results Seventeen eyes of 17 RRD patients were included in the final analysis. There was a reduction in VD of the deep retinal capillary plexus in affected eyes compared to fellow eyes (p = 0.046). RRD eyes with reduced VD in DCP compared with their fellow control eyes had worse visual acuity after repair compared to those without (p = 0.032). No significant microvasculature changes were detected in the FAZ area and VD in the superficial capillary plexus and choriocapillaris compared to fellow eyes. Conclusion In macula-off RRD eyes, significant microvascular changes were detected in the DCP using OCT-A even after successful anatomical repair. Decreased VD in the DCP compared to the fellow healthy eyes was correlated with worse visual acuity.

Increased iron levels and dysregulated iron homeostasis, or both, occur in several lung diseases. Here, the effects of iron accumulation on the pathogenesis of pulmonary fibrosis and associated lung function decline was investigated using a combination of murine models of iron overload and bleomycin-induced pulmonary fibrosis, primary human lung fibroblasts treated with iron, and histological samples from patients with or without idiopathic pulmonary fibrosis (IPF). Iron levels are significantly increased in iron overloaded transferrin receptor 2 (Tfr2) mutant mice and homeostatic iron regulator (Hfe) gene-deficient mice and this is associated with increases in airway fibrosis and reduced lung function. Furthermore, fibrosis and lung function decline are associated with pulmonary iron accumulation in bleomycin-induced pulmonary fibrosis. In addition, we show that iron accumulation is increased in lung sections from patients with IPF and that human lung fibroblasts show greater proliferation and cytokine and extracellular matrix responses when exposed to increased iron levels. Significantly, we show that intranasal treatment with the iron chelator, deferoxamine (DFO), from the time when pulmonary iron levels accumulate, prevents airway fibrosis and decline in lung function in experimental pulmonary fibrosis. Pulmonary fibrosis is associated with an increase in Tfr1+ macrophages that display altered phenotype in disease, and DFO treatment modified the abundance of these cells. These experimental and clinical data demonstrate that increased accumulation of pulmonary iron plays a key role in the pathogenesis of pulmonary fibrosis and lung function decline. Furthermore, these data highlight the potential for the therapeutic targeting of increased pulmonary iron in the treatment of fibrotic lung diseases such as IPF. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Objective: Pediatric primary care sports medicine physicians and pediatric sports medicine orthopedic surgeons, in conjunction with physician assistants (PAs), often manage patients with fractures....

Hypertension is a risk factor for the vascular permeability and neovascularization that threatens vision in diabetic retinopathy. Excess reactive oxygen species derived from the Nox (NADPH oxidase) isoforms, Nox1 and Nox4, contributes to vasculopathy in diabetic retinopathy; however, if Nox1/4 inhibition is beneficial in hypertensive diabetic retinopathy is unknown. Here, we determined that diabetic spontaneously hypertensive rats had exacerbated retinal vascular permeability and expression of angiogenic and inflammatory factors, compared with normotensive diabetic Wistar Kyoto rats. GKT136901, a specific dual inhibitor of Nox1 and Nox4, prevented these events in diabetic Wistar Kyoto rats and spontaneously hypertensive rats. Retinal neovascularization does not develop in diabetic rodents, and therefore, the oxygen-induced retinopathy model is used to evaluate this pathology. We previously demonstrated that Nox1/4 inhibition reduced retinal neovascularization in oxygen-induced retinopathy. However, although Nox5 is expressed in human retina, its contribution to retinopathy has not been studied in vivo, largely due to its absence from the rodent genome. We generated transgenic mice with inducible human Nox5 expressed in endothelial cells (vascular endothelial-cadherin + Nox5 + mice). In vascular endothelial-cadherin + Nox5 + mice with oxygen-induced retinopathy, retinal vascular permeability and neovascularization, as well as the expression of angiogenic and inflammatory factors, were increased compared with wild-type littermates. In bovine retinal endothelial cells, which express Nox1, Nox4, and Nox5, Nox1/4 inhibition, as well as Nox5 silencing RNA, reduced the high glucose–induced upregulation of oxidative stress, angiogenic, and inflammatory factors. Collectively, these data indicate the potential of Nox1, Nox4, and Nox5 inhibition to reduce vision-threatening damage to the retinal vasculature.

Objective Determine whether an electronic tablet-based Wireless Automated Hearing-Test System can perform high-quality audiometry to assess schoolchildren for hearing loss in the field in Nicaragua. Study design Cross-sectional. Setting A school and hospital-based audiology clinic in Jinotega, Nicaragua. Subjects and methods Second and third graders (n = 120) were randomly selected for hearing testing in a school. Air conduction hearing thresholds were obtained bilaterally using a Wireless Automated Hearing-Test System at 1000, 2000, and 4000 Hz. Referral criteria were set at more than 25 dBHL at one or more frequencies. A cohort of children was retested with conventional audiometry in a hospital-based sound booth. Factors influencing false-positive examinations, including ambient noise and behavior, were examined. Results All children with hearing loss were detected using an automated, manual, or two-step (those referred from automated testing were tested manually) protocol in the school (sensitivity = 100%). Specificity was 76% for automated testing, 97% for manual testing, and 99% for the two-step protocol. The variability between thresholds obtained with automated testing was greater than manual testing when compared with conventional audiometry. The percentage of participant responses when no stimulus tone was presented during automated testing was higher in children with false-positive examinations. Conclusion A Wireless Automated Hearing-Test System identified all children with hearing loss in a challenging field setting. A two-step protocol (those referred from automated testing are tested manually) reduced false-positive examinations and unnecessary referrals. Children who respond frequently when no tone is presented are more likely to have false-positive automated examinations and should be tested manually.

Immune system dysfunction may contribute to the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). We examined the effects of the anthocyanin, cyanidin 3-O-glucoside (C3G), and the diuretic, hydrochlorothiazide (HCT), on T-cell function in SHR. Five-week-old male SHR and Wistar–Kyoto (WKY) rats received water (n = 8/SHR; n = 8/WKY), 10 mg kg−1 day−1 C3G (n = 8/SHR; n = 8/WKY), 10 mg kg−1 day−1 HCT (n = 8/SHR; n = 8/WKY), or 10 mg kg−1 day−1 C3G + 10 mg kg−1 day−1 HCT (n = 8/SHR; n = 8/WKY) by oral gavage for 15 weeks. Spleens were used to assess T-cell phenotypes via flow cytometry and concanavalin A stimulated ex vivo cytokine production (IL-2, IL-10, TNFα, IFNγ) using a cytometric bead array. SHR had lower proportions of helper T-cells (Th) that were T-regulatory, CD62Llo, CD62L− and CD25+ compared to WKY. C3G treated SHR had higher proportions of Th that were CD62Llo and CD62L−, while HCT treated rats had higher CD62Lhi and CD62Llo and lower CD62L− compared to SHR control. The proportion of T-regulatory and Th that were CD25+ were not affected by treatment in SHR. Stimulated splenocytes from SHR produced lower concentrations of cytokines compared to WKY. C3G treated SHR produced higher while HCT treated SHR produced lower TNFα and IFNγ concentrations compared to controls. Our findings suggest that C3G has positive effects, whereas HCT further suppresses T-cell function in SHR.

PURPOSE To determine factors associated with 360-degree laser retinopexy (360LR) during primary pars plana vitrectomy ± scleral buckle for rhegmatogenous retinal detachment (RRD) and its impact on surgical outcomes. METHODS This is a multicenter, retrospective, interventional study. Patients undergoing primary pars plana vitrectomy or primary pars plana vitrectomy + scleral buckle for noncomplex primary RRD in 2015 were evaluated. Primary outcomes were single surgery anatomical success (SSAS) and final anatomical success. Secondary outcomes included final logarithm of the minimum angle of resolution visual acuity, epiretinal membrane formation, cystoid macular edema development, and number of subsequent vitrectomies. Multivariate regressions were performed. RESULTS Two thousand two hundred and forty-eight surgeries by 61 surgeons were included; of which, 516 underwent 360LR. Younger age (P = 0.01), more retinal breaks (P = 0.01), more extensive RRD (P < 0.001), and surgeon ID (P < 0.001) were significantly associated with 360LR. No significant associations between 360LR and single surgery anatomical success (P = 0.44), epiretinal membrane formation (P = 0.14), cystoid macular edema development (P = 0.28), or number of subsequent vitrectomies (P = 0.41) were found. Controlling for case complexity, 360LR was significantly associated with lower final anatomical success (P < 0.001) and worse final logarithm of the minimum angle of resolution visual acuity (P < 0.001). CONCLUSION Multiple factors influenced whether 360LR was performed during primary pars plana vitrectomy ± scleral buckle for RRD. However, 360LR was not associated with improved surgical outcomes, and in fact, it may be associated with poorer outcomes.

A 66-year-old man was referred for management of a visually significant epiretinal membrane (ERM) with persistent cystoid macular edema after surgery for recurrent retinal detachment with proliferative vitreoretinopathy. The membrane was noted to be particularly thick and vascularized on preoperative optical coherence tomography. During the subsequent vitrectomy, the “membrane” was found to be an inverted retinal flap and successfully removed. The inverted retinal flap was thought to have been related to retinal slippage during prior surgery. This is the first report of an epimacular inverted flap simulating an ERM and highlights the importance of careful review of preoperative imaging. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:293–295.]

Background: Osteochondritis dissecans (OCD) occurs most commonly in the knees of young individuals. This condition is known to cause pain and discomfort in the knee and can lead to disability and early knee osteoarthritis. The cause is not well understood, and treatment plans are not well delineated. The Research in Osteochondritis Dissecans of the Knee (ROCK) group established a multicenter, prospective cohort to better understand this disease. Purpose: To provide a baseline report of the ROCK multicenter prospective cohort and present a descriptive analysis of baseline data for patient characteristics, lesion characteristics, and clinical findings of the first 1000 cases enrolled into the prospective cohort. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients were recruited from centers throughout the United States. Baseline data were obtained for patient characteristics, sports participation, patient-reported measures of functional capabilities and limitations, physical examination, diagnostic imaging results, and initial treatment plan. Descriptive statistics were completed for all outcomes of interest. Results: As of November 2020, a total of 27 orthopaedic surgeons from 17 institutions had enrolled 1004 knees with OCD, representing 903 patients (68.9% males; median age, 13.1 years; range, 6.3-25.4 years), into the prospective cohort. Lesions were located on the medial femoral condyle (66.2%), lateral femoral condyle (18.1%), trochlea (9.5%), patella (6.0%), and tibial plateau (0.2%). Most cases involved multisport athletes (68.1%), with the most common primary sport being basketball for males (27.3% of cases) and soccer for females (27.6% of cases). The median Pediatric International Knee Documentation Committee (Pedi-IKCD) score was 59.9 (IQR, 45.6-73.9), and the median Pediatric Functional Activity Brief Scale (Pedi-FABS) score was 21.0 (IQR, 5.0-28.0). Initial treatments were surgical intervention (55.4%) and activity restriction (44.0%). When surgery was performed, surgeons deemed the lesion to be stable at intraoperative assessment in 48.1% of cases. Conclusion: The multicenter ROCK group has been able to enroll the largest knee OCD cohort to date. This information is being used to further understand the pathology of OCD, including its cause, associated comorbidities, and initial presentation and symptoms. The cohort having been established is now being followed longitudinally to better define and elucidate the best treatment algorithms based on these presenting signs and symptoms.

Background and aimsFunctional dyspepsia is characterised by chronic symptoms of post- prandial distress or epigastric pain not associated with defined structural pathology. Increased peripheral gut-homing T cell have been previously identified in patients. To date, it is unknown if these T cells were antigen-experienced, or if a specific immunophenotype was associated with FD. This study aimed to characterise immune populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology.MethodsWe identified duodenal T cell populations from 23 controls and 49 Rome III FD patients by flow cytometry. We also analysed duodenal eosinophils and T cell populations in peripheral blood from 37 controls and 49 patients and investigated if subtyping patients based on reported symptoms or co-morbidity identified specific immunophenoptypes.ResultsIn addition to increased duodenal mucosal CD4+ effector cells, FD patients demonstrated a shift in the T helper cell balance compared to controls. Patients had increased duodenal mucosal Th2 populations in the effector (13.03±16.11, 19.84±15.51, p=0.038), central memory (23.75±18.97, 37.52±17.51, p=0.007) and effector memory (9.80±10.50 vs 20.53±14.15, p=0.001) populations. Th17 populations were also increased in the effector (31.74±24.73 vs 45.57±23.75, p=0.03) and effector memory (11.95±8.42 vs 18.44±15.63, p=0.027) subsets.ConclusionOur findings confirm the involvement of adaptive responses in the aetiopathogenesis of FD, specifically a Th2 and Th17 signature in the duodenal mucosa. The presence of effector and memory cells suggest that the microinflammation in FD is antigen driven.

Background Media-based educational materials (EMs) are becoming prominent. The purpose of this study was to compare print versus media-based EMs given to caregivers of pediatric and young adult patients undergoing surgery. We aimed to see whether print or media-based EMs lead to greater caregiver satisfaction, comfort, and preparedness for outpatient peripheral nerve catheter and pain pump management. We also assessed caregiver preference for EM modality. Hypothesis We hypothesized that media-based EMs would demonstrate greater overall efficacy and thus generate higher caregiver preference. Study design Randomized control trial. Methods After IRB approval, clinicaltrials.gov registration (17-0638), and informed consent, caregivers were randomized to either media or print-based EM groups. Caregivers reviewed their assigned EM and completed a standardized assessment of their comprehension. We assessed caregiver satisfaction, preparedness, and comfort level with the content on a 5-point Likert scale. On postoperative days 1 to 2, caregivers reported satisfaction, comfort, and preference for EM modality. An intent-to-treat analysis was used to compare the 2 groups. Results From our final cohort of 135 caregivers, we found no difference [P>0.05] in satisfaction, comfort level, level of preparedness, or discharge readiness scores between groups. After the caregivers were given both EMs, they were evenly split in their preference for print (49.6%) versus video (50.4%) based methods. Conclusions We did not detect a significant difference in caregiver preference or feelings of preparedness between groups. Interestingly, a significant proportion of caregivers (25%) did not feel comfortable managing the peripheral nerve catheter and its pain pump at home. Future studies should work to improve caregiver comfort with educational content before patient discharge. Clinical relevance Providers and institutions should feel comfortable providing both print and media-based patient and caregiver education. Caregiver education may be best suited based on caregiver preference of one EM modality versus the other. Level of evidence Level I.

IntroductionAge-related macular degeneration (AMD) is a blinding condition for which there is currently no early-stage clinical biomarker. AMD is characterized by thinning of the outer retina and drusen formation leading to thickening of the Bruch’s membrane and RPE complex, but the timing between these two events, as well as the role of genetic variants in these processes, are unclear. Here, we jointly analyzed genomic, electronic health record, and optical coherence tomography (OCT) data across 44,823 individuals from the UK Biobank to characterize the epidemiological and genetic associations between retinal layer thicknesses and AMD.MethodsThe Topcon Advanced Boundary Segmentation algorithm was used for automated retinal layer segmentation. We associated 9 retinal layer thicknesses with prevalent AMD (present at enrollment) in a logistic regression model, and with incident AMD (diagnosed after enrollment) in a Cox proportional hazards model. Next, we tested the association of AMD-associated genetic alleles, individually and as a polygenic risk score (PRS), with retinal layer thicknesses. All analyses were adjusted for age, age2, sex, smoking status, and principal components of ancestry.ResultsPhotoreceptor segment (PS) thinning was observed throughout the lifespan of individuals analyzed and accelerated at age 45, while retinal pigment epithelium and Bruch’s membrane complex (RPE+BM) thickening started after age 57. Each standard deviation (SD) of PS thinning and RPE+BM thickening were associated with prevalent AMD (PS: OR 1.37, 95% CI 1.25-1.49, P=2.5×10−12; RPE+BM: OR=1.34, 95% CI 1.27-1.41, P=8.4×10−28) and incident AMD (PS: HR 1.35, 95% CI 1.23-1.47, P=3.7×10−11; RPE+BM: HR 1.14, 95% CI 1.06-1.22, P=0.00024). An AMD polygenic risk score (PRS) was associated with PS thinning (Beta -0.21 SD per 2-fold genetically increased risk of AMD, 95% CI -0.23 to -0.19, P=2.8×10−74), and its association with RPE+BM was U-shaped (thinning with AMD PRSndpercentile and thickening with AMD PRS>92ndpercentile suggestive of drusen formation). The loci with strongest support were AMD risk-raising variantsCFH:rs570618-T,CFH:10922109-C, andARMS2/HTRA1:rs3750846-C on PS thinning, andSYN3/TIMP3:rs5754227-T on RPE+BM thickening.ConclusionsEpidemiologically, PS thinning precedes RPE+BM thickening by decades, and is the retinal layer most strongly predictive of future AMD risk. Genetically, AMD risk variants are associated with decreased PS thickness. Overall, these findings support PS thinning as an early-stage clinical biomarker for future AMD development.

A patient developed a reticulated gray-brown rash after completing a 21-day unclothed African survival challenge. During the challenge, the patient slept near a fire and inside a rock igloo. Exam and history were consistent with erythema ab igne, a rash related to heat exposure from fire or other heating sources.

Number of involved lymph nodes (LNs) is a crucial stratification factor in staging of numerous disease sites, but has not been incorporated for endometrial cancer. We evaluated whether number of involved LNs provide improved prognostic value.Patients diagnosed with node-positive endometrial adenocarcinoma without distant metastasis were identified in the National Cancer Database. We trained a machine-learning based model of overall survival. Shapley additive explanation values (SHAP) based on the model were used to identify cutoffs of number of LNs involved. Results were validated using a Cox proportional hazards regression model.We identified 11,381 patients with endometrial cancer meeting the inclusion criteria. Using the SHAP values, we selected the following thresholds: 1-3 LNs, 4-5 LNs, and 6+ LNs. The 3-year OS was 82.0% for 1-3 LNs, 74.3% for 4-5 LNs (hazard ratio [HR] 1.38; p 0.001), and 59.9% for 6+ LNs (HR 2.23; p 0.001). On univariate Cox regression, PA nodal involvement was a significant predictor of OS (HR 1.20; p 0.001) but was not significant on multivariate analysis when number of LNs was included (HR 1.05; p = 0.273). Additionally, we identified an interaction between adjuvant therapy and number of involved LNs. Patients with 1-3 involved LNs had 3-year OS of 85.2%, 78.7% and 74.2% with chemoradiation (CRT), chemotherapy, and radiation, respectively. Patients with 6+ involved LNs had 3-yr OS of 67.8%, 49.6%, and 48.9% with CRT, chemotherapy, and radiation, respectively (p 0.001).Number of involved LNs is a stronger prognostic and predictive factor compared to PA node involvement.

Background: The incidence of anterior cruciate ligament (ACL) injury in the adolescent population is increasing. The quadriceps tendon–patellar bone autograft (QPA) has been established as a reliable graft choice for ACL reconstruction in the adult population. Purpose: To investigate graft failure, ability to return to sport, patient-reported functional outcomes, joint laxity, and subsequent injury among adolescent patients >2 years after primary ACL reconstruction with the QPA. Study Design: Case series; Level of evidence, 4. Methods: Consecutive patients who underwent QPA ACL reconstruction performed by a single surgeon were identified from an existing database. Information available in the database included demographics, concomitant/subsequent injuries, surgical procedures, graft failure, return to sport, and Lachman examination collected by medical record review. Pediatric International Knee Documentation Committee (Pedi-IKDC) and Lysholm scores were collected by telephone or during a clinic visit >2 years postoperatively. Results: The final cohort included 81 of 104 consecutive adolescent patients aged 10 to 18 years (mean ± SD, 15.9 ± 1.7 years at the time of surgery) for whom follow-up information was collected at >2 years after surgery. The cumulative incidence of graft failure within the 36-month follow-up period was 1.2% (95% CI, 0.1%-11.4%). The rate of ipsilateral non-ACL injuries was similar (1.2%; 95% CI, 0.2%-7.6%). Contralateral ACL and non-ACL injuries requiring surgical intervention were documented in 9.8% (95% CI, 4.9%-19.5%). The median Pedi-IKDC score was 94 (interquartile range, 89-98). The median Lysholm score was 99.5 (interquartile range, 89.0-100.0). At 36 months after surgery, 87.9% (95% CI, 81.4%-94.9%) of individuals had returned to play. Conclusion: The quadriceps tendon–patellar autograft is a novel graft that demonstrates excellent stability and favorable patient-reported outcomes. Based on these results, the QPA is a reliable choice for primary ACL reconstruction in adolescent patients.

Purpose Optical coherence tomography angiography (OCT-A) has emerged as a novel tool for the non-invasive imaging and evaluation of the retinal microvasculature. There is little existing literature that compares OCT-A microvasculature metrics across different OCT-A devices in chorioretinal diseases. Herein, we examined these metrics on three available OCT-A platforms. Patients and methods All subjects were scanned on each of three OCT-A devices: Optovue Avanti Angiovue, Topcon DRI-OCT Triton Swept-Source OCT, and Zeiss Cirrus 5000-HD-OCT Angioplex. Two investigators independently measured foveal avascular zone (FAZ) area. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel densities (VD) were calculated from binarized images with ImageJ software. Image quality across devices was qualitatively compared. Interclass correlation coefficient (ICC), Bland-Altman analysis, repeated measures ANOVA, and post-hoc tests were performed for statistical analysis. Results Thirteen eyes of seven patients with chorioretinal diagnoses were reviewed. ICC for FAZ measurement was 0.95. There was no significant difference in FAZ area across the three devices (p= 0.792). There was a significant difference in the SCP VD between the OCT-A devices (Triton 0.344 ± 0.013, Angiovue 0.323 ± 0.013, Angioplex 0.367 ± 0.014, p < 0.05). Significantly greater DCP VD was observed with Angioplex (0.385 ± 0.010) in comparison to both Triton (0.331 ± 0.009) and Angiovue (0.341 ± 0.020). A comparison of image quality revealed that Angiovue gives the highest quality, followed by Angioplex and Triton. Conclusion Core macular microvasculature metrics are now readily accessible on a variety of available OCT-A devices. While the FAZ can be reliably measured across all three devices in this study, there were significant differences for the vessel density in both the SCP and DCP. As a result, clinicians should be careful when comparing microvasculature metrics across different devices when using patient data in multicenter research investigations and clinical trials.

Medications to treat major depressive disorder (MDD) are not equally effective across patients. Given that neural response to rewards is altered in MDD and given that reward-related circuitry is modulated by dopamine and serotonin, we examined, for the first time, whether reward-related neural activity moderated response to sertraline, an antidepressant medication that targets these neurotransmitters. 222 unmedicated adults with MDD randomized to receive sertraline (n=110) or placebo (n=112) in the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study completed demographic and clinical assessments, and pre-treatment functional magnetic resonance imaging while performing a reward task. We tested whether an index of reward system function in the ventral striatum (VS), a key reward circuitry region, moderated differential response to sertraline versus placebo, assessed with the Hamilton Rating Scale for Depression over 8 weeks. We observed a significant moderation effect of the reward index, reflecting the temporal dynamics of VS activity, on Week-8 depression levels (Fs≥9.67,ps≤0.002). Specifically, VS responses that were abnormal with respect to predictions from reinforcement learning theory were associated with lower Week-8 depression symptoms in the sertraline versus placebo arms. Thus, a more abnormal pattern of pre-treatment VS dynamic response to reward expectancy (expected outcome value) and prediction error (difference between expected and actual outcome), likely reflecting serotonergic and dopaminergic deficits, was associated with better response to sertraline than placebo. Pre-treatment measures of reward-related VS activity may serve as objective neural markers to advance efforts to personalize interventions by guiding individual-level choice of antidepressant treatment. Trial Registration: NCT01407094; http://clinicaltrials.gov/show/NCT01407094

OBJECTIVE: Evidence suggests damage to brain auditory pathways, rather than inner ear damage, underlies the hearing difficulties HIV+ individuals report. But, anti-retroviral therapy (ART) may affect the hearing system and also lead to hearing complaints. DESIGN: Longitudinal study of HIV+ and HIV- individuals in Dar es Salaam Tanzania. A subset of this cohort started ART while in the study allowing the effects of ART to be studied directly. METHODS: The ability to hear quiet sounds (pure-tone audiometry), cochlear outer hair cell function (distortion-product otoacoustic emissions (DPOAEs), and gaps-in-noise detection thresholds (a central auditory processing test) were assessed at each visit. Visits were scheduled for 6-month intervals, but the number and spacing of visits varied. In the group that started ART while in the study, 107 HIV+ individuals had audiometric thresholds, 98 had DPOAEs, and 98 had gap measurements suitable for analysis. Data were analyzed using a linear mixed model with time and starting ART as fixed effects and individual subject repeated measures as random effects. RESULTS: Starting ART did not affect audiometric or gap detection thresholds. The slope of the DPOAE amplitude vs. time relationship was more negative after starting ART but did not differ from the HIV- group. Gap thresholds were higher in the HIV+ group. CONCLUSION: ART did not affect audiometric thresholds significantly suggesting common ART drugs are not major ototoxins. The gap detection results from the study show effects on central auditory processing in HIV+ individuals, supporting the origin of HIV-related hearing complaints in the central auditory system.

Excessive production of reactive oxygen species (ROS) plays a detrimental role in the progression of diabetic kidney disease (DKD). Renal oxidative stress activates proinflammatory cytokines, chemokines and profibrotic factors in DKD. Increased expression of the prooxidant enzyme NADPH oxidase (NOX) 5 in kidneys of diabetic individuals has been hypothesised to correlate with renal injury and progression of DKD. Since the gene encoding NOX5 is not expressed in the mouse genome, we examined the effect of inducible human NOX5 expression in renal cells, selectively in either endothelial cells or vascular smooth muscle cells (VSMCs)/mesangial cells in a model of insulin-deficient diabetes, the Akita mouse. Renal structural injury, including glomerulosclerosis, mesangial expansion and extracellular matrix protein accumulation, as well as renal inflammation, ROS formation and albuminuria, were examined in the NOX5 transgenic Akita mouse model of DKD. Expression of NOX5 in either endothelial cells or VSMCs/mesangial cells in diabetic Akita mice was associated with increased renal inflammation (monocyte chemoattractant protein-1, NF-κB and toll-like receptor-4) and glomerulosclerosis, as well as upregulation of protein kinase C-α and increased expression of extracellular matrix genes (encoding collagen III, fibronectin and α-smooth muscle actin) and proteins (collagen IV), most likely mediated via enhanced renal ROS production. The effect of VSMC/mesangial cell-specific NOX5 expression resulted in more pronounced renal fibrosis in comparison with endothelial cell-specific NOX5 expression in diabetic mice. In addition, albuminuria was significantly increased in diabetic VEcad+NOX5+ mice (1192 ± 194 μg/24 h) when compared with diabetic VEcad+NOX5− mice (770 ± 98 μg/24 h). Furthermore, the regulatory components of NOX5 activation, including heat shock protein 90 and transient receptor potential cation channel subfamily C member 6, were upregulated only in the presence of both NOX5 and diabetes. The findings from this study highlight the importance of NOX5 in promoting diabetes-related renal injury and provide the rationale for the development of a selective NOX5 inhibitor for the prevention and/or treatment of DKD.

To examine anesthesia recovery duration after ophthalmologic procedures performed at an ambulatory surgical center (ASC) and provide information that could be used to increase postanesthesia recovery unit efficiency.Ambulatory surgical center at tertiary medical center, Rochester, Minnesota, USA.Retrospective case series.Health records of adult patients having ophthalmologic procedures at an ASC from July 1, 2010, through September 30, 2016 were reviewed, and anesthesia recovery duration was calculated. Potential associations were assessed between clinical factors and prolonged recovery (upper 10th percentile of recovery duration by anesthesia type [general, intravenous sedation, or topical]).Among 20 116 procedures, the median recovery was 36 minutes (interquartile range [IQR], 28 to 48); general anesthesia had the longest recovery (79 minutes; IQR, 52 to 104 minutes) (P .001). Recovery was longest for orbitotomy and strabismus procedures and shortest for cataract procedures. Female sex, obstructive sleep apnea, greater disease burden, longer procedures, and intraoperative fentanyl administration were associated with prolonged recovery. Patients with prolonged recovery had more severe pain episodes (pain score ≥7 [scale 0 to 10]; 138 patients [6.9%] versus 140 [0.8%]; P .001) and received opioid analgesics during recovery (278 patients [13.8%] versus 293 [1.6%]; P .001). Prolonged recovery involved higher rates of emergency department visits and hospitalizations in the first 48 postoperative hours and higher 30-day mortality rates.Anesthesia recovery after ophthalmologic procedures at an ASC was associated primarily with the procedure and anesthesia type. Prolonged recoveries were associated with intraoperative fentanyl use, severe postoperative pain, and postoperative opioid requirements.

Background: The anterior cruciate ligament (ACL) repair technique avoids graft harvest and therefore the risk of donor site morbidity. However, early failure rates after ACL repair with suture ligament augmentation (SLA) remain high. Purpose: To compare surgical failure, functional outcomes, return to sport, and joint laxity between adolescents who underwent ACL repair with SLA and those who underwent ACL reconstruction with quadriceps tendon–patellar bone autograft (QPA). Study Design: Cohort study; Level of evidence, 3. Methods: Adolescent patients (7-18 years old) underwent ACL repair with SLA or ACL reconstruction with QPA. The authors collected data from those who had postoperative information pertaining to repaired ligament or graft failure, range of motion, complications, and return to sport at a minimum of 6 months after surgery. Participants were contacted after surgery to complete study questionnaires. Results: The cohort included 22 consecutive patients in the SLA group and 157 in the QPA group. The median duration of follow-up was 2.7 years (interquartile range, 2.0-3.6 years) in the QPA group and 3.2 years (2.2-3.4 years) in the SLA group. After adjustment for sex, age, body mass index, and time from injury to surgery, the hazard of graft failure in the SLA group was 10.66 times (95% CI, 3.41-32.92; P < .0001) that of the QPA group. The cumulative incidence of graft failure in the first 3 years after surgery was 48.8% (95% CI, 28.9%-73.1%) in the SLA group, as opposed to 4.7% (2.1%-10.3%) in the QPA group. There was no difference in return to sport between the groups. Among individuals who did not rerupture their ACL, International Knee Documentation Committee and Lysholm scores were comparable between the groups, as well as range of motion. Conclusion: The risk of failure was significantly increased in the SLA group relative to the QPA group. The high risk of failure for the SLA group in this short-term follow-up should be considered when selecting the treatment for adolescent patients with an ACL injury.

PurposeTo investigate the choroidal thickness (CT) and choroidal vascular densities (CVD) of patients with macular telangiectasia type 2 (MacTel2) and their association with other multimodal imaging features, using swept-source optical coherence tomography (SS-OCT).MethodsProspective, cross-sectional study. Consecutive patients with MacTel2 along with controls without any macular disease were included. Fundus photography, confocal blue reflectance, near-infrared reflectance, autofluorescence, fluorescein angiography, spectral domain OCT and SS-OCT were performed. Images were independently analysed by two graders, and CVD was calculated from binarised en face SS-OCT images. CT was obtained from the SS-OCT platform via built-in automated segmentation. Multilevel mixed-effects models were used for statistical analysis.ResultsThirty-nine eyes of 20 patients with MacTel2 and 29 eyes of 15 control patients were included. Average CT and perifoveal temporal CT did not differ significantly between eyes with MacTel2 and control eyes (p≥0.350), when accounting for confounding factors. Overall and temporal CVD also did not significantly differ between the two groups (p≥0.490).ConclusionCT and CVD did not significantly differ between MacTel2 and control eyes in this study using SS-OCT. Even though MacTel2 may include abnormalities involving the choroid, these are likely minor in comparison to the predominant retinal changes.

Background Both obesity and high dietary fat intake activate the nucleotide oligomerization domain–like receptor protein 3 (NLRP3) inflammasome. Objective We aimed to examine NLRP3 inflammasome activity in the airways of obese asthmatic patients after macronutrient overload and in immune cells challenged by inflammasome triggers. Methods Study 1 was a cross-sectional observational study of nonobese (n = 51) and obese (n = 76) asthmatic adults. Study 2 was a randomized, crossover, acute feeding study in 23 asthmatic adults (n = 12 nonobese and n = 11 obese subjects). Subjects consumed 3 isocaloric meals on 3 separate occasions (ie, saturated fatty acid, n-6 polyunsaturated fatty acid, and carbohydrate) and were assessed at 0 and 4 hours. For Studies 1 and 2, airway inflammation was measured based on sputum differential cell counts, IL-1β protein levels (ELISA), and sputum cell gene expression (Nanostring nCounter). In Study 3 peripheral blood neutrophils and monocytes were isolated by using Ficoll density gradient and magnetic bead separation and incubated with or without palmitic acid, LPS, or TNF-α for 24 hours, and IL-1β release was measured (ELISA). Results In Study 1 NLRP3 and nucleotide oligomerization domain 1 (NOD1) gene expression was upregulated, and sputum IL-1β protein levels were greater in obese versus nonobese asthmatic patients. In Study 2 the saturated fatty acid meal led to increases in sputum neutrophil percentages and sputum cell gene expression of Toll-like receptor 4 (TLR4) and NLRP3 at 4 hours in nonobese asthmatic patients. In Study 3 neutrophils and monocytes released IL-1β when challenged with a combination of palmitic acid and LPS or TNF-α. Conclusion The NLRP3 inflammasome is a potential therapeutic target in asthmatic patients. Behavioral interventions that reduce fatty acid exposure, such as weight loss and dietary saturated fat restriction, warrant further exploration.

Jay C Wang, Kenneth M McKay, Arjun B Sood, Inês Laíns, Lucia Sobrin, John B Miller Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA Purpose: To characterize and compare choroidal neovascularization (CNV) secondary to white dot syndromes (WDS) and age-related macular degeneration (AMD) using optical coherence tomography angiography (OCT-A).Methods: This is a cross-sectional study in which we imaged patients with CNV secondary to WDS and AMD with either the Zeiss Angioplex OCT-A or Optovue AngioVue OCT-A. Relevant demographic and clinical characteristics were collected and analyzed. CNV area and vessel density (VD) were measured by three independent graders, and linear regression analysis was subsequently performed.Results: Three patients with multifocal choroiditis and panuveitis, one patient each with birdshot chorioretinopathy, presumed ocular histoplasmosis syndrome, and persistent placoid maculopathy, and eleven patients with AMD with sufficient image quality were included. CNV associated with WDS was significantly smaller than that secondary to AMD (0.56±0.32 vs 2.79±1.80mm2, β=-2.22, P=0.01), while no difference in VD was detected (0.46±0.09 vs 0.44±0.09, β=0.02, P=0.71).Conclusion: CNV networks secondary to WDS appear to be smaller than those secondary to AMD but have similar VD. OCT-A is a powerful tool to investigate properties of CNV from various etiologies. Larger studies are needed for further characterization and understanding of CNV pathogenesis in inflammatory conditions. Keywords: white dot syndromes, age-related macular degeneration, choroidal neovascularization, optical coherence tomography angiography, uveitis, inflammation, choroidal neovascular membrane

Background Telomeres are repetitive DNA sequences of TTAGGG at the ends of chromosomes. Many studies have shown that telomere shortening is associated with aging-related diseases, such as cardiovascular diseases, hypertension, diabetes, cancer, and various neurodegenerative diseases, including Alzheimer's disease, vascular dementia, Parkinson's disease, and dementia with Lewy bodies. However, changes in telomere length (TL) in patients with frontotemporal dementia (FTD) syndrome are unclear. Accordingly, in this study, we assessed TL in blood samples from patients with FTD syndrome. Methods Absolute TL was measured in peripheral blood leukocytes from 53 patients with FTD syndromes (25 with behavioral variant FTD, 19 with semantic variant primary progressive aphasia [PPA], six with nonfluent/agrammatic variant PPA, and three with amyotrophic lateral sclerosis [ALS] plus) and 28 cognitively unimpaired (CU) controls using terminal restriction fragment analysis. Results TL was significantly longer in the FTD group than in the CU group. All FTD subtypes had significantly longer TL than controls. There were no significant differences in TL among FTD syndromes. No significant correlations were found between TL and demographic factors in the FTD group. Conclusions Longer telomeres were associated with FTD syndrome, consistent with a recent report demonstrating that longer telomeres are related to ALS. Therefore, our results may support a shared biology between FTD and ALS. More studies with larger sample sizes are needed.

Testosterone deficiency is common among Canadian men and is associated with significant health conditions that negatively impact quality of life. Based on a national needs assessment of Canadian physicians, the diagnosis, management, and risks associated with TD were identified as areas in need of educational tools and standard-setting to enhance the quality of clinical practice. The current guideline is offered as a practical, user-friendly, evidence-based reference to support healthcare providers and ensure that men in need of testosterone therapy are diagnosed and treated effectively and safely.

Background and Objectives: There is a shortage of physicians in rural communities in the United States. More than other types of primary care physicians, family physicians are the foundation for care in rural areas.1 There are also critical shortages of other specialties such as general surgery, pediatrics, internal medicine, and psychiatry in rural America.2-7 This study assessed student participation in the University of Washington School of Medicine’s (UWSOM) Targeted Rural Underserved Track (TRUST) program as a predictor for family medicine (FM) and needed workforce specialty residency match. Methods: The study group was 156 medical students from 2009-2014; 102 were accepted to the TRUST program compared to a control group of 54 who were not accepted into the TRUST program but did matriculate to UWSOM. Student characteristics for the two groups were compared using t tests. Logistic regression analysis determined whether acceptance in TRUST predicted the outcomes measures of FM residency match or residency match into a needed rural physician workforce specialty; t tests compared match rates to family medicine for TRUST applicants and graduates, UWSOM graduates, and US allopathic seniors. Results: TRUST program graduates had the same FM residency match rate and match rate in needed workforce specialties as the control group. The FM match rate for TRUST graduates was 29.1% compared to UWSOM at 16.9% and US seniors at 8.7% (P

Internal jugular flow is reduced in space compared with supine values, which can be associated with internal jugular vein (IJV) thrombosis. The mechanism is unknown but important to understand to prevent potentially serious vein thromboses on long duration flights. We used a novel, microgravity‐focused numerical model of the cranial vascular circulation to develop hypotheses for the reduced flow. This model includes the effects of removing hydrostatic gradients and tissue compressive forces – unique effects of weightlessness. The IJV in the model incorporates sensitivity to transmural pressure across the vein, which can dramatically affect resistance and flow in the vein. The model predicts reduced IJV flow in space. Although tissue weight in the neck is reduced in weightlessness, increasing transmural pressure, this is more than offset by the reduction in venous pressure produced by the loss of hydrostatic gradients and tissue pressures throughout the body. This results in a negative transmural pressure and increased IJV resistance. Unlike the IJV, the walls of the vertebral plexus are rigid; transmural pressure does not affect its resistance and so its flow increases in microgravity. This overall result is supported by spaceflight measurements, showing reduced IJV area inflight compared with supine values preflight. Significantly, this hypothesis suggests that interventions that further decrease internal IJV pressure (such as lower body negative pressure), which are not assisted by other drainage mechanisms (e.g. gravity), might lead to stagnant flow or IJV collapse with reduced flow, which could increase rather than decrease the risk of venous thrombosis., Internal jugular flow is reduced in space, which can be associated with internal jugular vein (IJV) thrombosis. We used a novel, microgravity‐focused numerical model of the cranial vascular circulation to develop hypotheses for the reduced flow. Weightlessness reduces venous pressures throughout the body which reduces internal jugular vein diameter and thus internal jugular venous flow.

Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of coronavirus disease 2019 (COVID-19), is readily transmitted person to person. Optimal control of COVID-19 depends on directing resources and health messaging to mitigation efforts that are most likely to prevent transmission, but the relative importance of such measures has been disputed. Objective To assess the proportion of SARS-CoV-2 transmissions in the community that likely occur from persons without symptoms. Design, Setting, and Participants This decision analytical model assessed the relative amount of transmission from presymptomatic, never symptomatic, and symptomatic individuals across a range of scenarios in which the proportion of transmission from people who never develop symptoms (ie, remain asymptomatic) and the infectious period were varied according to published best estimates. For all estimates, data from a meta-analysis was used to set the incubation period at a median of 5 days. The infectious period duration was maintained at 10 days, and peak infectiousness was varied between 3 and 7 days (−2 and +2 days relative to the median incubation period). The overall proportion of SARS-CoV-2 was varied between 0% and 70% to assess a wide range of possible proportions. Main Outcomes and Measures Level of transmission of SARS-CoV-2 from presymptomatic, never symptomatic, and symptomatic individuals. Results The baseline assumptions for the model were that peak infectiousness occurred at the median of symptom onset and that 30% of individuals with infection never develop symptoms and are 75% as infectious as those who do develop symptoms. Combined, these baseline assumptions imply that persons with infection who never develop symptoms may account for approximately 24% of all transmission. In this base case, 59% of all transmission came from asymptomatic transmission, comprising 35% from presymptomatic individuals and 24% from individuals who never develop symptoms. Under a broad range of values for each of these assumptions, at least 50% of new SARS-CoV-2 infections was estimated to have originated from exposure to individuals with infection but without symptoms. Conclusions and Relevance In this decision analytical model of multiple scenarios of proportions of asymptomatic individuals with COVID-19 and infectious periods, transmission from asymptomatic individuals was estimated to account for more than half of all transmissions. In addition to identification and isolation of persons with symptomatic COVID-19, effective control of spread will require reducing the risk of transmission from people with infection who do not have symptoms. These findings suggest that measures such as wearing masks, hand hygiene, social distancing, and strategic testing of people who are not ill will be foundational to slowing the spread of COVID-19 until safe and effective vaccines are available and widely used.