Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH

Backprojection for Training Feedforward Neural Networks in the Input and Feature Spaces

After the tremendous development of neural networks trained by backpropagation, it is a good time to develop other algorithms for training neural networks to gain more insights into networks. In this paper, we propose a new algorithm for training feedforward neural networks which is fairly faster than backpropagation. This method is based on projection and reconstruction where, at every layer, the projected data and reconstructed labels are forced to be similar and the weights are tuned accordingly layer by layer. The proposed algorithm can be used for both input and feature spaces, named as backprojection and kernel backprojection, respectively. This algorithm gives an insight to networks with a projection-based perspective. The experiments on synthetic datasets show the effectiveness of the proposed method.Comment: Accepted (to appear) in International Conference on Image Analysis and Recognition (ICIAR) 2020, Springe

Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice

<div><p>Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice.</p></div

Imperforate anus with a rectovestibular fistula and pseudotail: a case report

<p>Abstract</p> <p>Introduction</p> <p>Human tails and pseudotails are rare sacrococcygeal lesions that are associated with a wide variety of anomalies and syndromes. Anorectal malformations are also relatively uncommon congenital defects that often occur in conjunction with syndromes or other congenital abnormalities. The anomalies associated with both disorders determine the timing and approach to surgical correction. We present an unusual case of a patient with both imperforate anus and a pseudotail in the absence of a syndrome or other associated anomalies and we emphasize the necessity of a thorough preoperative evaluation.</p> <p>Case presentation</p> <p>A Caucasian girl was born at term after an uncomplicated pregnancy and was noted at birth to have a skin-covered posterior midline mass and imperforate anus with a fistula to the vaginal vestibule. Ultrasound and magnetic resonance imaging revealed a predominately fatty lesion without presacral extension and ruled out associated spinal and cord abnormalities. The patient underwent diversion with colostomy and a mucous fistula in the newborn period as a fistulogram demonstrated a long fistulous tract to normal rectum and it was anticipated that anoplasty and resection of the mass would require extensive posterior dissection. The sacrococcygeal mass was removed during posterior sagittal anorectoplasty at the age of six weeks which was determined to be a pseudotail because of the composition of brown fat and cartilage. The patient is now 14 months old with normal bowel function after a colostomy takedown.</p> <p>Conclusion</p> <p>A comprehensive preoperative assessment and thoughtful operative plan were necessary in this unusual case because of the extensive differential diagnosis for sacrococcygeal masses in the newborn and the frequency of anomalies and syndromes associated with tail variants and imperforate anus. The pediatricians and neonatologists who initially evaluate such patients and the surgeons who correct these disorders must be aware of the potential pitfalls in their management.</p

Principal Component Analysis Using Structural Similarity Index for Images

Despite the advances of deep learning in specific tasks using images, the principled assessment of image fidelity and similarity is still a critical ability to develop. As it has been shown that Mean Squared Error (MSE) is insufficient for this task, other measures have been developed with one of the most effective being Structural Similarity Index (SSIM). Such measures can be used for subspace learning but existing methods in machine learning, such as Principal Component Analysis (PCA), are based on Euclidean distance or MSE and thus cannot properly capture the structural features of images. In this paper, we define an image structure subspace which discriminates different types of image distortions. We propose Image Structural Component Analysis (ISCA) and also kernel ISCA by using SSIM, rather than Euclidean distance, in the formulation of PCA. This paper provides a bridge between image quality assessment and manifold learning opening a broad new area for future research.Comment: Paper for the methods named "Image Structural Component Analysis (ISCA)" and "Kernel Image Structural Component Analysis (Kernel ISCA)

Formalin Application for the Treatment of Radiation-Induced Hemorrhagic Proctitis

Radiation-induced hemorrhagic proctitis (RIHP) is a serious complication of pelvic irradiation, and a 4% formalin solution has been used for 20 years in treating this sequelae. The first case involving formalin application for treatment of RIHP in Korea was reported in 1996, but there are no additional studies beyond this date. Our study reviews the use of formalin instillation and selective application. The purpose of this study was to retrospectively evaluate the outcome of such treatments, beginning with the first case at our hospital. From 1996 to 2005, five RIHP patients had received formalin treatment for RIHP symptoms intractable to other medical treatments. All treatments were performed by a single surgeon in the operating room, under spinal anesthesia or intravenous sedation. The mean duration of symptoms before treatment was 15.6 months (which was longer than in other studies), and the transfusion before treatment varied from once per month to twice per week. Using sigmoidoscopy, 100ml of a 4% formalin solution was instilled directly (or by using a formalin-soaked gauze) and irrigated for five minutes. Formalin-soaked cotton was then applied selectively to focal remnant lesions. Four patients improved after the first treatment, but one patient received the treatment twice because of recurrent symptoms. Complications after treatment included perianal pain (one case), and aggravated incontinence (one case), which improved three months after conservative management. In conclusion, the formalin combination application method in our study is comparable to other formalin treatments for intractable RIHP

Comprehensive Brain MRI Segmentation in High Risk Preterm Newborns

Most extremely preterm newborns exhibit cerebral atrophy/growth disturbances and white matter signal abnormalities on MRI at term-equivalent age. MRI brain volumes could serve as biomarkers for evaluating the effects of neonatal intensive care and predicting neurodevelopmental outcomes. This requires detailed, accurate, and reliable brain MRI segmentation methods. We describe our efforts to develop such methods in high risk newborns using a combination of manual and automated segmentation tools. After intensive efforts to accurately define structural boundaries, two trained raters independently performed manual segmentation of nine subcortical structures using axial T2-weighted MRI scans from 20 randomly selected extremely preterm infants. All scans were re-segmented by both raters to assess reliability. High intra-rater reliability was achieved, as assessed by repeatability and intra-class correlation coefficients (ICC range: 0.97 to 0.99) for all manually segmented regions. Inter-rater reliability was slightly lower (ICC range: 0.93 to 0.99). A semi-automated segmentation approach was developed that combined the parametric strengths of the Hidden Markov Random Field Expectation Maximization algorithm with non-parametric Parzen window classifier resulting in accurate white matter, gray matter, and CSF segmentation. Final manual correction of misclassification errors improved accuracy (similarity index range: 0.87 to 0.89) and facilitated objective quantification of white matter signal abnormalities. The semi-automated and manual methods were seamlessly integrated to generate full brain segmentation within two hours. This comprehensive approach can facilitate the evaluation of large cohorts to rigorously evaluate the utility of regional brain volumes as biomarkers of neonatal care and surrogate endpoints for neurodevelopmental outcomes

Paternal and Maternal History of Myocardial Infarction and Cardiovascular Diseases Incidence in a Dutch Cohort of Middle-Aged Persons

Background - A positive parental history of myocardial infarction (MI) is an independent risk factor for cardiovascular diseases (CVD). However, different definitions of parental history have been used. We evaluated the impact of parental gender and age of onset of MI on CVD incidence. Methods - Baseline data were collected between 1993 and 1997 in 10¿524 respondents aged 40–65 years. CVD events were obtained from the National Hospital Discharge Register and Statistics Netherlands. We used proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for CVD incidence and adjusted for lifestyle and biological risk factors. Results - At baseline, 36% had a parental history of MI. During 10-year follow-up, 914 CVD events occurred. The age and gender adjusted HR was 1.3 (95% CI 1.1–1.5) for those with a paternal MI, 1.5 (1.2–1.8) for those with a maternal MI and 1.6 (1.2–2.2) for those with both parents with an MI. With decreasing parental age of MI, HR increased from 1.2 (1.0–1.6) for age =70 years to 1.5 (1.2–1.8) for ag

Relatively Low HIV Infection Rates in Rural Uganda, but with High Potential for a Rise: A Cohort Study in Kayunga District, Uganda

BACKGROUND: Few studies have been conducted in Uganda to identify and quantify the determinants of HIV-1 infection. We report results from a community-based cohort study, whose primary objectives were to determine HIV-1 prevalence, incidence, and determinants of these infections, among other objectives. METHODOLOGY: Consenting volunteers from the rural district of Kayunga in Uganda aged 15-49 years were enrolled between March and July 2006. Participants were evaluated every six months. A questionnaire that collected information on behavioral and other HIV-1 risk factors was administered, and a blood sample obtained for laboratory analysis at each study visit. PRINCIPAL FINDINGS: HIV-1 prevalence among the 2025 participants was 9.9% (95% CI = 8.6%-11.2%). By the end of 12 months of follow-up, 1689.7 person-years had been accumulated, with a median follow-up time of 11.97 months. Thirteen HIV-1 incident cases were detected giving an annual HIV-1 incidence of 0.77% (95% CI = 0.35-1.19). Prevalence of HSV-2 infection was 57% and was strongly associated with prevalent HIV-1 infection (adjusted Odds Ratio = 3.9, 95% CI = 2.50-6.17); as well as incident HIV-1 infection (adjusted Rate Ratio (RR) = 8.7, 95% CI = 1.11-67.2). The single most important behavioral characteristic associated with incident HIV infection was the number of times in the past 6 months, a participant had sex with person(s) they suspected/knew were having sex with others; attaining statistical significance at 10 times and higher (adjusted RR = 6.3, 95% CI = 1.73-23.1). By the end of 12 months of follow-up, 259 participants (13%) were lost to follow-up, 13 (0.6%) had died, and 2 (0.1%) had withdrawn consent. CONCLUSIONS: Despite relatively low HIV-1 incidence observed in this community, prevalence remains relatively high. In the presence of high prevalence of HSV-2 infection and the behavioral characteristic of having sex with more than one partner, there is potential for increase in HIV-1 incidence