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The partial/complete loss of one X chromosome in a human female leads to Turner syndrome (TS). TS individuals display a range of phenotypes including short stature, osteoporosis, ovarian malfunction, diabetes, and thyroid dysfunction. Epigenetic factors and regulatory networks are distinctly different in X monosomy (45, X). In a lifetime, an individual is exposed to a variety of stress conditions. To study whether X monosomy cells display a differential response upon exposure to mild stress as compared to normal 46, XX cells and whether this may contribute to various co-morbidities in aneuploid individuals, we have carried out a transcriptomic analysis of human fibroblasts 45, X and 46, XX after exposure to mild oxidative stress. Under these conditions, over 350 transcripts were seen to be differentially expressed in 45, X and 46, XX cells. Pathways associated with oxidative stress were differentially expressed highlighting the differential regulation of genes and associated phenotypes. It could be seen that X monosomy cells are more susceptible to oxidative stress as compared to normal cells and have altered molecular pathways both in normal conditions and also upon exposure to mild oxidative stress. To explore this aspect in detail, we have mapped the expressions of transcription factors (TFs) in 45, X and 46, XX cells. The network of transcription activating factors is differentially regulated in 45, X and 46, XX cells under stress exposure. It is tempting to speculate that the altered ability of 45, X (Turner) cells to respond to stress may play a significant role in the physiological function and altered phenotypes in Turner syndrome.

The recent discovery of hydropersulfides (RSSH) in mammalian systems suggests their potential roles in cell signaling. However, the exploration of RSSH biological significance is challenging due to their instability under physiological conditions. Herein, we report the preparation, RSSH-releasing properties, and cytoprotective nature of alkylamine-substituted perthiocarbamates. Triggered by a base-sensitive, self-immolative moiety, these precursors show efficient RSSH release and also demonstrate the ability to generate carbonyl sulfide (COS) in the presence of thiols. Using this dually reactive alkylamine-substituted perthiocarbamate platform, the generation of both RSSH and COS is tunable with respect to half-life, pH, and availability of thiols. Importantly, these precursors exhibit cytoprotective effects against hydrogen peroxide-mediated toxicity in H9c2 cells and cardioprotective effects against myocardial ischemic/reperfusion injury, indicating their potential application as new RSSH- and/or COS-releasing therapeutics.

This is an unusual case of an obstructive rectal squamous cell carcinoma (SCC), causing perforation and a pelvic abscess, requiring source control and diverting colostomy. A 50-year-old female with chronic constipation presented with worsening right buttock pain for 1 month. On exam, the patient reported right hip tenderness. A computer tomography (CT) revealed rectal wall thickening with a presacral abscess. Due to the concern of rectal perforation with abscess she was taken to the operating room for proctoscopy with biopsy, colostomy diversion and drainage of the abscess over the right buttock. Pathology reported invasive rectal SCC. Rectal SCC presents similarly to rectal adenocarcinoma but its diagnosis must include special markers for cytokeratins. The treatment approach is controversial but adequately treated offers better survival than rectal ADC. Rectal SCC is rare and treated with chemoradiation however it must also be tailored to the variable acute presentations.

Purpose: Studies have shown that individuals with retinal blood vessel abnormalities often present with other biomarkers associated with diabetic peripheral neuropathy (DPN). Existing software requires extensive manual intervention to measure structures in the retinal vasculature (e.g., arterial caliber, artery/vein ratios, fractals, etc.) for the purpose of studying the relationship of these structures to DPN. The goal of this study was to demonstrate an artificial intelligence (AI) software system for determining DPN risk based on retinal vascular abnormalities. Our approach circumvented the need to explicitly measure vessel characteristics by using AI as applied to a state-of-the-art methodology known as “convolutional neural networks” (CNN) to characterize the retinal vascular structures. CNNs have been demonstrated to be effective in a number of medical applications. This study is the first time CNNs have been used to extract retinal vascular features for DPN risk assessment. Methods: From a database of 25,000 cases previously labeled as healthy (controls), unaffected diabetes (DM), or DPN, we have identified 331 cases that fit the requirements for this study. Controls (N=103) had monofilament and vibration tests to confirm normal peripheral nerve function. DM patients (N=163) were classified based on their medical records and monofilament and vibration tests. DPN patients (N=65) were confirmed by clinical examination and their medical record. With these cases, an AI classifier was trained to identify individuals with DPN biomarkers based on spatial features extracted from the retinal abnormalities. Results: 80% of cohort data were used for training and 20% was used for testing. The resulting AI tool demonstrated 95% specificity and 78% sensitivity when using the clinical exam as the reference standard. Conclusions: AI-based CNN analysis of retinal vascular features show promise for identifying subjects with DPN and reduced human manipulation and measurement of tedious vessel geometries. Disclosure M.R. Burge: None. P. Soliz: None. J. Benson: None. V. Joshi: None. Funding National Institutes of Health (DK104578)

Cerebral Malaria (CM) is a severe neurological syndrome of malaria mainly found in children and is associated with highly specific retinal lesions. The manifestation of these indications of CM in the retina is called malarial retinopathy (MR). All patients showing clinical signs of CM are commonly diagnosed and treated accordingly; however, 23% of them are misdiagnosed as they suffer from another infection with identical clinical symptoms. Due to these underlying symptoms, the false positive cases may go untreated and could result in death of the patients. A diagnostic test is needed that is highly specific in order to reduce false positives. The purpose of this study to demonstrate a technique based on a transfer learning technique using images from three different retinal cameras to identify the hemorrhages and whitening lesions in the retina which can accurately identify the patients with MR. The MR detection model gives a specificity of 100% and a sensitivity of 90% with an AUC of 0.98. The algorithm demonstrates the potential of accurate MR detection with a low-cost retinal camera.

Purpose: Neurological clinical exams, quantitative sensory tests (QST), and nerve conduction studies (NCS) have been reported to have low accuracy in diagnosing diabetic peripheral neuropathy (DPN). This study explores the use of infrared (thermal) video imaging to detect small and large fiber DPN. Methods: 48 subjects with and 148 subjects without DPN were studied and compared to age-matched control subjects (n=84). All subjects’ feet were examined for sores, deformities, and other signs of disease, and patients with recent foot surgeries were excluded. Monofilament and vibration threshold testing ware performed on all subjects. Thermal videos were collected for all subjects, and NCS exams were performed on a subset of subjects. Thermal imaging followed a standard procedure: Imaging pre- and post-cooling to 2°C. A thermal classification model using thermal features extracted from the videos was developed with NCS as the reference standard to assess the performance of thermoregulation models. Results: Monofilament and vibration test results were compared with clinical diagnoses and had sensitivities of 52% and 57%, respectively. Sensitivity and specificity increase to 74% and 85% when the two tests were combined in an “either/or” decision. NCS was performed on 39 subjects: 11 control subjects, 12 subjects with clinical DPN, and 16 subjects with DM but without DPN. QST demonstrated a best sensitivity of 59% for the vibration test and a best individual specificity of 100% for the monofilament test when compared to NCS. When combined, QST demonstrated best overall sensitivity and specificity of 63% and 87%. The thermal model returned a sensitivity/specificity of 82%/94% and 91%/75% for different cut-points. Conclusions: Thermal recovery modeling from a cold stimulus yielded superior agreement with clinical and NCS diagnoses as compared to QST in the detection of DPN. A thermal imaging device can be made that is feasible for use in clinics at a lower cost than NCS devices. Disclosure M.R. Burge: None. C.S. Calder: None. J. Wigdahl: None. V. Joshi: None. X. Guo: None. J.C. Carmichael: None. P. Soliz: Stock/Shareholder; Self; VisionQuest Biomedical LLC. Funding National Institutes of Health

The purpose of this study was to identify biomarkers that are indicative of diabetic peripheral neuropathy (DPN). From a cohort of 21 DPN and 18 controls, optic disc- and macula-centered images were taken. Sixty vascular parameters were measured using computer-assisted software. Statistically significant differences in vascular parameters between subjects with DPN and controls showed that DPN subjects could be differentiated from controls using retinal biomarkers. Statistical significance (p < 0.05) was obtained for 13 retinal features, including fractal dimension, vein width, number of 1st branching vessels, and vessel tortuosity. The reduced fractal dimensions in DPN patients indicate a deterioration of the retinal vascular architecture. The reduced total number of vessels, as well as the total number of venules, contribute to the lower fractals in the DPN patients and supports the findings of a sparser retinal vascular network for DPN subjects. A difference in standard deviation for vessel width may suggest a greater loss of vascular tone and regulation in DPN subjects. A difference in the number of 1st branching vessels in venules was observed, which may indicate that the DPN subjects had fewer numbers of these first bifurcations. This feature would also contribute to the lower fractal dimension as well as a sparser retinal vascular network. Similarly, the statistical difference in the angle of the first daughter vessel suggests that the retinal vascular architecture has deviated from its optimal flow and/or function due to the disease process. The increased difference in curvature tortuosity in the arterioles in DPN correlates with chronic hypertensive retinopathy. We found statistically significant differences in 13 out of 60 retinal vascular features (22%) between control and DPN subjects. As such, the retina reflects the widespread vascular structural abnormalities occurring in diabetic patients with DPN. Disclosure S.C. Nemeth: None. M.R. Burge: None. J. Wigdahl: None. J.C. Carmichael: None. X. Guo: None. V. Joshi: None. P. Soliz: Stock/Shareholder; Self; VisionQuest Biomedical LLC. Funding National Institutes of Health (R43DK104578-01)

Purpose Randomized controlled trials have shown mixed findings regarding the association of statins and diabetes. This systematic literature review and network meta-analysis (NMA) was performed to update evidence on this association to possibly assist clinicians in making more informed treatment choices. Methods We identified studies relevant to our NMA by performing study searches in databases like Embase, Cochrane, and PubMed, published between August 2010 and June 2014. Pre-2010 studies were identified from bibliography of previously published meta-analyses. Unpublished study data were found from clinicaltrial.gov. Data synthesis was performed by pairwise meta-analysis and NMA within a Frequentist framework. Results Twenty nine trials in which 1 63 039 participants had been randomized were included in this review; among these 1 41 863 were non-diabetic patients. The direct meta-analysis showed that statins, as a class, significantly increased the likelihood of developing diabetes by 12% (pooled OR 1.12; 95%CI 1.05–1.21; I2 36%; p = 0.002; 18 RCTs). In the NMA, atorvastatin 80 mg was associated with a highest risk of diabetes, with OR of 1.34 (95%CI 1.14–1.57) followed by rosuvastatin (OR: 1.17; 95%CI: 1.02–1.35). The ORs (95%CIs) for simvastatin 80 mg, simvastatin, atorvastatin, pravastatin, lovastatin and pitavastatin were 1.21 (0.99–1.49), 1.13 (0.99–1.29), 1.13 (0.94–1.34), 1.04 (0.93–1.16), 0.98 (0.69–1.38) and 0.74 (0.31–1.77), respectively. High-dose atorvastatin increased the odds of developing diabetes even when compared with pravastatin, simvastatin and low-dose atorvastatin in the NMA. Conclusions Based on the results, statins, as a class, increased the risk of diabetes significantly in the pairwise meta-analysis. Overall, there appears to be a small increased risk of incident diabetes, particularly with more intensive statin therapy, although more data would be valuable to increase the robustness of this interpretation, given that the lower confidence intervals of our study analyses are close to, or just crossing one. Copyright © 2016 John Wiley & Sons, Ltd.

Cerebral malaria (CM) is a life-threatening clinical syndrome associated with 5-10% of malarial infection cases, most prevalent in Africa. About 23% of cerebral malaria cases are misdiagnosed as false positives, leading to inappropriate treatment and loss of lives. Malarial retinopathy (MR) is a retinal manifestation of CM that presents with a highly specific set of lesions. The detection of MR can reduce the false positive diagnosis of CM and alert physicians to investigate for other possible causes of the clinical symptoms and apply a more appropriate clinical intervention of underlying diseases. In order to facilitate easily accessible and affordable means of MR detection, we have developed an automated software system that detects the retinal lesions specific to MR, whitening and hemorrhages, using retinal color fundus images. The individual lesion detection algorithms were combined into an MR detection model using partial least square classifier. The classifier model was trained and tested on retinal image dataset obtained from 64 patients presenting with clinical signs of CM (44 with MR, 20 without MR). The MR detection model yielded specificity of 92% and sensitivity of 68%, with an AUC of 0.82. The proposed MR detection system demonstrates potential for broad screening of MR and can be integrated with a low-cost and portable retinal camera, to provide a bed-side tool for confirming CM diagnosis.

Purpose: To quantify the association between diabetic peripheral neuropathy (DPN) and diabetic retinopathy (DR), as expressed in terms of thermal regulation of the plantar foot and vascular abnormalities in the retina. Background: DPN accounts for around 73,000 lower-limb amputations in diabetics annually in the U.S., partially due to low compliance with periodic screening for DPN. Similarly, annual retinal screening for DR in diabetics is recommended by ADA and others. Identifying and referring individuals at risk for DPN by using biomarkers in retina could improve compliance for DPN screening. Methods: Subjects (55-75 years) clinically diagnosed with DPN (N=20) and a set of age-matched controls (N=29) were selected. Thermal videos and retinal images were collected for all subjects. Subjects’ feet were imaged with an infrared (thermal) imager to obtain: 1) baseline temperature for 3 min, and 2) thermal recovery temperature for 10 min after a cold-patch provocation. Presence of DPN was determined by clinical examination. Retinal imaging was performed on each eye to obtain macula- and disc-centered images. A certified grader read the retinal images for severity level of DR and other retinal abnormalities. A logistic regression analysis was performed to compare retinal and thermal features, with the clinical diagnosis of DPN. Results: A logistic regression determined a statistically significant difference (p < 0.05) in DR severity levels between DPN subjects and controls. The association between thermal features and DPN was demonstrated by statistically significant difference in recovery temperatures for both feet obtained in 1 min after cold provocation (p < 0.01), between DPN and controls. Discussion: This study demonstrates the value of using characteristics of DR screening to identify individuals also at risk for DPN. A thermal imager located at the same screening site as a retinal camera could improve compliance with DPN screening and potentially prevent unnecessary foot complications. Disclosure Z. Jarry: None. V. Joshi: None. M. Vahtel: None. M.R. Burge: Research Support; Self; VisionQuest Biomedical LLC.. P. Soliz: None.

Summary Background Charts of size at birth are used to assess the postnatal growth of preterm babies on the assumption that extrauterine growth should mimic that in the uterus. Methods The INTERGROWTH-21 st Project assessed fetal, newborn, and postnatal growth in eight geographically defined populations, in which maternal health care and nutritional needs were met. From these populations, the Fetal Growth Longitudinal Study selected low-risk women starting antenatal care before 14 weeks' gestation and monitored fetal growth by ultrasonography. All preterm births from this cohort were eligible for the Preterm Postnatal Follow-up Study, which included standardised anthropometric measurements, feeding practices based on breastfeeding, and data on morbidity, treatments, and development. To construct the preterm postnatal growth standards, we selected all live singletons born between 26 and before 37 weeks' gestation without congenital malformations, fetal growth restriction, or severe postnatal morbidity. We did analyses with second-degree fractional polynomial regression models in a multilevel framework accounting for repeated measures. Fetal and neonatal data were pooled from study sites and stratified by postmenstrual age. For neonates, boys and girls were assessed separately. Findings From 4607 women enrolled in the study, there were 224 preterm singleton births, of which 201 (90%) were enrolled in the Preterm Postnatal Follow-up Study. Variance component analysis showed that only 0·2% and 4·0% of the total variability in postnatal length and head circumference, respectively, could be attributed to between-site differences, justifying pooling the data from all study sites. Preterm growth patterns differed from those for babies in the INTERGROWTH-21 st Newborn Size Standards. They overlapped with the WHO Child Growth Standards for term babies by 64 weeks' postmenstrual age. Interpretation Our data have yielded standards for postnatal growth in preterm infants. These standards should be used for the assessment of preterm infants until 64 weeks' postmenstrual age, after which the WHO Child Growth Standards are appropriate. Size-at-birth charts should not be used to measure postnatal growth of preterm infants. Funding Bill & Melinda Gates Foundation.

Cisplatin is a widely used antineoplastic drug, but its clinical usefulness is limited due to dose dependent nephrotoxicity. Nordihydroguaiaretic acid (NDGA) is a natural compound with broad pharmacological properties like antioxidant, anti-inflammatory and anticancer activity. The present study was undertaken to evaluate the possible beneficial effects of NDGA on cisplatin induced nephrotoxicity as well as its anticancer activity in rats bearing DMBA induced mammary tumors. The effect of NDGA on cisplatin induced nephrotoxicity was evaluated by checking serum nephrotoxicity markers, antioxidant enzymes and inflammatory markers level and kidney histopathology. NDGA induced amelioration of cisplatin nephrotoxicity was clearly visible from significant reductions in serum blood urea nitrogen (86.51 g/dl) and creatinine (5.30 g/dl) levels and significant improvement in body weight change (-10.34 g) and kidney weight (728 mg/kg). The protective effect of NDGA against cisplatin induced nephrotoxicity in the rats was further confirmed by significant restoration of antioxidant enzymes like SOD (86.28% inhibition), inflammatory markers like TNF-α (34.6 pg/ml) and histopathological examination. Moreover, our results showed that NDGA potentiated anti-breast cancer activity of cisplatin through an increment in the expression of antioxidant enzymes like SOD (85.35% inhibition) in breast cancer tissue. These results indicated that NDGA potentiated the anti-breast cancer activity of cisplatin, which was clearly evident from the tumor volume and % tumor inhibition in breast cancer rats. The current study demonstrated that NDGA may modify the therapeutic effect of cisplatin in DMBA induced breast cancer in female Sprague-Dawley rats.

Breast cancer (BC) is the second most common cause of cancer deaths. Triple-negative breast cancer (TNBC) does not show immunohistochemical expression of oestrogen receptors, progesterone receptors or HER2. At present, no suitable treatment option is available for patients with TNBC. This dearth of effective conventional therapies for the treatment of advanced stage breast cancer has provoked the development of novel strategies for the management of patients with TNBC. This review presents recent information associated with different therapeutic options for the treatment of TNBC focusing on promising targets such as the Notch signalling, Wnt/β-catenin and Hedgehog pathways, in addition to EGFR, PARP1, mTOR, TGF-β and angiogenesis inhibitors.

Cancer is the second largest leading cause of death worldwide and breast cancer is the most prevailing cause of mortality among all cases of malignant neoplastic disease in adult females. The incidence rate of breast malignant neoplastic disease is predominantly higher in Western women, when compared to women in Asian nations. The definitive reason for this conflict is even unknown, but dietary factors have been conceived to account for approximately 30% of cancers in Western nations. It has been hypothesized that ethnicity, including use of a variety of spices in the food would be a major reason. Among all spices, turmeric (Curcuma longa) has been proven for its better anticancer potential. In this review different molecular mechanisms including cell cycle arrest; G0/G1 and/or G2/M phase cell cycle arrest by up-regulating Cdk inhibitor, p21/WAF/CIPI and p53, inhibition of transcriptional factors; NFκB, AP-1, TNFα, IL, STAT-3, and PPAR-γ, downstream gene regulation; c-myc, Bcl-2, COX-2, NOS, Cyclin D1, TNFα, interleukins and MMP-9, growth factors; bFGF, EGF, GCSF, IL-8, PDGF, TGFα, TNF, VEGF and cell adhesion molecules; fibronectin, vitronectin, and collagen which are involved in angiogenesis and metastasis, alsothe effectiveness of curcumin, when given in combination with chemotherapeutics like cyclophosphamide, doxorubicin, mitomycin etc. in treating breast cancer have been reviewed.

Diabetic peripheral neuropathy (DPN) accounts for around 73,000 lower-limb amputations annually in the US on patients with diabetes. Early detection of DPN is critical. Current clinical methods for diagnosing DPN are subjective and effective only at later stages. Until recently, thermal cameras used for medical imaging have been expensive and hence prohibitive to be installed in primary care setting. The objective of this study is to compare results from a low-cost thermal camera with a high-end thermal camera used in screening for DPN. Thermal imaging has demonstrated changes in microvascular function that correlates with nerve function affected by DPN. The limitations for using low-cost cameras for DPN imaging are: less resolution (active pixels), frame rate, thermal sensitivity etc. We integrated two FLIR Lepton (80x60 active pixels, 50° HFOV, thermal sensitivity < 50mK) as one unit. Right and left cameras record the videos of right and left foot respectively. A compactible embedded system (raspberry pi3 model Bv1.2) is used to configure the sensors, capture and stream the video via ethernet. The resulting video has 160x120 active pixels (8 frames/second). We compared the temperature measurement of feet obtained using low-cost camera against the gold standard highend FLIR SC305. Twelve subjects (aged 35-76) were recruited. Difference in the temperature measurements between cameras was calculated for each subject and the results show that the difference between the temperature measurements of two cameras (mean difference=0.4, p-value=0.2) is not statistically significant. We conclude that the low-cost thermal camera system shows potential for use in detecting early-signs of DPN in under-served and rural clinics.

Despite advances in thromboprophylaxis, the relationship between preexisting deep venous thromboses (DVTs) and postoperative thromboembolic complications is not fully established. The aim of this study was to assess the utility of selective and nonselective preoperative lower extremity venous Doppler screening protocols as tools in reducing the incidence of thromboembolic events (DVT/pulmonary embolism [PE]) after total joint arthroplasty. In the 2-year period from August 2013 to August 2015, a total of 455 consecutive elective primary total joint arthroplasties were identified from the authors' database. During the first year, a selective preoperative Doppler ultrasound screening protocol (only patients with a history of DVT/PE) was used for 182 patients, 31 of whom had preoperative ultrasound scans. The following year, a nonselective screening protocol was used for 273 consecutive patients, all of whom had preoperative Doppler ultrasound scans. All patients were followed for a minimum of 3 months postoperatively for postoperative Doppler ultrasound scans, emergency department visits, and readmissions related to DVT/PE. Preoperatively, there was no difference between the selective and nonselective cohorts regarding preoperative DVTs (3 and 1, respectively; P =.307); all patients were known to have prior DVT. Postoperative thromboembolic events were found in 4 (2.6%) of the patients in the selective cohort and 2 (0.7%) of the patients in the nonselective cohort ( P =.196). Use of a nonselective preoperative Doppler ultrasound screening protocol did not improve the identification of preoperative DVTs or reduce postoperative thromboembolic complications. [ Orthopedics. 2018; 41(2):e202–e206.]

Background: Pneumoperitoneum in laparoscopic procedures is associated with hemodynamic response, due to the release of catecholamines and vasopressin. Magnesium and clonidine have been used to attenuate such hemodynamic responses by inhibiting release of these mediators. We conducted this randomized, double-blinded study to assess which of the two attenuates hemodynamic response better. Materials and Methods: Ninety American Society of Anesthesiologists health status Classes I and II patients posted for elective laparoscopic cholecystectomy were randomized into three groups of thirty patients each. Group C received injection clonidine 1 μg/kg diluted in 10 mL normal saline over 10 min, prior to pneumoperitoneum. Group M received injection magnesium sulfate 50 mg/kg diluted in 10 mL normal saline over 10 min, prior to pneumoperitoneum. Group NS received 10 mL normal saline intravenously over 10 min, prior to pneumoperitoneum. Hemodynamic parameters were recorded before induction (baseline values), at the end of magnesium sulfate/clonidine/saline administration and before pneumoperitoneum (P0), 5 min (P5), 10 min (P10), 20 min (P20), 30 min (P30), and 40 min (P40) after pneumoperitoneum. Results: Systolic blood pressure, diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were all significantly higher in the normal saline group compared to magnesium and clonidine. On comparing patients in Group M and Group C, DBP, MAP, and HR were significantly lower in the magnesium group. Mean extubation time and time to response to verbal commands were significantly longer in the magnesium group. Conclusions: Both magnesium and clonidine attenuated the hemodynamic response to pneumoperitoneum. However, magnesium 50 mg/kg, attenuated hemodynamic response better than clonidine 1 μg/kg.

Background: Recently, there has been interest in non-mammalian collagen sources such as fish collagen in periodontal regeneration. In the present study, collagen barrier membrane of fish origin was assessed in the treatment of periodontal intrabony defects. Materials and Methods: Ten systemically healthy chronic periodontitis patients having a paired osseous defect in the mandibular posterior teeth were selected and randomly assigned to receive a collagen membrane (test) or open flap debridement (control) in a split mouth design. Clinical parameters such as Plaque index, Gingival bleeding index, Probing pocket depth, Relative attachment level, and Recession were recorded at baseline, 3, 6, and at 9 months, while radiographic evaluation was done to assess alveolar crestal bone level and percentage of defect fill at 6 and 9 months using autoCAD 2007 software. Student's t test (two-tailed, dependent) was used to find the significance of study parameters on continuous scale. Significance was set at 5% level of significance. Wilcoxon signed rank test was used to find the significance of percentage change of defect fill. Results: The comparison between the two groups did not show any statistically significant differences in the parameters assessed ( P > 0.05) but, within each group, clinical parameters showed statistically significant differences from baseline to 9 months ( P Conclusion: Within the limits of the study, it can be inferred that no significant differences were found either by using collagen membrane of fish origin or open flap debridement in the treatment of periodontal intrabony defects.

Cerebral malaria (CM) is a severe neurological complication associated with malarial infection. Malaria affects approximately 200 million people worldwide, and claims 600,000 lives annually, 75% of whom are African children under five years of age. Because most of these mortalities are caused by the high incidence of CM misdiagnosis, there is a need for an accurate diagnostic to confirm the presence of CM. The retinal lesions associated with malarial retinopathy (MR) such as retinal whitening, vessel discoloration, and hemorrhages, are highly specific to CM, and their detection can improve the accuracy of CM diagnosis. This paper will focus on development of an automated method for the detection of retinal whitening which is a unique sign of MR that manifests due to retinal ischemia resulting from CM. We propose to detect the whitening region in retinal color images based on multiple color and textural features. First, we preprocess the image using color and textural features of the CMYK and CIE-XYZ color spaces to minimize camera reflex. Next, we utilize color features of the HSL, CMYK, and CIE-XYZ channels, along with the structural features of difference of Gaussians. A watershed segmentation algorithm is used to assign each image region a probability of being inside the whitening, based on extracted features. The algorithm was applied to a dataset of 54 images (40 with whitening and 14 controls) that resulted in an image-based (binary) classification with an AUC of 0.80. This provides 88% sensitivity at a specificity of 65%. For a clinical application that requires a high specificity setting, the algorithm can be tuned to a specificity of 89% at a sensitivity of 82%. This is the first published method for retinal whitening detection and combining it with the detection methods for vessel discoloration and hemorrhages can further improve the detection accuracy for malarial retinopathy.

Cerebral malaria (CM) is a life-threatening clinical syndrome associated with malarial infection. It affects approximately 200 million people, mostly sub-Saharan African children under five years of age. Malarial retinopathy (MR) is a condition in which lesions such as whitening and vessel discoloration that are highly specific to CM appear in the retina. Other unrelated diseases can present with symptoms similar to CM, therefore the exact nature of the clinical symptoms must be ascertained in order to avoid misdiagnosis, which can lead to inappropriate treatment and, potentially, death. In this paper we outline the first system to detect the presence of discolored vessels associated with MR as a means to improve the CM diagnosis. We modified and improved our previous vessel segmentation algorithm by incorporating the ‘a’ channel of the CIELab color space and noise reduction. We then divided the segmented vasculature into vessel segments and extracted features at the wall and in the centerline of the segment. Finally, we used a regression classifier to sort the segments into discolored and not-discolored vessel classes. By counting the abnormal vessel segments in each image, we were able to divide the analyzed images into two groups: normal and presence of vessel discoloration due to MR. We achieved an accuracy of 85% with sensitivity of 94% and specificity of 67%. In clinical practice, this algorithm would be combined with other MR retinal pathology detection algorithms. Therefore, a high specificity can be achieved. By choosing a different operating point in the ROC curve, our system achieved sensitivity of 67% with specificity of 100%.

The incidence of cardiovascular disease (CVD) is on the rise and reported to be the world's leading cause of death. Retinal vascular abnormalities and lesions of hypertensive retinopathy (HR) have been shown to be highly predictive risk factors for CVD. However, the inter-reader agreement on detection of HR abnormalities by trained retinal readers is only fair to moderate, such as κ=0.56 for artery-venous nicking and κ=0.42 for arterial narrowing, indicating a significant inconsistency. We have developed a system for automated analysis of retinal photographs for HR abnormalities, which can assist a retinal reader in the grading process and provide additional insight into CVD risk. This includes a set of algorithms for retinal vessel network analysis and detection of HR abnormalities. Three retinal readers graded a set of 120 retinal images with and without the assistance of the system. Assistance resulted in an average 30% improvement in the reader's sensitivity to retinopathy detection, with a 32% reduction in average reading time. The inter-reader agreement using this system increased by an average of 54%, which indicates improvement in grading standardization. The system increases the efficiency of the grading process, and demonstrates increased reproducibility of the retinal grading that can standardize the diagnosis.

Adenocarcinoma of the body and tail of the pancreas are more often than not inoperable to begin with. Factors predicting the prognosis in the resected tumors of pancreatic body and tail were analyzed. Between 1989 and 2006, 43 patients with adenocarcinoma of the body and tail of the pancreas underwent resection at Chang Gung Memorial Hospital, Taoyuan, Taiwan. Univariate and multivariate analysis of clinicopathological factors affecting the prognosis were analyzed. Totally, 32 patients were available for the analysis. The median follow-up was 13.6 months (1.5–87.5 months). The median survival time was 14.2 months and the 1-, 3-, and 5-year survival rates were 58.1, 25.8, and 6.5 %, respectively. On univariate analysis, the factors which influenced the survival were tumor size >4 cm (p = 0.004), lymphatic invasion (p = 0.001), and positive resection margin (p = 0.030). On multivariate analysis, only the tumor size and the lymphatic invasion were independent prognostic factors. Even after macroscopic curative resection, the prognosis remains poor for pancreatic body and tail adenocarcinoma. Early diagnosis is the key to achieving long-term survival. Newer effective adjuvant treatment after curative resection is needed to improve the survival

Paraganglioma of the urinary bladder is a rare entity, and accounts for less than 0.5% of all bladder tumors. In the genitourinary tract, the urinary bladder is the most common site for paragangliomas. These tumors commonly present with hematuria and intermittent hyper-tension during micturition along with generalized symptoms due to raised catecholamines. Surgical removal is the treatment of choice, with most of the patients requiring at least a partial cystectomy. We herewith report a 38-year-old lady who presented with a two month history of pain abdomen, burning micturition, headache and uncontrolled hypertension. Detailed investi-gations revealed a pheochromocytoma of the urinary bladder, which was treated with partial cystectomy, following which her blood pressure stabilized.

The coupled oxygen transport in the avascular wall of a coronary artery stenosis is studied numerically by solving the convection–diffusion equations. Two geometries replicating stenosis before and after percutaneous transluminal coronary angioplasty (PTCA) are used for the analysis. The results are compared to evaluate the effect of the degree of stenosis on oxygen transport. Important physiological aspects, such as oxygen consumption in the wall, oxygen carried by the hemoglobin, non-Newtonian viscosity of the blood, and supply of oxygen from the vasa vasorum are included. The results show that the P O 2 in the medial region of the arterial wall is ∼10 mmHg. The oxygen flux to the wall increases in the flow acceleration region, whereas it decreases at the flow reattachment zone. Near the location of flow separation, there is a small rise followed by a sharp fall in the oxygen flux. The drop in the oxygen flux to the wall at the point of flow reattachment for pre-PTCA stenosis is four times that for post-PTCA stenosis. The minimum P O 2 in the avascular wall, P O 2 , min , at this location decreases to ∼6.0 and 4.2 mmHg for post- and pre-PTCA stenosis, respectively. The drop in P O 2 , w and P O 2 , min at the point of flow reattachment for pre-PTCA is ∼2 times that for post-PTCA stenosis. Thus, the present study quantifies the oxygen transport to the arterial wall before and after cardiovascular intervention.

This article reports the utilization of exostosis as a source of autogenous bone for the treatment of osseous defects. A patient presented with an exostosis on the mandibular lingual region on the right side of the jaw. Exostosis was surgically removed using a chisel and mallet. The autograft thus obtained was used to treat a shallow osseous crater between 46 and 47. New bone formation was noticed at the grafted site 6 months after grafting. Bone formed in the grafted areas showed comparable clinical features to those of native bone.

One of the most important signs of systemic disease that presents on the retina is vascular abnormalities such as in hypertensive retinopathy. Manual analysis of fundus images by human readers is qualitative and lacks in accuracy, consistency and repeatability. Present semi-automatic methods for vascular evaluation are reported to increase accuracy and reduce reader variability, but require extensive reader interaction; thus limiting the software-aided efficiency. Automation thus holds a twofold promise. First, decrease variability while increasing accuracy, and second, increasing the efficiency. In this paper we propose fully automated software as a second reader system for comprehensive assessment of retinal vasculature; which aids the readers in the quantitative characterization of vessel abnormalities in fundus images. This system provides the reader with objective measures of vascular morphology such as tortuosity, branching angles, as well as highlights of areas with abnormalities such as artery-venous nicking, copper and silver wiring, and retinal emboli; in order for the reader to make a final screening decision. To test the efficacy of our system, we evaluated the change in performance of a newly certified retinal reader when grading a set of 40 color fundus images with and without the assistance of the software. The results demonstrated an improvement in reader's performance with the software assistance, in terms of accuracy of detection of vessel abnormalities, determination of retinopathy, and reading time. This system enables the reader in making computer-assisted vasculature assessment with high accuracy and consistency, at a reduced reading time.

Multiple myeloma (MM) is a hematologic malignancy characterized as an abnormal proliferation and invasion of plasma cells into the bone marrow. Toll-like receptors (ТLRs) connect the innate and adaptive immune responses and represent a significant and potentially linking element between inflammation and cancer. When TLRs bind to their ligands, they trigger two major signaling pathways such that both share overlapping downstream signals: one is a myeloid differentiation primary response 88 (MyD88)-dependent production and activation of nuclear factor-κB, whereas the other is a MyD88-independent production of type-I interferon. Whereas the MyD88 pathway results in proinflammatory cytokine production, the other pathway stimulates cell proliferation. Dysregulations of these pathways may eventually lead to abnormal cell proliferation and MM. Despite recent biomedical advances, MM continues to be an incurable disease. There are an increasing number of TLR-based therapeutic approaches currently being tested in a number of preclinical and clinical studies. We here attempt to outline in detail the currently available information on TLRs in various types of cancer.

PURPOSE: To develop an automated method for the detection of retinal hemorrhages on color fundus images to characterize malarial retinopathy, which may help in the assessment of patients with cerebral malaria. METHODS: A fundus image dataset from 14 patients (200 fundus images, with an average of 14 images per patient) previously diagnosed with malarial retinopathy was examined. We developed a pattern recognition-based algorithm, which extracted features from image watershed regions called splats (tobogganing). A reference standard was obtained by manual segmentation of hemorrhages, which assigned a label to each splat. The splat features with the associated splat label were used to train a linear k-nearest neighbor classifier that learnt the color properties of hemorrhages and identified the splats belonging to hemorrhages in a test dataset. In a crossover design experiment, data from 12 patients were used for training and data from two patients were used for testing, with 14 different permutations; and the derived sensitivity and specificity values were averaged. RESULTS: The experiment resulted in hemorrhage detection sensitivities in terms of splats as 80.83%, and in terms of lesions as 84.84%. The splat-based specificity was 96.67%, whereas for the lesion-based analysis, an average of three false positives was obtained per image. The area under the receiver operating characteristic curve was reported as 0.9148 for splat-based, and as 0.9030 for lesion-based analysis. CONCLUSIONS: The method provides an automated means of detecting retinal hemorrhages associated with malarial retinopathy. The results matched well with the reference standard. With further development, this technique may provide automated assistance for screening and quantification of malarial retinopathy.

Retinal blood vessels show morphologic modifications in response to various retinopathies. However, the specific responses exhibited by arteries and veins may provide a precise diagnostic information, i.e., a diabetic retinopathy may be detected more accurately with the venous dilatation instead of average vessel dilatation. In order to analyze the vessel type specific morphologic modifications, the classification of a vessel network into arteries and veins is required. We previously described a method for identification and separation of retinal vessel trees; i.e. structural mapping. Therefore, we propose the artery-venous classification based on structural mapping and identification of color properties prominent to the vessel types. The mean and standard deviation of each of green channel intensity and hue channel intensity are analyzed in a region of interest around each centerline pixel of a vessel. Using the vector of color properties extracted from each centerline pixel, it is classified into one of the two clusters (artery and vein), obtained by the fuzzy-C-means clustering. According to the proportion of clustered centerline pixels in a particular vessel, and utilizing the artery-venous crossing property of retinal vessels, each vessel is assigned a label of an artery or a vein. The classification results are compared with the manually annotated ground truth (gold standard). We applied the proposed method to a dataset of 15 retinal color fundus images resulting in an accuracy of 88.28% correctly classified vessel pixels. The automated classification results match well with the gold standard suggesting its potential in artery-venous classification and the respective morphology analysis.

Structural analysis of retinal vessel network has so far served in the diagnosis of retinopathies and systemic diseases. The retinopathies are known to affect the morphologic properties of retinal vessels such as course, shape, caliber, and tortuosity. Whether the arteries and the veins respond to these changes together or in tandem has always been a topic of discussion. However the diseases such as diabetic retinopathy and retinopathy of prematurity have been diagnosed with the morphologic changes specific either to arteries or to veins. Thus a method describing the separation of retinal vessel trees imaged in a two dimensional color fundus image may assist in artery-vein classification and quantitative assessment of morphologic changes particular to arteries or veins. We propose a method based on mathematical morphology and graph search to identify and label the retinal vessel trees, which provides a structural mapping of vessel network in terms of each individual primary vessel, its branches and spatial positions of branching and cross-over points. The method was evaluated on a dataset of 15 fundus images resulting into an accuracy of 92.87 % correctly assigned vessel pixels when compared with the manual labeling of separated vessel trees. Accordingly, the structural mapping method performs well and we are currently investigating its potential in evaluating the characteristic properties specific to arteries or veins.

The demonstration that ganglioside GM1 pretreatment reduced the ethanol induced neurobehavioral effects in adult pups exposed to ethanol in utero, prompted study to examine whether GM1 crosses the placenta and penetrates fetal tissues. The present results indicate that 3H-galactose labeled GM1 not only passes the placenta but also served as a substrate for the synthesis of polysialogangliosides, and remained in various tissues up to 48 h after maternal (3H)-GM1 administration.

Abnormalities in the vascular pattern of the retina are associated with retinal diseases and are also risk factors for systemic diseases, especially cardiovascular diseases. The three-dimensional retinal vascular pattern is mostly formed congenitally, but is then modified over life, in response to aging, vessel wall dystrophies and long term changes in blood flow and pressure. A characteristic of the vascular pattern that is appreciated by clinicians is vascular tortuosity, i.e. how curved or kinked a blood vessel, either vein or artery, appears along its course. We developed a new quantitative metric for vascular tortuosity, based on the vessel's angle of curvature, length of the curved vessel over its chord length (arc to chord ratio), number of curvature sign changes, and combined these into a unidimensional metric, Tortuosity Index (TI). In comparison to other published methods this method can estimate appropriate TI for vessels with constant curvature sign and vessels with equal arc to chord ratios, as well. We applied this method to a dataset of 15 digital fundus images of 8 patients with Facioscapulohumeral muscular dystrophy (FSHD), and to the other publically available dataset of 60 fundus images of normal cases and patients with hypertensive retinopathy, of which the arterial and venous tortuosities have also been graded by masked experts (ophthalmologists). The method produced exactly the same rank-ordered list of vessel tortuosity (TI) values as obtained by averaging the tortuosity grading given by 3 ophthalmologists for FSHD dataset and a list of TI values with high ranking correlation with the ophthalmologist's grading for the other dataset. Our results show that TI has potential to detect and evaluate abnormal retinal vascular structure in early diagnosis and prognosis of retinopathies.

The biochemical mechanism of alcohol teratotogenicity is not knowm. We have demonstrated that alcohol administration to pregnant rats during gestation days (GD) 6 and 7 and/or 13 and 14 leads to significant accumulation of ethyl esters of long chain fatty acids (FAEEs) in both maternal and fetal organs. This observation extends the report of Bearer et al. ( Pediat Res 31 : 492–495, 1992) who detected the presence of metabolites in maternal and fetal organs of pregnant C57Bl/6J mice exposed to alcohol on GD 7 and/or GD 14. The ethyl esters of arachidonic, linoleic, oleic, stearic and palmitic acids were major metabolites detected in both maternal and fetal organs. It was also demonstrated that detectable levels of FAEEs remain 14 days (GD 20) after initial exposure to alcohol on GD 7. Ganglioside GM1 treatment 1 and 24 hr prior to alcohol exposure on both GD 7 and/or GD 14 reduced the accumulation of FAEEs. A similar regimen was shown to prevent development of tolerance to alcohol in the adult pups exposed to alcohol in utero in our previous studies. Thus, the ganglioside GM1 may have therapeutic value in reducing neurobehavioral effects of alcohol exposure in utero .

We have investigated the effect of in utero ethanol exposure and ganglioside GM1 pretreatment on the endogenous ganglioside profile of the rat fetal brain. Prenatal ethanol exposure on gestation day (GD) 7 and GD8 and/or GD13 and GD14 leads to a very significant increase in the ganglioside GM1 content in at least 50% of the pup brains when assayed on GD20. This treatment protocol also results in significant decrease in the content of polysialogangliosides GD1a, GT1b, and GQ1b. GM1 treatment of pregnant dams before ethanol administration prevented this alteration in pup brain ganglioside profile. Ganglioside GM1 pretreatment appears to block the cellular membrane changes associated with fetal alcohol effects and thereby minimizes alterations in brain maturation and associated behavioral dysfunction.

Using a consistent, reproducible and reliable cortical focal ischemia in rat (permanent unilateral occlusion of the left middle cerebral arterythe ipsilateral common carotid artery [MCAo + CCAo] with a 1 h temporary occlusion of the contralateral CCA), the levels of four major membrane fatty acids (palmitic, C16:0; stearic, C18:0; Oleic, C18:1 and arachidonic, C20:4) were analyzed at 3, 36 and 72 h, and 2 and 4 wk following ischemia to determine the critical point of irreversibility of the cellular plasma membrane disorganization in primary ischemic (Area 1, parietal cortex) and peri-ischemic (Area 2, tempero-occipital cortex) areas. The cortical focal ischemia resulted in time dependent differential loss in four of these major membrane fatty acids. The quantitative differences among primary and peri-ischemic areas reflected the different degree of ischemic injury inflicted to these regions. Acute treatment with ganglioside GM1 protected the further losses of all of these fatty acids and differentially restored their levels in these various injury sites over periods of time. The changes in levels of these membrane fatty acids indicate that the primary ischemic area suffers an irreversible injury and peri-ischemic area suffers reversible injury. After acute treatment (2 h) with ganglioside GM1, a partial recovery was observed in primary ischemic area and complete recovery was observed in peri-ischemic areas. These studies support the hypothesis that, ischemia leads to a irreversible plasma membrane disorganization which underlies the eventual cell death, and protection and restoration of these membrane changes by drugs, such as ganglioside GM1 leads to neuroprotection against ischemic injury.

Background Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disease beginning with facial and shoulder girdle weakness with variable progression. Exudative retinal detachment, retinal vessel irregularities on fluorescein angiography, and retinal vessel tortuosity have been found in association with FSHD. Methods In this retrospective study, muscle affectedness severity was rated as mild, moderate, or severe by a neurologist masked to the retinal images. Three ophthalmologists masked to disease severity graded the degree of arterial and venous tortuosity on a scale of 1 to 4. An automated method estimated an index of tortuosity for arteries and veins from color fundus photographs. Spearman rank correlation coefficients were used to describe the relationship between retinal vessel tortuosity and disease severity. Results Seven patients with an average age of 13 years (range, 7-36 years) were selected. Correlation between the subjective tortuosity for arteries, and the severity of FSHD was 0.78 ( p = 0.039). The correlation coefficient for venous tortuosity was −0.06 and was not significant ( p = 0.882). The correlation coefficient between the average algorithmic computer-generated tortuosity indices for arteries and FSHD severity was high (0.85, p = 0.016), but for veins it was low and not significant (0.19, p = 0.662). Conclusions The authors of previous reports have shown retinal vascular abnormalities did not correlate to FSHD disease severity. Our results suggest a correlation between the tortuosity of arteries and the severity of disease in FSHD patients. These results suggest the tortuosity of arteries can serve as a biomarker of severity of disease in these FSHD patients, either as determined by human experts or by an automated method.

Purpose : Penile carcinoma is a common disease in India. This paper shows the results of sentinel node biopsy using methylene blue and discusses the incidence of false-negative rates. Materials and Methods: From September 2005 to March 2008, 22 newly diagnosed penile carcinoma patients (T1, T2, N0) were included in this prospective study. Intraoperative lymphatic mapping was done using methylene blue dye and the sentinel node was identified and removed. Lymphadenectomy was performed for positive inguinal lymph node metastasis. Results : There were 22 patients (mean age 52.7). The tumors were mostly located in the glans (73%). Eighty six percent was T1 lesions and 14% was T2. Ninety one percent of the patients underwent partial penectomy, and 9% underwent total penectomy. Sentinel node was identified in 20 patients (90.9%). In total, 49 sentinel nodes were identified (2.45 nodes per person). Only one patient had a positive pathological lymph node metastasis at the time of the surgery. Additionally, two patients became inguinal lymph node positive at the follow-up. This data yielded a sensitivity rate of 33% and a false-negative rate of 66%. There were no complications due to methylene blue. Conclusion : Sentinel node biopsy using only methylene blue for penile carcinoma has a very low sensitivity and a high false-negative rate. However, methylene blue can be used as a substitute for lymphazurin.

Carcinoid tumors of ampulla are rare clinical entities. They form 0.35% of all the gastrointestinal carcinoids. So far, only 109 cases have been reported in the literature, mostly as individual case reports. Since the metastatic potential and the tumor size have no correlation, unlike in duodenal carcinoids, pancreatoduodenectomy is considered the treatment of choice. Here we present a case of carcinoid of ampulla presenting to our department.