Vitamin D supplementation leading to hypervitaminosis D in a breastfed infant: A case report.

Breast milk alone is a poor and inadequate source of vitamin D. Many guidelines suggest supplementation of vitamin D to the newborns to prevent vitamin D deficiency. However, due to practices of outdoor breastfeeding and sunbathing, vitamin D supplementation may not be routinely required in our settings. Overzealous use of vitamin D supplementation and over-the-counter prescription may result in hypervitaminosis D.

Loss of Retinogeniculate Synaptic Function in the DBA/2J Mouse Model of Glaucoma.

Retinal ganglion cell (RGC) axons comprise the optic nerve and carry information to the dorsolateral geniculate nucleus (dLGN), which is then relayed to the cortex for conscious vision. Glaucoma is a blinding neurodegenerative disease that commonly results from intraocular pressure (IOP)-associated injury leading to RGC axonal pathology, disruption of RGC outputs to the brain, and eventual apoptotic loss of RGC somata. The consequences of elevated IOP and glaucomatous pathology on RGC signaling to the dLGN are largely unknown yet are likely to contribute to vision loss. Here, we used anatomic and physiological approaches to study the structure and function of retinogeniculate (RG) synapses in male and female DBA/2J (D2) mice with inherited glaucoma before and after IOP elevation. D2 mice showed progressive loss of anterograde optic tract transport to the dLGN and vGlut2 labeling of RGC axon terminals while patch-clamp measurements of RG synaptic function showed that synaptic transmission was reduced in 9-month and 12-month D2 mice because of the loss of individual RGC axon inputs. TC neuron dendrites had reduced Sholl complexity at 12 months, suggestive of delayed reorganization following reduced synaptic input. There was no detectable change in RGC density in 11- to 12-month D2 retinas, quantified as the number of ganglion cell layer-residing somata immuno-positive for NeuN and immuno-negative for the amacrine marker choline acetyltransferase (ChAT). Thus, observed synaptic defects appear to precede RGC somatic loss. These findings identify glaucoma-associated and IOP-associated deficits in an important subcortical RGC projection target, shedding light on processes linking IOP to vision loss.

A transfer learning based deep learning model to diagnose covid-19 CT scan images.

To save the life of human beings during the pandemic conditions we need an effective automated method to deal with this situation. In pandemic conditions when the available resources becomes insufficient to handle the patient's load, then we needed some fast and reliable method which analyse the patient medical data with high efficiency and accuracy within time limitations. In this manuscript, an effective and efficient method is proposed for exact diagnosis of the patient whether it is coronavirus disease-2019 (covid-19) positive or negative with the help of deep learning. To find the correct diagnosis with high accuracy we use pre-processed segmented images for the analysis with deep learning. In the first step the X-ray image or computed tomography (CT) of a covid-19 infected person is analysed with various schemes of image segmentation like simple thresholding at 0.3, simple thresholding at 0.6, multiple thresholding (between 26-230) and Otsu's algorithm. On comparative analysis of all these methods, it is found that the Otsu's algorithm is a simple and optimum scheme to improve the segmented outcome of binary image for the diagnosis point of view. Otsu's segmentation scheme gives more precise values in comparison to other methods on the scale of various image quality parameters like accuracy, sensitivity, f-measure, precision, and specificity. For image classification here we use Resnet-50, MobileNet and VGG-16 models of deep learning which gives accuracy 70.24%, 72.95% and 83.18% respectively with non-segmented CT scan images and 75.08%, 80.12% and 99.28% respectively with Otsu's segmented CT scan images. On a comparative study we find that the VGG-16 models with CT scan image segmented with Otsu's segmentation gives very high accuracy of 99.28%. On the basis of the diagnosis of the patient firstly we go for an arterial blood gas (ABG) analysis and then on the behalf of this diagnosis and ABG report, the severity level of the patient can be decided and according to this severity level, proper treatment protocols can be followed immediately to save the patient's life. Compared with the existing works, our deep learning based novel method reduces the complexity, takes much less time and has a greater accuracy for exact diagnosis of coronavirus disease-2019 (covid-19).

Medical students' attitude towards cultural diversity: a cross-sectional study at a health sciences university in eastern Nepal.

OBJECTIVES: To assess the attitude of medical students towards cultural diversity aiming to elucidate our current status in understanding cultural awareness and sensitivity. DESIGN, SETTING AND PARTICIPANTS: A web-based cross-sectional study was carried out among 601 undergraduate health science students (medical and dental courses) at a health sciences university in eastern Nepal via various modes of social-media platforms like WhatsApp, Messenger, Gmail, etc. OUTCOME MEASURES: Medical students' attitude towards cultural diversity and its association with the sociodemographic profile of the students. RESULTS: A total of 601 students participated in the study, out of which, 64.2% were men with a sex ratio of 1.8:1 and a mean age of 22.3±1.9 years. More than two-thirds (77.2%) of the students had an excellent to good attitude towards cultural diversity. The proportion of students reporting 'excellent' attitude towards cultural diversity was higher among male students compared with female students (37.8% vs 20.5%) and students aged >22 years compared with younger students (37.1% vs 26.7%). Gender (p<0.001) and age (p=0.009) were significantly associated with the attitude towards cultural diversity. CONCLUSIONS: Medical students, in general, are aware of the impacts of a cross-cultural society on the delivery of quality healthcare and also about the need to be aware of prejudices doctors may have towards certain cultures. Majority suggest the inclusion of concepts of multicultural awareness and sensitivity in the medical curriculum itself.

Spatial mutual information based detail preserving magnetic resonance image enhancement.

Medical imaging is a widespread method of envisioning the inside of the human anatomy without causing harm. In magnetic resonance imaging (MRI), poor contrast images may not support adequate information for visual reading of affected areas. As a result, image enhancement technique is essential to enhance image views and keep the image processing approach computationally low. Because of the anatomical complexity of the brain, low contrast is a challenging aspect to deal with in MRI imaging. The issue of conserving structural features while maintaining brightness is also a significant consideration. The histogram equalization (HE) based technique is frequently applied to enhance contrast in brain MRI images. A unique enhancing approach is presented to increase the brightness and contrast of the MRI picture. Spatial mutual information-based algorithm analyses a clinically gathered dataset of MRI images, producing good results. The proposed approach tested both healthy and unhealthy brain MRI pictures. Contrast and brightness improvement are the two divisions of the suggested technique. Adaptive gamma correction using weighted distribution method is applied on the value channel (V) in HSV color model. It provides the brightness gain matrix, which enhances the image brightness. Spatial mutual information methods act on the luminosity space (L) of the CIE 1976 L*a*b* color space for contrast enhancement. Finally, an efficacious brightness and contrast modification strategy for MRI images is provided, with its performance compared to several state-of-the-art approaches using a well-known performance measure.

Structural and Functional Plasticity in the Dorsolateral Geniculate Nucleus of Mice following Bilateral Enucleation.

Within the nervous system, plasticity mechanisms attempt to stabilize network activity following disruption by injury, disease, or degeneration. Optic nerve injury and age-related diseases can induce homeostatic-like responses in adulthood. We tested this possibility in the thalamocortical (TC) neurons in the dorsolateral geniculate nucleus (dLGN) using patch-clamp electrophysiology, optogenetics, immunostaining, and single-cell dendritic analysis following loss of visual input via bilateral enucleation. We observed progressive loss of vGlut2-positive retinal terminals in the dLGN indicating degeneration post-enucleation that was coincident with changes in microglial morphology indicative of microglial activation. Consistent with the decline of vGlut2 puncta, we also observed loss of retinogeniculate (RG) synaptic function assessed using optogenetic activation of RG axons while performing whole-cell voltage clamp recordings from TC neurons in brain slices. Surprisingly, we did not detect any significant changes in the frequency of miniature post-synaptic currents (mEPSCs) or corticothalamic feedback synapses. Analysis of TC neuron dendritic structure from single-cell dye fills revealed a gradual loss of dendrites proximal to the soma, where TC neurons receive the bulk of RG inputs. Finally, analysis of action potential firing demonstrated that TC neurons have increased excitability following enucleation, firing more action potentials in response to depolarizing current injections. Our findings show that degeneration of the retinal axons/optic nerve and loss of RG synaptic inputs induces structural and functional changes in TC neurons, consistent with neuronal attempts at compensatory plasticity in the dLGN.

Exploratory study of VVZ-149, a novel analgesic molecule, in the affective component of acute postoperative pain after laparoscopic colorectal surgery.

STUDY OBJECTIVE: VVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A. In the present study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after colorectal surgery. DESIGN: Randomized, parallel group, double-blind Phase 2 clinical trial (NCT02489526). SETTING: 3 academic institutions in the United States. PATIENTS: 60 patients undergoing laparoscopic colorectal surgery. INTERVENTIONS: A continuous 8-h intravenous infusion of VVZ-149 Injections (n = 40) or placebo (n = 20) administered after emergence from anesthesia. MEASUREMENTS: The outcome measures included pain intensity (PI), opioid consumption via patient-controlled analgesia (PCA), and rescue dosing provided "as needed". Early rescue dosing with opioids postoperatively was associated with preoperative negative affect (anxiety, depression, and pain catastrophizing), enabling it to be used as an indirect measure of the affective component of pain. Efficacy outcomes were compared between treatment groups based on preoperative negative affect and early rescue dosing of opioids. MAIN RESULTS: Postoperative PI was non-significantly lower in patients receiving VVZ-149 compared to those receiving placebo. The VVZ-149 group had a 34.2% reduction in opioid consumption for 24 h post-dose, along with fewer PCA demands. Somnolence and headache was higher in the intervention group. For patients characterized by high levels of preoperative negative affect, the VVZ-149 group experienced a significant pain reduction and 40% less opioid use compared to the placebo group. CONCLUSIONS: VVZ-149 resulted in a non-significant reduction of postoperative pain during the first 8 h after surgery. Post hoc analysis indicates that VVZ-149 may benefit patients with negative affect who otherwise have higher postoperative opioid use. REGISTRATION NUMBER: www.clinicaltrials.gov, ID: NCT02489526.

A Context-Based Image Contrast Enhancement Using Energy Equalization With Clipping Limit.

In this paper, a new context-based image contrast enhancement process using energy curve equalization (ECE) with a clipping limit has been proposed. In a fundamental anomaly to the existing contrast enhancement practice using histogram equalization, the projected method uses the energy curve. The computation of the energy curve utilizes a modified Hopfield neural network architecture. This process embraces the image's spatial adjacency information to the energy curve. For each intensity level, the energy value is calculated and the overall energy curve appears to be smoother than the histogram. A clipping limit applies to evade the over enhancement and is chosen as the average of the mean and median value. The clipped energy curve is subdivided into three regions based on the standard deviation value. Each part of the subdivided energy curve is equalized individually, and the final enhanced image is produced by combining transfer functions computed by the equalization process. The projected scheme's qualitative and quantitative efficiency is assessed by comparing it with the conventional histogram equalization techniques with and without the clipping limit.

Triple Clipped Histogram-Based Medical Image Enhancement Using Spatial Frequency.

In this paper, a novel triple clipped histogram model-based fusion approach has been proposed to improve the basics features, brightness preservation and contrast of the medical images. This incorporates the features of the equalized image and input image together. In the initial step, the low-contrast medical image is equalized using the triple clipped dynamic histogram equalization technique for which the histogram of the input medical image is split into three sections on the basis of standard deviation with almost equal number of pixels. The clipping process of the histogram is performed on every histogram section and mapped to a new dynamic range using simple calculations. In the second step, the sub-histogram equalization process is performed separately. Approximation and detail coefficients of equalized and input images are separated using discrete wavelet transform (DWT). Thereafter, the approximation coefficients are modified using some basic calculation-based fusion which involves singular value decomposition (SVD) and its inverse. Detail coefficients are fused using spatial frequency features. This yields modified approximation and detail coefficients for an enhanced image. Finally, inverse discrete wavelet transform (IDWT) has been applied to the modified coefficients which result in an enhanced image with improved visual quality. These improvements are analyzed qualitatively and quantitatively.

Early-Stage Ocular Hypertension Alters Retinal Ganglion Cell Synaptic Transmission in the Visual Thalamus.

Axonopathy is a hallmark of many neurodegenerative diseases including glaucoma, where elevated intraocular pressure (ocular hypertension, OHT) stresses retinal ganglion cell (RGC) axons as they exit the eye and form the optic nerve. OHT causes early changes in the optic nerve such as axon atrophy, transport inhibition, and gliosis. Importantly, many of these changes appear to occur prior to irreversible neuronal loss, making them promising points for early diagnosis of glaucoma. It is unknown whether OHT has similarly early effects on the function of RGC output to the brain. To test this possibility, we elevated eye pressure in mice by anterior chamber injection of polystyrene microbeads. Five weeks post-injection, bead-injected eyes showed a modest RGC loss in the peripheral retina, as evidenced by RBPMS antibody staining. Additionally, we observed reduced dendritic complexity and lower spontaneous spike rate of On-αRGCs, targeted for patch clamp recording and dye filling using a Opn4-Cre reporter mouse line. To determine the influence of OHT on retinal projections to the brain, we expressed Channelrhodopsin-2 (ChR2) in melanopsin-expressing RGCs by crossing the Opn4-Cre mouse line with a ChR2-reporter mouse line and recorded post-synaptic responses in thalamocortical relay neurons in the dorsal lateral geniculate nucleus (dLGN) of the thalamus evoked by stimulation with 460 nm light. The use of a Opn4-Cre reporter system allowed for expression of ChR2 in a narrow subset of RGCs responsible for image-forming vision in mice. Five weeks following OHT induction, paired pulse and high-frequency stimulus train experiments revealed that presynaptic vesicle release probability at retinogeniculate synapses was elevated. Additionally, miniature synaptic current frequency was slightly reduced in brain slices from OHT mice and proximal dendrites of post-synaptic dLGN relay neurons, assessed using a Sholl analysis, showed a reduced complexity. Strikingly, these changes occurred prior to major loss of RGCs labeled with the Opn4-Cre mouse, as indicated by immunofluorescence staining of ChR2-expressing retinal neurons. Thus, OHT leads to pre- and post-synaptic functional and structural changes at retinogeniculate synapses. Along with RGC dendritic remodeling and optic nerve transport changes, these retinogeniculate synaptic changes are among the earliest signs of glaucoma.

Neutrophils release extracellular DNA traps during storage of red blood cell units.

BACKGROUND: Blood transfusion is associated with an increased risk of organ damage, infection, and alloimmunity. Neutrophil extracellular traps (NETs) are extracellular chromatin fibers decorated with neutrophil granular proteins that have been linked to cytotoxicity, thrombosis, and autoimmunity. We questioned whether neutrophils in blood products release NETs during storage and thus could contribute to adverse reactions from blood transfusions. STUDY DESIGN AND METHODS: We analyzed supernatants and blood smears of human red blood cell (RBC) units that either were or were not leukoreduced before storage for markers of NETs. RESULTS: We identified extracellular DNA, which was associated with histones and myeloperoxidase, a marker of neutrophil granules, in supernatants and blood smears of nonleukoreduced RBC units. These markers of NETs were absent in leukoreduced RBC units. Importantly, NETs passed through blood transfusion filters and could therefore potentially be infused into patients. CONCLUSIONS: Our studies indicate that NETs are liberated during storage of nonleukoreduced RBC units. Future studies should address whether NETs in RBC units could potentially contribute to transfusion-associated complications.

Histones induce rapid and profound thrombocytopenia in mice.

Histones are released from dying cells and contribute to antimicrobial defense during infection. However, extracellular histones are a double-edged sword because they also damage host tissue and may cause death. We studied the interactions of histones with platelets. Histones bound to platelets, induced calcium influx, and recruited plasma adhesion proteins such as fibrinogen to induce platelet aggregation. Hereby fibrinogen cross-linked histone-bearing platelets and triggered microaggregation. Fibrinogen interactions with αIIbß3 integrins were not required for this process but were necessary for the formation of large platelet aggregates. Infused histones associated with platelets in vivo and caused a profound thrombocytopenia within minutes after administration. Mice lacking platelets or αIIbß3 integrins were protected from histone-induced death but not from histone-induced tissue damage. Heparin, at high concentrations, prevented histone interactions with platelets and protected mice from histone-induced thrombocytopenia, tissue damage, and death. Heparin and histones are evolutionary maintained. Histones may combine microbicidal with prothrombotic properties to fight invading microbes and maintain hemostasis after injury. Heparin may provide an innate counter mechanism to neutralize histones and diminish collateral tissue damage.