Philosophy

Denotation as Complex and Chronologically Extended: anvitābhidhāna in Śālikanātha's  Vākyārthamātṛkā - I Abstract The two theories of verbal cognition, namely abhihitānvaya and anvitābhidhāna, first put forth by the Bhāṭṭa and Prābhākara Mīmāṃsakas respectively in the second half of the first millennium C.E., can be considered as being foundational as all subsequent thinkers of the Sanskritic intellectual tradition (philosophers as well as ālaṃkārikas) engaged with and elaborated upon these while debating the nature of language and meaning. In this paper, I focus on the first chapter (pariccheda) of Śālikanātha's Vākyārthamātṛkā and outline the process of anvitābhidhāna described therein. Śālikanātha explains this as comprising three steps, and thereafter discusses each of these three to elaborate upon and philosophically defend this conception of how one cognizes sentential meaning. The aim of this paper is to present Śālikanātha's three-step model, and thus demonstrate especially the distinct conception of abhidhāna (denotation) for the Prābhākara Mīmāṃsakas (particularly Śālikanātha) as complex and chronologically extended as contrasted with the Bhāṭṭa conception of abhidhāna as non-complex and instantaneous. Such an understanding of the disparate semantic contents with which the Bhāṭṭas and Prābhākaras use the identical term abhidhāna is crucial for any correct study of their respective doctrines.

Aśvaghoṣa's Apologia: Brahmanical Ideology and Female Allure Abstract The question I pose in this paper is simple but crucial: Why did Aśvaghoṣa present Brahmanism as the backdrop for the emergence of Buddhism? In both his epic poems, he presents Brahmanism as the obvious and natural condition of society and kings, in the same way that it is depicted in the Brahmanical writings themselves. It has become increasingly clear that Brahmanical texts present ideologically motivated programs for social engineering rather than accurate descriptions of social reality. If social reality did not obligate Aśvaghoṣa to adopt this posture, then why did Aśvaghoṣa buy into this ideological position of Brahmanism? Why did he not describe the social reality underlying Buddhism in a way similar to Aśoka? While attempting to explore these questions, I will analyze Aśvaghoṣa's arguments against some central theological positions of Brahmanism: First, there is the theological argument that a person must turn to asceticism only after he has raised a family and performed his other religious obligations spelt out in the trivarga and the āśrama system. Second, there is the issue of kāma, both within the trivarga and within the common conception of a householder's life. The paper will attempt to analyze the way Aśvaghoṣa in his two epic poems deals with these two areas, one more strictly theological and the other dealing with themes of sex, eroticism, and conjugal love, all of which present obstacles to the Buddhist path of liberation that runs through the celibate monastery.

After the Unsilence of the Birds: Remembering Aśvaghoṣa's Sundarī Abstract Once encountered in Beautiful Nanda, Aśvaghoṣa's Sundarī is unforgettable. It is easy, then, to forget that we are given to see and hear her only in two of the eighteen chapters of Aśvaghoṣa's long, lyrical narrative of Nanda. When she is given to speak, her words and voice resonate powerfully, but the narrative reduces her at last to silence. Among the last images of her, there is the moment when she is likened to a screaming bird, bereaved of her mate, her voice transformed and eventually drowned out (Beautiful Nanda 6.30). This essay argues for a new interpretation of the salience of this figurative transformation, and of two different ways in which Sundarī is lost to view as she is forgotten or overlooked by characters in the narrative. Along with a close-reading of Sundarī?s loss of voice, this essay offers readings of the depiction of Sundarī?s grief (Beautiful Nanda 6.28-29) and Nanda?s ?disremembering? of her (Beautiful Nanda 7.5-7.9). In conclusion, I suggest that re-reading such passages recommends taking very seriously the possibility that for Aśvaghoṣa there might be a close relationship between the kind of sensitivity his poetry enables and a variety of moral attention.

Aśvaghoṣa and His Canonical Sources (III): The Night of Awakening ( Buddhacarita 14.1–87) Abstract The present paper is the third in a series dedicated to uncovering the canonical sources of Aśvaghoṣa's Buddhacarita and, to the extent possible, the monk-poet's sectarian affiliation. Whereas parts I and II focused on Chapter 16's indebtedness to (Mūla)sarvāstivāda Vinaya and/or Sūtra literature, this third part inquires into the sources of Aśvaghoṣa's account of the Buddha's enlightenment in Chapter 14 (whose first 31 verses have been preserved in their Sanskrit original). Detailed analysis reveals this chapter's intimate relationship with T. 189, a (Mūla)sarvāstivāda (?) biographical sūtra extant in Chinese translation only, but also with textual materials that have come to belong to Mūlasarvāstivāda literature and, as already demonstrated by Kajiyama Yūichi, with the Nagar(opam)asūtra of the Saṃyuktāgama. Among these likely sources, some provide a lively description of the five destinies, others relate to the iconographic prescriptions laid down for drawing the so-called Wheel of saṃsāra/existence, while yet others spell out the doctrine of dependent origination. The detailed comparison of these materials is followed by an admittedly speculative attempt to assess the relationship between these sources.

The Sincerest Form of Flattery: On Imitations of Aśvaghoṣa's Mahākāvyas Abstract Imitations of the works of Aśvaghoṣa, especially the Buddhacarita, are widely attested, both in the form of extra verses interpolated into the texts themselves and of entire texts in Sanskrit and Tocharian (preserved only in fragmentary form) which are restructured versions of Aśvaghoṣa's work. Such imitations and restructurings are here evaluated from the point of view of Sanskrit literary theorists, who describe similar techniques of refashioning pre-existing poems, showing that such works should not be considered as plagiarism but rather as tributes to the original author.

Aśvaghoṣa's Viśeṣaka : The Saundarananda and Its Pāli "Equivalents" Abstract When compared with the Pāli versions of the Nanda tale—the story of the ordainment and liberation of the Buddha's half-brother—some of the peculiar features of Aśvaghoṣa's telling in the Saundarananda come to the fore. These include the enticing love games that Nanda plays with his wife Sundarī before he follows Buddha out of the house, and the powerful, troubling scene in which Buddha forces Nanda to ordain. While the Pāli versions are aware of fantastic elements such as the flight to the Himālayas, and while each adds its own unique emphases that re-shape the events, none raise such deep ambivalence as done by Aśvaghoṣa. The Comparison of the different tellings then raises a more general theoretical point in relation to Buddhist literature—that genre defines the special features of each adaptation of the story, rather than any historical conditions regarding transmission; the versions each conform to the specific intellectual context of the text that appropriates them. This understanding allows an advancement of the idea of genre in Buddhist canonical and semi-canonical texts.

Making It Nice: Kāvya in the Second Century Abstract Around the second century of our era, kāvya steps out from the shadows. What was kāvya at this early moment? What ties together the kāvya produced within the Kuṣāṇa empire in North India, in Sanskrit, with that produced within the Sātavāhana empire of the South, in Prakrit? What ties the Buddhist kāvya of Mātṛceṭa, Aśvaghoṣa, and Kumāralāta to the Jain kāvya of Pālitta and the secular kāvya found in the Seven Centuries? One answer involves the idea of ornamentation (alaṃkāra): the features that, when worked into a text, transform it into an aesthetic object, not simply the "figures" of sound and sense with which this word would later be associated. In the Prakrit texts associated with the Sātavāhana court, ornamentation is essential—the Seven Centuries proclaims that all of its verses have it—but it was just as essential for it to be inconspicuous. The paradox of "artless artifice" was central to the aesthetic of these texts. In the Sanskrit texts of the North, the reverse was the case: massive effort was expended in making the artless appear artful, in casting the teachings and stories of Buddhism as kāvya. I will offer a few speculations about why the North and South took these different "paths," and conclude by connecting them with the later discussion in Sanskrit poetics about the two "paths" of kāvya.

Processions, Seductions, Divine Battles: Aśvaghoṣa at the Foundations of Old Javanese Literature Abstract The influence of Aśvaghoṣa on the later tradition of kāvya was largely passed over in the South Asian tradition, even though the debt to his influence is clear in processional scenes developed by Kālidāsa and the attempted seduction of Arjuna developed by Bhāravi in his Kirātārjunīyam. We know from the testimony of the Chinese pilgrim Yijing that the Buddhacarita was a revered object of study in the Sumatran capital Śrībhoga near the close of the seventh century CE. It thus perhaps comes as no surprise that three tropes or themes developed by Aśvaghoṣa were developed by several important composers of kakawin, the Old Javanese literary genre comparable to the kāvya of South Asia. This paper looks at the development of the themes of processions, divine battles and attempted seductions in a long history beginning with Aśvaghoṣa and closing with the work of the Javanese author Mpu Tantular, who completed the Buddhist kakawin Sutasoma c. 1365–1389 CE. This paper is partly based on a revised perspective on the history of the Shailendra and Sañjaya dynasties of central Java developed by examining the role of the "Shailendra royal preceptors" in bringing Sanskrit learning to Central Java in the period 778–847 CE.

A Bibliography of Aśvaghoṣa Abstract Though quite extensive in its coverage, the present bibliography does not claim to be exhaustive. Among the many works traditionally (but incorrectly) ascribed to Aśvaghoṣa, some, such as the *Mahāyānaśraddhotpādaśāstra (Taishō no. 1666, 1667) or, to a lesser degree, the Kalpanāmaṇḍitikā alias Sūtrālaṅkāra, have lived their own lives in modern scholarship and received virtually as much attention as Aśvaghoṣa himself. An attempt has been made to list all the contributions that have proved decisive in questioning and finally rejecting the poet's authorship of them. In much the same way, most of what has been written about the Chinese and Japanese elaborations of the figure of Aśvaghoṣa (as a patriarch, as a god of sericulture, etc.) has been disregarded. Collecting in a systematic way all Indian editions and translations in modern-day Indian languages (Bengali, Hindi, etc.) has proved practically impossible. Finally, this bibliography does not include all the entries on Aśvaghoṣa in dictionaries, encyclopedias, histories of Indian literature, etc. Only the earliest and the historically or scholarly most significant ones (e.g., those of Winternitz and Keith, and, very recently, Salomon) have found their way into the list. This bibliography would have been even more limited in its coverage had Nobuyoshi Yamabe not generously agreed to include the most important Japanese titles on the subject. In carrying out this task he acknowledges his indebtedness to Kiyoshi Okano's online bibliography (http://gdgdgd.g.dgdg.jp/asvaghosa-index.html). This bibliography is meant as a work in progress. We would like to invite all those who are writing on Aśvaghoṣa to send us their publications or at least detailed references to them so that the bibliography (an online version of which should be available soon) can be regularly updated (vincent.eltschinger@ephe.psl.eu; yamabe@waseda.jp). The sign "†" signals references that were not/could not be accessed directly.

Reading Aśvaghoṣa Across Boundaries: An Introduction Abstract The prominence and the importance of Aśvaghoṣa's works and persona—to the understanding of the history of Sanskrit poetry, to the understanding of Indian Buddhism in a transitional stage and to its introduction to other parts of Asia—is well acknowledged in contemporary scholarship. But with few exceptions the existing scholarship on Aśvaghoṣa has tended to be highly specialized and focused, inviting further reading that builds on this in-depth research to offer an integrated treatment of the variegated aspects and contexts of his works. This special issue of the Journal of Indian Philosophy is intended as a modest step toward a holistic exploration of Aśvaghoṣa works, which reads them across disciplinary as well as regional and temporal boundaries. This introduction is designed to highlight, very schematically, some points of interest and recurring concerns with respect to Aśvaghoṣa works; to point out how the set of articles address these concerns, and to suggest a particular order in which they can be profitably read.

Computer Assisted Radiology and Surgery

Multi-organ segmentation of the head and neck area: an efficient hierarchical neural networks approach Abstract Purpose In radiation therapy, a key step for a successful cancer treatment is image-based treatment planning. One objective of the planning phase is the fast and accurate segmentation of organs at risk and target structures from medical images. However, manual delineation of organs, which is still the gold standard in many clinical environments, is time-consuming and prone to inter-observer variations. Consequently, many automated segmentation methods have been developed. Methods In this work, we train two hierarchical 3D neural networks to segment multiple organs at risk in the head and neck area. First, we train a coarse network on size-reduced medical images to locate the organs of interest. Second, a subsequent fine network on full-resolution images is trained for a final accurate segmentation. The proposed method is purely deep learning based; accordingly, no pre-registration or post-processing is required. Results The approach has been applied on a publicly available computed tomography dataset, created for the MICCAI 2015 Auto-Segmentation challenge. In an extensive evaluation process, the best configurations for the trained networks have been determined. Compared to the existing methods, the presented approach shows state-of-the-art performance for the segmentation of seven different structures in the head and neck area. Conclusion We conclude that 3D neural networks outperform the most existing model- and atlas-based methods for the segmentation of organs at risk in the head and neck area. The ease of use, high accuracy and the test time efficiency of the method make it promising for image-based treatment planning in clinical practice.

A novel image-based retrieval system for characterization of maxillofacial lesions in cone beam CT images Abstract Purpose The objective of medical content-based image retrieval (CBIR) is to assist clinicians in decision making by retrieving the most similar cases to a given query image from a large database. Herein, a new method for content-based image retrieval of cone beam CT (CBCT) scans is presented. Methods The introduced framework consists of two main phases: training database construction and querying. The goal of the training phase is database construction, which consists of three main steps. First, automatic segmentation of lesions using 3D symmetry analysis is performed. Embedding the prior shape knowledge of the 3D symmetry characteristics of the healthy human head structure increases the accuracy of automatic segmentation. Then, spatial pyramid matching is used for feature extraction, and the relative importance of each feature is learned using classifiers. Results The method was applied to a dataset of 1145 volumetric CBCT images with four classes of maxillofacial lesions. A symmetry-based analysis model for automatic lesion segmentation was evaluated using similarity measures. Mean Dice coefficients of 0.89, 0.85, 0.92, and 0.87 were achieved for maxillary sinus perforation, radiolucent lesion, unerupted tooth, and root fracture classes, respectively. Moreover, the execution time of automatic segmentation was reduced to 3 min per case. The performance of the proposed search engine was evaluated using mean average precision and normalized discounted cumulative gain. A mean average retrieval accuracy and normalized discounted cumulative gain of 0.90 and 0.92, respectively, were achieved. Conclusion Quantitative results show that the proposed approach is more effective than previous methods in the literature, and it can facilitate the introduction of CBIR in clinical CBCT applications.

EyeSAM: graph-based localization and mapping of retinal vasculature during intraocular microsurgery Abstract Purpose Robot-assisted intraocular microsurgery can improve performance by aiding the surgeon in operating on delicate micron-scale anatomical structures of the eye. In order to account for the eyeball motion that is typical in intraocular surgery, there is a need for fast and accurate algorithms that map the retinal vasculature and localize the retina with respect to the microscope. Methods This work extends our previous work by a graph-based SLAM formulation using a sparse incremental smoothing and mapping (iSAM) algorithm. Results The resulting technique, "EyeSAM," performs SLAM for intraoperative vitreoretinal surgical use while avoiding spurious duplication of structures as with the previous simpler technique. The technique also yields reduction in average pixel error in the camera motion estimation. Conclusions This work provides techniques to improve intraoperative tracking of retinal vasculature by handling loop closures and achieving increased robustness to quick shaky motions and drift due to uncertainties in the motion estimation.

Interactive patient-customized curvilinear reformatting for improving neurosurgical planning Abstract Purpose Visualizing a brain in its native space plays an essential role during neurosurgical planning because it allows the superficial cerebral veins and surrounding regions to be preserved. This paper describes the use of a visualization tool in which single gadolinium contrast-enhanced T1-weighted magnetic resonance imaging was applied in nondefective and nonresective skulls to promote visualization of important structures. Methods A curvilinear reformatting tool was applied on the supratentorial compartment to peel the tissues to the depth of the dura mater and thereby revealing cortical and vascular spatial relationships. The major advantage of our proposed tool is that it does not require coregistration of anatomical and vascular volumes. Results The reliability of this technique was supported by comparisons between preoperative images and digital photographs of the brain cortical surface obtained after the dura mater was removed in 20 patients who underwent surgery in the Clinics Hospital of the University of Campinas from January 2017 to April 2018. Conclusion Single fat-suppressed GAD contrast-enhanced T1-weighted magnetic resonance scans provide accurate preoperative 3D views of cortical and vascular relationships similar to neurosurgeons' intraoperative views. In developing countries with limited access to state-of-the-art health technologies, this imaging approach may improve the safety of complex neurosurgeries.

A direct volume rendering visualization approach for serial PET–CT scans that preserves anatomical consistency Abstract Purpose Our aim was to develop an interactive 3D direct volume rendering (DVR) visualization solution to interpret and analyze complex, serial multi-modality imaging datasets from positron emission tomography–computed tomography (PET–CT). Methods Our approach uses: (i) a serial transfer function (TF) optimization to automatically depict particular regions of interest (ROIs) over serial datasets with consistent anatomical structures; (ii) integration of a serial segmentation algorithm to interactively identify and track ROIs on PET; and (iii) parallel graphics processing unit (GPU) implementation for interactive visualization. Results Our DVR visualization more easily identifies changes in ROIs in serial scans in an automated fashion and parallel GPU computation which enables interactive visualization. Conclusions Our approach provides a rapid 3D visualization of relevant ROIs over multiple scans, and we suggest that it can be used as an adjunct to conventional 2D viewing software from scanner vendors.

Missed paranasal sinus compartments in sinus surgery with and without image-guidance systems: a pilot feasibility study Abstract Purpose Image-guidance systems (IGS) have gained widespread use in endoscopic sinus surgery (ESS) and have been thoroughly analysed. In this study, we looked for a new parameter to determine if patients could directly benefit from the use of IGS during primary ESS. We questioned if IGS could improve the quality of ESS in chronic rhinosinusitis (CRS) patients via allowing a more comprehensive treatment of all involved sinus compartments. Methods In a pilot feasibility study, we evaluated uncomplicated CRS patients following primary ESS with and without IGS between January 2011 and June 2012 using preoperative and postoperative CT scans. The preoperative CT scans identified the sinus compartments requiring surgery. The postoperative CT scans were used to evaluate the treatment effect in these compartments. From these data, we calculated a missing ratio (missed compartments/compartments requiring surgery) for each patient. Results Of the 169 ESS patients who were treated, ten patients were retrospectively identified as complying with the inclusion and exclusion criteria following ESS with IGS. Ten patients treated without IGS were then randomly chosen. The median missing ratio for non-IGS patients was 36%, and for IGS patients, the median missing ratio was 0% (p = 0.046). However, the missing ratio was depended on the number of compartments requiring surgery. Stratification of the number of compartments requiring surgery resulted in an exact p value of 0.13. Conclusions IGS could help the surgeon to more completely address diseased sinus compartments. For better scientific merit, a comparative study of ESS with and without IGS seems feasible, using the proposed failing score missed compartments/compartments requiring surgery as the primary outcome parameter.

Random forest classifiers aid in the detection of incidental osteoblastic osseous metastases in DEXA studies Abstract Purpose Dual-energy X-ray absorptiometry (DEXA) studies are used for screening patients for low bone mineral density (BMD). Patients with breast and prostate cancer are often treated with hormone-altering drugs that result in low BMD. These patients may have incidental osteoblastic metastases of the spine that may be detected on screening DEXA studies. The aim of this pilot study is to assess whether random forest classifiers or support vector machines can identify patients with incidental osteoblastic metastases of the spine from screening DEXA studies and to evaluate which technique is better. Methods We retrospectively reviewed the DEXA studies from 200 patients (155 normal control patients and 45 patients with osteoblastic metastases of one or more lumbar vertebral bodies from L1 to L4). The dataset was split into training (80%) and validation (20%) datasets. The optimal random forest (RF) and support vector machine (SVM) classifiers were obtained. Receiver-operator-characteristic curves were compared with DeLong's test. Results The sensitivity, specificity, accuracy and area under the curve (AUC) of the optimal RF classifier were 77.8%, 100.0%, 98.0% and 0.889, respectively, in the validation dataset. The sensitivity, specificity, accuracy and AUC of the optimal SVM classifier were 33.3%, 96.8%, 82.5% and 0.651 in the validation dataset. The RF classifier was significantly better than the SVM classifier (P = 0.008). Only 7 of the 45 patients with osteoblastic metastases (15.6%) were prospectively identified by the radiologist interpreting the study. Conclusions RF classifiers can be used as a useful adjunct to identify incidental lumbar spine osteoblastic metastases in screening DEXA studies.

A novel multiple communication paths for surgical telepresence videos delivery of the maxilla area in oral and maxillofacial surgery Abstract Purpose A surgical telepresence between two surgical sites where a local surgeon in the surgery site, who is less experienced, needs help from the expert surgeon located at a remote site. Furthermore, the primary aim of this paper is to improve the quality of surgical video sent and received to-and-from both surgical sites, which has been a major quality issue so far. Method This work considers flow rate allocation and resource availability to determine the network path quality. Furthermore, a segmented backup path is used to provide a timely recovery in case of failure in the link. A neighbour detection technique in segmented backup is used to reduce the detection latency of the network in case of link failure. Results The results depict that the proposed system improves the quality of the surgical video by an average of 5.5 db over the current system. Furthermore, the neighbour detection technique detects the network failure 40–45% faster than the currently used end-to-end detection system. The experimental results have done on the maxilla areas in oral and maxillofacial surgery. Conclusion The proposed system concentrates on reducing the network failure detection latency and improves the received and sent video quality by using an enhanced path quality technique. Thus, this study enhances the video quality and provides a backup option in case of failure, which offers timely recovery for communication between two surgeons.

A practical marker-less image registration method for augmented reality oral and maxillofacial surgery Abstract Background Image registration lies in the core of augmented reality (AR), which aligns the virtual scene with the reality. In AR surgical navigation, the performance of image registration is vital to the surgical outcome. Methods This paper presents a practical marker-less image registration method for AR-guided oral and maxillofacial surgery where a virtual scene is generated and mixed with reality to guide surgical operation or provide surgical outcome visualization in the manner of video see-through overlay. An intraoral 3D scanner is employed to acquire the patient's teeth shape model intraoperatively. The shape model is then registered with a custom-made stereo camera system using a novel 3D stereo matching algorithm and with the patient's CT-derived 3D model using an iterative closest point scheme, respectively. By leveraging the intraoral 3D scanner, the CT space and the stereo camera space are associated so that surrounding anatomical models and virtual implants could be overlaid on the camera's view to achieve AR surgical navigation. Results Jaw phantom experiments were performed to evaluate the target registration error of the overlay, which yielded an average error of less than 0.50 mm with the time cost less than 0.5 s. Volunteer trial was also conducted to show the clinical feasibility. Conclusions The proposed registration method does not rely on any external fiducial markers attached to the patient. It performs automatically so as to maintain a correct AR scene, overcoming the misalignment difficulty caused by patient's movement. Therefore, it is noninvasive and practical in oral and maxillofacial surgery.

Subject-specific modelling of pneumoperitoneum: model implementation, validation and human feasibility assessment Abstract Purpose The aim of this study is to propose a model that simulates patient-specific anatomical changes resulting from pneumoperitoneum, using preoperative data as input. The framework can assist the surgeon through a real-time visualisation and interaction with the model. Such could further facilitate surgical planning preoperatively, by defining a surgical strategy, and intraoperatively to estimate port positions. Methods The biomechanical model that simulates pneumoperitoneum was implemented within the GPU-accelerated NVIDIA FleX position-based dynamics framework. Datasets of multiple porcine subjects before and after abdominal insufflation were used to generate, calibrate and validate the model. The feasibility of modelling pneumoperitoneum in human subjects was assessed by comparing distances between specific landmarks from a patient abdominal wall, to the same landmark measurements on the simulated model. Results The calibration of simulation parameters resulted in a successful estimation of an optimal set parameters. A correspondence between the simulation pressure parameter and the experimental insufflation pressure was determined. The simulation of pneumoperitoneum in a porcine subject resulted in a mean Hausdorff distance error of 5–6 mm. Feasibility of modelling pneumoperitoneum in humans was successfully demonstrated. Conclusion Simulation of pneumoperitoneum provides an accurate subject-specific 3D model of the inflated abdomen, which is a more realistic representation of the intraoperative scenario when compared to preoperative imaging alone. The simulation results in a stable and interactive framework that performs in real time, and supports patient-specific data, which can assist in surgical planning.

Molecular and Cellular Neuroscience

Klotho deficiency affects the spine morphology and network synchronization of neurons Publication date: Available online 13 April 2019 Source: Molecular and Cellular Neuroscience Author(s): Hai T. Vo, Mary L. Phillips, Jeremy H. Herskowitz, Gwendalyn D. King Abstract Klotho-deficient mice rapidly develop cognitive impairment and show some evidence of the onset of neurodegeneration. However, it is impossible to investigate the long-term consequences on the brain because of the dramatic shortening of lifespan caused by systemic klotho deficiency. As klotho expression is downregulated with advancing organismal age, understanding the mechanisms of klotho action is important for developing novel strategies to support healthy brain aging. Previously, we reported that klotho-deficient mice show enhanced long-term potentiation prior to the onset of cognitive impairment. To inform this unusual phenotype, herein, we examined neuronal structure and in vitro synaptic function. Our results indicate that klotho deficiency causes the population of dendritic spines to shift towards increased head diameter and decreased length consistent with mature, mushroom type spines. Multi-electrode array recordings from klotho-deficient neurons show increased synchronous firing and activity changes reflective of increased neuronal network activity. Supplementation of the neuronal growth media with recombinant shed klotho corrected some but not all of the activity changes caused by KL deficiency. Last, in vivo we found that klotho-deficient mice have a decreased latency to induced seizure activity. Together these data show that klotho-deficient memory impairments are underpinned by structural and functional changes that may preclude ongoing normal cognition.

An FTLD-associated SQSTM1 variant impacts Nrf2 and NF-κB signalling and is associated with reduced phosphorylation of p62 Publication date: Available online 4 April 2019 Source: Molecular and Cellular Neuroscience Author(s): A. Foster, D. Scott, R. Layfield, S.L. Rea Abstract Elevated oxidative stress has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). In response to oxidative stress, the Nrf2 transcription factor activates protective antioxidant genes. A critical regulator of Nrf2 is the inhibitory protein Keap1, which mediates Nrf2 degradation. In response to cellular stress an interaction between Keap1 and SQSTM1/p62 (p62), a signalling adaptor protein, allows for increased Nrf2 signalling as it escapes degradation. Mutations in SQSTM1 (encoding p62) are linked with ALS-FTLD. Previously, two ALS-FTLD-associated p62 mutant proteins within the Keap1 interacting region (KIR) of p62 were found to be associated with decreased Keap1-p62 binding and Nrf2 activation. Here we report that a non-KIR domain FTLD-associated variant of p62 (p.R110C), affecting a residue close to the N-terminal PB1 oligomerisation domain, also reduces Keap1-p62 binding in cellulo and thereby reduces Nrf2 activity in reporter assays. Further, we observed that expression of p.R110C increased NF-κB activation compared with wild type p62. Altered signalling appeared to be linked with reduced phosphorylation of p62 at Serine residues −349 and −403. Our results confirm that ALS-FTLD mutations affecting multiple domains of p62 result in a reduced stress response, suggesting that altered stress signalling may directly contribute to the pathology of some ALS-FTLD cases.

Small molecules as therapeutic drugs for Alzheimer's disease Publication date: April 2019 Source: Molecular and Cellular Neuroscience, Volume 96 Author(s): Darryll M.A. Oliver, P. Hemachandra Reddy Abstract Mitochondrial dysfunction is a central protagonist of Alzheimer's disease (AD) pathogenesis. Mitochondrial dysfunction stems from various factors including mitochondrial DNA damage and oxidative stress from reactive oxygen species, membrane and ionic gradient destabilization, and interaction with toxic proteins such as amyloid beta (Aβ). Therapeutic drugs such as cholinesterase and glutamate inhibitors have proven to improve synaptic neurotransmitters, but do not address mitochondrial dysfunction. Researchers have demonstrated that oxidative damage may be reduced by increasing endogenous antioxidants, and/or increasing exogenous antioxidants such as vitamin C & E, beta-carotene and glutathione. Nonetheless, as AD pathology intensifies, endogenous antioxidants are overwhelmed, and exogenous antioxidants are unable to reach neuronal mitochondria as they are blocked by the blood brain barrier. Current therapeutic methods however include novel usage of lipophilic phosphonium cation bound to antioxidants, to effect neuronal mitochondria targeted activity. Mitochondria targeted MitoQ, MitoVitE, MitoTempo, MitoPBN and MCAT concentrate within mitochondria where they scavenge free-radicals, and augment mitochondrial dysfunction. Additional molecules include Szeto-Schiller (SS) peptides which target stability of the inner mitochondrial membrane, and DDQ molecule capable of improving bioenergetics and reduce mitochondrial fragmentation. This article discusses advantages and disadvantages of small molecules, their ability to mitigate Aβ induced damage, and ability to ameliorate synaptic dysfunction and cognitive loss.

Growth and excitability at synapsin II deficient hippocampal neurons Publication date: April 2019 Source: Molecular and Cellular Neuroscience, Volume 96 Author(s): Heidi Matos, Raymond Quiles, Rodrigo Andrade, Maria Bykhovskaia Abstract Synapsins are neuronal phosphoproteins that fine-tune synaptic transmission and suppress seizure activity. Synapsin II (SynII) deletion produces epileptic seizures and overexcitability in neuronal networks. Early studies in primary neuronal cultures have shown that SynII deletion results in a delay in synapse formation. More recent studies at hippocampal slices have revealed increased spontaneous activity in SynII knockout (SynII(−)) mice. To reconcile these observations, we systematically re-examined synaptic transmission, synapse formation, and neurite growth in primary hippocampal neuronal cultures. We find that spontaneous glutamatergic synaptic activity was suppressed in SynII(−) neurons during the initial developmental epoch (7 days in vitro, DIV) but was enhanced at later times (12 and18 DIV). The density of synapses, transmission between connected pairs of neurons, and the number of docked synaptic vesicles were not affected by SynII deletion. However, we found that neurite outgrowth in SynII(−) neurons was suppressed during the initial developmental epoch (7 DIV) but enhanced at subsequent developmental stages (12 and18 DIV). This finding can account for the observed effect of SynII deletion on synaptic activity. To test whether the observed phenotype resulted directly from the deletion of SynII we expressed SynII in SynII(−) cultures using an adeno-associated virus (AAV). Expression of SynII at 2 DIV rescued the SynII deletion-dependent alterations in both synaptic activity and neuronal growth. To test whether the increased neurite outgrowth in SynII(−) observed at DIV 12 and18 represents an overcompensation for the initial developmental delay or results directly from SynII deletion we performed "late expression" experiments, transfecting SynII(−) cultures with AAV at 7 DIV. The late SynII expression suppressed neurite outgrowth at 12 and 18 DIV to the levels observed in control neurons, suggesting that these phenotypes directly depend on SynII. These results reveal a novel developmentally regulated role for SynII function in the control of neurite growth.

Taxifolin protects neurons against ischemic injury in vitro via the activation of antioxidant systems and signal transduction pathways of GABAergic neurons Publication date: April 2019 Source: Molecular and Cellular Neuroscience, Volume 96 Author(s): M.V. Turovskaya, S.G. Gaidin, V.N. Mal'tseva, V.P. Zinchenko, E.A. Turovsky Abstract Cerebral blood flow disturbances lead to the massive death of brain cells. The death of >80% of cells is observed in hippocampal cell cultures after 40 min of oxygen and glucose deprivation (ischemia-like conditions, OGD). However, there are some populations of GABAergic neurons which are characterized by increased vulnerability to oxygen-glucose deprivation conditions. Using fluorescent microscopy, immunocytochemical assay, vitality tests and PCR-analysis, we have shown that population of GABAergic neurons are characterized by a different (faster) Ca2+ dynamics in response to OGD and increased basal ROS production under OGD conditions. A plant flavonoid taxifolin inhibited an excessive ROS production and an irreversible cytosolic Ca2+ concentration increase in GABAergic neurons, preventing the death of these neurons and further excitation of a neuronal network; neuroprotective effect of taxifolin increased after incubation of 24 h and correlated with increased expression of antiapoptocic and antioxidant genes Stat3 Nrf-2 Bcl-2, Bcl-xL, Ikk2, and genes coding for AMPA and kainate receptor subunits; in addition, taxifolin decreased expression of prooxidant enzyme NOS and proinflammatory cytokine IL-1β.

Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflammation as a neuroprotective strategy Publication date: April 2019 Source: Molecular and Cellular Neuroscience, Volume 96 Author(s): Mariana Oliveira Mendes, Alexandra Isabel Rosa, Andreia Neves Carvalho, Maria João Nunes, Pedro Dionísio, Elsa Rodrigues, Daniela Costa, Sara Duarte-Silva, Patrícia Maciel, Cecília Maria Pereira Rodrigues, Maria João Gama, Margarida Castro-Caldas Abstract Parkinson's disease (PD) is a progressive neurological disorder, mainly characterized by the progressive loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc) and by the presence of intracellular inclusions, known as Lewy bodies. Despite SNpc being considered the primary affected region in PD, the neuropathological features are confined solely to the nigro-striatal axis. With disease progression other brain regions are also affected, namely the cerebral cortex, although the spreading of the neurologic damage to this region is still not completely unraveled. Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid that has been shown to have antioxidant properties and to exhibit a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of PD. Moreover, TUDCA anti-inflammatory properties have been reported in glial cells, making it a prominent therapeutic agent in PD. Here, we used C57BL/6 mice injected with MPTP in a sub-acute paradigm aiming to investigate if the neurotoxic effects of MPTP could be extended to the cerebral cortex. In parallel, we evaluated the anti-oxidant, neuroprotective and anti-inflammatory effects of TUDCA. The anti-inflammatory mechanisms elicited by TUDCA were further dissected in microglia cells. Our results show that MPTP leads to a decrease of ATP and activated AMP-activated protein kinase levels in mice cortex, and to a transient increase in the expression of antioxidant downstream targets of nuclear factor erythroid 2 related factor 2 (Nrf-2), and parkin. Notably, MPTP increases pro-inflammatory markers, while down-regulating the expression of the anti-inflammatory protein Annexin-A1 (ANXA1). Importantly, we show that TUDCA treatment prevents the deleterious effects of MPTP, sustains increased levels of antioxidant enzymes and parkin, and most of all negatively modulates neuroinflammation and up-regulates ANXA1 expression. Additionally, results from cellular models using microglia corroborate TUDCA modulation of ANXA1 synthesis, linking inhibition of neuroinflammation and neuroprotection by TUDCA.

Modulation of Cav2.3 channels by unconjugated bilirubin (UCB) – Candidate mechanism for UCB-induced neuromodulation and neurotoxicity Publication date: April 2019 Source: Molecular and Cellular Neuroscience, Volume 96 Author(s): Walid Albanna, Jan Niklas Lüke, Gerrit Alexander Schubert, Maxine Dibué-Adjei, Konstantin Kotliar, Jürgen Hescheler, Hans Clusmann, Hans-Jakob Steiger, Daniel Hänggi, Marcel A. Kamp, Toni Schneider, Felix Neumaier Abstract Elevated levels of unbound unconjugated bilirubin (UCB) can lead to bilirubin encephalopathy and kernicterus. In spite of a large number of studies demonstrating UCB-induced changes in central neurotransmission, it is still unclear whether these effects involve alterations in the function of specific ion channels. To assess how different UCB concentrations and UCB:albumin (U/A) molar ratios affect neuronal R-type voltage-gated Ca2+channels, we evaluated their effects on whole-cell currents through recombinant Cav2.3 + β3 channel complexes and ex-vivo electroretinograms (ERGs) from wildtype and Cav2.3-deficient mice. Our findings show that modestly elevated levels of unbound UCB (U/A = 0.5) produce subtle but significant changes in the voltage-dependence of activation and prepulse inactivation, resulting in a stimulation of currents activated by weak depolarization and inhibition at potentials on the plateau of the activation curve. Saturation of the albumin binding capacity (U/A = 1) produced additional suppression that became significant when albumin was omitted completely and might involve a complete loss of channel function. Acutely administered UCB (U/A = 0.5) has recently been shown to affect transsynaptic signaling in the isolated vertebrate retina. The present report reveals that sustained exposure of the murine retina to UCB significantly suppresses also late responses of the inner retina (b-wave) from wildtype compared to Cav2.3-deficient mice. In addition, recovery during washout was significantly more complete and faster in retinae lacking Cav2.3 channels. Together, these findings show that UCB affects cloned and native Cav2.3 channels at clinically relevant U/A molar ratios and indicate that supersaturation of albumin is not required for modulation but associated with a loss of channel functional that could contribute to chronic neuronal dysfunction.

Interleukin-16 inhibits sodium channel function and GluA1 phosphorylation via CD4- and CD9-independent mechanisms to reduce hippocampal neuronal excitability and synaptic activity Publication date: March 2019 Source: Molecular and Cellular Neuroscience, Volume 95 Author(s): Shehla U. Hridi, Aimée J.P.M. Franssen, Hui-Rong Jiang, Trevor J. Bushell Abstract Interleukin 16 (IL-16) is a cytokine that is primarily associated with CD4+ T cell function, but also exists as a multi-domain PDZ protein expressed within cerebellar and hippocampal neurons. We have previously shown that lymphocyte-derived IL-16 is neuroprotective against excitotoxicity, but evidence of how it affects neuronal function is limited. Here, we have investigated whether IL-16 modulates neuronal excitability and synaptic activity in mouse primary hippocampal cultures. Application of recombinant IL-16 impairs both glutamate-induced increases in intracellular Ca2+ and sEPSC frequency and amplitude in a CD4- and CD9-independent manner. We examined the mechanisms underlying these effects, with rIL-16 reducing GluA1 S831 phosphorylation and inhibiting Na+ channel function. Taken together, these data suggest that IL-16 reduces neuronal excitability and synaptic activity via multiple mechanisms and adds further evidence that alternative receptors may exist for IL-16.

Sympathomimetics regulate neuromuscular junction transmission through TRPV1, P/Q- and N-type Ca2+ channels Publication date: March 2019 Source: Molecular and Cellular Neuroscience, Volume 95 Author(s): Anna Zaia Carolina Rodrigues, Zhong-Min Wang, María Laura Messi, Osvaldo Delbono Abstract Increasing evidence indicates that, first, the sympathetic nervous system interacts extensively with both vasculature and skeletal muscle fibers near neuromuscular junctions (NMJs) and, second, its neurotransmitter, noradrenaline, influences myofiber molecular composition and function and motor innervation. Since sympathomimetic agents have been reported to improve NMJ transmission, we examined whether two in clinical use, salbutamol and clenbuterol, affect the motor axon terminal via extracellular Ca2+ and molecular targets, such as TRPV1 and P/Q- and N-type voltage-activated Ca2+ channels. Electrophysiological recordings in ex-vivo preparations of peroneal nerves and lumbricalis muscles from young adult mice focused on spontaneous miniature end-plate potentials and singly and repetitively evoked end-plate potentials. Adding one dose of salbutamol or clenbuterol to the nerve/muscle preparation or repeatedly administering salbutamol to a mouse for 4 weeks increased spontaneous and evoked synaptic vesicle release but induced a steep decline in EPP amplitude in response to repetitive nerve stimulation. These effects were mediated primarily by ω-agatoxin IVA-sensitive P/Q-type and secondarily by ω-conotoxin GVIA-sensitive N-type Ca2+ channels. Presynaptic arvanil-sensitive TRPV1 channels seem to regulate Ca2+ at the motor neuron terminal at rest, while putative presynaptic β-adrenergic receptors may mediate sympathomimetic and catecholamine effects on presynaptic Ca2+channels during NMJ activation.

Norepinephrine control of ventromedial hypothalamic nucleus glucoregulatory neurotransmitter expression in the female rat: Role of monocarboxylate transporter function Publication date: March 2019 Source: Molecular and Cellular Neuroscience, Volume 95 Author(s): A.S.M. Hasan Mahmood, Santosh K. Mandal, Khaggeswar Bheemanapally, Mostafa M.H. Ibrahim, K.P. Briski Abstract The ventromedial hypothalamic nucleus (VMN) is a critical component of the neural circuitry that regulates glucostasis. Astrocyte glycogen is a vital reserve of glucose and its oxidizable metabolite L-lactate. In hypoglycemic female rats, estradiol-dependent augmentation of VMN glycogen phosphorylase (GP) protein requires hindbrain catecholamine input. Research here investigated the premise that norepinephrine (NE) regulation of VMN astrocyte metabolism shapes local glucoregulatory neurotransmitter signaling in this sex. Estradiol-implanted ovariectomized rats were pretreated by intra-VMN administration of the monocarboxylate transporter inhibitor alpha-cyano-4-hydroxy-cinnamic acid (4CIN) or vehicle before NE delivery to that site. NE caused 4CIN-reversible reduction or augmentation of VMN glycogen synthase and phosphorylase expression. 4CIN prevented NE stimulation of gluco-inhibitory (glutamate decarboxylase65/67) and suppression of gluco-stimulatory (neuronal nitric oxide synthase) neuron marker proteins. These outcomes imply that effects of noradrenergic stimulation of VMN astrocyte glycogen depletion on glucoregulatory transmitter signaling may be mediated, in part, by glycogen-derived substrate fuel provision. NE control of astrocyte glycogen metabolism may involve down-regulated adrenoreceptor (AR), e.g. alpha1 and alpha2, alongside amplified beta1 AR and estrogen receptor-beta signaling. Noradrenergic hypoglycemia was refractory to 4CIN, implying that additional NE-sensitive VMN glucoregulatory neurochemicals may be insensitive to monocarboxylate uptake. Augmentation of circulating free fatty acids by combinatory NE and 4CIN, but not NE alone implies that acute hypoglycemia induced here is an insufficient stimulus for mobilization of these fuels, but is adequate when paired with diminished brain monocarboxylate fuel availability.

Surgery

Geriatric trauma: A population-based study Saint Shiou-Sheng Chen, Li-Chien Chien Formosan Journal of Surgery 2019 52(2):39-44 Background: Geriatric trauma demands attention in aging societies. The trauma hospitalization rate gradually increases in elderly populations because they are more vulnerable to accidental injuries. High trauma admission rates among elderly groups led to further research about injury patterns and outcomes. We hope to understand more about the demographic patterns and mortality rate of geriatric trauma. Methods: Information about all injured in-hospital patients ≥64 years was retrieved from a claims dataset from 2007 to 2008 from the Bureau of National Health Insurance in Taiwan. Statistical analyses were conducted on the population-based dataset to discover the incidence, mortality rate, percentage of chronic illness, and associations among variables such as age group, gender, injury mechanism, injury severity, and mortality. Results: A total of 134,024 patients (28.2% of total inpatients' admissions) ≥64 years were admitted in 2007 and 2008; 45.0% were male patients, and 43.9% were rural residents. These resulted in 4120 deaths. Nearly 40.0% of patients had at least one chronic illness. Diabetes mellitus was the most common comorbidity (20.2%). Injury was most commonly caused by falls on the same level, followed by motorcycle accidents. A higher mortality rate was observed in the subgroup with higher injury severity scores. Logistic regression showed that the mortality rate was significantly higher in subgroups comprising patients aged 75–84 and >84 years, with higher Charlson index, and with mechanisms such as pedestrians hit by vehicles or falls from height. Conclusion: High trauma hospitalization rates among elderly people can be reduced. Choosing a target population for injury prevention policy is required to reduce the geriatric trauma hospitalization rate. A regionalized trauma system providing the elderly population with optimal trauma care is mandatory.

Biodegradation patterns of injected composite bone cements in porcine vertebral bodies: A study using quantitative computed tomography Chi-Ching Yeh, Chii-Jen Chen, Yun Tang, Kai-Chiang Yang, Chang-Chin Wu Formosan Journal of Surgery 2019 52(2):45-51 Background: For vertebroplasty, newly synthesized bone cements are proposed to replace traditional polymethylmethacrylate (PMMA). Most inventors initially evaluated these newly developed cements in animal spine models. However, even these time- and work-consuming histological inspections performed meticulously by experienced hands, there are still lots of specimen lost during the processing procedures. Although the histological sections can reveal new bone formations and surrounding tissue reactions to implanted materials, it is difficult to identify the degradation processes of the injected cement. In fact, there is no standard method to quantify the volume changes of injected substitutes postoperation. Methods: Previously, we developed two new biodegradable cements and evaluated performances in fixed-volume and fixed-shaped holes in vertebral bodies of porcine lumbar spine. The animals were sacrificed and the retrieved spines were analyzed after 3 and 6 months. Herein, we further used computed tomography (CT) and three-dimensional CT (3D-CT) to quantitate volumes and biodegradation of cements inside vertebral bodies after previous attestation of CT findings. Exteriors of controls and injected materials were reconstructed with different Hounsfield units (HU); changes of HU as well as cement volumes were later calculated. Results: The results revealed that the volumes and shapes of these biodegradable cements can be determined by 3D-CT. After meticulous comparisons among gross specimens, histologies, and CT images, the different patterns observed in CT implied consistency among all three observations. Gradual reductions of HU and volumes of newly synthesized cements showed the degradability. Meanwhile, consistent HU and volumes of PMMA meant its inertness. Conclusion: CT imaging may be a preliminary, quantitative, and liable way for evaluating injectable bone cements in the vertebral bodies.

A randomized clinical trial comparing a collagen-based composite dressing versus topical antibiotic ointment on healing full-thickness skin wounds to promote epithelialization Hsin-Chung Tsai, Hui-Ching Shu, Li-Chuan Huang, Chuan-Mu Chen Formosan Journal of Surgery 2019 52(2):52-56 Background: Acute traumatic wounds are a common and distressing event for patients presenting to plastic surgery clinics. There are no definitive conclusions regarding the benefits of collagen-based wound care products toward the application on full-thickness wounds compared to traditional ointment or gauze care. In this clinical trial, we aimed to define the potential benefits of collagen-based dressings on healing through the comparison of collagen-based composite dressings with antibiotic ointment dressings. Methods: This was a randomized two-tailed controlled clinical trial. The acute full-thickness wounds underwent wound cleansing, debridement, and were secured with different dressings in both experimental and control groups. The wounds were subsequently photographed weekly, and the wound areas were calculated using ImageJ software to evaluate wound healing rate. Results: The results demonstrate that the collagen-based triple layer composite dressings which consisted of silver sheet, collagen sponge, and foam films promoted better epithelialization and healing than antibiotic ointment treatment. Collagen supplementation improved wound healing and epithelialization by providing a dry environment during the late stage of wound healing. Conclusion: We demonstrated that the collagen-based triple layer wound dressing could potentially increase the healing rate when used for traumatic full-thickness wound care compared to the conventional antibiotic ointment dressing, providing a new prospective in the future applications of wound care.

A simple technique to create spur in loop colostomy Gurmeet Singh, Anand Pandey, Jiledar Rawat, Sudhir Singh Formosan Journal of Surgery 2019 52(2):57-59 A colostomy is one of the most popular techniques used as a protective maneuver for a distal anastomosis and/or temporary fecal diversion loop colostomy is used mainly for fecal diversion so as to protect the distal bowel. We report a new simple technique for the creation of mucosal spur in between the proximal and distal stoma without using either a tube or skin flap. The essence of this technique is the creation of mucosal spur by placing two additional sutures in the bridge in between the proximal and distal stoma. The placement of sutures creates the spur and helps in defunctioning of distal stoma. Seventeen patients were operated by this technique over a period of 1 year. The creation of the mucosal spur was excellent. There was no requirement of a tube or skin flap in any of the patients in the follow-up. There was no problem of loss of spur over a period. This is a simple technique, which needs few additional sutures apart from the necessary sutures needed for maturation of colostomy.

Periorbital purulent drainage of resulting from bacterial pansinusitis Chia-Ming Lin, Pin-Keng Shih Formosan Journal of Surgery 2019 52(2):60-62 Periorbital cellulitis is much more common in younger children than in adolescents or adults, and most cases of uncomplicated periorbital cellulitis can be treated with antibiotics alone. Here, we report a case of a 53-year-old man with periorbital purulent discharge. Computed tomography imaging revealed pansinusitis. Pus culture isolated a pathogen of Streptococcus constellatus, but it was refractory to 2 weeks of antibiotic therapy with amoxicillin–clavulanate. The patient underwent debridement and functional endoscopic sinus surgery, followed by 10 days of hyperbaric oxygen treatment. The above antibiotic was changed to full-dose intravenous clindamycin. Two weeks after the surgery, the patient was discharged from the hospital. At 1-month follow-up, no purulent discharge was noted; however, mild left-eyelid contracture was observed. This study suggested that if conservative therapy for periorbital purulent discharge in an adult is not effective, progressive treatment, including surgery, should be considered.

Closing of postoperative integument, skull bones and dura defects Jia Wei Lin, Evgeny G Sobakar, Oleg V Ivanov, Evgeny V Semichev Formosan Journal of Surgery 2019 52(2):63-65 This article describes skull defect plastic, which is especially relevant, and in particular, cases, is a great challenge for surgeons. The clinical case described covers formation of a defect in the cranial vault bones, complicated by skin integument, skull bones, and the dura matter defects.

Innovative methods of maintaining operation records using the online Google spreadsheet BA Ramesh, Singaravelu Viswanathan, Souparna Manjunath, Deyonna Deepthi Fernandez, Candy Priyadarshini, Gaurav B Shetty Formosan Journal of Surgery 2019 52(2):66-69 Background: Maintaining an operation record in any surgical department is mandatory. The current method is to make entries in a designated register manually. However, this method has disadvantages such as space occupancy, high maintenance cost, and difficulty in record compilation. Proper storing of medical records is necessary for future reference. We found that using the free online, Google spreadsheet for maintaining surgical records is an innovative and effective method. Methods: Online Google spreadsheet entry September 2017 to August 2018 is compared with manual entry done from September 2016 to August 2017. Results: This online method has the following advantages: fewer errors, low cost, free maintenance, and easy record compilation as per requirements. Finally, filters can be applied, and separate numbers for each category can be obtained. Conclusion: The proposed method is useful, low cost, and versatile way of storing and retrieving operative records.

Occult medullary breast carcinoma in a male Mahmood Dhahir Al-Mendalawi Formosan Journal of Surgery 2019 52(2):70-70

Obstetrics and Gynaecology

Fetal imaging and diagnosis services in developing countries – A call to action JA Akinmoladun, D OC Anumba Tropical Journal of Obstetrics and Gynaecology 2019 36(1):1-7 Fetal congenital anomalies are among the leading causes of perinatal death or survival with disability worldwide. Their accurate antenatal detection employing a range of fetal imaging techniques enables parental choices to be made and for postnatal care of affected babies to be planned. While such prenatal care is well developed in developed countries of the world, it remains poor in many low- and middle-income countries (LMICs). This review article examines the scope of the problem and proffers strategies for service organization and fetal imaging that will improve care in LMIC settings.

A 35-year standardized prediction estimates for gynecological lesions in oil and gas exploration and production city in the Niger Delta M Onyije Felix, A Ngokere Ajuluchukwu, E Ligha Aloysius, O Mgbere Osaro, O Avwioro Godwin Tropical Journal of Obstetrics and Gynaecology 2019 36(1):8-14 Background: The impact of constant emission of hydrocarbons and contaminated water level through oil spillage in the oil and gas exploration and production areas of Niger Delta on women's health cannot be underestimated. We developed a 35-year standardized prediction estimates for gynecological lesions using data obtained from an integrated specialist hospital serving the residence of the oil and gas exploration and production City of Port Harcourt and the surrounding areas of Niger Delta, Nigeria. Methods: The study participants comprised of 697 females who received medical care at the Braithwaite Memorial Specialist Hospital (BMSH), Port Harcourt, Rivers State, Nigeria, between 2010 and 2014. Predictive modeling of the diseases was performed using JMP statistical discovery™ software, version 12.0 (SAS Institute, Cary, NC, USA). Results: The distribution of the gynecological lesions (n = 697) differed significantly (P < 0.001) by year of diagnosis, developmental stage, age category, and types of lesion. The mean age of study participants was 39.1 ± 12.8 years, and most of the lesions (61.8%) occurred among females who were 30- to 49-year old. Leiomyoma recorded the highest 5-year standardized prevalence rate of 0.508, and with no intervention, it is estimated that the number of cases diagnosed will rise from 235 in 2015 to 1883 by the year 2050. This was followed by ovarian cyst with a prevalence rate of 0.124 and projected increase from 57 in 2015 to 461 by the year 2050. Similarly, the product of conception is also estimated to increase from 34 to 277 by the year 2050. Conclusion: The over 700% increased prediction of gynecological lesions by 2050 calls for urgent attention by both governmental and private agencies to fund awareness campaigns and screenings for women, especially for those residing in the oil- and gas-producing areas of Niger Delta.

Maternal and neonatal outcomes in premature rupture of membranes at University of Maiduguri Teaching Hospital, Maiduguri, North-Eastern Nigeria A Idrisa, S Pius, M Bukar Tropical Journal of Obstetrics and Gynaecology 2019 36(1):15-20 Background: Premature rupture of membrane (PROM) is linked to significant adverse events in the prenatal, peripartum and neonatal period. Both, PROM and PPROM are associated with maternal and neonatal morbidities and mortalities. Severe oligohydramnios after PROM is associated with foetal abnormalities, pulmonary hypoplasia, respiratory distress syndromes, intrauterine growth restriction, intrauterine foetal death, foetal/neonatal sepsis, presence of meconium and an Apgar score lower than seven at five minutes. Objective: To determine the factors that influenced maternal and neonatal outcomes following a premature rupture of membranes. Subjects and Methods: This retrospective cross-sectional study was conducted over five years between 1st January 2012 and 31st December 2016 on mother neonate pair delivered at the University of Maiduguri Teaching Hospital Maiduguri. Results: During the period of the study there were 7200 deliveries at the labour ward of (UMTH), out of which 91 (1.3%) had PROM. Seventy three ( 80.2%) of the case files were retrieved and analysed. Thirty six women (49.3%) were delivered by emergency caesarean section (EMCS), while 37 (50.7%) were delivered vaginally (SVD). In the bivariate (crude) analysis, Apgar score < 7 at 5 minutes (P = 0.008, OR 95 % CL: 0.092 (0.011, 0.742), birth weight ≥ 2500g (P = 0.006, 8.944 (1.892, 42.284), and absence of APH (P = 0.007, 4.83 (1.440, 16.196) were factors modifying neonatal outcome. When adjusted regression with only factors with P value < 0.2 in crude analysis were done, only birth weight ≥ 2500 g (P = 0.024, 6.677 [1.286, 34.664]) and absence of APH (P = 0.038, 4.406 [1.085, 17.883]) were independent predictors of neonatal outcome. Thus, neonates with birth weight ≥ 2500 g were about 6.7 times more like to show favourable outcome than those with birth weight < 2500g while those without APH showed 4.4 times more likelihood for a favourable neonatal outcome. Antenatal corticosteroids use also was associated with favourable outcome as it had significantly improved preterm neonatal survival. Conclusion: Intervention with steroids, antibiotics in labour and delivery within 24 hours of PROM will greatly reduce maternal complications and enhances favourable neonatal outcome.

Disrespect and abuse during facility based childbirth: The experience of mothers in Kano, Northern Nigeria TG Amole, MJ Tukur, SL Farouk, AO Ashimi Tropical Journal of Obstetrics and Gynaecology 2019 36(1):21-27 Context: An important but little understood concept that retards the goal to reduce maternal mortality and increase universal access to reproductive health is disrespect and abuse (D&A) during childbirth. Aim: This study aims to determine the prevalence, pattern, perpetrators, and determinants of D&A during childbirth among recently parturient women in Kano, north western Nigeria. Settings and Design: Using a cross-sectional design, 332 women accessing child immunization and postnatal services at Murtala Muhammad Specialist Hospital, Kano, were selected. Subjects and Methods: Respondents were selected using systematic sampling technique and data collected using an adapted, interviewer administered tool. Statistical Analysis: Data was analysed using IBM SPSS version 21.0 and level of significance set at 0.05. Results: Respondents (n = 306) had a mean age of 27.7 ± 6.3 years and more than half (55.9%; n = 171) had experienced at least one form of D&A during childbirth. Commonest forms of abuse were abandonment and nonconfidential care (84.5%, n = 142; 67.9%, n = 114, respectively). Main perpetrators were nurses/midwives (83.0%, n = 142). The experience during the last childbirth was significantly higher among respondents of non-Hausa/Fulani ethnic group (χ2 = 6.10; P = 0.014), of the Christian faith (χ2 = 8.62; P = 0.003), and with formal education (χ2 = 19.94; P = 0.0001). After controlling for confounders, formal education remained a predictor for experiencing abuse at childbirth (AOR = 2.43; 95% confidence interval = 1.11--5.32). Conclusions: D&A during childbirth is prevalent in our setting. Educating healthcare providers and women about their responsibilities and rights will enhance provision and utilization of quality maternal health services.

The effect of hyoscine butyl bromide in shortening the duration of first stage of labor: A single-blind randomized control study R Ibrahim, EI Nwobodo, KA Tunau, AT Burodo, B Sulaiman, JA Garba, AD Saidu Tropical Journal of Obstetrics and Gynaecology 2019 36(1):28-32 Background: Active management of labor reduces the number of prolonged labor and the duration of labor without having any adverse effects on the mother and the fetus. Intervention with drugs is among the options used for active management of labor. This includes use of analgesics, oxytocics, prostaglandins derivatives, and smooth muscle relaxants. The objectives of the study were to determine whether hyoscine N butyl bromide (HNBB) shortens the first stage of labor in term pregnancies, to compare the mean duration of labor between primigravidae and multigravidae in HBB group, to compare the maternal and fetal outcome between HBB and control group, and also to determine the side effects of HBB in parturients. Materials and Methods: The study was a single-blind randomized control study carried out in Usmanu Danfodiyo University Teaching Hospital (UDUTH) over 4-month period. A total of 204 pregnant women at term in spontaneous labor who presented in active phase of labor at UDUTH and have met the inclusion criteria were recruited and randomized into 102 women as case group and 102 women as control. The women in the case group received 40 mg (2 mls) of HBB, while those in the control group received 2 mls of normal saline. Data entry and analysis was done with IBM SPSS version 20. The duration and outcome was monitored. Results: The mean duration of labor in the first stage among the case group was 5:44 ± 2:11, while it was 6:52 ± 2:11 among the control group representing a decrease of 16.5%. This was statistically significant (P < 0.05). There was no difference in the duration of the second and third stages of labor among the two groups. There was no difference in the maternal and neonatal outcome among the two groups. Vomiting was the only maternal side effect that was statistically significant among the HBB group. Conclusion: HBB reduced the duration of first stage of labor in both primigravid and multigravid women without adverse maternal and neonatal complications. It is recommended that HBB to be given to women in active phase of labor to reduce the incidence of prolonged labor.

Awareness and attitude of female undergraduates toward human papillomavirus vaccine in Ibadan T AO Oluwasola, OO Bello, AA Odukogbe Tropical Journal of Obstetrics and Gynaecology 2019 36(1):33-38 Introduction: The human papillomavirus (HPV) has significant public health importance because of its high prevalence, mode of transmission, major causative role in cervical cancer, and having effective vaccines. The main thrust of this study was to ascertain the level of awareness of HPV and its vaccines among students as well as their attitudes toward receiving the vaccines. Materials and Methods: A descriptive cross-sectional survey conducted among female undergraduates of the University of Ibadan using structured self-administered questionnaires. The questionnaires sought to obtain information about their awareness of HPV, their sexual behavior, previous vaccination, and willingness to access HPV vaccination. Results: A total of 489 students, with a mean age of 19.7 ± 3.2 years, satisfactorily responded to the survey. Overall, 411 (84%) had an overall good knowledge about vaccines, 218 (44.6%) recalled that they had been previously vaccinated in childhood, and 147 (30.1%) were aware of HPV. Only 66 (13.5%) were aware of HPV vaccines, and 10 (2%) had ever been vaccinated against HPV. A majority were willing to get vaccinated if the current price is further reduced. Conclusion: There is a low level of awareness of HPV and its vaccines among female undergraduates. When available, uptake is restricted by cost. There is an urgent need to support public health programs that increase awareness through adequate information dissemination on mechanisms of cancer prevention and also to strengthen policy efforts that address the barriers of HPV vaccination.

Intrauterine adhesions in the University of Uyo Teaching Hospital, Uyo, South-South, Nigeria: A ten year review N Utuk, AM Abasiattai, O Asuquo Tropical Journal of Obstetrics and Gynaecology 2019 36(1):39-43 Background: Asherman's syndrome is a clinical entity that can cause menstrual abnormalities and infertility. Objectives: This study was done to determine the risk factors, and management outcome of intrauterine adhesions in our hospital. Subjects and Methods: We carried out a retrospective study of the patients who were treated for intrauterine adhesions at the University of Uyo Teaching Hospital over a 10 years period-from January 1st 2006 to December 2016. Results: During the study period, a total of 1977 gynecological surgeries were performed of which 83 were for intrauterine adhesions, giving a rate of 4.2%. However, only 52 folders were retrieved, giving a retrieval rate of 62.5%. Analyses, using ratios and percentages, was based on these. Most patients belonged to the 30-34 age group (28.9%) followed by the 20-24 age group (25.0%). The majority of the patients were nulliparous (58.9%), married (65.4%) and had a tertiary education (50.0%). Dilatation and curettage for induced abortion (42.3%), open myomectomy (26.9%), and caesarean section (19.2%) were the common risk factors. Amenorrhoea (65.4%), and hypomenorrhoea (30.8%) were the commonest modes of presentation. All the patients were managed by blind adhesiolysis, done overwhelmingly by the resident doctors, under anaesthesia with a significant percentage (65.3%) showing that there is no change in menstrual condition. Conclusion: Ashermans syndrome is a relatively common condition, and it is necessary to train doctors in the use of, and acquire, a hysteroscope, for the proper management of this condition. Meanwhile, more senior personnel should be involved in the blind adhesiolysis, and Foley catheter that appears superior as a uterine splint to the intrauterine contraceptive device.

Co morbidities associated with vesico vaginal fistula in patients managed in Maryam Abacha Fistula Hospital Sokoto, Northwestern Nigeria M Hassan, S Nasir Tropical Journal of Obstetrics and Gynaecology 2019 36(1):44-48 Background: Prolong obstructed labor is a preventable obstetric complication in the developing countries with devastating consequences and comorbidities. This study aimed to determine the frequencies of the common comorbidities in patients managed for obstetrics fistula at Maryam Abacha Women and Children Hospital, Sokoto, and also to identify the association of age and parity on the occurrence of some of the comorbidities observed. Materials and Methods: This was a cross-sectional study involving 179 patients with obstetric vesicovaginal fistula seen at Maryam Abacha women and Children VVF center, Sokoto, from January to December 2017. A proforma was used to assess the sociodemograhic features and also to record comorbidities during preoperative evaluation. Results: Foot drop was the commonest comorbidity seen in 106 (59.2%), followed by depression in 104 (58.1%). There was statistically significant association between age, parity, and foot drop P = 0.025. Depression was found to be higher in the primipara P = <0.001.Urinary dermatitis occurred more frequently in the older age group and multipara 62.7% and 80%, respectively. Amenorrhea was commoner among age group 30 years and above 62.7%. Out of 179 patients analyzed, 36 (20.1%) had eclampsia whereas gynaetresia was present in 29 (16.2%). Conclusion: Significant comorbid conditions accompany obstetrics trauma and vesicovaginal fistula. Foot drop had statistically significant association with age. Depression was common in all age groups. There was significant association between depression and parity. Urinary dermatitis occurred more frequently in the older age group and multiparae.

Effectiveness of mobile phone text message reminder on birth preparedness in a rural community in Kenya Cheptum Joyce, Omoni Grace, Mirie Waithira Tropical Journal of Obstetrics and Gynaecology 2019 36(1):49-53 Background: Birth preparedness is a strategy that has been found effective in preventing obstetric delays. Use of mobile technology can enable access and efficiency of health messages delivered during antenatal care. The mobile technology can be more effective in conveying health messages owing to its accessibility and enables follow up. Materials and Methods: This was a randomized control trial carried out among pregnant women attending public health antenatal clinics in Migori County. Four health facilities were randomized. Two facilities each were randomly picked for the study and control groups respectively. A total of 379 participants were recruited into the study. The study group participants received a verbal message on birth preparedness and a mobile phone text message reminder one month to their expected date of delivery. Follow up was done to both groups through their mobile phone contacts. Data was collected using an interviewer-administered questionnaire and analyzed using Stata version 11. Proportion tests were done to compare the groups. Results: The success rate of the study was 90.5% (n = 343). Most of the participants (73%) were aged between 20 and 34 years. Majority of them were married (79.2%) and most of them had primary level of education. Protestant was the predominant religion (55.2%). Housewives and businesswomen constituted 34.2% and 27%, respectively. The respondents in the study group who were birth prepared were 74.3% (n = 136) while those in the control group were 48.1% (n = 77). Conclusion: The use of mobile phone text message reminder in addition to verbal messages is more effective.

Can hsCRP be the sole investigation for predicting the severity and outcome in women with pre-eclampsia presenting late in pregnancy? N Mishra, K Pradhan, GD Sahoo, M Rohilla, M Meena Tropical Journal of Obstetrics and Gynaecology 2019 36(1):54-60 Context: Healthcare facilities in developing countries are over burdened and proper triage of patients requiring attention more than others is needed in every sub speciality of medical sciences in them. Patients with pre-eclampsia require attention to prevent any associated complication. Aims: The aim of this study was to evaluate whether hsCRP alone or in combination could be used as an indicator of severity and predictor of outcome in women with PE presenting to a healthcare facility late in the third trimester. Settings and Design: Prospective observational study conducted at a teaching medical college and referral hospital catering primarily to rural, semi urban and tribal population. Methods and Material: 85 women with PE who reported to the hospital after completed 36 weeks of gestation were included. Patients were divided in three groups. hsCRP, biochemical and hematological investigations were performed for each patient. Results were expressed as median. Independent samples Kruskall Wallis one way ANOVA and Mann Whitney U tests were performed and correlation of hsCRP with other parameters and fetal outcome was examined. Statistical Analysis Used: Kruskall Wallis one way ANOVA and Mann Whitney U tests. Results: hsCRP was significantly elevated in severe PE as compared to PE without severe features and normal patients. Higher requirement of labour induction and caesarean section was seen in severe PE patients along with higher still births and low baby weight babies. hsCRP had positive correlation with other markers of severity of PE and negative correlation with still births and fetal weight in severe PE patients. However, although raised in every case of severe PE, a wide variation was noted in hsCRP values. Conclusions: hsCRP alone cannot be recommended as a marker of severity or a predictor of outcome in women presenting late in the third trimester of pregnancy. However, in combination with serum uric acid it can be used for that purpose.

Oral and Maxillofacial Pathology

Extracellular matrix in invasion and metastasis of oral squamous cell carcinoma K Vinod Kumar, KN Hema Journal of Oral and Maxillofacial Pathology 2019 23(1):10-16 Oral squamous cell carcinoma is a common cancer in developing countries with highly invasive and metastasis credentials. The Lymphnode metastasis in oral squamous cell carcinoma is regarded as the factor that decides on disease survival of patients. Steps have been made towards research in the field of Oral squamous cell carcinoma for better understanding of the molecular events involved in invasion and metastasis. Recently, the role of Extracellular matrix (ECM) of oral squamous cell carcinoma in invasion and metastasis has gained interest, as ECM is known to actively contribute in events that regulate transcriptional controls and cell signalling mechanisms involved in invasion and metastasis. Understanding such contributing role of ECM may pave way for newer methodologies in early detection, prevention and therapeutic strategies for oral squamous cell carcinoma.

Kamino bodies Deepak Venkatesh, T Smitha Journal of Oral and Maxillofacial Pathology 2019 23(1):17-18

Oral epithelial dysplasia: Classifications and clinical relevance in risk assessment of oral potentially malignant disorders Kannan Ranganathan, Loganathan Kavitha Journal of Oral and Maxillofacial Pathology 2019 23(1):19-27 After more than a decade, the World Health Organization (WHO) published the revised grading system for oral epithelial dysplasia in 2017. The revised classification has changes reflecting our evolution of understanding of the dysplastic process. Although the WHO 2017 three-tier grading system is the gold standard for histological diagnosis of oral potentially malignant disorders, it has certain limitations. Suggestions to overcome these limitations include the use of clinical determinants and molecular markers to supplement the grading system. It has also been suggested that a two-tier system may be more reproducible and clinically translatable for better management. These advances in the understanding of epithelial dysplasia are very important globally and for us in the Indian subcontinent, given the prevalence of habits (tobacco/areca nut) and burden of oral cancer in this part of the world. The following review traces the evolution of the grading system of dysplasia, its relevance and clinical utility.

Identification of Candida albicans using different culture media and its association in leukoplakia and oral squamous cell carcinoma Vivek Gupta, Khare Abhisheik, Shreedhar Balasundari, Niranjan K Devendra, Kalim Shadab, Mahendra Anupama Journal of Oral and Maxillofacial Pathology 2019 23(1):28-35 Context: Candida, leukoplakia and oral squamous cell carcinoma. Aims: The aim of the present study has assessed the association of Candida albicans with normal control group, leukoplakia and oral squamous cell carcinoma lesions of the oral cavity by using cornmeal broth +5% milk and milk serum liquid culture media. Settings and Design: Thepresent study comprised of total 80 patients,which included, 30 patients of Leukoplakia, 30 patients of oral squamous cell carcinoma and normal control group comprised of 20 healthy individuals who were not having any relevant medical, dental and habit history. Subjects and Methods: Saliva and Biopsy was taken from clinically suspected leukoplakia and oral squamous cell carcinoma lesions for the confirmation of histopathological diagnosis. Saliva samples were inoculated for fungal growth in Sabouraud Dextrose Agar, and culture-positive samples had undergone for the germ tube test. Germ tube-positive samples were further taken for chlamydospore production in milk serum and cornmeal broth +5% milk media separately at 8 and 16 h. Statistical Analysis Used: Chi-square test, Fischer extract test. Results: In the normal control group, no fungus growth was found; however, leukoplakia and oral squamous cell carcinoma showed fungus growth with positive germ tube test and chlamydospore formation; the result also showed rapid and quantitatively more chlamydospore formation in cornmeal broth +5% milk in comparison to serum milk culture media. There was no growth of Candida in mild and moderate form of leukoplakia. Whereas in a severe form of leukoplakia, there was more quantitative chlamydospore growth in cornmeal broth +5% milk liquid media. Conclusions: In this study, we have tried to compare the efficacy of cornmeal broth +5% milk and milk serum for the identification of C. albicans. Both the culture media were able to promote the growth of chlamydospore in C. albicans. Among different grades of leukoplakia, the growth of C. albicans was seen in severe dysplastic patient only while mild and moderate dysplasia showed no Candidal growth.

From the Editor's Desk T Smitha Journal of Oral and Maxillofacial Pathology 2019 23(1):1-1

President's Message B Veerendra Kumar Journal of Oral and Maxillofacial Pathology 2019 23(1):2-2

Hon. Secretary's Message Nadeem Jeddy Journal of Oral and Maxillofacial Pathology 2019 23(1):3-3

Hon. Treasurer's Message S Ratheesh Kumar Nandan Journal of Oral and Maxillofacial Pathology 2019 23(1):4-4

Delineating the scope of oral pathology and microbiology: Present scenario and future prospects Bhuvan Nagpal Journal of Oral and Maxillofacial Pathology 2019 23(1):5-7

Prof. (Dr.) R R Paul Mousumi Pal Journal of Oral and Maxillofacial Pathology 2019 23(1):8-9