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Byline: S. Dwarakanath, A. Bansal, S. Rudrappa, S. Gopal, N. Venkataramana 'White cerebellum sign' is a classic yet uncommon radiological finding in severe pediatric head injury. We present a case [...]

The present study was envisaged with the objective of isolation of Mycoplasma species from suspected sheep and goat, molecular characterization of immuno-dominant protein of such isolated Mycoplasma species for diagnostic and immunoprophylactic purpose. The pneumonic lungs at postmortem and nasal swabs from suspected sheep were collected in PPLO broth and were kept in CO2 (5-10%) incubator at 370C for 24 hours. Thereafter, incubation of PPLO agar plate that were inoculated with clear turbid in incubator at 370C for 4-7days showed a typical "fried egg appearance". PCR analysis revealed amplicon size of 715 and 885 bp mycoplasma (group specific primer) and Mycoplasma arginini (species specific primer), respectively. Upon gel permeation chromatography on Sephadex G-100, membrane protein was resolved into two peaks. Each elutes of individual peaks were subjecting for SDS-PAGE and western blotting and found the presence of antigenic protein molecular mass of 120 and 85 kDa along with 67 kDa in Peak-I, whilst peak-II elutes revealed molecular mass of 50 and 67 kDa. Similarly, the result of the present study indicated the presence of 50 and 67 kDa protein in aqueous phase membrane protein and cytoplasmic protein. [ABSTRACT FROM AUTHOR]

Concomitant ruptured intracranial aneurysm and severe contralateral internal carotid artery (ICA) stenosis pose a surgical dilemma. There are no guidelines. Most reports suggest an ipsilateral association. The outcome depends on planning and strategy. This 49-year-old male with ruptured C6 segment ICA aneurysm had 90% calcific carotid stenosis contralaterally. He underwent simultaneous surgery for both. The surgical steps involved and the reason behind the sequence of steps are unique to this situation and led to a good outcome. The strategy and the technicalities involved are discussed in this report.

The article presents an abstract of the research paper "Glucose availability alters chicken thymocyte interleukin-7 receptor gene expression, T-cell receptor rearrangement and T-cell differentiation," by B.D. Humphrey and colleagues.

Concurrent occurrence of schwannoma and meningiomas are rare, and are found especially in association with neurofibromatosis type 2 (NF2). Occurrence of mixed tumor without the aforementioned conditions is extremely rare. We present three cases of mixed tumor in different locations, including two with NF2 and one without NF2. We analyse the relationship of mixed tumor with NF2 and its clinical implications. Presence of mixed schwannoma-meningioma should prompt screening for NF2. Thus aids in early diagnosis of unsuspected NF2 cases. We observed that irrespective of different locations, cases with NF2 showed frequent recurrence of schwannoma as compared to case who did not fit in the existing clinical criteria for NF2. Collision tumor and thereby NF2 mutations indicates the prognosis and recurrence of the tumor, thereby guides in deciding the management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: There are no conflicts of interest.

Genes duplicate, mutate, recombine, fuse or fission to produce new genes, or when genes are formed from de novo, novel functions arise during evolution. Researchers have tried to quantify the causes of these molecular diversification processes to know how these genes increase molecular complexity over a period of time, for instance protein domain organization. In contrast to global sequence similarity, protein domain architectures can capture key structural and functional characteristics, making them better proxies for describing functional equivalence. In Prokaryotes and eukaryotes it has proven that, domain designs are retained over significant evolutionary distances. Protein domain architectures are now being utilized to categorize and distinguish evolutionarily related proteins and find homologs among species that are evolutionarily distant from one another. Additionally, structural information stored in domain structures has accelerated homology identification and sequence search methods. Tools for functional protein annotation have been developed to discover, protein domain content, domain order, domain recurrence, and domain position as all these contribute to the prediction of protein functional accuracy. In this review, an attempt is made to summarise facts and speculations regarding the use of protein domain architecture and modularity to identify possible therapeutic targets among cellular activities based on the understanding their linked biological processes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Conflict of Interest None declared.

Competing Interests: There are no conflicts of interest.

Sacral tumors are rare and can be benign or malignant. Their management is multifactorial and is based on the pathology, extent, and local and distant spread. Managing sacral tumors is challenging due to their proximity to visceral and neural structures. Surgical wide excision has been the standard of care for aggressive benign and malignant tumors. Our purpose was to evaluate the outcomes of a multimodal approach to managing primary sacral tumors in Sakra World Hospital, a tertiary spine care center in Bengaluru, India and perform a literature review to determine a workflow pathway. Our study was a retrospective review of patient records and included 15 patients with primary sacral tumors. Eleven surgically treated patients were evaluated clinically and radiologically and underwent biopsy before surgical excision by an all-posterior approach. A multidisciplinary approach that included intraoperative neural monitoring, plastic reconstruction, adjuvant chemotherapy, and radiotherapy was implemented whenever necessary. Sacral root preservation was attempted whenever feasible. Functional outcomes (based on the Visual Analog Scale [VAS] and Biagini scoring system) were analyzed along with disease control, with a minimum of 2 years of follow-up. The mean follow-up was 29±9.8 months. The mean VAS score significantly improved from 7.8±2.6 to 3.7±3.8 (p =0.026). Bowel function showed statistically significant improvement, from a mean score of 0.81±0.47 to 0.63±0.52 (p =0.026) at 2 years of follow-up. The mean pretreatment motor and bladder function scores were 0.53±0.31 and 0.74±0.44, respectively, improving to 0.48±0.33 and 0.68±0.56 at follow-up but without statistical significance. There was no significant loss of function, which is expected in radical sacral resections. In conclusion, primary sacral tumors require a multidisciplinary approach and management for optimal outcomes. A stand-alone posterior approach can be employed to treat most sacral lesions. En-bloc wide resection is the optimal treatment for primary malignant and aggressive benign tumors. Preservation of at least one functional S2 nerve root is imperative to preserve bowel and bladder function.

Folate (vitamin B 9 ) and its biologically active derivatives are well-known antioxidant molecules protecting cells from oxidative degradation. The presence of high glucose, often found in diabetic patients, causes oxidative stress resulting in cellular stress and inflammatory injury. Cells in organs such as the lung are highly prone to inflammation, and various protective mechanisms exist to prevent the progressive disorders arising from inflammation. In the present study, the synthetic form of folate, i.e. folic acid, and active forms of folate, i.e. 5-methyltetrahydrofolate and 10-formyltetrahydrofolate, were evaluated for their antioxidant and antiinflammatory potential against high glucose (50 mM)-mediated oxidative stress and inflammation in BEAS-2B cells, an immortalised bronchial epithelial cell line. High glucose treatment showed a 67% reduction in the viability of BEAS-2B cells, which was restored to the viability levels seen in control cultures by the addition of active folate derivatives to the culture media. The DCFH-DA fluorometric assay was performed for oxidative stress detection. The high glucose-treated cells showed a significantly higher fluorescence intensity (1.81- and 3.8-fold for microplate assay and microscopic observation, respectively), which was normalised to control levels on supplementation with active folate derivatives. The proinflammatory NF-κB p50 protein expression in the active folate derivative-supplemented high glucose-treated cells was significantly lower compared to the folic acid treatment. In support of these findings, in silico microarray GENVESTIGATOR database analysis showed that in bronchiolar small airway epithelial cells exposed to inflammatory condition, folate utilization pathway genes are largely downregulated. However, the folate-binding protein gene, which encodes to the folate receptor 1 (FOLR1), is significantly upregulated, suggesting a high demand for folate by these cells  in inflammatory situations. Supplementation of the active folate derivatives 5-methyltetrahydrofolate and 10-formyltetrahydrofolate resulted in significantly higher protection over the folic acid from high glucose-induced oxidative stress and inflammation. Therefore, the biologically active folate derivatives could be a suitable alternative over the folic acid for alleviating inflammatory injury-causing oxidative stress., (© 2022. The Society for In Vitro Biology.)

Background: The relative role of skeletal muscle mechano-transduction in comparison with systemic hormones, such as testosterone (T), in regulating hypertrophic responses to exercise is contentious. We investigated the mechanistic effects of chemical endogenous T depletion adjuvant to 6 weeks of resistance exercise training (RET) on muscle mass, function, myogenic regulatory factors, and muscle anabolic signalling in younger men., Methods: Non-hypogonadal men (n = 16; 18-30 years) were randomized in a double-blinded fashion to receive placebo (P, saline n = 8) or the GnRH analogue, Goserelin [Zoladex (Z), 3.6 mg, n = 8], injections, before 6 weeks of supervised whole-body RET. Participants underwent dual-energy X-ray absorptiometry (DXA), ultrasound of m. vastus lateralis (VL), and VL biopsies for assessment of cumulative muscle protein synthesis (MPS), myogenic gene expression, and anabolic signalling pathway responses., Results: Zoladex suppressed endogenous T to within the hypogonadal range and was well tolerated; suppression was associated with blunted fat free mass [Z: 55.4 ± 2.8 to 55.8 ± 3.1 kg, P = 0.61 vs. P: 55.9 ± 1.7 to 57.4 ± 1.7 kg, P = 0.006, effect size (ES) = 0.31], composite strength (Z: 40 ± 2.3% vs. P: 49.8 ± 3.3%, P = 0.03, ES = 1.4), and muscle thickness (Z: 2.7 ± 0.4 to 2.69 ± 0.36 cm, P > 0.99 vs. P: 2.74 ± 0.32 to 2.91 ± 0.32 cm, P < 0.0001, ES = 0.48) gains. Hypogonadism attenuated molecular transducers of muscle growth related to T metabolism (e.g. androgen receptor: Z: 1.2 fold, P > 0.99 vs. P: 1.9 fold, P < 0.0001, ES = 0.85), anabolism/myogenesis (e.g. IGF-1Ea: Z: 1.9 fold, P = 0.5 vs. P: 3.3 fold, P = 0.0005, ES = 0.72; IGF-1Ec: Z: 2 fold, P > 0.99 vs. P: 4.7 fold, P = 0.0005, ES = 0.68; myogenin: Z: 1.3 fold, P > 0.99 vs. P: 2.7 fold, P = 0.002, ES = 0.72), RNA/DNA (Z: 0.47 ± 0.03 to 0.53 ± 0.03, P = 0.31 vs. P: 0.50 ± 0.01 to 0.64 ± 0.04, P = 0.003, ES = 0.72), and RNA/ASP (Z: 5.8 ± 0.4 to 6.8 ± 0.5, P > 0.99 vs. P: 6.5 ± 0.2 to 8.9 ± 1.1, P = 0.008, ES = 0.63) ratios, as well as acute RET-induced phosphorylation of growth signalling proteins (e.g. AKT ser473 : Z: 2.74 ± 0.6, P = 0.2 vs. P: 5.5 ± 1.1 fold change, P < 0.001, ES = 0.54 and mTORC1 ser2448 : Z: 1.9 ± 0.8, P > 0.99 vs. P: 3.6 ± 1 fold change, P = 0.002, ES = 0.53). Both MPS (Z: 1.45 ± 0.11 to 1.50 ± 0.06%·day -1 , P = 0.99 vs. P: 1.5 ± 0.12 to 2.0 ± 0.15%·day -1 , P = 0.01, ES = 0.97) and (extrapolated) muscle protein breakdown (Z: 93.16 ± 7.8 vs. P: 129.1 ± 13.8 g·day -1 , P = 0.04, ES = 0.92) were reduced with hypogonadism result in lower net protein turnover (3.9 ± 1.1 vs. 1.2 ± 1.1 g·day -1 , P = 0.04, ES = 0.95)., Conclusions: We conclude that endogenous T sufficiency has a central role in the up-regulation of molecular transducers of RET-induced muscle hypertrophy in humans that cannot be overcome by muscle mechano-transduction alone., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Pulmonary artery sling (PAS) is usually associated with long-segment congenital tracheal stenosis (LSCTS). This combination of abnormalities can also be associated with lung hypoplasia abnormalities (hypoplasia, aplasia, or agenesis). This study analyzed the association of lung hypoplasia abnormalities with combined PAS and LSCTS and its influence on its surgical outcomes., Methods: All patients (0 to 18 years) who underwent surgical procedures for both PAS and LSCTS from 1995 to 2019 were analyzed retrospectively for mortality, ventilation days, and intensive care unit days by dividing them into those with normal lungs (group 1) and hypoplastic lungs (group 2)., Results: Included were 75 patients (30 girls [40%]), who were a median age of 5.7 months (interquartile range [IQR], 2.9-13.3 months), median weight of 5.5 kg (IQR, 4.1-7.9 kg), and had a median follow-up of 99.8 months (IQR, 54.5-152.0 months); of these, 8 patients (10.7%) had hypoplastic right lung, comprising hypoplasia in 7 (87.5%), aplasia in 1 (12.5%), and agenesis in 0 (0%). There was a significant difference in mortality (group 1, 9.0%; group 2, 50%; P = .007) but no significant difference in median ventilation days (group 1, 9.0; group 2, 9.0; P = .89) or in median intensive care unit days (group 1, 14.0; group 2, 11.5; P = .44)., Conclusions: Lung hypoplasia associated with PAS and LSCTS is usually right-sided. As a result of severe airway obstruction and single-lung physiology, there is a high requirement of preoperative cardiorespiratory support and a significant association with adverse surgical outcomes., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Vascular rings are rare congenital abnormalities of the aortic arch. There are many embryological variants including a double aortic arch. In symptomatic children, division of ring and release of airway structures may be sufficient. Persistence of symptoms can be related to an anterior angle formed between the two arches. The aim of this study is to evaluate the clinical efficacy in improving symptoms and on changing this angle at the primary surgery., Methods: All children who had surgery for double aortic arch between 2005 and 2020, were studied. Relevant factors were analyzed for persistent symptoms including anatomical substrates and surgical details., Results: A total of 87 out of 224 children had surgery for a double aortic arch. At presentation, airway symptoms ( n = 74/87) were more common than esophageal symptoms ( n = 27/87). Early onset symptoms within 1 year were seen in 49 children. In addition to division of one arch, surgical steps also included realigning the anterior left arch, thereby eliminating the acute angle in 36 children (after 2014). After surgery, symptom relief within 12 months following surgery was seen in 64% of children (56 out of 87) but in 27 out of 36 children (75%) with additional surgical modification, as against 29 out of 51 (57%) in those with division of the arch. Symptoms persisted beyond 1 year needing reintervention in eight children., Conclusion: Anterior arch angulation plays an important role in double aortic arch by causing a "nutcracker" phenomenon. Repair in double aortic arch should consider this aspect and include modification of surgical steps by realigning the corresponding aortic arch branches and an anterior pexy in selected cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Beeman, Ramaswamy, Srinivasan, Rudrappa, Christov, Marek, Derrick and Muthialu.)

Study Design: Retrospective observational study., Purpose: To share our experience of multimodal intraoperative neurophysiological monitoring (IONM) used in Sakra World Hospital, Bengaluru in various spine surgeries., Overview of Literature: The development of new onset postoperative neurological deficits can be completely avoided. In order to avoid these, IONM has become a standard of care in recent times for early detection and manipulation of the surgical procedure to prevent postoperative neurological deficits., Methods: This retrospective study was performed on 408 patients who had undergone spine surgeries with IONM during April 2014 to March 2020 at a single center. The operative report, anesthesia record, and IONM were reviewed. All the patients were reassessed for postoperative neurological deficits in the postoperative period and followed up based on the intraoperative findings and neurological deficits for 4 weeks. Signal changes in IONM were reviewed, and the obtained results were further categorized into true positive, true negative, false positive, or false negative. If changes were observed during the IONM, the patients were managed as per the algorithm., Results: Of the 408 patients being monitored continuously during the intraoperative period, 38 showed changes in recordings, 28 developed postoperative neurological deficits, and one developed neurological deficit without any change in the IONM. Nine patients had transient neurological deficits, and the other 20 had permanent neurological deficits. Overall, the multimodal IONM used in our study had a sensitivity of 96.6%, specificity of 97.4%, a positive predictive value of 73.7%, and a negative predictive value of 99.7%., Conclusions: Use of decision algorithm and multimodal neuromonitoring consisting of motor evoked potentials, somatosensory evoked potentials, and electromyography complement each other in the detection of neurological injury during the course the surgery, improve intraoperative care, and prevent further damage and morbidity in patients.

In this paper, we draw on three ethnographic studies of surrogacy we carried out separately in different contexts: the western US state of California, the south Indian state of Karnataka, and the western Russian metropolis of St Petersburg. In our interviews with surrogate mothers, intended parents, and surrogacy professionals, we traced the meanings and ideologies through which they understood the clinical labour of surrogacy. We found that in the US, interviewed surrogates, intended parents and professionals understood surrogacy as an exchange of both gifts and commodities, where gift-giving, reciprocity, and relatedness between surrogates and intended parents were the major tropes. In India, differing narratives of surrogacy were offered by its different parties: whilst professionals and intended parents framed it as a win-win exchange with an emphasis on the economic side, the interviewed surrogate mothers talked about surrogacy as creative labour of giving life. In Russia, approaches to surrogacy among the interviewed surrogate mothers, professionals and intended parents overlapped in framing it as work and a businesslike commodity exchange. We suggest these three different ways of ethical reasoning about the clinical labour of surrogacy, including justifications of women's incorporation into this labour, were situated in local moral frameworks. We name them "repro-regional moral frameworks", inspired by earlier work on moral frameworks as well as on reproductive nationalisms and transnational reproduction. Building on these findings, we argue that any international or global regulation of surrogacy, or indeed any moral stance on it, needs to take these local differences into account.

Background: Junctional kyphosis (JK) is usually observed in long-level instrumented fusion surgeries. Various contributing factors are proposed, the pre-existing and postoperative spinal imbalance is considered as the single most important factor for the development of JK in adult spinal deformity surgeries. Distal JK (DJK) is seldom reported compared to proximal JK (PJK), and scarce literature exists., Methods: We report 2 unique cases of distal junctional failure (DJF) with worsening of neurology, secondary to nontraumatic fracture of a lower instrumented vertebra operated for thoracic canal stenosis without deformity. The first case had acute worsening of the Neurology during follow up and on evaluation, the supine CT and MRI scan revealed well decompressed spinal canal, no implant migration to the canal, no screw loosening, or rod failure. Supine sitting radiographs demonstrated DJK with Fracture and the patient underwent extension of fusion till the pelvis with 3-rod construct and interbody fusion, because of the instability at the L1 level.The second case remained neurologically stable for a month and then had an acute onset of back pain, sensory deficit, and urine incontinence. The supine-sitting dynamic radiograph done demonstrated L1 fracture with DJK at D12-L1 levels. The patient was counseled for extension of fusion, which was deferred by the patient., Results: Patients in our series, had an acute worsening of neurological deficit within a month of posterior spinal fixation. Their supine imaging was almost normal, and the diagnosis of DJK with L1 fracture instability was possible only on a supine-sitting dynamic radiograph. Various factors like obesity, TL kyphosis, osteoporosis, etc. can be the attributing factors for the development of DJK CONCLUSION: A high index of suspicion is required for diagnosing nontraumatic fracture in long-level fusion patients with acute neurological worsening. The supine-sitting dynamic radiograph is an important diagnostic tool for DJF in patients having difficulty standing erect., Level of Evidence: 4., Clinical Relevance: Application of sitting and supine dynamic radiographs to diagnose instability in patients unable to stand for flexion and extension radiographs., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2021 ISASS.)

Context: Autologous bone is the most commonly used flap in cranioplasty to repair the defect; however, synthetic materials are available. Poly methyl methacrylate (PMMA) is an effective polymer owing to its thermoplastic and radiolucent properties comparable to bone strength. Three-dimensional (3D) printing combined with computer-assisted design (CAD) is a simple, low-cost method to print molds that ensure surgical success., Materials and Methods: A total of 114 patients underwent cranioplasty (July 2015-April 2018), and 25 of them using 3D printed template molds due to unavailability of autologous bone. The clinical features, patient demographics, and surgical parameters were analyzed. The visual analog score for cosmesis (VASC) and Odom's score was obtained pre and post-op., Results: The mean age of the patients is 38.4 ± 14.6 years (Range, 9-66). The primary pathology for undergoing craniectomy is stroke (n = 13; 52%), traumatic brain injury (10; 40%) and tumor (2; 8%). The reason for nonavailability of flap was infection (n = 14;56%), flap resorption (4;16%), and trauma or tumor (7;28%). The mean time for manufacturing the 3D printed template is 13.2 ± 2.1 h. On follow-up, median Odom's score is excellent in 52% of cases, good in 40%, and fair in 8%. The mean VASC score on follow up is 8.2 ± 1.3. Three patients developed minor postoperative complications., Conclusion: This is the first study from a single tertiary care center in India to systematically evaluate the outcomes in 3D cranioplasty using CAD and 3D printing technology. This method would be optimal especially in developing countries since PMMA is cost effective and also gives an ideal cosmetic effect., Competing Interests: None

Background: Hangman fracture or traumatic spondylolisthesis of the axis associated with a traumatic vertebral venous fistula (VVF) is a rare entity and sparsely reported in literature. Standard recommendations for management of such rare and complex scenarios are not available and hence the strategy has to be individualized on a case-by-case basis., Methods: We report a 70-year-old man having an unstable hangman fracture with VVF. Both pathologies were simultaneously managed uniquely. The VVF was managed by endovascular occlusion. The fracture was managed by anterior fusion alone as posterior fusion was deemed riskier in the aftermath of a recently occluded VVF. The patient had good neck function and bony fusion at 1-year follow-up., Conclusion: This case report emphasizes the need for timely recognition and management of a VVF, which can rarely coexist with hangman fracture, and discusses the interesting surgical paradigms in the management. We also present a review of literature., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The treatment of atlantoaxial instability (AAI) involves stable fixation and fusion with adequate decompression of spinal cord. After the advent of the Goel posterior joint manipulation technique, most of the once irreducible atlantoaxial dislocations (AAD) could be reduced and the need for transoral odontoidectomy became almost nil. Here we tried to iterate the indications of anterior transoral odontoid surgery for AAI in the current scenario., Methods: A retrospective study compiling the clinical, radiological, and surgical characteristics of 6 cases (5 scenarios). These patients underwent anterior transoral surgery alone or in combination with a posterior approach., Results: Two patients had a well-formed occipito-cervical fusion mass, with a displaced odontoid and unreduced C1-C2 joint causing cervical myelopathy. A middle-aged woman presented with unreduced AAD following failed C1-C2 joint distraction technique. A displaced dystopic os odontoideum ossicle was found in an adolescent boy, prohibiting the reduction of AAD. A young man had displacement of the fractured odontoid segment with intact transverse alar ligament and C1-C2 joint complex. One patient had a rare scenario of abnormal orientation of the C1-C2 joint. All 6 patients were successfully treated with adequate spinal cord decompression achieved by the anterior transoral route and stabilization by either the anterior approach itself or in combination with posterior surgery. All had significantly better postoperative outcomes except for 1 patient who expired due to poor respiratory reserve., Conclusion: We tried to emphasize the indications for using transoral anterior odontoid surgery over the posterior approach in the management of AAI. This will prevent the surgical technique of anterior odontoidectomy from becoming an obsolete procedure in the current practice., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2020 ISASS.)

Background : In Singapore, the Health Sciences Authority (HSA) reviews an average of 20,000 spontaneous adverse event (AE) reports yearly. Potential safety signals are identified manually and discussed on a weekly basis. In this study, we compared the use of four quantitative data mining (QDM) methods with weekly manual review to determine if signals of disproportionate reporting (SDRs) can improve the efficiency of manual reviews and thereby enhance drug safety signal detection. Methods : We formulated a QDM triage strategy to reduce the number of SDRs for weekly review and compared the results against those derived from manual reviews alone for the same 6-month period. We then incorporated QDM triage into the manual review workflow for the subsequent two 6-month periods and made further comparisons against QDM triage alone. Results : The incorporation of QDM triage into routine manual reviews resulted in a reduction of 20% to 30% in the number of drug-AE pairs identified for further evaluation. Sequential Probability Ratio Test (SPRT) detected more signals that mirror human manual signal detection than the other three methods. Conclusions : The adoption of QDM triage into our manual reviews is a more efficient way forward in signal detection, avoiding missing important drug safety signals.

Background: The andropause is associated with declines in serum testosterone (T), loss of muscle mass (sarcopenia), and frailty. Two major interventions purported to offset sarcopenia are anabolic steroid therapies and resistance exercise training (RET). Nonetheless, the efficacy and physiological and molecular impacts of T therapy adjuvant to short-term RET remain poorly defined., Methods: Eighteen non-hypogonadal healthy older men, 65-75 years, were assigned in a random double-blinded fashion to receive, biweekly, either placebo (P, saline, n = 9) or T (Sustanon 250 mg, n = 9) injections over 6 week whole-body RET (three sets of 8-10 repetitions at 80% one-repetition maximum). Subjects underwent dual-energy X-ray absorptiometry, ultrasound of vastus lateralis (VL) muscle architecture, and knee extensor isometric muscle force tests; VL muscle biopsies were taken to quantify myogenic/anabolic gene expression, anabolic signalling, muscle protein synthesis (D 2 O), and breakdown (extrapolated)., Results: Testosterone adjuvant to RET augmented total fat-free mass (P=0.007), legs fat-free mass (P=0.02), and appendicular fat-free mass (P=0.001) gains while decreasing total fat mass (P=0.02). Augmentations in VL muscle thickness, fascicle length, and quadriceps cross-section area with RET occured to a greater extent in T (P < 0.05). Sum strength (P=0.0009) and maximal voluntary contract (e.g. knee extension at 70°) (P=0.002) increased significantly more in the T group. Mechanistically, both muscle protein synthesis rates (T: 2.13 ± 0.21%·day -1 vs. P: 1.34 ± 0.13%·day -1 , P=0.0009) and absolute breakdown rates (T: 140.2 ± 15.8 g·day -1 vs. P: 90.2 ± 11.7 g·day -1 , P=0.02) were elevated with T therapy, which led to higher net turnover and protein accretion in the T group (T: 8.3 ± 1.4 g·day -1 vs. P: 1.9 ± 1.2 g·day -1 , P=0.004). Increases in ribosomal biogenesis (RNA:DNA ratio); mRNA expression relating to T metabolism (androgen receptor: 1.4-fold; Srd5a1: 1.6-fold; AKR1C3: 2.1-fold; and HSD17β3: two-fold); insulin-like growth factor (IGF)-1 signalling [IGF-1Ea (3.5-fold) and IGF-1Ec (three-fold)] and myogenic regulatory factors; and the activity of anabolic signalling (e.g. mTOR, AKT, and RPS6; P < 0.05) were all up-regulated with T therapy. Only T up-regulated mitochondrial citrate synthase activity (P=0.03) and transcription factor A (1.41 ± 0.2-fold, P=0.0002), in addition to peroxisome proliferator-activated receptor-γ co-activator 1-α mRNA (1.19 ± 0.21-fold, P=0.037)., Conclusions: Administration of T adjuvant to RET enhanced skeletal muscle mass and performance, while up-regulating myogenic gene programming, myocellular translational efficiency and capacity, collectively resulting in higher protein turnover, and net protein accretion. T coupled with RET is an effective short-term intervention to improve muscle mass/function in older non-hypogonadal men., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Objective: This study was performed to review the literature and to present the most up-to-date information and recommendations on the indications, complications, and success rate of anterior surgical techniques for cervical spondylotic myelopathy (CSM). The commonly performed anterior surgical procedures are multiple-level anterior cervical discectomy and fusion, anterior cervical corpectomy and fusion and its variants (skip corpectomy and hybrid surgery), and oblique corpectomy without fusion., Methods: A comprehensive literature search and analysis were performed using MEDLINE (PubMed), the Cochrane Register of Controlled Trials, and the Web of Science for peer-reviewed articles published in English during the last 10 years., Results: Corpectomy is mandated for ventral compression of fewer than 3 vertebral segments where single-level disc and osteophyte excision is inadequate to decompress the cord. Endoscopic or oblique partial corpectomy improves the sagittal canal diameter by 67% and obviates the need for an additional bone graft procedure., Conclusion: The indications of anterior surgery in patients with CSM include a straightened or kyphotic spine with a compression level lower than 3. With an appropriate choice of implants and meticulous surgical technique, surgical complications can be seen only rarely. Improvements after anterior surgery for CSM have been reported in 70% to 80% of patients.

Background: Spinal pseudomeningocele refers to an abnormal accumulation of cerebrospinal fluid (CSF) in a fibrous sac without arachnoid lining that occurs mostly as a result of an accidental dural opening. When accidental dural openings are found intraoperatively, they should be repaired to prevent further complications. Sometimes inadequately dealt dural openings, unnoticed, or postoperative dural openings may produce complications., Case Description: Three patients had complications as a result of spine surgery and presented several days after the surgery with episodic symptoms of raised intracranial pressure, including headache, opisthotonos, altered breathing patterns, and altered sensorium. These symptoms increased whenever pressure was applied on the operated area suggesting hydrocephalic attacks. All 3 patients had a giant pseudomeningocele at the operated area, a complication that resulted from the spine surgery. Magnetic resonance imaging CSF flow study revealed hyperdynamic flow and increase in absolute stroke volume across the cerebral aqueduct when constant pressure was applied on the pseudomeningocele sac., Conclusions: Usually pseudomeningoceles are asymptomatic, and if symptomatic, the common presentations are local swelling, back pain, radiculopathy, and orthostatic headache. To our knowledge, this is the first article in the literature reporting the uncommon presentation of hydrocephalic attacks in 3 cases subsequent to CSF backflow from the sac, confirmed with MRI CSF flow study. This case series emphasizes rare presentations can result from transiently increased intracranial pressure related to postoperative pseudomeningocele in spine surgeries., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Rosette-forming glioneuronal tumour [RGNT] is a relatively rare entity first identified as a separate entity in 2002. We are reporting the second case of RGNT in the opticochiasmatic region., Case Description: We report a case report and literature review of RGNT with syndromic association., Conclusions: Although initial reports were predominantly in the fourth ventricle, many recent reports have identified the possibility of its occurrence outside fourth ventricle in pineal gland, spinal cord, septum pellucidum, lateral ventricle, and suprasellar region. To date, only 1 case of RGNT involving the opticochiasmatic region has been reported in a patient with neurofibromatosis type 1. Genetic analysis of this rare tumor identified 3 hotspots involving somatic mutations of FGFR-1 and PIK3CA and a germline mutation involving PTPN11, which can be targets for therapeutic intervention in cases where complete resection is not possible. To the best of our knowledge, we report the first case of RGNT involving the opticochiasmatic region without any syndromic association. Other cases of RGNT with syndromic associations provide us with insight into possible therapeutic interventions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Techno-pastoral desires are statist aspirations for orderly, hierarchical landscapes where land, beasts and nature are managed through technical expertise to generate profits. Women and land, I argue, occupy particular places in Indian techno-pastoral imaginaries as the nation-state recalibrates profits that can be harvested from the regenerative capacities of life itself. Through a case study of southern Karnataka, where the megapolis of Bangalore is located, I show that working class women and agricultural land have a shared genealogy in the region's bio-economic development. I study three historical moments where population and food production have vexed state authorities: the South Indian famine of 1875-1876 that left more than 20% of the population dead; the early 20th century efforts at building the Krishnaraja Sagar Dam, and state-sponsored birth control clinics in the 1930s; and the 1950s-1960s population control programmes and Green Revolution interventions. The growing literature on bio-economies focuses on pharmaceutical industries; clinical trials; and commodification of organs, tissues and cells; however, by working with surrogate mothers incorporated not as labourers but with their wombs coded as land, this study attempted to map the long histories of bio-economies, spanning land and living tissue, in and around Bangalore. I argue that rather than bio-economies, the term 'necro-economies' might be more useful for describing how land and women are incorporated into techno-pastoral desires.

Background: Giant cell tumors (GCTs) are benign tumors with a predilection for the epimetaphyseal region of the long bones. GCTs involving the skull base are rare, and only a few available cases have been reported. Surgical gross total resection is the recommended method of treatment for GCTs. In the case of skull base tumors, it is very difficult to achieve such a result by direct surgical resection alone without any morbidities. Denosumab is a fully humanized monoclonal anti-receptor activator of nuclear factor-κB ligand antibody that has been recently approved by the Food and Drug Administration for the treatment of GCTs that are surgically unresectable, metastatic, and have a high risk of progression and recurrence. Denosumab has been used in many cases involving the long bones. However, in cases of skull base GCTs, only a limited number of cases have been reported. In addition, in such cases, it was used as postoperative chemotherapy owing to subtotal resection., Case Description: For the present patient, we adopted a unique approach in which denosumab was administered as neoadjuvant chemotherapy to reduce the size of the tumor to a resectable level. Subsequently, surgical resection was performed with good functional and histopathological outcomes., Conclusions: Our findings emphasize the use of denosumab as a neoadjuvant treatment routinely for all cases of skull base GCTs to achieve safe and complete excision of the tumor., (Copyright © 2018. Published by Elsevier Inc.)

Primary vertebral body tumours constitute only about 5% of skeletal tumours. Their morbidity is high due to instability and neurological deficits related to the spine. The complex anatomy further highlights the expertise needed in their management. A multidisciplinary management has heralded tremendous improvements in the treatment of primary vertebral body tumours. From incomplete resection with a high recurrence of these tumours in the early 20 th century, to the present day complete en-bloc excision of the tumours, guided by the well-established staging and classification systems, have been the significant changes brought about in the long course of treatment of these complex tumours. The overall results are better with radical excision in combination with adjuvant therapies. Complex and previously unimaginable surgical techniques are accomplished easily with a multi-disciplinary approach and with newer spinal instrumentation. Understanding of the evolution of surgical techniques and the prevalent classifications are essential in the surgical management of vertebral body tumours., Competing Interests: There are no conflicts of interest

Introduction: Spinal pseudomeningoceles are extradural collections of cerebrospinal fluid that result following a breach in the dural-arachnoid layer and is reported as one of the complications of lumbar disc surgery. Although they are often self subsiding and asymptomatic, they may occasionally cause low-back pain, headaches, and even nerve root entrapment. The purpose of this case report is to present an unreported presentation of pseudomeningocele PRESENTATION OF CASE: A 34 year obese male presented one month post lumbar discectomy with symptoms suggestive of raised intra cranial pressure presenting as repetitive decerebrate rigidity and altered sensorium lasting for few minutes when there is pressure on the pseudomeningocele sac and subsiding with change in position of the patient. He underwent surgical repair of the dural tear and was improved symptomatically with no recurrence of symptoms at five years follow up., Discussion: Radiological investigation helped in ruling out the other causes of decerebrate rigidity and the possible mechanism of development of such symptom in pseudomeningocele is discussed., Conclusion: To the best of our knowledge, this is the first reported case of pseudomeningooele presenting as decerebrate rigidity. Spinal pseudomeningocele can present in varied ways and earliest detection is the key to avoid such complications., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)