Optochiasmatic Cavernomas: Updated systematic review and proposal of a novel classification with surgical approaches.

Cavernomas are histologically benign vascular malformations found at different sites in the brain. A rare site for such cavernomas, however, is the anterior optic pathway, comprising the optic nerve, chiasma, and optic tract-called optochiasmatic cavernomas (OCC). These lesions usually present with sudden onset or progressive vision loss, headache, and features mimicking pituitary apoplexy. In this paper, we describe a case of OCC operated at our center. We carry out an updated review of literature depicting cases of OCC, their clinical presentation, management, and postoperative complications. We also propose a novel classification system based on lesion location and further analyze these cavernoma types with respect to the surgical approach used and visual outcome. A 30-year-old lady had presented with a 3-week history of progressive bilateral vision loss and headache. Based on imaging, she was suspected to have a cavernous angioma of the chiasma and left optic tract. Due to progressive vision deterioration, the lesion was surgically excised using pterional craniotomy. Postoperatively, her visual symptoms improved, but she developed diabetes insipidus. Clinical and radiological follow-up has been done for 18 months after surgery. A total of 81 cases have been described in the literature, including the present case. Chiasmal apoplexy is the most common presentation. Surgical excision is the standard of care. Our analysis based on lesion location shows the most appropriate surgical approach to be used for each cavernoma type. Visual outcome correlates with the preoperative visual status. Visual outcome is good in patients presenting with acute chiasmal apoplexy, and when complete surgical excision is performed. The endonasal endoscopic approach was found to provide the best visual outcome. In addition to preoperative visual status, complete surgical excision predicts favorable visual outcomes in OCC. Our proposed classification system guides the appropriate surgical approach required for a particular location of the cavernoma.

Synthetic sub-genomic transcript promoter from Horseradish Latent Virus (HRLV).

MAIN CONCLUSION: We characterized an efficient chimeric sub-genomic transcript promoter from Horseradish Latent Virus, FHS4, active in both dicot and monocot plants, and it could be a potential tool for plant biotechnology. Plant pararetroviruses are a rich source of novel plant promoters widely used for biotechnological applications. Here, we comprehensively characterized a unique sub-genomic transcript (Sgt) promoter of Horseradish Latent Virus (HRLV) and identified a fragment (HS4; - 340 to + 10; 351 bp) that showed the highest expression of reporter genes in both transient and transgenic assays as evidenced by biochemical, histochemical GUS reporter assay and transcript analysis of uidA gene by qRT-PCR. Phylogenetic analysis showed that the HSgt promoter was closely related to the sub-genomic promoter of the Cauliflower Mosaic Virus (CaMV19S). We found that the as-1 element and W-box played an important role in the transcriptional activity of the HS4 promoter. Furthermore, the HS4 promoter was also induced by salicylic acid. Alongside, we enhanced the activity of the HS4 promoter by coupling the enhancer region from Figwort Mosaic Virus (FMV) promoter to the upstream region of it. This hybrid promoter FHS4 was around 1.1 times stronger than the most commonly used promoter, 35S (Cauliflower Mosaic Virus full-length transcript promoter), and was efficient in driving reporter genes in both dicot and monocot plants. Subsequently, transgenic tobacco plants expressing an anti-microbial peptide BrLTP2.1 (Brassica rapa lipid transport protein 2.1), under the control of the FHS4 promoter, were developed. The in vitro anti-fungal assay revealed that the plant-derived BrLTP2.1 protein driven by an FHS4 promoter manifested increased resistance against an important plant fungal pathogen, Alternaria alternata. Finally, we concluded that the FHS4 promoter can be used as an alternative to the 35S promoter and has a high potential to become an efficient tool in plant biotechnology.

Haematopoietic stem and progenitor cells from human pluripotent stem cells.

A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders.

Delayed post-operative aggravation of sleep related disturbances in patients of basilar invagination with Chiari malformation: case report and review of the literature.

Sleep apnoea is common in patients with Basilar Invagination with Arnorld Chiari Malformation (ACM). Various studies have shown its incidence in the range of 60-70% among such patients. Most of the studies have shown improvement in sleep disturbances after decompressive surgeries for Chiari Malformations. There is no report of postoperative deterioration due to sleep apnoea in these patients. Authors report two cases of basilar invagination associated with ACM and Platybasia, who deteriorated probably due to worsening of pre-existing sleep disorders on 3rd and 7th postoperative days after their surgeries, despite clinico-radiological improvements during their early post-operative courses. Authors discuss literature related to sleep apnoea in basilar invagination associated with Chiari Malformations and share precautions, which are relevant and should be undertaken in such patients especially during early post-operative periods to avoid alarming complication which may occur even in experienced hands.

Identification and characterization of mutations in the SARS-CoV-2 RNA-dependent RNA polymerase as a promising antiviral therapeutic target.

The causative agent of COVID-19 is a novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV-2), which has emerged as a pandemic of global concern. Considering its rapid transmission, WHO has declared public health emergency on 11th March 2020 worldwide. SARS-CoV-2 is a genetically diverse positive sense RNA virus that typically exhibit high rates of mutation than DNA viruses. Higher rates of mutation bring higher genomic variability which may lead to viral evolution and enabling viruses to evade the pre-existing immunity of host and quickly acquire drug resistance properties. The objective of our study was to compare the SARS-CoV-2 RdRp sequences of Indian SARS-CoV-2 isolates with those of Wuhan type virus. A total of 384 point mutations were detected from 488 sequence of the RdRp protein of Indian SARS-CoV-2 genome, out of which seven were used for subsequent study. Furthermore, prediction of secondary structure, protein modeling and its dynamics were performed which revealed that seven mutations (R118C, T148I, Y149C, E802A, Q822H, V880I and D893Y) significantly altered the stability and flexibility of RdRp protein. Present study was therefore, undertaken to analyze the variations occurring in RdRp due to multiple mutations leading to the alterations in the structure and function of RNA-dependent RNA polymerase which is essential for the replication /transcription of this virus and hence can be utilized as a promising therapeutic target to curb SARS-CoV-2 infections.

Simulation of surgery for supratentorial gliomas in virtual reality using a 3D volume rendering technique: a poor man's neuronavigation.

OBJECTIVE: Different techniques of performing image-guided neurosurgery exist, namely, neuronavigation systems, intraoperative ultrasound, and intraoperative MRI, each with its limitations. Except for ultrasound, other methods are expensive. Three-dimensional virtual reconstruction and surgical simulation using 3D volume rendering (VR) is an economical and excellent technique for preoperative surgical planning and image-guided neurosurgery. In this article, the authors discuss several nuances of the 3D VR technique that have not yet been described. METHODS: The authors included 6 patients with supratentorial gliomas who underwent surgery between January 2019 and March 2021. Preoperative clinical data, including patient demographics, preoperative planning details (done using the VR technique), and intraoperative details, including relevant photos and videos, were collected. RadiAnt software was used for generating virtual 3D images using the VR technique on a computer running Microsoft Windows. RESULTS: The 3D VR technique assists in glioma surgery with a preoperative simulation of the skin incision and craniotomy, virtual cortical surface marking and navigation for deep-seated gliomas, preoperative visualization of morbid cortical surface and venous anatomy in surfacing gliomas, identifying the intervenous surgical corridor in both surfacing and deep-seated gliomas, and pre- and postoperative virtual 3D images highlighting the exact spatial geometric residual tumor location and extent of resection for low-grade gliomas (LGGs). CONCLUSIONS: Image-guided neurosurgery with the 3D VR technique using RadiAnt software is an economical, easy-to-learn, and user-friendly method of simulating glioma surgery, especially in resource-constrained countries where expensive neuronavigation systems are not readily available. Apart from cortical sulci/gyri anatomy, FLAIR sequences are ideal for the 3D visualization of nonenhancing diffuse LGGs using the VR technique. In addition to cortical vessels (especially veins), contrast MRI sequences are perfect for the 3D visualization of contrast-enhancing high-grade gliomas.

Immunoinformatics Identification of B- and T-Cell Epitopes in the RNA-Dependent RNA Polymerase of SARS-CoV-2.

SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is a newly emerged beta coronavirus and etiolating agent of COVID-19. Considering the unprecedented increasing number of COVID-19 cases, the World Health Organization declared a public health emergency internationally on 11th March 2020. However, existing drugs are insufficient in dealing with this contagious virus infection; therefore, a vaccine is exigent to curb this pandemic disease. In the present study, B- and T-cell immune epitopes were identified for RdRp (RNA-dependent RNA polymerase) protein using immunoinformatic techniques, which is proved to be a rapid and efficient method to explore the candidate peptide vaccine. Subsequently, antigenicity and interactions with HLA (human leukocyte antigen) alleles were estimated. Further, physicochemical properties, allergenicity, toxicity, and stability of RdRp protein were evaluated to demonstrate the specificity of the epitope candidates. Interestingly, we identified a total of 36 B-cell and 16 T-cell epitopes using epitopes predictive tools. Among the predicted epitopes, 26 B-cell and 9 T-cell epitopes showed non-allergenic, non-toxic, and highly antigenic properties. Altogether, our study revealed that RdRp of SARS-CoV-2 (an epitope-based peptide fragment) can be a potentially good candidate for the development of a vaccine against SARS-CoV-2.

Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity.

Methylation of histone H3 lysine 36 (H3K36me) by yeast Set2 is critical for the maintenance of chromatin structure and transcriptional fidelity. However, we do not know the full range of Set2/H3K36me functions or the scope of mechanisms that regulate Set2-dependent H3K36 methylation. Here, we show that the APC/CCDC20 complex regulates Set2 protein abundance during the cell cycle. Significantly, absence of Set2-mediated H3K36me causes a loss of cell cycle control and pronounced defects in the transcriptional fidelity of cell cycle regulatory genes, a class of genes that are generally long, hence highly dependent on Set2/H3K36me for their transcriptional fidelity. Because APC/C also controls human SETD2, and SETD2 likewise regulates cell cycle progression, our data imply an evolutionarily conserved cell cycle function for Set2/SETD2 that may explain why recurrent mutations of SETD2 contribute to human disease.

Giant skull vault defect in a child caused by Langerhans cell histiocytosis: the "calvaria-eating disease".

Langerhans cell histiocytosis (LCH) is a rare disease of young children that can be difficult to diagnose and treat. Clinical manifestations can sometimes be quite unusual, and bony lesions can reach a large size before treatment is sought. We present a unique case of a 3-year-old male child with a painless giant calvarial defect and cystic swelling. Complete removal of the cyst with curettage of the involved bone margins and cranioplasty was done using bone cement (polymethyl methacrylate, PMMA). However, there was a flare up of the disease due to abnormal inflammatory reaction to PMMA, and cranioplasty bone flap had to be removed. The child did well after PMMA bone flap removal.LCH should be suspected in a male child presenting with a large calvarial defect and no history of trauma. The use of materials, viz., hydroxyapatite, poly-DL-lactide (PDLLA), and PMMA for cranioplasty in LCH, may cause reactivation of the disease process and therefore must be used cautiously in these patients.

Abiotic stress hormesis: An approach to maintain quality, extend storability, and enhance phytochemicals on fresh produce during postharvest.

Postharvest losses of whole and fresh-cut fruits and vegetables cause significant reductions in food availability and an increase in economic losses/damages. Additionally, regulatory agencies are increasingly restricting the postharvest use of synthetic chemicals. This has strengthened the need to develop environmentally friendly approaches to postharvest management, such as utilization of natural compounds, antagonist microorganisms, and treatments with abiotic stresses, among others. The current review focuses on the potential of low doses of abiotic stresses to extend the shelf life, increase the amount of health beneficial phytochemicals, and reduce postharvest losses of fresh produce. The positive effects of the responses to low doses of abiotic stresses are based on a biological phenomenon termed hormesis. Research to develop new technologies to improve postharvest handling of fresh fruit and vegetables as well as minimally processed products is critical. The phenomenon of abiotic stress hormesis in fresh fruit and vegetables shows the potential not only to enhance defense compounds that could reduce diseases during postharvest storage and extend shelf life but also to elevate the content of health-promoting substances. The beneficial effects of UV-C hormesis have been extensively investigated in numerous types of fresh produce. However, our knowledge on hormesis exhibited by other abiotic stresses is still limited. Hence, the objective of this review is to discuss the relevance of hormesis for postharvest research by examining whether all abiotic stresses exhibit the phenomenon, its biological significance, the potential application in various commodities, and how it may direct the future of postharvest research.

Structure/Function Analysis of Recurrent Mutations in SETD2 Protein Reveals a Critical and Conserved Role for a SET Domain Residue in Maintaining Protein Stability and Histone H3 Lys-36 Trimethylation.

The yeast Set2 histone methyltransferase is a critical enzyme that plays a number of key roles in gene transcription and DNA repair. Recently, the human homologue, SETD2, was found to be recurrently mutated in a significant percentage of renal cell carcinomas, raising the possibility that the activity of SETD2 is tumor-suppressive. Using budding yeast and human cell line model systems, we examined the functional significance of two evolutionarily conserved residues in SETD2 that are recurrently mutated in human cancers. Whereas one of these mutations (R2510H), located in the Set2 Rpb1 interaction domain, did not result in an observable defect in SETD2 enzymatic function, a second mutation in the catalytic domain of this enzyme (R1625C) resulted in a complete loss of histone H3 Lys-36 trimethylation (H3K36me3). This mutant showed unchanged thermal stability as compared with the wild type protein but diminished binding to the histone H3 tail. Surprisingly, mutation of the conserved residue in Set2 (R195C) similarly resulted in a complete loss of H3K36me3 but did not affect dimethylated histone H3 Lys-36 (H3K36me2) or functions associated with H3K36me2 in yeast. Collectively, these data imply a critical role for Arg-1625 in maintaining the protein interaction with H3 and specific H3K36me3 function of this enzyme, which is conserved from yeast to humans. They also may provide a refined biochemical explanation for how H3K36me3 loss leads to genomic instability and cancer.

"Genome-wide identification of bZIP gene family in Pearl millet and transcriptional profiling under abiotic stress, phytohormonal treatments; and functional characterization of PgbZIP9".

Abiotic stresses are major constraints in crop production, and are accountable for more than half of the total crop loss. Plants overcome these environmental stresses using coordinated activities of transcription factors and phytohormones. Pearl millet an important C4 cereal plant having high nutritional value and climate resilient features is grown in marginal lands of Africa and South-East Asia including India. Among several transcription factors, the basic leucine zipper (bZIP) is an important TF family associated with diverse biological functions in plants. In this study, we have identified 98 bZIP family members (PgbZIP) in pearl millet. Phylogenetic analysis divided these PgbZIP genes into twelve groups (A-I, S, U and X). Motif analysis has shown that all the PgbZIP proteins possess conserved bZIP domains and the exon-intron organization revealed conserved structural features among the identified genes. Cis-element analysis, RNA-seq data analysis, and real-time expression analysis of PgbZIP genes suggested the potential role of selected PgbZIP genes in growth/development and abiotic stress responses in pearl millet. Expression profiling of selected PgbZIPs under various phytohormones (ABA, SA and MeJA) treatment showed differential expression patterns of PgbZIP genes. Further, PgbZIP9, a homolog of AtABI5 was found to localize in the nucleus and modulate gene expression in pearl millet under stresses. Our present findings provide a better understanding of bZIP genes in pearl millet and lay a good foundation for the further functional characterization of multi-stress tolerant PgbZIP genes, which could become efficient tools for crop improvement.

Use of cost-effective software for lesion localization in brain surgery: Technical note.

Lesion localization has been an important aspect of neurosurgery and has advanced significantly with technological evolution. The journey started from the localization of lesion based on clinical findings to the current era where neuronavigation and virtual reality are being used for the purpose. However, the financial implications of these advanced equipments have made them inaccessible for patients in the majority of low- and middle-income countries. The authors describe techniques to use software, which are cost effective and can be used effectively for the localization of a lesion of the brain.

The status of COVID-19 vaccines in India: A review.

The outbreak of SARS-CoV-2, an etiologic agent of the COVID-19 pandemic disease in late December 2019 has left the whole world aghast with huge health and economic losses. Due to a lack of specific knowledge and understanding at the initial stages, an unprecedented rise in COVID-19 cases has been recorded globally. Various preventive measures and strategies were implemented, however, for the radical control of SARS-CoV-2 infections; it seems that the only effective way to control the ongoing infections is large-scale vaccination. So far, WHO has approved 11 vaccines for emergency use namely Pfizer/BioNTech, Oxford/Astra Zeneca, Johnson and Johnson, Moderna, Covilo, Novavax, Covovax, Spikevax, Can Sino, Comirnaty, and Coronavac while five other needs approval. The worldwide vaccination dataset reveals that 65.7% of the world population has received their first dose of the COVID-19 vaccine. As a consequence of the proactive implementation of India's vaccination program, a historical milestone of administering over 1.9 billion doses of COVID-19 vaccines have been achieved on 19th May 2022. This review summarizes the different types of traditional and modern vaccine designing strategies with an emphasis on COVID-19. Moreover, the review highlights the status of vaccines for COVID-19 approved in India which includes both indigenous and non-indigenous vaccines. The present article also encompasses vaccine designing and developmental strategies, efficacy, safety profile and usage among the population, and the efficacy of modern vaccines over traditional ones.

El brote de SARS-CoV-2, un agente etiológico de la enfermedad pandémica COVID-19, a fines de diciembre de 2019, ha dejado al mundo entero horrorizado con enormes pérdidas económicas y de salud. Debido a la falta de conocimiento y comprensión específicos en las etapas iniciales, se ha registrado un aumento sin precedentes en los casos de COVID-19 a nivel mundial. Sin embargo, se implementaron diversas medidas y estrategias preventivas para el control radical de las infecciones por SARS-CoV-2; parece que la única forma eficaz de controlar las infecciones en curso es la vacunación a gran escala. Hasta el momento, la OMS ha aprobado 11 vacunas para uso de urgencia Pfizer/BioNTech, Oxford/Astra Zeneca, Johnson and Johnson, Moderna, Covilo, Novavax, Covovax, Spikevax, Can Sino, Comirnaty y Coronavac, mientras que otras cinco necesitan aprobación. El conjunto de datos de vacunación mundial revela que el 65,7% de la población mundial ha recibido su primera dosis de la vacuna COVID-19. Como consecuencia de la implementación proactiva del programa de vacunación de la India, el 19 de mayo de 2022 se logró un hito histórico de administrar más de 1900 millones de dosis de vacunas contra el COVID-19. Esta revisión resume los diferentes tipos de estrategias de diseño de vacunas tradicionales y modernas con énfasis sobre COVID-19. Además, la revisión destaca el estado de las vacunas para COVID-19 aprobadas en India, que incluye vacunas tanto indígenas como no indígenas. El presente artículo también abarca estrategias de diseño y desarrollo de vacunas, eficacia, perfil de seguridad y uso entre la población, y la eficacia de las vacunas modernas sobre las tradicionales.

MYB Transcription Factor Family in Pearl Millet: Genome-Wide Identification, Evolutionary Progression and Expression Analysis under Abiotic Stress and Phytohormone Treatments.

Transcription factors (TFs) are the regulatory proteins that act as molecular switches in controlling stress-responsive gene expression. Among them, the MYB transcription factor family is one of the largest TF family in plants, playing a significant role in plant growth, development, phytohormone signaling and stress-responsive processes. Pearl millet (Pennisetum glaucum L.) is one of the most important C4 crop plants of the arid and semi-arid regions of Africa and Southeast Asia for sustaining food and fodder production. To explore the evolutionary mechanism and functional diversity of the MYB family in pearl millet, we conducted a comprehensive genome-wide survey and identified 279 MYB TFs (PgMYB) in pearl millet, distributed unevenly across seven chromosomes of pearl millet. A phylogenetic analysis of the identified PgMYBs classified them into 18 subgroups, and members of the same group showed a similar gene structure and conserved motif/s pattern. Further, duplication events were identified in pearl millet that indicated towards evolutionary progression and expansion of the MYB family. Transcriptome data and relative expression analysis by qRT-PCR identified differentially expressed candidate PgMYBs (PgMYB2, PgMYB9, PgMYB88 and PgMYB151) under dehydration, salinity, heat stress and phytohormone (ABA, SA and MeJA) treatment. Taken together, this study provides valuable information for a prospective functional characterization of the MYB family members of pearl millet and their application in the genetic improvement of crop plants.

A Prospective Comparative Study between 99mTc MIBI Myocardial Perfusion Single-Photon Emission Computed Tomography and Dobutamine Stress Echocardiography to Detect Viable Myocardium in Patients with Coronary Artery Disease.

Introduction: The objective of this study was to compare 99mTc MIBI myocardial perfusion SPECT and Dobutamine Stress Echocardiography (DSE) in detecting viable myocardium in patients with Coronary Artery Disease. Materials and Methods: Total of 50 patients who with CAD and poor LV function were idenitifed on 2D Echo using 16 segment cardiac model. These patients underwent 99mTc MIBI myocardial perfusion SPECT and Dobutamine Stress Echocardiography and the results were compared with the gold standard 18F-FDG PET-CT findings. Results: A Total of 550 dysfunctional segments were identified in datasets of 50 patients on 2D echo. No significant difference was noted between the pairwise positive outcome of viable segment between MIBI SPECT and DSE (p=0.875). MIBI SPECT showed a sensitivity of 86.5% and specificity of 90.0% when compared with 18F-FDG PET-CT which was comparable with DSE having a sensitivity of 87.6% and specificity of 90.7%. Conclusion: 99mTc MIBI SPECT is an effective good alternative for evaluation of viable myocardial segments in patients with dysfunctional myocardium and can be considered especially in elderly or obese patients and patients with lung disease having poor echocardiographic imaging window due to lack of an optimal acoustic window.

Mucous Extractor for Tumor Tissue Sampling in Neurosurgery.

Objective Collection of sample for histopathological analysis is highly important during any surgical procedure. The histopathology report helps determine the diagnosis, prognosis further management, and follow-up plan. The use of a reliable sample collection technique is doubly important in neurosurgical procedures because lesions are often deep-seated and difficult to access. Materials and Methods Conventional techniques of sample collection, such as use of tumor-grasping forceps and collection of material from the ultrasonic aspirator device suffer from limitations of access and unreliability. We propose a novel technique of sample collection using readily available mucous aspirator device. Results This device is economical, sterile, and disposable. It can be used even in low-resource settings because it is easily available. It can also be connected to suction cannula and the negative pressure settings can be adjusted as required. Conclusion The use of this device for neurosurgical procedures has been tried in the transcranial and transnasal neurosurgical procedures and found to be effective. The sample collected in the canister of the mucous aspirator can be directly sent to the laboratory for histopathological analysis.

Use of Multimodality Intraoperative Neuromonitoring in Tethered Cord Syndrome - Experience from a Tertiary Care Center.

Detethering of the spinal cord is done in nearly all cases of tethered cord syndrome (TCS), which can damage nerve roots, and hence, there is a need to identify filum terminale during surgery. Multimodality intraoperative neuromonitoring (IONM) may be useful in this regard to prevent postoperative morbidity. Twenty-six patients (13 males and 13 females, age range: one year to 56 years) with TCS were recruited for the study. Triggered electromyography (t-EMG), transcranial motor evoked potential (TcMEP) and free-running electromyography (f-EMG) were used in the study on a case-to-case basis. Warning criteria were followed according to the standard guidelines. Nerve roots and filum terminale were successfully identified and detethered in all cases. There was no new postoperative deficit seen. Transcranial motor evoked potentials did not change during surgery and no new limb weakness was seen in any of the investigated cases. Triggered EMG successfully helps in identifying nerve roots and filum terminale, while TcMEP is a good prognostic indicator of motor viability. Multimodality IONM use during tethered cord surgery should be encouraged to prevent postoperative deficits.