A unique miR775-GALT9 module regulates leaf senescence in Arabidopsis during post-submergence recovery by modulating ethylene and the abscisic acid pathway.

The submergence-induced hypoxic condition negatively affects the plant growth and development, and causes early onset of senescence. Hypoxia alters the expression of a number of microRNAs (miRNAs). However, the molecular function of submergence stress-induced miRNAs in physiological or developmental changes and recovery remains poorly understood. Here, we show that miR775 is an Arabidopsis thaliana-specific young and unique miRNA that possibly evolved non-canonically. miR775 post-transcriptionally regulates GALACTOSYLTRANSFERASE 9 (GALT9) and their expression is inversely affected at 24 h of complete submergence stress. The overexpression of miR775 (miR775-Oe) confers enhanced recovery from submergence stress and reduced accumulation of RBOHD and ROS, in contrast to wild-type and MIM775 Arabidopsis shoot. A similar recovery phenotype in the galt9 mutant indicates the role of the miR775-GALT9 module in post-submergence recovery. We predicted that Golgi-localized GALT9 is potentially involved in protein glycosylation. The altered expression of senescence-associated genes (SAG12, SAG29 and ORE1), ethylene signalling (EIN2 and EIN3) and abscisic acid (ABA) biosynthesis (NCED3) pathway genes occurs in miR775-Oe, galt9 and MIM775 plants. Thus, our results indicate the role for the miR775-GALT9 module in post-submergence recovery through a crosstalk between the ethylene signalling and ABA biosynthesis pathways.

Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination: A systematic review and meta-analysis.

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.

Exploring the Higher Order Structure and Conformational Transitions in Insulin Microcrystalline Biopharmaceuticals by Proton-Detected Solid-State Nuclear Magnetic Resonance at Natural Abundance.

The integrity of a higher order structure (HOS) is an essential requirement to ensure the efficacy, stability, and safety of protein therapeutics. Solution-state nuclear magnetic resonance (NMR) occupies a unique niche as one of the most promising methods to access atomic-level structural information on soluble biopharmaceutical formulations. Another major class of drugs is poorly soluble, such as microcrystalline suspensions, which poses significant challenges for the characterization of the active ingredient in its native state. Here, we have demonstrated a solid-state NMR method for HOS characterization of biopharmaceutical suspensions employing a selective excitation scheme under fast magic angle spinning (MAS). The applicability of the method is shown on commercial insulin suspensions at natural isotopic abundance. Selective excitation aided with proton detection and non-uniform sampling (NUS) provides improved sensitivity and resolution. The enhanced resolution enabled us to demonstrate the first experimental evidence of a phenol-escaping pathway in insulin, leading to conformational transitions to different hexameric states. This approach has the potential to serve as a valuable means for meticulously examining microcrystalline biopharmaceutical suspensions, which was previously not attainable in their native formulation states and can be seamlessly extended to other classes of biopharmaceuticals such as mAbs and other microcrystalline proteins.

Platelet functions in lymphatic filariasis patients.

Filariasis is a chronic disease where parasitic worms survive in human hosts even for decades and lead to complications like lymphedema and elephantiasis. Despite the persistent existence of filarial parasites in human hosts, fatal and thrombotic complications are not known, unlike other parasitic diseases like malaria. This suggests that filarial parasites might be affecting the host's platelet functions. This study was conducted to examine platelet functions in confirmed filariasis patients and healthy controls. Results showed that filariasis patients had larger platelets, inhibited aggregation, and slower speed of aggregation, compared to controls. However, in vivo markers of platelet activation and degranulation (beta thromboglobulin and soluble P-selectin) were not affected. Observations suggested that there is increased platelet turnover, cellular apoptosis and inhibited platelet functions in filariasis patients compared to controls. Platelet function inhibition was not associated with the duration of disease, lymphedema-affected organs, or gender of patients. This study confirms that filarial parasites modulate platelet functions in human hosts.

Multi-level authentication for security in cloud using improved quantum key distribution.

Cloud computing is an on-demand virtual-based technology to develop, configure, and modify applications online through the internet. It enables the users to handle various operations such as storage, back-up, and recovery of data, data analysis, delivery of software applications, implementation of new services and applications, hosting websites and blogs, and streaming of audio and video files. Thereby, it provides us many benefits although it is backlashed due to problems related to cloud security like data leakage, data loss, cyber attacks, etc. To address the security concerns, researchers have developed a variety of authentication mechanisms. This means that the authentication procedure used in the suggested method is multi-levelled. As a result, a better QKD method is offered to strengthen cloud security against different types of security risks. Key generation for enhanced QKD is based on the ABE public key cryptography approach. Here, an approach named CPABE is used in improved QKD. The Improved QKD scored the reduced KCA attack ratings of 0.3193, this is superior to CMMLA (0.7915), CPABE (0.8916), AES (0.5277), Blowfish (0.6144), and ECC (0.4287), accordingly. Finally, this multi-level authentication using an improved QKD approach is analysed under various measures and validates the enhancement over the state-of-the-art models.

Bridging the spinal dysraphism spectrum between terminal myelocystocele and spinal cord lipoma: a report of two cases of true terminal lipomyelocystocele with holo-cord syrinx.

Terminal myelocystocele (TMC) is a rare form of spinal dysraphism which arises due to aberration in the secondary neurulation process involving the caudal cell mass. Terminal myelocystocele has been defined by Pang et al. based on essential and non-essential features. One of the non-essential features includes non dysraphic lipomas which do not tether to the neural placode. We are presenting two cases which meets all the essential criteria outlined by Pang et al. for TMC but also show the presence of a lipomatous component tethering to the neural placode, similar to a dysraphic lipoma. Through this article, we want to showcase a subset which represents "true" terminal lipomyelocystocele (TLMC), bridging the spectrum of spinal dysraphism between TMC and lipomyelomeningocele (LMM).

Occipital encephalocele: a retrospective analysis and assessment of post-surgical neurodevelopmental outcome.

BACKGROUND: Encephalocele represent a group of disorders which is characterised by extracranial herniation of the leptomeninges, brain, and CSF through a structural defect in the cranium. They are usually associated with other intracranial anomalies which may impact the neurological development. AIM: This study aimed to assess the predictors of neurological development of patients undergone surgical excision of occipital encephalocele. METHODS: All patients with occipital encephaloceles operated over the last decade (2012-2022). The sac size, presence of hydrocephalous, and associated anomalies were noted. The biopsy of these patients were reviewed and categorised as those which contains mature neural tissue and those without. The neurological outcomes were assessed by social, language, cognitive, and motor milestone and has been stratified into no delay, mild (1 of 4), moderate (2 or 3 of 4), and severe development delay (4 of 4). RESULTS: Total of 35 patients were included with median age of 10 months (IQR = 5-20 months). Fifteen (42.9%) patients had sac size of ≥ 5 cm, and 23 (65.7%) patients had mature neural tissues on biopsy. The median follow-up period was 6.4 years (IQR = 4.38-10.65) years. Seventeen (49.6%) patients had moderate to severe developmental delay. The sac size of ≥ 5 cm (AOR = 33.5; 95%CI = 3.35-334.8) (p = 0.003) and presence of mature neural content in the sac (AOR = 13.32; 95%CI = 1.1-160.36) (p = 0.041) were associated with significant neurodevelopmental delay. CONCLUSION: The presence of a large sac of ≥ 5 cm and the presence of mature neural tissues on histopathological specimen of patients with encephalocele point towards the possibility of poor neurological development.

Under recognized yet a clinically relevant impact of aneurysm location in Distal Anterior Cerebral Artery (DACA) aneurysms: insights from a contemporary surgical experience.

Aneurysms of the distal anterior cerebral artery (DACA) are rare but surgically challenging. Despite a known therapeutic implication of the aneurysm location on the DACA territory, the literature is unclear about its clinical and prognostic significance. Our surgical experience over the last 5 years was reviewed to compare the clinical, operative, and outcome characteristics between aneurysms located below the mid portion of the genu of the corpus callosum (called proximal aneurysms) to those distal to this point (called distal aneurysms). A prognostic factor analysis was done using uni and multivariable analysis. A total of 34 patients were treated (M: F = 1:2.3). The distal group had a higher frequency of poor clinical grade at presentation (n = 9, 47.4%) in contrast to (n = 2, 13.3%) proximal aneurysms (p = 0.039). Despite an overall tendency for a delayed functional improvement in these patients, the results were mainly due to favorable outcomes in the proximal group (favourable functional outcomes at discharge and at last follow-up being 80% and 86.7% respectively). On the multivariable analysis, only WFNS grade (> 2) at presentation (OR = 13.75; 95CI = 1.2-157.7) (p = 0.035) and application of temporary clips (AOR = 34.32; 95CI = 2.59-454.1) (p = 0.007), both of which were more in the distal group, independently predicted a poor long term functional outcome. Thus, the aneurysm location impacts the preoperative clinical grade, the intraoperative aneurysm rupture risk rate as well as the temporary clipping requirement. A combination of these factors leads to worse short and long-term functional outcomes in the distal DACA aneurysms.

Trans-temporal trans-choroidal resection of thalamic and thalamopeduncular tumors: how I do it.

BACKGROUND:  Surgical resection is the cornerstone of treatment for low-grade tumors, albeit total excision is beneficial. As the thalamus is surrounded by vital neurovascular system, lesions here present a surgical challenge. METHOD: This article aims to demonstrate the trans-temporal, trans-choroidal fissure approach's effective surgical therapy on patients with thalamic lesions. With this approach, we were able to remove the tumor completely in three patients and almost completely in six more. Here we discuss a few technical details and potential hazards of the procedure with an operative video. CONCLUSION: This approach  provides excellent access to the deep areas of brain.

Recent Trends in Nanocarrier-Based Drug Delivery System for Prostate Cancer.

Prostate cancer remains a significant global health concern, requiring innovative approaches for improved therapeutic outcomes. In recent years, nanoparticle-based drug delivery systems have emerged as promising strategies to address the limitations of conventional cancer chemotherapy. The key trends include utilizing nanoparticles for enhancing drug delivery to prostate cancer cells. Nanoparticles have some advantages such as improved drug solubility, prolonged circulation time, and targeted delivery of drugs. Encapsulation of chemotherapeutic agents within nanoparticles allows for controlled release kinetics, reducing systemic toxicity while maintaining therapeutic efficacy. Additionally, site-specific accumulation within the prostate tumor microenvironment is made possible by the functionalization of nanocarrier with targeted ligands, improving therapeutic effectiveness. This article highlights the basics of prostate cancer, statistics of prostate cancer, mechanism of multidrug resistance, targeting approach, and different types of nanocarrier used for the treatment of prostate cancer. It also includes the applications of nanocarriers for the treatment of prostate cancer and clinical trial studies to validate the safety and efficacy of the innovative drug delivery systems. The article focused on developing nanocarrier-based drug delivery systems, with the goal of translating these advancements into clinical applications in the future.

Serratiopeptidase Attenuates Lipopolysaccharide-Induced Vascular Inflammation by Inhibiting the Expression of Monocyte Chemoattractant Protein-1.

Lipopolysaccharide (LPS) has potent pro-inflammatory properties and acts on many cell types including vascular endothelial cells. The secretion of the cytokines MCP-1 (CCL2), interleukins, and the elevation of oxidative stress by LPS-activated vascular endothelial cells contribute substantially to the pathogenesis of vascular inflammation. However, the mechanism involving LPS-induced MCP-1, interleukins, and oxidative stress together is not well demonstrated. Serratiopeptidase (SRP) has been widely used for its anti-inflammatory effects. In this research study, our intention is to establish a potential drug candidate for vascular inflammation in cardiovascular disorder conditions. We used BALB/c mice because this is the most successful model of vascular inflammation, suggested and validated by previous research findings. Our present investigation examined the involvement of SRP in vascular inflammation caused by lipopolysaccharides (LPSs) in a BALB/c mice model. We analyzed the inflammation and changes in the aorta by H&E staining. SOD, MDA, and GPx levels were determined as per the instructions of the kit protocols. ELISA was used to measure the levels of interleukins, whereas immunohistochemistry was carried out for the evaluation of MCP-1 expression. SRP treatment significantly suppressed vascular inflammation in BALB/c mice. Mechanistic studies demonstrated that SRP significantly inhibited the LPS-induced production of proinflammatory cytokines such as IL-2, IL-1, IL-6, and TNF-α in aortic tissue. Furthermore, it also inhibited LPS-induced oxidative stress in the aortas of mice, whereas the expression and activity of monocyte chemoattractant protein-1 (MCP-1) decreased after SRP treatment. In conclusion, SRP has the ability to reduce LPS-induced vascular inflammation and damage by modulating MCP-1.

Combined Liquid-State and Solid-State Nuclear Magnetic Resonance at Natural Abundance for Comparative Higher Order Structure Assessment in the Formulated-State of Biphasic Biopharmaceutics.

A higher-order structure (HOS) is critical to a biopharmaceutical drug as the three-dimensional structure governs its function. Even the partial perturbation in the HOS of the drug can alter the biological efficiency and efficacy. Due to current limitations in analytical technologies, it is imperative to develop a protocol to characterize the HOS of biopharmaceuticals in the native formulated state. This becomes even more challenging for the suspension formulations where solution and solid phases co-exist. Here, we have used a combinatorial approach using liquid (1D 1H) and solid-state (13C CP MAS) NMR methodology to demonstrate the HOS in the biphasic microcrystalline suspension drug in its formulated state. The data were further assessed by principal component analysis and Mahalanobis distance (DM) calculation for quantitative assessment. This approach is sufficient to provide information regarding the protein HOS and the local dynamics of the molecule when combined with orthogonal techniques such as X-ray scattering. Our method can be an elegant tool to investigate batch-to-batch variation in the process of manufacture and storage as well as a biosimilarity comparison study for biphasic/microcrystalline suspension.

An integrated computational pipeline for designing high-affinity nanobodies with expanded genetic codes.

Protein engineering and design principles employing the 20 standard amino acids have been extensively used to achieve stable protein scaffolds and deliver their specific activities. Although this confers some advantages, it often restricts the sequence, chemical space, and ultimately the functional diversity of proteins. Moreover, although site-specific incorporation of non-natural amino acids (nnAAs) has been proven to be a valuable strategy in protein engineering and therapeutics development, its utility in the affinity-maturation of nanobodies is not fully explored. Besides, current experimental methods do not routinely employ nnAAs due to their enormous library size and infinite combinations. To address this, we have developed an integrated computational pipeline employing structure-based protein design methodologies, molecular dynamics simulations and free energy calculations, for the binding affinity prediction of an nnAA-incorporated nanobody toward its target and selection of potent binders. We show that by incorporating halogenated tyrosines, the affinity of 9G8 nanobody can be improved toward epidermal growth factor receptor (EGFR), a crucial cancer target. Surface plasmon resonance (SPR) assays showed that the binding of several 3-chloro-l-tyrosine (3MY)-incorporated nanobodies were improved up to 6-fold into a picomolar range, and the computationally estimated binding affinities shared a Pearson's r of 0.87 with SPR results. The improved affinity was found to be due to enhanced van der Waals interactions of key 3MY-proximate nanobody residues with EGFR, and an overall increase in the nanobody's structural stability. In conclusion, we show that our method can facilitate screening large libraries and predict potent site-specific nnAA-incorporated nanobody binders against crucial disease-targets.

Morpho-functional characterization of the submucosal glands at the nasopharyngeal end of the auditory tube in humans.

BACKGROUND: The auditory tube (AT), an osteocartilaginous channel, connects the nasopharynx to the middle ear cavity. At the nasopharyngeal opening of the AT, there are dense collections of submucosal glands. In a recent article, Valstar et al. proposed these nasopharyngeal tubal glands conglomerate as salivary glands, which starkly contrasts with their previously known anatomy for being a component of the respiratory tract. This study examines the contesting views regarding the taxonomical categorization of the nasopharyngeal tubal glands. MATERIALS AND METHODS: The AT glands in context were examined in human cadavers grossly, and microscopically using routine and special (Hematoxylin and Eosin [H&E] and Periodic acid-Schiff [PAS] respectively), as well as immunohistochemical (for alpha-SMA and salivary amylase) staining methods and compared with the major and minor salivary glands and the submucosal glands in the trachea. Further, a biochemical analysis was performed to detect the presence of salivary amylase in the oral and nasopharyngeal secretions of the four living human subjects, representing major salivary glands and tubal glands, respectively. RESULTS: The submucosal seromucous glands with a surface lining of respiratory epithelium were observed at the nasopharyngeal end of AT. The cells in the tubal glands showed cytoplasmic positivity for alpha-SMA, which indicated the presence of the myoepithelial cells; however, this expression was significantly lower than in the seromucous submucosal glands within the trachea. Salivary alpha-amylase was undetectable in the cadaveric tissue samples. Moreover, the amylase level in the nasopharyngeal swabs was negligible compared to the oral swabs. CONCLUSION: The anatomical location along the respiratory tract, the presence of respiratory epithelium in the overlying mucosa, their morpho-functional resemblance to the seromucous glands in the trachea, and the absence of salivary amylase strongly indicate that the tubal glands are taxonomically different from the salivary glands. Given the available evidence, their existing recognition as a part of the respiratory tract and an integral component of the AT seems more appropriate.

Machine learning for predicting diabetic metabolism in the Indian population using polar metabolomic and lipidomic features.

AIMS: To identify metabolite and lipid biomarkers of diabetes in the Indian subpopulation in newly diagnosed diabetic and long-term diabetic individuals. To utilize the global polar metabolomic and lipidomic profiles to predict the susceptibility of an individual to diabetes using machine learning algorithms. MATERIALS AND METHODS: 87 individuals, including healthy, newly diabetic, and long-term diabetics on medication, were included in the study. Post consent, their serum was used to isolate polar metabolome and lipidome. NMR and LCMS were used to identify the polar metabolites and lipids, respectively. Statistical analysis was done to determine significantly altered molecules. NMR and LCMS comprehensive data were utilized to generate diabetic models using machine learning algorithms. 10 more individuals (pre-diabetic) were recruited, and their polar metabolomic and lipidomic profiles were generated. Pre-diabetic metabolic profiles were then utilized to predict the diabetic status of the metabolome and lipidome beyond glucose levels. RESULTS: Mannose, Betaine, Xanthine, Triglyceride (38:1), Sphingomyelin (d63:7), and Phosphatidic acid (37:2) are some of the top key biomarkers of diabetes. The predictive model generated showed the receiver operating characteristic area under the curve (ROC-AUC) as 1 on both test and validation data indicating excellent accuracy. This model then predicted the diabetic closeness of the metabolism of pre-diabetic individuals based on probability scores. CONCLUSION: Polar metabolic and lipid profile of diabetic individuals is very different from that of healthy individuals. Lipid profile alters before the polar metabolic profile in diabetes-susceptible individuals. Without regard to glucose, the diabetic closeness of the metabolism of any individual can be determined.

COVID-19 vaccination may enhance hippocampal neurogenesis in adults.

Emerging evidence suggests a detrimental impact of COVID-19 illness on the continued hippocampal neurogenesis in adults. In contrast, the existing literature supports an enhancing effect of COVID-19 vaccination on adult hippocampal neurogenesis. Vaccines against respiratory infections, including influenza, have been shown to enhance hippocampal neurogenesis in adult-age animals. We propose that a similar benefit may happen in COVID-19 vaccinated adults. The vaccine-induced enhancement of the hippocampal neurogenesis in adults thus may protect against age-related cognitive decline and mental disorders. It alsohints at an added mental health benefit of the COVID-19 vaccination programs in adults.

Inhibition of AGEs formation, antioxidative, and cytoprotective activity of Sumac (Rhus typhina L.) tannin under hyperglycemia: molecular and cellular study.

It is well known that accumulation of advanced glycation ends products (AGEs) lead to various diseases such as diabetes and diabetic complications. In this study we showed that hydrolysable tannin from Sumac (Rhus typhina L.)-3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-ß-D-glucose (C55H40O34) inhibited generation of glycation markers in bovine serum albumin such as AGEs, dityrosine, N'-formylkynurenine and kynurenine under high glucose treatment. This effect was accompanied by stabilization of the protein structure, as was shown using ATR-FT-IR spectroscopy and fluorescence methods. C55H40O34 exhibited also a neuroprotective effect in high glucose-exposed Neuro2A cells suppressing ROS formation and expression of phospho NF-κß and iNOS. At the same time C55H40O34 increased expression of heme oxygenase-1 and NAD(P)H: quinone oxidoreductase and mitochondrial complex I and V activities. Results from this study demonstrates a potent antiglycation activity of C55H40O34 in vitro and indicates its possible therapeutic application in glycation related diseases.

Molecular evolution steered structural adaptations in the DNA polymerase III α subunit of halophilic bacterium Salinibacter ruber.

A significant portion of the earth has a salty environment, and the literature on bacterial survival mechanisms in salty environments is limited. During molecular evolution, halophiles increase acidic amino acid residues on their protein surfaces which leads to a negatively charged surface potential that helps them to maintain the protein integrity and protect them from denaturation by competing with salt ions. Through protein family analysis, we have investigated the molecular-level adaptive features of DNA polymerase III's catalytic subunit (alpha) and its structure-function relationship. This study throws light on the novel understanding of halophilic bacterial replication and the molecular basis of salt adaptation. Comparisons of the amino acid contents and electronegativity of halophilic and mesophilic bacterial proteins revealed adaptations that allow halophilic bacteria to thrive in high salt concentrations. A significantly lower isoelectric point of halophilic bacterial proteins indicates the acidic nature. Also, an abundance of disordered regions in halophiles suggests the requirement of the salt ions that play a crucial role in their stable protein folding. Despite having similar topology, mesophilic and halophilic proteins, a set of very prominent molecular modifications was observed in the alpha subunit of halophiles.

Many-Body Quantum Chemistry on Massively Parallel Computers.

The deployment of many-body quantum chemistry methods onto massively parallel high-performance computing (HPC) platforms is reviewed. The particular focus is on highly accurate methods that have become popular in predictive description of chemical phenomena, such as the coupled-cluster method. The account of relevant literature is preceded by a discussion of the modern and near-future HPC landscape and the relevant computational traits of the many-body methods, in their canonical and reduced-scaling formulations, that underlie the challenges in their HPC realization.

Tension pneumocephalus in a patient with NF1 following ventriculoperitoneal shunt-deciphering the cause and proposed management strategy.

INTRODUCTION: Spontaneous pneumocephalus following ventriculoperitoneal shunting is a very unique complication, seen in a handful of patients. Small bony defects form as a result of chronically raised intracranial pressure, which can later lead to pneumocephalus once intracranial pressure decreases following ventriculoperitoneal shunting. CASE REPORT: Here, we present a case of a 15-year-old girl with NF1 who presented to us with pneumocephalus 10 months following shunting and our management strategy along with a literature review of this condition. CONCLUSION: NF1 & hydrocephalus can lead to skull base erosion, which needs to be looked up before proceeding with VP shunting to avoid delayed onset pneumocephalus. SOKHA with the opening of LT is a minimally invasive approach suitable to tackle both problems simultaneously.