Multiple HAPS-based space-air-ground network with FSO communication: a performance analysis.

Due to the fact that the existing generation of wireless communication cannot possibly keep up with the current traffic explosion and emerging applications, research and development on next-generation (i.e., sixth generation, 6G) wireless technologies is being carried out worldwide. In this regard, it is anticipated that the space-air-ground (SAG) network with free space optics (FSO) communication can provide the terabits per second throughput necessary to sustain various potential 6G applications. However, FSO communications are susceptible to atmospheric turbulence, pointing errors, and beam scintillation effects. To remedy the severe atmospheric effects, we propose a multiple high-altitude platform station (HAPS)-based SAG network with a HAPS selection scheme. For the proposed system, we have derived the closed-form expressions for outage probability, average symbol error rate (SER), ergodic capacity, and outage capacity over Málaga distribution with pointing errors. Further, the asymptotic expressions for outage probability, average SER, and outage capacity were derived to enhance the comprehension of the system from a practical standpoint. It is observed from the numerical results that the multiple HAPS-based FSO system performs better than the existing HAPS-based FSO systems.

Intelligent-reflecting-surfaces-assisted hybrid FSO/RF communication with diversity combining: a performance analysis.

Free space optics (FSO) and radio frequency (RF) communication systems exhibit complementary characteristics, with FSO being susceptible to fog, turbulence, and pointing errors, whereas RF is susceptible to rain and small scale fading. These inherent complementary characteristics between FSO and RF communication systems enable the hybrid configuration to effectively alleviate the impact of environmental impediments. This paper presents the performance analysis of an intelligent reflecting surfaces (IRSs)-assisted hybrid FSO/RF system under atmospheric turbulence (AT), pointing errors (PE), small scale fading effects, and attenuation due to climatic conditions such as fog, rain, etc. To characterize the AT, gamma-gamma distribution is used, and the multipath fading in the RF link is modeled using Nakagami-m distribution. At the receiver, signals from both the FSO and RF links are combined using either the selection combining (SC) or maximal-ratio combining (MRC) technique. We derive the exact closed-form expressions for outage probability and average symbol error rate (ASER) for both diversity combining schemes. The proposed system is compared with the direct link (DL) FSO system, IRSs-assisted FSO system, and hybrid FSO/RF system with diversity combining schemes. Further, the performance comparison between the SC and MRC schemes is also reported. Finally, the accuracy of the analytical expressions is verified by utilizing Monte Carlo simulations.

Multihop IRS-assisted free space optics communication with DF relaying: a performance analysis.

Free space optics communication (FSO) offers several advantages over its counterpart radio frequency (RF) systems in terms of bandwidth, data rates, and cost efficiency. However, FSO, being a line-of-sight (LoS) communication system, is hindered by various environmental factors. In this paper, we propose a multihop decode-and-forward (DF) relaying-based intelligent reflecting surface (IRS)-assisted FSO system with an aim to deal with the impediments in FSO communication, and it is assumed that each IRS consists of multiple reflecting elements. Specifically, we derive end-to-end expressions for cumulative distribution function (CDF) of output instantaneous signal-to-noise ratio (SNR). Furthermore, with the aid of the CDF statistics, we study the performance of the proposed system by obtaining the expressions for outage probability (OP) and average symbol error rate (ASER) in terms of multivariate Fox's H-function. Moreover, we have quantified the system performance by numerical results. The numerical results show that the multihop IRS-assisted FSO system provides better performance when compared to a single-hop IRS-assisted FSO system and multihop FSO system without IRS. Finally, the derived expressions of OP and ASER are validated using Monte-Carlo simulations.

An assessment of childhood cancer care services in India - gaps, challenges and the way forward.

Background: Childhood cancers are emerging as an essential concern in India where there is lack of a specific programme component or policy to address childhood cancer control. There is limited information on the status and quality of childhood cancer care services in India. This paper describes the childhood cancer care services available at secondary and tertiary-level hospitals in India through a cross sectional study design. Methods: The survey was conducted in 137 tertiary-level and 92 secondary-level hospitals in 26 states and 4 Union Territories (UTs), ensuring a uniform representation of public and private care hospitals. The study tool collected data on the organisational infrastructure, type of oncology services, health workforce, equipment, treatment and referral protocols, and treatment guidelines. Descriptive statistics was used to primarily present the health service status and data on childhood cancer care services in proportions and mean. Findings: A dedicated pediatric oncology department was available in 41.6% of the public, 48.6% of private, and 64% Non Government Organization (NGO) managed tertiary-level hospitals. In 36 (39%) of the 92 hospitals providing secondary care, childhood cancer care was provided. The availability of bone (41.5%) and positron emission tomography (PET) scans (25.9%) was lower in public tertiary hospitals, whereas histopathology, computerised tomography (CT scan), and magnetic resonance imaging (MRI) were lower in public secondary hospitals than private and NGO managed hospitals for the corresponding level of care. Most tertiary hospitals had the required supportive care facilities except for play therapy and hospice care. Less than 50% of the public tertiary hospitals had stocks of the four categories of cancer-treating drugs and essential infrastructure for radiotherapy and chemotherapy. Most secondary-level hospitals not treating childhood cancer had referral linkages with tertiary hospitals. Interpretation: The situational analysis of childhood cancer care services in India showed the concentration of availability of childhood cancer care services at the tertiary level of health care. There were gaps in the availability of specialised pediatric oncology care in all the tertiary hospitals. The availability of childhood cancer care services was higher in private and NGO-managed hospitals than in public hospitals. Integration of childhood cancer as a part of the national cancer control response should be taken up as a matter of priority. The need of the hour is to formulate a childhood cancer policy that will enable timely access to care universally. Funding: World Health Organization, India provided funding and technical support.

Assessment of Registry-Based Surveillance Statistics Used for Cancer Control in the Dindigul District in South India.

Background: Cancer incidence rates from the Dindigul district were lower by 50% than Chennai in Tamil Nadu for most cancers. This study describes the cancer surveillance statistics and provides an assessment of missing cases from routine registration in the Dindigul Ambilikkai Cancer Registry (DACR), covering a predominantly rural population in the Dindigul district. Method: A total of 21,214 incident cancers in the DACR during 2003-2017 were examined for this study. Cancer registration was carried out by active case-finding following standard international norms. A total of 12,541 incident cancers registered during 2003-2012 and followed through 2014 were used to estimate survival. Data on follow-up were obtained through a mixture of active and passive methods. Survival probability was estimated by actuarial methods. A random survey carried out independently was used to assess the quality of case ascertainment. Results: The age-standardized rate (ASR) per 100,000 population was higher among women (76.2) than men (61) in 2013-2017, with both sexes reporting a 17% increase compared to 2003-2007. The most common cancers were cervix (ASR,18.5) and female breast (ASR,17.1), with percentage changes of -19% and +46.1%, respectively. Lung cancer (ASR, 5.5) was top among men with an increasing trend (+57.1%). The percent change in ASR of mouth cancer showed opposite trends among men (+24.3%) and women (- 21.4%). The ASR of colorectal cancers almost doubled among men between 2003-2007 and 2013-2017 (3.9; +94.7%). The 5- and 10-year absolute survival for all cancers were 31% and 20%, respectively. Out of 365 incident cancers that occurred during 2003-2010 in the surveyed areas, 310 (84.9%) were already registered in the DACR, while 55 were newly identified from the survey (15.1%). Inadequate coverage of sources outside the Dindigul district was significant (P = .002), with the highest number of missed cases from hospitals under nongovernment sectors (58.3%). Underascertainment was higher among cancer patients living in hilly regions (60%) and border areas (47.4%) than in core regions (P = .05). Conclusion: Because of an enacted government order making cancer a notifiable disease, the registry-based cancer surveillance could be extended, covering a population of 80 million in a cost-effective manner with enhanced coverage and systematic evaluation of cancer-screening programs.

Dynamics of oral human papillomavirus infection in healthy population and head and neck cancer.

The recent increase in high-risk human papillomavirus (HR-HPV)-associated oral and oropharyngeal cancers has gained considerable importance due to their distinct clinical and molecular characteristics. However, the natural history of oral HPV from acquisition to persistence and malignant transformation is still unclear. The global prevalence of oral HPV infection in healthy individuals ranges from 0.67% to 35%, while 31%-38.5% in head and neck cancer (HNC). The persistence rate of oral HR-HPV infection is 5.5% -12.8% globally. India has the highest HNC burden due to apparent differences in predisposing factors compared with the West. The prevalence of oral HPV in healthy individuals and its contribution to HNC is less evident in Indian studies. HR-HPV-associated HNC in this region accounts for 26%, with an active infection in 8%-15% of these tumors. There is a lack of concordance in the expression of p16 as a surrogate marker for HPV detection in HNC because of differences in behavioral risk factors. Due to a lack of evidence, treatment de-escalation cannot be implemented despite the improved outcome of HPV-associated oropharyngeal cancers. This review critically analyzes the existing literature on the dynamics of oral HPV infection and HPV-associated HNC, identifying potential avenues for future research. A better understanding of the oncogenic role of HR-HPV in HNC will help to formulate novel therapeutic approaches and is expected to have a significant public health impact as preventive strategies can be implemented.

A systematic review on efficacy, safety and cost-effectiveness of office-based laryngeal biopsy.

OBJECTIVE: Laryngeal cancer is the second most prevalent head and neck malignancy in the USA. With recent advances in technology, this procedure is increasingly performed under local anaesthesia. This study aimed to identify the efficacy, safety and cost-effectiveness of laryngeal biopsy in out-patients by conducting a systematic review. METHOD: A literature search was conducted using PubMed, Medline, Google Scholar and Embase over a 20-year period. Inclusion criteria were: studies performed on out-patient diagnostic biopsy procedures of the larynx. Exclusion criteria included all therapeutic procedures. The outcome measures were sensitivity and specificity, complication rate and cost-savings. RESULTS: Thirty-five studies were included in the analysis. The sensitivity and specificity varied from 60 to 100 per cent with a low complication rate and cost savings. CONCLUSION: Office-based laryngeal biopsies are increasingly used in the diagnosis of laryngeal cancers, resulting in earlier diagnosis and commencement of treatment. The barrier to undertaking this procedure is low sensitivity.

Cold atmospheric plasma driven self-assembly in serum proteins: insights into the protein aggregation to biomaterials.

The self-assembly of proteins is crucial in many biomedical applications. This work deals with understanding the role of cold atmospheric plasma (CAP) on the self-assembly of two different proteins present in the serum - BSA and hemoglobin and to elucidate the process associated with the direct application of physical plasma on or in the human (or animal) body, which has implications in therapeutics. The work has been corroborated by several spectroscopic studies such as fluorescence spectroscopy, circular dichroism spectroscopy, and SEM analysis. Through steady-state fluorescence spectroscopy and by following the tryptophan fluorescence, we observed that the emission intensity was quenched for the protein when treated with plasma radiation. Circular dichroism spectroscopy revealed that the structure of the protein was altered both in the case of BSA and hemoglobin. N-Acetyl tryptophanamide (NATA), which resembles the tryptophan in the protein, was treated with CAP and we observed the similar quenching of fluorescence as in the proteins, indicating that the protein underwent self-assembly. Time-resolved fluorescence spectroscopy with a decrease in the lifetime revealed that the protein self-assembly was promoted with CAP treatment, which was also substantiated by SEM micrographs. The ROS/RNS produced in the CAP has been correlated with the protein self-assembly. This work will help to design protein self-assembled systems, and in the future, may bring possibilities of creating novel biomaterials with the help of plasma radiation.

Retrospective analysis of the risk of neoplasia associated with unilateral maxillary sinus opacification on computed tomography.

BACKGROUND: Unilateral maxillary sinus opacification on computed tomography may reflect an inflammatory or neoplastic process. The neoplasia risk is not clear in the literature. METHODS: In this retrospective study, computed tomography sinus scans performed over 12 months were screened for unilateral maxillary sinus opacification, and the rates of inflammatory and neoplastic diagnoses were calculated. RESULTS: Of 641 computed tomography sinus scans, the rate of unilateral maxillary sinus opacification was 9 per cent. Fifty-two cases were analysed. The risk of neoplasia was 2 per cent (inverted papilloma, n = 1). No cases of unilateral maxillary sinus opacification represented malignancy, but one case of lymphoma had an incidental finding of unilateral maxillary sinus opacification on the contralateral side. Patients with an antrochoanal polyp (n = 3), fungal disease (n = 1), inverted papilloma and lymphoma all had a unilateral nasal mass. CONCLUSION: Our neoplasia rate of 2 per cent was lower than previously reported. A unilateral mass was predictive of pathology that required operative management. Clinical findings, rather than simple findings of opacification on computed tomography, should drive the decision to perform biopsy.

Assessment of Mental Workload by Visual Motor Activity among Control Group and Patient Suffering from Depressive Disorder.

Major depressive disorder (MDD) is a mood state that is not usually associated with vision problems. Recent research has found that the inhibitory neurotransmitter GABA levels in the occipital brain have dropped. Aim. The aim of the research is to evaluate mental workload by single channel electroencephalogram (EEG) approach through visual-motor activity and comparison of parameter among depressive disorder patient and in control group. Method. Two tests of a visual-motor task similar to reflect drawings were performed in this study to compare the visual information processing of patients with depression to that of a placebo group. The current study looks into the accuracy of monitoring cognitive burden with single-channel portable EEG equipment. Results. The alteration of frontal brain movement in reaction to fluctuations in cognitive burden stages generated through various vasomotor function was examined. By applying a computerised oculomotor activity analogous to reflector image diagram, we found that the complexity of the path to be drawn was more important than the real time required accomplishing the job in determining perceived difficulty in depressive disorder patients. The overall perceived difficulty of the exercise is positively linked with EEG activity measured from the motor cortex region at the start of every experiment test. The average rating for task completion for depression patients and in control group observed and no statistical significance association reported between rating scale and time spent on each trial (p=1.43) for control group while the normalised perceived difficulty rating had 0.512, 0.623, and 0.821 correlations with the length of the pathway, the integer of inclination in the pathway, and the time spent to complete every experiment test, respectively (p < 0.0001) among depression patients. The findings imply that alterations in comparative cognitive burden levels during an oculomotor activity considerably modify frontal EEG spectrum. Conclusion. Patients with depression perceived the optical illusion in the arrays as weaker, resulting in a little bigger disparity than individuals who were not diagnosed with depression. This discovery provided light on the prospect of adopting a user-friendly mobile EEG technology to assess mental workload in everyday life.

Magnetic resonance imaging of the internal auditory meatus for vestibular schwannoma in ENT practice: a retrospective analysis with literature and guidelines review.

OBJECTIVES: Magnetic resonance imaging scans of the internal acoustic meatus are commonly requested in the investigation of audio-vestibular symptoms for potential vestibular schwannoma. There have been multiple studies into protocols for requesting magnetic resonance imaging for vestibular schwannoma, but none have been reported based on UK National Institute for Health and Care Excellence guidelines for investigating audio-vestibular symptoms. This study intended to identify the local magnetic resonance imaging detection rates and patterns of vestibular schwannoma, and to audit the conformity of scan requests with the National Institute for Health and Care Excellence guidelines, with a review of relevant literature. METHOD: A retrospective analysis of 1300 magnetic resonance imaging scans of the internal acoustic meatus, compared against National Institute for Health and Care Excellence guidelines, was conducted over two years. RESULTS AND CONCLUSION: Sixteen scans were positive for vestibular schwannoma, with a detection rate of 1.23 per cent. All positive cases fit the guidelines; three of these could have been missed using other criteria. A total of 281 requests did not meet the guideline criteria but revealed no positive results, supporting the use of National Institute for Health and Care Excellence guidelines in planning magnetic resonance imaging scans for audio-vestibular symptoms.

Trends in breast and cervical cancer in India under National Cancer Registry Programme: An Age-Period-Cohort analysis.

BACKGROUND: Trend analysis in cancer quantifies the incidence rate and explains the trend and pattern. Breast and cervical cancers are the two most common cancers among Indian women which contributed 39.4 % to the total cancer in India for the year 2020. This study aimed to report the time trends in cancer incidence of breast and cervical cancer using Age-Period-Cohort (APC) model from five Population Based Cancer Registries (PBCRs) in India for the period of 1985-2014. METHOD: Age-Period-Cohort model was fitted to five PBCRs of Bangalore, Chennai, Delhi, Bhopal and Barshi rural for breast and cervical cancer for 25-74 age-groups. The Estimated Annual Percent Change (EAPC) was calculated. Rate Ratio (RR) of cohort effects were estimated with a constraint of period slope to be zero (p = 0) since cohort has a stronger association with incidence than period. RESULT: A significant increase was noted in breast cancer in all PBCRs (EAPC, Range: Delhi, 1.2 % to Bangalore, 2.7 %) while significant decrease in cervical cancer (EAPC, Range: Bangalore -2.5 % to Chennai, -4.6 %) from all the PBCRs including Barshi rural during the period. RR estimates for breast cancer showed increasing trend whereas cervical cancer showed decreasing trend in successive birth cohorts across all five PBCRs. CONCLUSION: In both breast and cervical cancers, a significant age, cohort and period effect was noted in Bangalore, Chennai and Delhi. Despite period effect, the cohort effect was predominant and it may be attributed to the generational changes in risk factors among cancer breast and cervix.

Karanjin.

Karanjin [IUPAC: 3-methoxy-2-phenylfuro-(2,3-h-chrome-4-ol)], a bioactive furanoflavonoid and a potent biomolecule, was first isolated from Pongamia pinnata (L.). The crude extracts from root, leaf and seed having active constituent karanjin is highly valued in both traditional and modern knowledge systems. This review highlights, critically assesses, and presents the probable biosynthetic pathways of karanjin and its isolation methodologies with a view to actualizing its full potential. Karanjin exhibits multiple health benefits and applications, with evident anti-diabetic, anti-cancer, anti-inflammatory, anti-hyperglycemic, antioxidant, anti-colitis, anti-ulcer, and anti-Alzheimer properties. Consequently, the physiochemical properties and biological effects of karanjin have been detailed and analyzed. The efficacy of karanjin has been attenuated by toxicological studies that have proven karanjin to be non-toxic at physiological conditions as substantiated by in vitro and in vivo studies. In addition, the multiple insect repellent/insecticidal properties of karanjin and its availability as an acaricide/bio-insecticide have been reviewed. This review article underscores and endorses the immense potential for novel drug leads in various medicinal and industrial applications, suggesting a deeper insight into its metabolic fate, bioavailability, and cellular effects that await further investigations.

Evaluation of Cytogenetic Abnormalities in Patients with Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) accounts for 20% of all adult leukemias and is the most common leukemia during childhood (80%). We present data on cytogenetics of ALL from a tertiary centre in India correlating it with clinical factors. Karyotyping of bone marrow samples of 204 patients with newly diagnosed ALL was performed with standard G-banding technique. Clinical data of patients was obtained from case records. Survival was estimated using Kaplan-Meir curves and compared by the log-rank test. Univariate and multivariate analysis was done for survival with age, sex, immunophenotype, hyperleukocytosis, risk type, remission status and cytogenetics. The most common karyotypes observed were normal in 39.7% (N = 81), hyperdiploidy in 12.7% (N = 26), t(9;22) in 4.4% (N = 9), t(1;19) in 3.9% (N = 8). Adults with ALL had worse survival compared with pediatric patients (HR 3.62; 2.03-6.45 95% CI, p < 0.001). Patients not in morphologic remission after induction chemotherapy fared poorly (HR 4.86; 2.67-8.84 95% CI, p < 0.001). Patients with favourable cytogenetics had better overall survival (HR 0.36; 0.12-1.05 95% CI, p < 0.05). On multivariate analysis, achievement of morphologic remission emerged as single most significant predictor of survival (p < 0.001). MLL gene rearrangement and t(12;21) were seen less commonly as compared to Western data. However, incidence rates of various cytogenetic abnormalities were similar to that reported from other centres from India. Age, morphologic remission at end of induction chemotherapy and favourable cytogenetics correlated significantly with survival.

Short-term Changes in Urine Beta 2 Microglobulin Following Recovery of Acute Kidney Injury Resulting From Snake Envenomation.

INTRODUCTION: Urine ß2 microglobulin (ß2m) is a validated marker to diagnose sepsis and toxin-related acute kidney injury (AKI). In the current study, we used urine ß2m as a potential marker to identify persistent tubular dysfunction following a clinical recovery from snake venom-related AKI. METHODS: A total of 42 patients who developed AKI following hemotoxic envenomation were followed up for a period of 6 months. Urine albumin excretion, estimated glomerular filtration rate (eGFR), and urine ß2m levels were measured at 2 weeks, 3 months, and 6 months following discharge. RESULTS: At the end of 6 months of follow-up, 6 patients (14.3 %) progressed to chronic kidney disease (CKD) (eGFR < 60 ml and/or urine albumin excretion > 30 mg/d). The urine ß2m levels were 1590 µg/l (interquartile range [IQR] 425-5260), 610 µg/l (IQR 210-1850), 850 µg/l (IQR 270-2780) at 2 weeks, 3 months, and 6 months, respectively (P = 0.020). The levels of urine ß2m in the study population at the end of 6 months remained significantly higher compared with the levels in healthy control population (850 µg/l [IQR 270-2780] vs. 210 µg/l [IQR 150-480]; P = 0.001). The proportion of patients with urine ß2m levels exceeding the 95th percentile of control population (>644 µg/l) during the 3 follow-up visits were 70.7% (n = 29), 48.8 % (n = 20), and 51.2% (n = 21). Similar trends were noticed in a sensitivity analysis, after excluding patients with CKD. CONCLUSIONS: Urine ß2m levels remain persistently elevated in approximately half of the individuals who recover from AKI due to snake envenomation.

Mismatch of long Gamma intramedullary nail with bow of the femur: Does radius of curvature of the nail increase risk of distal femoral complications?

INTRODUCTION: Anterior cortical penetration of the distal nail tip is a recognized complication of intra-medullary nailing of the femur particularly in the geriatric population. This has been attributed to a mismatch between the femoral bow and the radius of curvature (ROC) of the femoral nail. We wanted to see if there was a reduction of this risk comparing cephalomedullary nails with ROC of 200 cm and 150 cm. METHODS: 52 patients were split into 2 groups similar with respect to age, sex and comorbidities. Group A with 25 patients used a nail with a ROC of 200 cm and Group B with 27 patients used a 150 cm ROC nail. Lateral radiographs of the distal femur were evaluated to note the position of the nail tip in relation to the femoral canal. The diameter of the femur at the tip of the nail was divided into 3 equal zones. The anterior one-third was designated as Zone1, the middle one-third as Zone 2 and the posterior one-third as Zone 3. RESULTS: 80% of the cases with a 200 cm ROC nail had the tip of the nail in the anterior one-third of the canal (zone 1). Fracture of the anterior femoral cortex distally by the nail tip was seen in 2 patients.Only 18.5% of cases with a 150 cm ROC nail had the tip of the nail in anterior one-third of the canal (zone 1). There were no incidences of complications such as fractures and anterior cortical perforation. CONCLUSIONS: A cephalomedullary nail with a ROC of 150 cm had its distal tip more towards the center of the femoral canal when compared to a nail with ROC of 200 cm. No case of anterior femoral penetration was seen when using a nail with an ROC of 150 cm.

Rare case of atypical femoral fracture with blocked medullary canal associated with bisphosphonate therapy.

Bisphosphonates are widely used for treatment of osteoporosis and its use is increasing in geriatric population. Atypical femoral fractures are associated with bisphosphonate therapy. We report an unusual case of femoral shaft fracture following bisphosphonate therapy where the femoral canal of the proximal and distal fracture fragments was blocked and its management.

Vitamin D deficiency in patients with tuberculous meningitis and its relationship with treatment outcome.

SETTING: Data on vitamin D deficiency in tuberculous meningitis (TBM) and its relationship with treatment outcomes are limited. Some of the beneficial effects of vitamin D might be mediated through interleukin-1ß (IL-1ß). OBJECTIVE: To assess the frequency of vitamin D deficiency among TBM patients, its association with treatment outcomes and correlation between vitamin D and IL-1ß levels in cerebrospinal fluid (CSF). DESIGN: We prospectively studied a consecutive sample of human immunodeficiency virus-negative patients with TBM treated at a hospital in southern India. We defined good outcome as survival without severe neurological disability. Serum total 25-hydroxy vitamin D (25[OH]D) and IL-1ß levels in CSF were estimated on pretreatment samples. RESULTS: We studied 40 patients with TBM; 22 (55%) patients had stage 3 disease. Treatment outcome was poor in 21 (53%) patients: 15 (38%) patients died and 6 (15%) had severe neurological disability. The overall mean serum 25(OH)D level was 32.30 ± 16.38 ng/ml. Ten (25%) patients had vitamin D deficiency (<20 ng/ml), and 12 (30%) patients had vitamin D insufficiency (20-30 ng/ml). However, pretreatment serum 25(OH)D levels did not differ significantly by outcome (good vs. poor outcome: 28.30 ± 14.96 vs. 35.92 ± 17.11 ng/ml, P = 0.141). Moreover, IL-1ß levels in CSF did not correlate with serum 25(OH)D levels (Spearman's ρ 0.083, P = 0.609). CONCLUSION: Vitamin D deficiency/insufficiency is common among patients with TBM. However, serum 25(OH)D levels are not associated with IL-1ß levels in CSF or treatment outcome.

MeCP2-regulated miRNAs control early human neurogenesis through differential effects on ERK and AKT signaling.

Rett syndrome (RTT) is an X-linked, neurodevelopmental disorder caused primarily by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes a multifunctional epigenetic regulator with known links to a wide spectrum of neuropsychiatric disorders. Although postnatal functions of MeCP2 have been thoroughly investigated, its role in prenatal brain development remains poorly understood. Given the well-established importance of microRNAs (miRNAs) in neurogenesis, we employed isogenic human RTT patient-derived induced pluripotent stem cell (iPSC) and MeCP2 short hairpin RNA knockdown approaches to identify novel MeCP2-regulated miRNAs enriched during early human neuronal development. Focusing on the most dysregulated miRNAs, we found miR-199 and miR-214 to be increased during early brain development and to differentially regulate extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase and protein kinase B (PKB/AKT) signaling. In parallel, we characterized the effects on human neurogenesis and neuronal differentiation brought about by MeCP2 deficiency using both monolayer and three-dimensional (cerebral organoid) patient-derived and MeCP2-deficient neuronal culture models. Inhibiting miR-199 or miR-214 expression in iPSC-derived neural progenitors deficient in MeCP2 restored AKT and ERK activation, respectively, and ameliorated the observed alterations in neuronal differentiation. Moreover, overexpression of miR-199 or miR-214 in the wild-type mouse embryonic brains was sufficient to disturb neurogenesis and neuronal migration in a similar manner to Mecp2 knockdown. Taken together, our data support a novel miRNA-mediated pathway downstream of MeCP2 that influences neurogenesis via interactions with central molecular hubs linked to autism spectrum disorders.