Immunological factors associated with discordant virological response postcombination antiretroviral therapy in pediatric human immunodeficiency virus infection.

OBJECTIVES: Evaluation of immunological factors responsible for discordant virological responses postcombination antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-positive children aged <5 years. MATERIALS AND METHODS: Immunological profiling of enrolled 30 HIV-positive children was done at enrollment, 6 and 12 months. Flow cytometric analysis was performed for enumeration of counts and percentage of CD4+, CD8+, and CD19+ cells; expression of CD19, CD86, PD-1, CD3, CD8 and CD28 on lymphocytes was evaluated using whole blood staining technique with monoclonal antibodies. HIV-1 viral load was quantified using a real-time polymerase chain reaction. Serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin (IgM), and interleukin (IL)-7 were quantitated using quantitative enzyme-linked immunosorbent assay kits. The HIV-infected children were categorized into virological responders (VRs; HIV-1 plasma viral load <47 copies/mL) and virological nonresponders (VNRs; HIV-1 plasma viral load >1000 copies/mL) following 1-year cART. RESULTS: The frequency of CD28+ CTLs cells was higher (P < 0.0001), and the frequency of CD28-CTLs cells was lower (P < 0.0001) in VRs than VNRs. CD28+ and CD28-CTLs cells correlated with HIV-1 plasma viremia (r = -0.4695, P = 0.01; r = 0.40, P = 0.03, respectively). VRs had higher CD19 percentage (P = 0.04) and count (P = 0.01) than VNRs. CD19+ B cells in the VRs had lower expression of CD86 (P = 0.03) and PD-1 (P = 0.002) than VNRs. VR had lower levels of serum IgG (P = 0.03), IgM (P = 0.04), and IL-7 (P = 0.01) than VNRs. CONCLUSIONS: High baseline B-cell counts, lower serum IgG, IgM, IL-7 levels, lower activation and exhaustion of B cells, and higher frequency of CD28+ CTLs are associated with positive virological response, whereas elevated CD28-CTLs are associated with the poor virological outcomes in HIV-infected children.

Development of a Sustainable and Biodegradable Sonchus asper Cotton Pappus Based Piezoelectric Nanogenerator for Instrument Vibration and Human Body Motion Sensing with Mechanical Energy Harvesting Applications.

Energy harvesting from natural resources has gained much attention due to the huge increase in the demand for portable electronic devices and the shortage of conventional energy resources in general. In the present work, the fabrication and realistic applications of a piezoelectric nanogenerator (PENG) using polydimethylsiloxane (PDMS) and the abundantly available, environment-friendly natural fiber Sonchus asper (SA) have been discussed. The biocompatible, low-cost SA fibers were flexible enough and showed high piezoelectric properties as active materials in the study. The SA pappus based piezoelectric nanogenerator demonstrated its ability to convert the harvested biomechanical energy into electrical energy from the various mechanical energy sources available in our environment. The SA pappus/PDMS thin film based piezoelectric nanogenerator (SPENG) fabricated in the laboratory showed colossal output performances (open circuit output voltage, V OC ∼81.2 V; short circuit current, I SC ∼1.0 µA) by continuous finger impartation. Uniform output performance was also obtained by the application of uniform force on the devices (e.g., ∼42 V for 5 N force at 10 Hz frequency). The SPENG was capable to charge a 2.2 µF capacitor to 3.2 V within a short time span (16 s) under continuous finger impartation and illuminate 39 commercial high-power blue LEDs that were connected in series. Thus, the fabricated SPENG can be used as a green and portable energy source to power up portable electronic devices. Apart from this, the SPENG may also be used as a self-powered energy supply for pacemakers or different types of health care units if properly improvised.

Snoring Remediation with Oral Appliance Therapy Potentially Reverses Cognitive Impairment: An Intervention Controlled Pilot Study.

Respiration rate (RR) dynamics entrains brain neural networks. RR differences between mild cognitive impairment (MCI) and Alzheimer's disease (AD) in response to oral appliance therapy (OAT) are unknown. This pilot study investigated if RR during stable sleep shows a relationship to pathological severity in subjects with MCI and AD who snore and if RR is influenced following stabilization of the upper airway using OAT. The study cohort was as follows: cognitively normal (CN; n = 14), MCI (n = 14) and AD (n = 9); and a sub-population receiving intervention, CN (n = 5), MCI (n = 7), AD (n = 6) subjects. The intervention used was an oral appliance plus a mouth shield (Tx). RR maximum (max) rate (breaths/minute) and RR fluctuation during 2116 stable sleep periods were measured. The Montreal cognitive assessment (MoCA) was administered before and after 4 weeks with Tx. Baseline data showed significantly higher RR fluctuation in CN vs. AD (p < 0.001) but not between CN vs. MCI (p = 0.668). Linear mixed model analysis indicated Tx effect (p = 0.008) for RR max. Tx after 4 weeks lowered the RR-max in MCI (p = 0.022) and AD (p < 0.001). Compared with AD RR max, CN (p < 0.001) and MCI (p < 0.001) were higher with Tx after 4 weeks. Some MCI and AD subjects improved executive and memory function after 4 weeks of Tx.

Recurrent angiosarcoma of scalp with opsoclonus myoclonus syndrome: role of salvage treatment.

Cutaneous angiosarcoma is a type of rare and locally aggressive malignancy requiring individualised treatment owing to paucity of randomised trials. We present the case of a middle-aged cancer survivor with locally advanced angiosarcoma of scalp managed with surgery, radiotherapy, chemotherapy and targeted therapy over a course of 6 years for two recurrences. The first recurrence was preceded by opsoclonus myoclonus syndrome, a type of paraneoplastic neurological syndrome (PNS), rarely reported in sarcomas. The second recurrence had a rapid clinical course, which led to a therapeutic dilemma of best supportive care versus active management. A trial of weekly paclitaxel was started that was continued for a total of 12 cycles with good objective clinical response. Presently, he is tolerating maintenance pazopanib well and is symptom free for 6 months. In cutaneous angiosarcoma patients, PNS may be a harbinger of recurrence and aggressive, multimodality treatment helps prolong survival.

Phosphate Brain Energy Metabolism and Cognition in Alzheimer's Disease: A Spectroscopy Study Using Whole-Brain Volume-Coil 31Phosphorus Magnetic Resonance Spectroscopy at 7Tesla.

INTRODUCTION: Mitochondrial dysfunction is a neurometabolic hallmark signaling abnormal brain energy metabolism (BEM) targeted as a potential early marker of Alzheimer's disease (AD). Advanced imaging technologies, such as 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7T, provide sensitive phosphate-BEM (p-BEM) data with precision. The study's first goal was to develop a methodology to measure phosphate energy and membrane metabolites simultaneously across the whole-brain using volume-coil 31P MRS at 7T in three groups-cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and AD. The second aim investigated whether p-BEM markers in the four brain regions-frontal, temporal, parietal, and occipital were significantly different across the three groups. The final goal examined correspondence between the p-BEM markers and cognition in the three groups. METHODS: Forty-one participants (CN = 15, aMCI = 15, AD = 11) were enrolled and completed cognitive assessment and scan. The cognitive domains included executive function (EF), memory, attention, visuospatial skills, and language. The p-BEM markers were measured using energy reserve index (PCr/t-ATP), energy consumption index (intracellular_Pi/t-ATP), metabolic state indicator (intracellular_Pi/PCr), and regulatory co-factors [magnesium (Mg2+) and intracellular pH]. RESULTS: Thirteen metabolites were measured simultaneously from the whole brain for all three group with high spectral resolution at UHF. In the aMCI group, a lower p-BEM was observed compared to CN group based on two markers, i.e., energy reserve (p = 0.009) and energy consumption (p = 0.05) indices; whereas in AD a significant increase was found in metabolic stress indicator (p = 0.007) and lower Mg2+ (p = 0.004) in the temporal lobes compared to aMCI using ANOVA between group analytical approach. Finally, using a linear mixed model, a significant positive correlation was found between Mg2+ and cognitive performance of memory (p = 0.013), EF (p = 0.023), and attention (p = 0.0003) in CN but not in aMCI or AD. CONCLUSION: To our knowledge, this is the first study to show that it is possible to measure p-BEM in vivo with precision at UHF across the three groups. Moreover, the findings suggest that p-BEM may be compromised in aMCI even before an AD diagnosis, which in future studies should explore to examine whether this energy crisis contributes to some of the earliest neuropathophysiologic changes in AD.

Multimodality treatment for Central Nervous System Germ Cell Tumors: Disease spectrum and management strategies - A tertiary care center experience from India.

OBJECTIVE: Intracranial germ cell tumors (GCTs) are relatively rare neoplasms, representing 2-3 % of paediatric brain tumors in Western countries and 8-15 % in East Asia. Here, we discuss the clinical features and treatment outcomes in patients with central nervous system (CNS) GCTs treated at our institute. METHODS: Medical records of all primary CNS GCT patients were retrieved retrospectively from 2007 to 2019. Demographic, clinical, treatment and follow up details were entered in a predesigned proforma. Overall survival (OS) and progression-free survival was computed using Kaplan-Meier method and Log-Rank test. Effect of various prognostic factors on survival outcomes was assessed by univariate and multivariate analysis. RESULTS: A total of 28 CNS GCT patients were included in this analysis. Median age at presentation was 17 years (range, 7-45 years) with a male to female ratio of 1.8:1. Pineal region was the commonest location, encountered in 15 patients (53.6 %). Pure germinoma was the most frequent histology observed, seen in 19 patients (67.9 %). Male gender and germinoma histology were highly associated with pineal location (p = 0.043 and p = 0.052, respectively). Fourteen patients underwent surgical intervention and nine patients underwent biopsy for diagnostic purpose or to relieve the obstructive symptoms. Only 23 patients (82.1 %) received chemotherapy. However, all patients received radiotherapy (Craniospinal irradiation/whole brain radiotherapy/whole ventricular radiotherapy/ or local radiotherapy). After a median follow-up of 53 months (range, 7-150), 23 patients (82.1 %) were alive. OS was significantly affected by histology (89 % in germinoma vs. 60 % in non-germinomatous, p = 0.054) and location (93 % in pineal region vs. 64.2 % in other location, p = 0.042). Age, gender and surgery did not have any impact on the survival outcomes. CONCLUSION: CNS GCTs are relatively rare and heterogeneous neoplasms commonly seen in pineal and suprasellar locations. A combination of chemotherapy and radiotherapy had shown excellent outcomes.

Relationship of Parieto-Occipital Brain Energy Phosphate Metabolism and Cognition Using 31P MRS at 7-Tesla in Amnestic Mild Cognitive Impairment.

BACKGROUND: The human brain has high energy requirements that continuously support healthy neuronal activity and cognition. A disruption in brain energy metabolism (BEM) may contribute to early neuropathological changes such as accumulation of ß-amyloid and tau in vulnerable populations. One such population is amnestic mild cognitive impairment (aMCI) where some individuals are at risk for developing dementia, i.e. Alzheimer's disease (AD). Recent advances in imaging technology are providing new avenues to measure BEM accurately using 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7-Tesla. This study investigates whether a methodology using partial volume-coil 31P MRS at 7T over parieto-occipital lobes can accurately quantify high-energy phosphate and membrane phospholipid metabolites in aMCI. A secondary objective was to explore BEM and membrane phospholipid indices' correspondence with cognitive performance in domains of executive function (EF), memory, attention, and visuospatial skills in aMCI, a heterogeneous population. METHODS: 19 aMCI participants enrolled in the study completed cognitive assessment and 31P MRS scan. BEM indices were measured using three energy indicators: energy reserve (PCr/t-ATP), energy consumption (intracellular_Pi/t-ATP), and metabolic state (PCr/intracellular_Pi) along with regulatory co-factors of BEM-intracellular Mg2 + and pH; whereas the ratio of phosphomonoesters (PMEs) to phosphodiesters (PDEs) - membrane phospholipid indicator. RESULTS: 31P MRS scan showed thirteen well-resolved peaks with precise quantification of the phosphorus metabolites at UHF. The higher BEM indices were associated with lower cognitive performance of memory [(energy reserve indicator: CVLT p = 0.004), (metabolic state indicator: CVLT p = 0.007)], executive function [(metabolic state indicator: TOSL (p = 0.044)], and attention [(pH: selective auditory task, p = 0.044)]. The finding of an inverse relationship observed in the parieto-occipital lobes suggests an association between neuronal energy markers with cognition in aMCI. CONCLUSION: The significant contribution of this preliminary research was to establish the feasibility of utilizing a methodology at UHF to accurately measure high-energy phosphate and membrane phospholipid metabolites in a population with heterogeneous outcomes. This work offers a novel approach for future work to further elucidate early dementia biomarkers or precursors to the downstream accumulation of amyloid and tau using the combination of MRS-PET imaging modalities in AD.

Challenges of radical chemoradiation planning in Stage III non-small-cell lung cancer: Can volumetric modulated arc radiotherapy overcome an unfavourable location?

BACKGROUND AND PURPOSE: Radiotherapy treatment planning of radical doses for concurrent chemoradiation in Stage III non-small-cell lung cancer (NSCLC) presents many challenges. This dosimetric study aimed to analyse the impact of spatial location of tumour and nodal burden in limiting the achievement of normal organ constraints and the use of appropriate radiotherapy technique to address it. MATERIALS AND METHODS: Fifteen Stage III NSCLC patients underwent 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) based treatment planning. VMAT (Volumetric Modulated Arc Radiotherapy) plans were made for all patients treated by 3D-CRT (3-Dimensional Conformal Radiotherapy). A binomial logistic regression was performed to ascertain the tumour and nodal characteristics that decreased the likelihood of being planned to 60 Gy. RESULTS: Inability to achieve normal tissue constraints, particularly spinal cord dose to less than 50 Gy, during initial planning by the assigned treatment technique was the primary dose limiting factor in four patients (p = 0.02). Alternate VMAT plans could achieve the dose constraints where 3D-CRT was unsuccessful in patients with bulky central disease in two patients. This technique fell short when there was gross vertebral body erosion. CONCLUSIONS: For tumours with bulky central disease, VMAT should be preferred. With gross vertebral body erosion, even VMAT falls short if the planning target volume includes the spinal cord. In a subset of Stage III NSCLC upfront chemoradiation to radical doses may not be feasible.

Cognitive Training and Transcranial Direct Current Stimulation in Mild Cognitive Impairment: A Randomized Pilot Trial.

BACKGROUND: Transcranial direct current stimulation (tDCS), a non-invasive stimulation, represents a potential intervention to enhance cognition across clinical populations including Alzheimer's disease and mild cognitive impairment (MCI). This randomized clinical trial in MCI investigated the effects of anodal tDCS (a-tDCS) delivered to left inferior frontal gyrus (IFG) combined with gist-reasoning training (SMART) versus sham tDCS (s-tDCS) plus SMART on measures of cognitive and neural changes in resting cerebral blood flow (rCBF). We were also interested in SMART effects on cognitive performance regardless of the tDCS group. METHODS: Twenty-two MCI participants, who completed the baseline cognitive assessment (T1), were randomized into one of two groups: a-tDCS + SMART and s-tDCS + SMART. Of which, 20 participants completed resting pCASL MRI scan to measure rCBF. Eight SMART sessions were administered over 4 weeks with a-tDCS or s-tDCS stimulation for 20 min before each session. Participants were assessed immediately (T2) and 3-months after training (T3). RESULTS: Significant group × time interactions showed cognitive gains at T2 in executive function (EF) measure of inhibition [DKEFS- Color word (p = 0.047)], innovation [TOSL (p = 0.01)] and on episodic memory [TOSL (p = 0.048)] in s-tDCS + SMART but not in a-tDCS + SMART group. Nonetheless, the gains did not persist for 3 months (T3) after the training. A voxel-based analysis showed significant increase in regional rCBF in the right middle frontal cortex (MFC) (cluster-wise p = 0.05, k = 1,168 mm3) in a-tDCS + SMART compared to s-tDCS + SMART. No significant relationship was observed between the increased CBF with cognition. Irrespective of group, the combined MCI showed gains at T2 in EF of conceptual reasoning [DKEFS card sort (p = 0.033)] and category fluency [COWAT (p = 0.055)], along with gains at T3 in EF of verbal fluency [COWAT (p = 0.009)]. CONCLUSION: One intriguing finding is a-tDCS to left IFG plus SMART increased blood flow to right MFC, however, the stimulation seemingly blocked cognitive benefits of SMART on EF (inhibition and innovation) and episodic memory compared to s-tDCS + SMART group. Although the sample size is small, this paper contributes to growing evidence that cognitive training provides a way to significantly enhance cognitive performance in adults showing memory loss, where the role of a-tDCS in augmenting these effects need further study.

Effect of Tulsi (Ocimum sanctum Linn.) Supplementation on Metabolic Parameters and Liver Enzymes in Young Overweight and Obese Subjects.

Ocimum sanctum Linn. (also known as Tulsi) is a sacred Indian plant, the beneficial role of which, in obesity and diabetes is described traditionally. This is a randomized, parallel group, open label pilot study to investigate the effect of O. sanctum on metabolic and biochemical parameters in thirty overweight/obese subjects, divided into two groups A and B. Group A (n = 16) received one 250 mg capsule of Tulsi (O. sanctum) extract twice daily in empty stomach for 8 weeks and group B (n = 14) received no intervention. Statistically significant improvements in the values of serum triglycerides (p = 0.019); low density lipoprotein (p = 0.001); high density lipoprotein (p = 0.001); very low density lipoprotein (p = 0.019); Body Mass Index, BMI (p = 0.005); plasma insulin (p = 0.021) and insulin resistance (p = 0.049) were observed after 8 weeks in the O. sanctum intervention group. The improvement in HDL-C in the intervention group when compared to the control group was also statistically significant (p = 0.037). There was no significant alteration of the liver enzymes SGOT and SGPT in both the intervention (p = 0.141; p = 0.074) and control arms (p = 0.102; p = 0.055) respectively. These observations clearly indicate the beneficial effects of O. sanctum on various biochemical parameters in young overweight/obese subjects.

A preliminary study on the adsorptive removal of Cr(VI) using seaweed, Hydrilla verticillata.

The Cr(VI) adsorption efficiency of the seaweed, Hydrilla verticillata, was studied in batches. The adsorbent was characterized using SEM, BET surface area analyzer, Malvern particle size analyzer, EDAX and FT-IR. Cr(VI) removal efficiency of the adsorbent was studied as a function of different adsorption parameters such as contact time, stirring speed, pH, adsorbent dose, particle size, adsorbate concentration, and temperature. Langmuir, Freundlich, and Temkin adsorption isotherm equations were used in the equilibrium modeling. The adsorption process followed pseudo second-order kinetics and intra-particle diffusion was found to be the rate-controlling step. Experimental data follow Langmuir adsorption isotherm. Thermodynamic parameters such as Gibbs free energy and enthalpy of the adsorption process were evaluated to find out the feasibility of the adsorption process. The negative values of Gibb's free energy and positive enthalpy values show the feasibility and endothermic nature of the process. The significance of different adsorption parameters along with their combined effect on the adsorption process has been established through a full 2(4) factorial design. Among the different adsorption parameters, pH has the most influential effect on the adsorption process followed by adsorbate concentration and combined effects of all the four parameters were tested. The correlation among different adsorption parameters were studied using multi-variate analysis.