Alcohol self-administration and nicotine withdrawal alter biomarkers of stress and inflammation and prefrontal cortex changes in Gß subunits.

Background: Although alcohol and nicotine are often used together, the biological consequences of these substances are not well understood. Identifying shared targets will inform cessation pharmacotherapies and provide a deeper understanding of how co-use of alcohol and nicotine impacts health, including biomarkers of stress and inflammation.Objective: We examined the effects of nicotine exposure and withdrawal on alcohol self-administration (SA), stress and inflammatory biomarkers, and a G-protein coupled receptor subunit (Gß) in brain areas associated with drug use.Methods: Male rats were trained to SA alcohol and then received a nicotine pump (n = 7-8 per group). We assessed alcohol intake for 12 days during nicotine exposure and then following pump removal to elicit withdrawal. After the behavioral studies, we assessed plasma leptin, corticosterone, and interleukin-1ß (IL-1ß), and Gß protein expression in the amygdala, nucleus accumbens (NAc), and prefrontal cortex (PFC).Results: Nicotine exposure or withdrawal did not alter alcohol intake (p > .05). Alcohol and nicotine withdrawal elevated corticosterone levels (p = .015) and decreased Gß levels in the PFC (p = .004). In the absence of nicotine, alcohol SA suppressed IL-1ß levels (p = .039). Chronic exposure to nicotine or withdrawal during alcohol SA did not alter leptin levels or Gß expression in the amygdala or NAc (p's > .05).Conclusions: The combination of alcohol SA and nicotine withdrawal produced a persistent increase in stress biomarkers and a suppression in Gß expression in the PFC, providing an important first step toward understanding the common biological mechanisms of alcohol/nicotine misuse.

A hybrid coupled cluster-machine learning algorithm: Development of various regression models and benchmark applications.

The iterative solution of the coupled cluster equations exhibits a synergistic relationship among the various cluster amplitudes. The iteration scheme is analyzed as a multivariate discrete time propagation of nonlinearly coupled equations, which is dictated by only a few principal cluster amplitudes. These principal amplitudes usually correspond to only a few valence excitations, whereas all other cluster amplitudes are enslaved and behave as auxiliary variables [Agarawal et al., J. Chem. Phys. 154, 044110 (2021)]. We develop a coupled cluster-machine learning hybrid scheme where various supervised machine learning strategies are introduced to establish the interdependence between the principal and auxiliary amplitudes on-the-fly. While the coupled cluster equations are solved only to determine the principal amplitudes, the auxiliary amplitudes, on the other hand, are determined via regression as unique functionals of the principal amplitudes. This leads to significant reduction in the number of independent degrees of freedom during the iterative optimization, which saves significant computation time. A few different regression techniques have been developed, which have their own advantages and disadvantages. The scheme has been applied to several molecules in their equilibrium and stretched geometries, and our scheme, with all the regression models, shows a significant reduction in computation time over the canonical coupled cluster calculations without unduly sacrificing the accuracy.

Is Gratitude Associated With Suicidal Ideation in Veterans With Mental Illness and Student Veterans With PTSD Symptoms?

ABSTRACT: The present study is aimed to identify the effect of gratitude as an adaptive regulating mechanism from suicidal ideation (SI) for veterans with mental illness (study 1) and student veterans with posttraumatic stress disorder (PTSD) symptoms (study 2) in the United States. Descriptive statistics and regression analyses were used to examine sociodemographic characteristics and relationships between gratitude and SI. Our study 1 consisted of 156 veterans with mental illness. The mean age for study 1 was 37.85. Our study 2 consisted of 232 student veterans with PTSD symptoms. The mean age for study 2 was 28.43. Higher gratitude scores in study 1 and study 2 were significantly associated with lower SI scores after adjusting for demographics and depression. This study partially supports the association between gratitude and SI in veterans with mental illness. Based on the results from this study, gratitude interventions may be effective in reducing SI when working with veterans with mental illness.

Peripheral cytokine levels and response to antidepressant treatment in depression: a systematic review and meta-analysis.

Predicting antidepressant treatment response has been a clinical challenge for major depressive disorder (MDD). The inflammation hypothesis of depression suggests that cytokines play a key role in the pathophysiology of MDD and alterations in peripheral cytokine levels are associated with antidepressant treatment outcome. Present meta-analysis aimed to examine the association between baseline peripheral cytokine levels and the response to antidepressant treatment and to evaluate whether changes of cytokine levels were associated with the response to antidepressant treatment in patients with MDD. Human-based studies published in any language in peer-reviewed journals were systematically searched from the PubMed, Embase and Web of Science databases, from inception up to October 2018. The search terms included cytokine, depressive disorder and antidepressant and their synonyms. Case-control or case-case studies reporting on levels of IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, CRP, TNF-α, IFN-γ, GM-CSF, MIP-1α, and Eotaxin-1 in patients with MDD based on validated depression scales both before and after antidepressant treatment were included. Of 7408 identified records, 44 studies met inclusion. Standardized mean differences in each cytokine were evaluated, and random-effects meta-analyses were performed. MDD patients who responded to antidepressant treatment had lower baseline IL-8 levels than the nonresponders (Hedge's g = -0.28; 95%CI, -0.43 to -0.13; P = 0.0003; FDR = 0.004). Antidepressant treatment significantly decreased levels of TNF-α (Hedge's g = 0.60; 95%CI, 0.26-0.94; P = 0.0006; FDR = 0.004) only in responders, and responders showed significantly more decreased TNF-α levels compared with nonresponders (P = 0.046). These findings suggested that alterations in peripheral cytokine levels were associated with antidepressant treatment outcomes in MDD. Further investigations are warranted to elucidate sources of heterogeneity and examine the potentiality of using inflammatory cytokines as novel predictive markers for the pharmacological treatment of MDD.

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD.

Platelet-Derived Growth Factor as an Antidepressant Treatment Selection Biomarker: Higher Levels Selectively Predict Better Outcomes with Bupropion-SSRI Combination.

Background: Platelet derived growth factor is integral to maintenance of blood brain barrier, increases in response to blood brain barrier disruption, and may reflect neuroinflammation. Based on previous reports of better outcomes with dopaminergic antidepressants in depressed patients with elevated inflammatory biomarkers, we hypothesize that elevated peripheral platelet derived growth factor levels can serve as a powerful biomarker for selecting dopaminergic antidepressants. Methods: Platelet derived growth factor, basic fibroblast growth factor, and granulocyte colony stimulating factor were measured as part of Bioplex Pro human cytokine 27-plex kit in participants of the Combining Medications to Enhance Depression Outcomes trial who provided baseline plasma (n=166) and were treated with either bupropion-plus-escitalopram, escitalopram-plus-placebo, or venlafaxine-plus-mirtazapine. Differential changes in overall symptom severity and anhedonia as well as side effects were tested with a treatment-arm-by-biomarker interaction in mixed model analyses. Effect of biomarkers with significant interaction was calculated in subsequent analyses stratified by treatment arm. Results: There was a significant treatment-arm-by-platelet derived growth factor interaction for depression severity (P=.03) and anhedonia (P=.008) but not for side effects (P=.44). Higher baseline platelet derived growth factor level was associated with greater reduction in depression severity (effect size=0.71, P=.015) and anhedonia (effect size=0.66, P=.02) in the bupropion- selective serotonin reuptake inhibitor but not the other two treatment arms. There was no significant treatment-arm-by-biomarker interaction for both depression severity and side effects with the other two biomarkers. Conclusion: As compared with selective serotonin reuptake inhibitor monotherapy or venlafaxine-plus-mirtazapine, bupropion-plus-escitalopram selectively improves anhedonia, which in turn results in improved overall depression severity in depressed patients with elevated platelet derived growth factor levels.

Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: Novel T cell biomarker for antidepressant medication selection.

BACKGROUND: Interleukin 17 (IL-17) is produced by highly inflammatory Th17 cells and has been implicated in pathophysiology of depression. IL-17 putatively disrupts the blood brain barrier and affects dopamine synthesis whereas dopamine has been shown to decrease Th17 cell-mediated immune response. Nevertheless, whether IL-17 can predict differential treatment outcome with antidepressants modulating dopaminergic transmission is unknown. METHODS: IL-17 and other T cell and non-T cell markers (Th1, Th2 and non-T cell markers) were measured with the Bioplex Pro™ human cytokine 27-plex kit in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants who provided baseline plasma and were treated with either bupropion plus escitalopram (bupropion-SSRI), escitalopram plus placebo (SSRI monotherapy), or venlafaxine plus mirtazapine (n=166). Differential changes in symptom severity and side-effects based on levels of IL-17 and other T and non-T cell markers were tested using a treatment-arm-by-biomarker interaction in separate repeated measures mixed model analyses. Subsequent analyses stratified by treatment arm were conducted for those markers with a significant interaction. RESULTS: There was a significant treatment-arm-by-IL-17 interaction for depression severity (p=0.037) but not for side-effects (p=0.28). Higher baseline IL-17 level was associated with greater reduction in depression severity (effect size=0.78, p=0.008) in the bupropion-SSRI but not the other two treatment arms. Other T and non-T cell markers were not associated with differential treatment outcomes. CONCLUSION: Higher baseline levels of IL-17 are selectively associated with greater symptomatic reduction in depressed patients treated with bupropion-SSRI combination.

Comparative evaluation of the efficacy of Triphala mouthwash and Curcumin mouthwash in the treatment of gingivitis - A randomized controlled study.

Background: Numerous studies on Triphala and Curcumin mouthwashes were analyzed individually and no study has compared the efficacy of Triphala mouthwash to Curcumin mouthwash in the management of gingivitis. Although various mouthwashes have shown reduction of plaque and gingivitis the search is still on for an ideal mouthwash with minimum side effects and better patient acceptance. Objectives: To access the efficacy of all the mouthwashes in the management of gingivitis. Methods: By purposive sampling, 81 patients of both sexes with gingivitis were randomized by lottery method into 3 groups - A, B and C. Group A received scaling and Triphala mouthwash, Group B received scaling and Curcumin mouthwash and Group C underwent scaling and received Chlorhexidine mouthwash. Oral hygiene was assessed using Plaque, Gingival and Bleeding indices at baseline,7th day and 14th day. The inter-group comparisons were analysed using One-way analysis of variance (ANOVA) and multiple comparisons using Tukey's Honest significant difference test (α = 0.05) and the intra-group comparisons for the indices across various time periods within each group were analysed using Repeated-measures ANOVA and Bonferroni-adjusted pairwise comparisons post hoc test (α = 0.05). The statistical significance was set at p ≤ 0.05. Results: The study has shown that herbal mouthwashes are as effective as chlorhexidine in treating gingivitis although curcumin mouthwash showed a greater potential in reducing gingival inflammation. Conclusion: Both Triphala and Curcumin mouthwashes were proven to be equally effective in reducing plaque, gingival and bleeding scores, although curcumin was better in reducing gingival inflammation. Hence herbal mouthwashes such as Triphala and Curcumin with no side effects can be considered as an alternative mouthwash to chlorhexidine.

Comparative analysis of renal calculi treatment via different extracorporeal shock wave lithotripsy (ESWL) pathways.

OBJECTIVE: To compare the efficacy and safety of Extracorporeal Shock Wave Lithotripsy (ESWL) for treating renal calculi under different shock wave pathways. METHODS: This study involved a prospective analysis of clinical data obtained from 264 eligible patients with renal stones treated at the Urology Department of Shanxi Bethune Hospital between January 2021 and June 2023. Among these patients, 125 underwent ESWL via the dorsal shock wave pathway (Group A), while 139 patients underwent ESWL via the ipsilateral clavicular midline shock wave pathway (Group B). Preoperatively, all patients underwent non-contrast abdominal CT (NCCT) scans to assess stone count, diameter, CT values, and Skin-to-Stone Distance (SSD). Intraoperatively, ultrasonography was utilized to remeasure SSD and monitor stone fragmentation continuously. The ESWL procedure employed a standardized intermittent stepwise energy escalation technique until treatment completion. Various metrics, including intraoperative Visual Analog Scale (VAS) pain scores, number of shocks, total shock wave energy, stone-free rate (SFR) at 4 weeks post-operation, and postoperative complication rates, were recorded and subjected to statistical analysis. RESULTS: There were no statistically significant differences between the two groups regarding gender, age, BMI, stone count, stone diameter, stone CT values, intraoperative VAS pain scores, and postoperative complication rates (P>0.05). Preoperative SSD was significantly higher in Group B than in Group A (P<0.05), but there were no significant differences in intraoperative SSD between the groups (P>0.05). Group B showed significantly lower total shock wave energy and number of shocks compared to Group A (P<0.05). The stone-free rate (SFR) after 4 weeks did not exhibit significant differences between the groups (P>0.05). However, when the stone diameter was ≥1.3 cm, the SFR at 4 weeks post-operation in Group B was significantly higher than in Group A (P<0.05). CONCLUSION: ESWL emerges as a safe and efficacious approach for treating renal calculi. Our findings suggest that utilizing the ipsilateral clavicular midline shock wave pathway in ESWL necessitates less shock wave energy and enhances efficiency, particularly in cases with larger stone burdens.

Off-season survival and life history of beet armyworm, Spodoptera exigua (Hubner) on various host plants.

The beet armyworm, Spodoptera exigua (Hubner) (Lepidoptera: Noctuidae), has become a significant pest of chickpea in recent years. The polyphagous nature allows it to survive on various hosts during the off-season, creating a great menace to the crop in the following season. To assess the incidence and document the alternate hosts of S. exigua, a rapid roving survey was conducted in 11 chickpea-growing areas of Prakasam district, Andhra Pradesh, India. Additionally, the life history traits of S. exigua were studied on major alternate host plants under laboratory conditions (27 ± 1 °C and 70 ± 2% RH) to understand the survival, life expectancy and potential contribution to future populations. The results show that, among the different crops surveyed, the maximum larval incidence was noticed in maize (1.93 larvae/plant), cowpea (1.73 larvae/plant), and sunflower (1.68 larvae/plant) during the off-season. Life history studies of S. exigua showed that highest larval survival percentage was observed on chickpea (83.6%), while the lowest was on maize (44.5%). The mean developmental time for larvae was longest on maize (27.1 days) and shortest on chickpea (14.9 days). Larvae did not develop beyond the third instar when fed with chilli. The growth index statistics showed chickpea (9.2) was the most suitable host plant, whereas maize (0.9) was the least suitable host. The age-stage-specific survival rate (Sxj) varied across developmental stages, and the survival curves overlapped, indicating different growth rates among individuals. The life expectancy (exj) at age zero was highest on groundnut (37.06 days). The intrinsic rate of increase (r) of S. exigua was lowest on maize (0.10 ± 0.0013) and highest on chickpea (0.22 ± 0.0010). Similarly, the net reproductive rate (R0) was highest on chickpea (846.39 ± 18.22) and lowest on maize (59.50 ± 2.06). The population doubled every 3.08 ± 0.011 days on chickpea compared to 7.22 ± 0.80 days on maize. The study conclusively indicates that chickpea and sunflower, primarily cultivated during the rabi season in India, are the most preferred hosts for S. exigua. In contrast, maize and cotton, mainly grown during the kharif season, are less preferred and merely support the pest's survival. Consequently, S. exigua switches hosts between different crops growing seasons, so effective management of S. exigua during the kharif season can help prevent pest outbreaks during the rabi season.

Morphological and molecular approaches revealed a new species of snapping shrimp genus Alpheus Fabricius, 1798 (Decapoda: Caridea: Alpheidae) from Lakshadweep Islands, India.

A new species of the alpheid genus Alpheus Fabricius, 1798, Alpheus sulcipalma sp. nov., is described and illustrated based on the specimens collected from the intertidal zone of Agatti Island, Lakshadweep, India at 0.5-1.0 m depth. This species belongs to the A. edwardsii group by absences of tooth in the orbital hoods and presence of compressed major chela with dorsal and ventral notches. Alpheus sulcipalma sp. nov. is morphologically closely related with A. pacificus Dana, 1852, absence of balaeniceps crests in the minor chela and absences of spine in the merus of major pereiopod of both sexes. However, the new species differs from A. pacificus in presence of strong and broad triangular groove on the dorsolateral and dorsomesial surface of the palm of major chela; length ratio and armature of fingers and palm of minor chela, carpus segments of second and third pereiopods and telson length. The results of phylogenetic analyses using partial sequences of mitochondrial COI gene data compared between A. sulcipalma sp. nov. with congener species which strongly support the description of new species with available limited sequences. The interspecific genetic divergences of the COI gene for A. sulcipalma sp. nov. and A. pacificus were observed higher in ranges (11.1-28.9%).

Sex and diet-dependent gene alterations in human and rat brains with a history of nicotine exposure.

Introduction: Chronic nicotine exposure induces changes in the expression of key regulatory genes associated with metabolic function and neuronal alterations in the brain. Many bioregulatory genes have been associated with exposure to nicotine, but the modulating effects of sex and diet on gene expression in nicotine-exposed brains have been largely unexplored. Both humans and rodents display motivation for nicotine use and the emergence of withdrawal symptoms during abstinence. Research comparing pre-clinical models with human subjects provides an important opportunity to understand common biomarkers of the harmful effects of nicotine as well as information that may help guide the development of more effective interventions for nicotine cessation. Methods: Human postmortem dorsolateral prefrontal cortex (dLPFC) tissue BA9 was collected from female and male subjects, smokers and non-smokers (N = 12 per group). Rat frontal lobes were collected from female and male rats that received a regular diet (RD) or a high-fat diet (HFD) (N = 12 per group) for 14 days following implantation of a osmotic mini-pump (Alzet) that delivered nicotine continuously. Controls (control-s) received a sham surgical procedure. RNA was extracted from tissue from human and rat samples and reversed-transcribed to cDNA. Gene expression of CHRNA10 (Cholinergic receptor nicotinic alpha 10), CERKL (Ceramide Kinase-Like), SMYD1 (SET and MYD Domin Containing 1), and FA2H (Fatty Acid 2-Hydrolase) in humans was compared to rats in each subset of groups and quantified by qPCR methods. Additionally, protein expression of FA2H was analyzed by immunohistochemistry (IHC) in human dLPFC. Results: Humans with a history of smoking displayed decreased CHRNA10 (p = 0.0005), CERKL (p ≤ 0.0001), and SMYD1 (p = 0.0005) expression and increased FA2H (p = 0.0097) expression compared to non-smokers (p < 0.05). Similar patterns of results were observed in nicotine exposed vs. control rats. Interestingly, sex-related differences in gene expression for CERKL and FA2H were observed. In addition, ANCOVA analysis showed a significant effect of nicotine in a sex-different manner, including an increase in CERKL in male and female rats with RD or HFD. In rats exposed to an HFD, FA2H gene expression was lower in nicotine-treated rats compared to RD rats treated with nicotine. Protein expression of FA2H (p = 0.001) by IHC was significantly higher in smokers compared to non-smokers. Conclusion: These results suggest that a history of long-term nicotine exposure in humans alters the expression of sphingolipid metabolism-related (CERKL, SMYD1, and FA2H) and neuronal (CHRNA10) marker genes similarly as compared to rats. Sex- and diet-dependent differences appear in nicotine-exposed rats, critical in regulating sphingolipid metabolism and nicotinic acetylcholine receptors. This research enhances the construct validity of rat models of nicotine usage by showing a similar pattern of changes in gene expression in human subjects with a smoking history.

A mathematical modelling to detect sickle cell anemia using Quantum graph theory and Aquila optimization classifier.

Recently genetic disorders are the most common reason for human fatality. Sickle Cell anemia is a monogenic disorder caused by A-to-T point mutations in the ß-globin gene which produces abnormal hemoglobin S (Hgb S) that polymerizes at the state of deoxygenation thus resulting in the physical deformation or erythrocytes sickling. This shortens the expectancy of human life. Thus, the early diagnosis and identification of sickle cell will aid the people in recognizing signs and to take treatments. The manual identification is a time consuming one and might outcome in the misclassification of count as there is millions of red blood cells in one spell. So as to overcome this, data mining approaches like Quantum graph theory model and classifier is effective in detecting sickle cell anemia with high precision rate. The proposed work aims at presenting a mathematical modeling using Quantum graph theory to extract elasticity properties and to distinguish them as normal cells and sickle cell anemia (SCA) in red blood cells. Initially, input DNA sequence is taken and the elasticity property features are extracted by using Quantum graph theory model at which the formation of spanning tree is made followed by graph construction and Hemoglobin quantization. After which, the extracted properties are optimized using Aquila optimization and classified using cascaded Long Short-Term memory (LSTM) to attain the classified outcome of sickle cell and normal cells. Finally, the performance assessment is made and the outcomes attained in terms of accuracy, precision, sensitivity, specificity, and AUC are compared with existing classifier to validate the proposed system effectiveness.

Correlation of Clinical Features in Oral Submucous Fibrosis: A 9-Year Retrospective Study.

BACKGROUND: Oral Submucous Fibrosis is a chronic debilitating disease and potentially malignant disorder of the oral cavity known in medical literature for a long time. The study aims to correlate the clinical staging of Oral Submucous Fibrosis with various clinical findings of the oral mucosa like hyperpigmentation, erosions, ulcerations, VAS score, tongue protrusion, and cheek flexibility. METHODS: A retrospective observational study was undertaken and records of 1267 clinically diagnosed cases of OSMF were included in the study. Clinical grading was done as per criteria by Lai DR et al. The observations were tabulated and subjected to statistical analysis using SPSS software. RESULTS: In our study, the incidence of hyperpigmentation, erosions, and ulcerations was higher in Group C OSMF. Visual analog scores in the range of 5-6 was noted in 40.9% of the total subjects, out of which 36.2% belonged to Group C OSMF. Tongue protrusion of less than 25 mm was seen in 10.65% of the subjects. Cheek flexibility of less than 0.6 cm was seen in 19.62% of the subjects, most of which belonged to Group D. CONCLUSION: In our study, we found an increase in the occurrence and severity of symptoms with an increase in grades of OSMF, but this increase was not observed to be consistent. Hence classification based on a single clinical entity cannot be sufficient and correlations to other clinical findings should be studied over a large population and a multi-tier classification could be proposed in the future.

Fibroblast growth factor 21 (FGF21) is increased in MDD and interacts with body mass index (BMI) to affect depression trajectory.

Fibroblast growth factor 21 (FGF21) is a key regulator of metabolic function and nutrient preference. It also affects biological pathways associated with major depressive disorder (MDD), including corticotrophin-releasing hormone (CRH), leptin, and sympathetic activity. Lower levels of cerebrospinal fluid FGF21 have been associated with higher Beck Depression Inventory scores. FGF21 was examined as a metabolic marker that could be associated with MDD and evaluated as a biomarker of antidepressant treatment response in a large, randomized placebo-controlled trial in chronic, early-onset MDD participants. FGF21 levels at baseline and during treatment were determined for participants in the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. FGF21 was analyzed by ELISA in individuals with chronic, early-onset MDD (first major depressive episode before 30 years) compared to healthy control participants. Participants with MDD had higher levels of FGF21 compared to healthy controls (HCs), even after controlling for baseline age, sex, race, Hispanic ethnicity, BMI, and site (ß-coefficient = 1.20, p < 0.0001, Cohen's d = 0.60). FGF21 did not change over time nor differ between treatment groups. Interestingly though, those with normal BMI and lower FGF21 levels showed a reduction in depression severity over time compared to all other groups. In conclusion, depression is associated with higher levels of FGF21 compared to healthy controls and those with lower levels of FGF21 (25th percentile of the sample) in the context of normal-weight BMI seem to have improved depression severity over time.

Multiple Sclerosis-associated Bacterial Ligand 654.

BACKGROUND AND AIMS: Many endogenous and exogenous risk factors are associated with multiple sclerosis (MS), but recent studies suggest that microbiome-derived ligands, play a role in the disease process. The goal of this study was to characterize the cellular response elicited in human microglia upon treatment with IFN-ß and Fingolimod, two first line medications for the management of MS, and determine whether these treatments affect the response of microglial cells to an MS-associated bacterial ligand, Lipid 654. MATERIALS AND METHODS: HMC3 human microglial cells were treated with IFN-ß or Fingolimod. Cytokine secretion was evaluated using a multiplex system, and microglia polarization was assessed by flow cytometry. RESULTS: We observed that treatment with IFN-ß or Fingolimod induced differential secretion of various pro-inflammatory cytokines. Upon cell stimulation with Lipid 654, we observed that IFN-ß and Fingolimod decreased the secretion of M1-associated cytokines. Using flow cytometry, we observed that the decrease in inflammatory cytokine secretion was likely due to a containment of M1 phenotype of microglia after stimulation with Lipid 654. CONCLUSIONS: Our findings provide new clues of still unknown mechanisms of action of IFN-ß and Fingolimod in human microglia, which will prompt new avenues of research on the use of these therapies in the regulation of the inflammatory response in MS.

Prognosis and Diagnostic Biomarkers of Mild Traumatic Brain Injury: Current Status and Future Prospects.

Mild traumatic brain injury (mTBI) is the most prevalent type of TBI (80-90%). It is characterized by a loss consciousness for less than 30 minutes, post-traumatic amnesia for less than 24 hours, and Glasgow Coma Score of 13-15. Accurately diagnosing mTBIs can be a challenge because the majority of these injuries do not show noticeable or visible changes on neuroimaging studies. Appropriate determination of mTBI is tremendously important because it might lead in some cases to post-concussion syndrome, cognitive impairments including attention, memory, and speed of information processing problems. The scientists have studied different methods to improve mTBI diagnosis and enhanced approaches that would accurately determine the severity of the trauma. The present review focuses on discussing the role of biomarkers as potential key factors in diagnosing mTBI. The present review focuses on 1) protein based peripheral and CNS markers, 2) genetic biomarkers, 3) imaging biomarkers, 4) neurophysiological biomarkers, and 5) clinical trials in mTBI. Each section provides information and characteristics on different biomarkers for mTBI.

Analysis of Young Infant Deaths Using Verbal Autopsies and Accuracy of Verbal Autopsy Tool in Chennai, India.

OBJECTIVE: To identify medical and non-medical factors associated with young infant deaths using verbal autopsies and to evaluate the validity of state verbal autopsy tool in identifying medical causes. DESIGN: Descriptive study to report factors associated with young infant deaths, and diagnostic accuracy study of the verbal autopsy tool. RESULTS: Prematurity related illnesses were the major contributors to mortality. Deliveries were predominantly in health care facilities (99%); lower maternal education (11.2%), lesser birth spacing (80%), and higher birth order (7.5%) were other factors noted. Verbal autopsy questionnaire had a diagnostic accuracy of ≥95% in identifying major causes of death (kappa value 0.8-1.0). CONCLUSION: Current state verbal autopsy tool is valid in identifying causes of death.

Knowledge, Attitude, and Awareness of Orthognathic Surgery among Orthodontic Patient-Prospective Study.

AIM: The aim of the current survey was conducted to assess the knowledge, attitude, and awareness regarding orthognathic surgery among orthodontic patients. MATERIALS AND METHODS: This is cross-sectional web-based questionnaire survey conducted among orthodontic patients in Tamil Nadu. The self-administered questions related to awareness of orthognathic surgery were collected from 500 subjects. The statistical analysis was done using the Statistical Package for the Social Sciences (V 22.0). The frequency distribution was computed. RESULTS: This survey revealed that 466 (93.2%) respondents had awareness about the role of orthognathic surgery. 332 (66.4%) had given the correct responses related to differentiating skeletal and dental malocclusion, 454 (90.6%) had the awareness of risk factors associated with orthognathic surgery and 40 (7.0%) were experienced regarding the procedure. CONCLUSION: The result of the current study showed that it clearly implies that the population was aware of orthognathic surgery as a treatment modality for correcting skeletal deformities.