Family Support to Women During Pregnancy and Its Impact on Maternal and Fetal Outcomes.

BACKGROUND: Family support is one of the determinants of lifestyle habits and relevant health behavior for pregnancy outcomes. In India, the joint family system is still practiced. Due to education, urbanization, and industrialization, the family institution continues to play a central role in people's lives. Pregnancy is a crucial period in women's lives. Good care during pregnancy is important for the health of the mother and the newborn baby. During this period, hormonal changes are complex and involve multiple hormones working together to support the developing fetus and prepare the mother's body for labor, delivery, and breastfeeding. To avoid maternal and fetal complications, she needs support from her family throughout pregnancy and the postnatal period. AIM AND OBJECTIVES: This study aims to evaluate the influence of the level and quality of family support during pregnancy on maternal and fetal outcomes and to identify any association between the sociodemographic variables and the impact of the level and quality of family support during the first trimester. MATERIAL AND METHODS: This study used a quantitative approach with a survey research design. Data were collected from four Primary Health Centers at Karad, Maharashtra, India, i.e., Rethare, Vadgaon, Kale, and Supane. A consecutive sampling technique was used to select the 344 subjects from the Rethare, Vadgaon, Kale, and Supane areas of Karad Taluka. Data were collected before the completion of the first three months of pregnancy, then during the second trimester and after delivery. Upon evaluation, the tool was validated by experts representing a range of specialties, including community health nursing, mental health nursing, obstetric gynecology, and pediatric care. A pilot study was conducted on 30 samples. The data collected were analyzed by using descriptive and inferential statistics. RESULT: The findings of the study show a significant association between the psychosocial support received in the first trimester and the total gestational weeks completed at the time of delivery (p < 0.05). The study suggests the need for psychosocial support during the first trimester for better maternal and fetal outcomes. CONCLUSION: Psychosocial family support is needed by pregnant women during the first trimester to achieve maternal and fetal outcomes.

Diverse type I and type II methanotrophs cultivated from an Indian freshwater wetland habitat.

Wetlands are the main natural sources of methane emissions, which make up a significant portion of greenhouse gas emissions. Such wetland patches serve as rich habitats for aerobic methanotrophs. Limited knowledge of methanotrophs from tropical wetlands widens the scope of study from these habitats. In the present study, a freshwater wetland in a tropical region in India was sampled and serially diluted to obtain methanotrophs in culture. This was followed by the isolation of methanotrophs on agarose-containing plates, incubated under methane: air atmosphere. Methanotrophs are difficult to cultivate, and very few cultures of methanotrophs are available from tropical wetlands. Our current study reports the cultivation of a diverse community of methanotrophs from six genera, namely, Methylomonas, Methylococcus, Methylomagnum, Methylocucumis (type I methanotrophs) along with Methylocystis, Methylosinus (type II methanotrophs). A high abundance of methanotrophs (106-1010 methanotrophs/g fresh weight) was observed in the samples. A Methylococcus strain could represent a putative novel species that was also isolated. Cultures of Methylomagnum and Methylocucumis, two newly described type I methanotrophs exclusively found in rice fields, were obtained. A large number of Methylomonas koyamae strains were cultured. Our study is pioneering in the documentation of culturable methanotrophs from a typical tropical wetland patch. The isolated methanotrophs can act as models for studying methanotroph-based methane mitigation from wetland habitats and can be used for various mitigation and valorization applications.

Intranasal neuropeptide Y1 receptor antagonism improves motor deficits in symptomatic SOD1 ALS mice.

OBJECTIVE: Neuropeptide Y (NPY) is a 36 amino acid peptide widely considered to provide neuroprotection in a range of neurodegenerative diseases. In the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), recent evidence supports a link between NPY and ALS disease processes. The goal of this study was to determine the therapeutic potential and role of NPY in ALS, harnessing the brain-targeted intranasal delivery of the peptide, previously utilised to correct motor and cognitive phenotypes in other neurological conditions. METHODS: To confirm the association with clinical disease characteristics, NPY expression was quantified in post-mortem motor cortex tissue of ALS patients and age-matched controls. The effect of NPY on ALS cortical pathophysiology was investigated using slice electrophysiology and multi-electrode array recordings of SOD1G93A cortical cultures in vitro. The impact of NPY on ALS disease trajectory was investigated by treating SOD1G93A mice intranasally with NPY and selective NPY receptor agonists and antagonists from pre-symptomatic and symptomatic phases of disease. RESULTS: In the human post-mortem ALS motor cortex, we observe a significant increase in NPY expression, which is not present in the somatosensory cortex. In vitro, we demonstrate that NPY can ameliorate ALS hyperexcitability, while brain-targeted nasal delivery of NPY and a selective NPY Y1 receptor antagonist modified survival and motor deficits specifically within the symptomatic phase of the disease in the ALS SOD1G93A mouse. INTERPRETATION: Taken together, these findings highlight the capacity for non-invasive brain-targeted interventions in ALS and support antagonism of NPY Y1Rs as a novel strategy to improve ALS motor function.

Thermotolerant methanotrophs belonging to the Methylocaldum genus dominate the methanotroph communities in biogas slurry and cattle dung: A culture-based study from India.

Biogas reactors run on various types of waste, with cattle dung and agricultural wastes being the primary sources in India. As biogas contains 50-60% methane, there is a possibility that the reactors harbour methanotrophs or methane-oxidizing bacteria. We set up serial endpoint dilution enrichments for the cultivation of methanotrophs using slurry from a small biogas reactor and cattle dung samples and obtained cultures of Methylocaldum gracile, a thermotolerant methanotroph. The study was expanded by sampling reactors of another small reactor of 20 L capacity and two 1000 L reactors. Dung samples were obtained from two Indian cattle breeds (Tharparkar and Gir). Pulverized rice straw used for feeding the biogas was also used for experiments. All the enrichment bottles were incubated at 39 °C, the reactors' in-situ temperature, and the rumen gut temperature. Our study isolated four pure cultures most related to Methylocaldum gracile VKM-14LT, two strains from cattle dung samples, and two from reactors. The study also resulted in the cultivation of four additional cultures of Methylocaldum gracile and Methylocaldum tepidum, which were non-axenic and identified by pmoA gene sequencing. Pure cultures Methylocaldum gracile RS-9 and CDP-2 were studied for optimum temperature and oxygen. Both the strains were thermotolerant and grew in the temperature range of 25-45 °C with the optimum between 37 and 45 °C. The cultures could grow with minimal oxygen (0.5%-1%) in the headspace, with growth up to 10% oxygen. To summarize, we report the cultivation and isolation of methanotrophs from biogas slurries and cattle dung samples. Methylocaldum was the dominant methanotroph cultured, probably due to its thermotolerant nature and the ability to grow under variable oxygen conditions. The present study also expands the existing knowledge about habitats known for the genus Methylocaldum. An analysis of the isolated cultures would help us design strategies for methane mitigation from ruminants.

Recurrent Neural Model to Analyze the Effect of Physical Training and Treatment in Relation to Sports Injuries.

Artificial intelligence has rapidly grown and has made the scenario that no field can function without it. Like every field, it also plays a vital role in the sports field nowadays. In certain sports, injuries happen very often due to heavy training and sudden speedy actions, especially in athletics and football. Here arises a need to analyze the effect of physical training in sportsperson by collecting data from their daily training. With the help of artificial intelligence, a recurrent neural model is developed to analyze the effect of physical training and treatment concerning sports injury. A Recurrent Neural Network (RNN) can be a subsection of Artificial Neural Networks (ANN) that uses the neural nodes connected in a temporal sequence. The temporal sequence is one of the essential terms in this research, which denotes a data sequence of events in a given timeframe. The recurrent neural model is an intelligent machine learning method that comprises a neural schema replicating humans. This neural schema studies the data it collects from the athletes/players and processes it by analyzing previous injuries. Sports injuries have to be analyzed because, in some cases, it becomes more dangerous to the sportsperson that they may even lose their career due to disability. Sometimes it may cause a massive loss to the club or company that hired the sportsperson for the sport. The prediction process can give the player rest until he recovers, thus becoming the safest approach in sports. Therefore, it is essential to analyze the sportsperson's track data to keep an eye on his health. In this research, RNN model is compared with the existing Support Vector Machine (SVM) in concerning to the effect of physical training and treatment for sports. The results show that the proposed model has achieved 99% accuracy, which is higher than the existing algorithm.

Estrogen Enhances Dendrite Spine Function and Recovers Deficits in Neuroplasticity in the prpTDP-43A315T Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) attacks the corticomotor system, with motor cortex function affected early in disease. Younger females have a lower relative risk of succumbing to ALS than males and older females, implicating a role for female sex hormones in disease progression. However, the mechanisms driving this dimorphic incidence are still largely unknown. We endeavoured to determine if estrogen mitigates disease progression and pathogenesis, focussing upon the dendritic spine as a site of action. Using two-photon live imaging we identify, in the prpTDP-43A315T mouse model of ALS, that dendritic spines in the male motor cortex have a reduced capacity for remodelling than their wild-type controls. In contrast, females show higher capacity for remodelling, with peak plasticity corresponding to highest estrogen levels during the estrous cycle. Estrogen manipulation through ovariectomies and estrogen replacement with 17ß estradiol in vivo was found to significantly alter spine density and mitigate disease severity. Collectively, these findings reveal that synpatic plasticity is reduced in ALS, which can be amelioriated with estrogen, in conjuction with improved disease outcomes.

Cultivation of Important Methanotrophs From Indian Rice Fields.

Methanotrophs are aerobic to micro-aerophilic bacteria, which oxidize and utilize methane, the second most important greenhouse gas. The community structure of the methanotrophs in rice fields worldwide has been studied mainly using culture-independent methods. Very few studies have focused on culturing methanotrophs from rice fields. We developed a unique method for the cultivation of methanotrophs from rice field samples. Here, we used a modified dilute nitrate mineral salts (dNMS) medium, with two cycles of dilution till extinction series cultivation with prolonged incubation time, and used agarose in the solid medium. The cultivation approach resulted in the isolation of methanotrophs from seven genera from the three major groups: Type Ia (Methylomonas, Methylomicrobium, and Methylocucumis), Type Ib (Methylocaldum and Methylomagnum), and Type II (Methylocystis and Methylosinus). Growth was obtained till 10-6-10-8 dilutions in the first dilution series, indicating the culturing of dominant methanotrophs. Our study was supported by 16S rRNA gene-based next-generation sequencing (NGS) of three of the rice samples. Our analyses and comparison with the global scenario suggested that the cultured members represented the major detected taxa. Strain RS1, representing a putative novel species of Methylomicrobium, was cultured; and the draft genome sequence was obtained. Genome analysis indicated that RS1 represented a new putative Methylomicrobium species. Methylomicrobium has been detected globally in rice fields as a dominant genus, although no Methylomicrobium strains have been isolated from rice fields worldwide. Ours is one of the first extensive studies on cultured methanotrophs from Indian rice fields focusing on the tropical region, and a unique method was developed. A total of 29 strains were obtained, which could be used as models for studying methane mitigation from rice fields and for environmental and biotechnological applications.

Differential NPY-Y1 Receptor Density in the Motor Cortex of ALS Patients and Familial Model of ALS.

Destabilization of faciliatory and inhibitory circuits is an important feature of corticomotor pathology in amyotrophic lateral sclerosis (ALS). While GABAergic inputs to upper motor neurons are reduced in models of the disease, less understood is the involvement of peptidergic inputs to upper motor neurons in ALS. The neuropeptide Y (NPY) system has been shown to confer neuroprotection against numerous pathogenic mechanisms implicated in ALS. However, little is known about how the NPY system functions in the motor system. Herein, we investigate post-synaptic NPY signaling on upper motor neurons in the rodent and human motor cortex, and on cortical neuron populations in vitro. Using immunohistochemistry, we show the increased density of NPY-Y1 receptors on the soma of SMI32-positive upper motor neurons in post-mortem ALS cases and SOD1G93A excitatory cortical neurons in vitro. Analysis of receptor density on Thy1-YFP-H-positive upper motor neurons in wild-type and SOD1G93A mouse tissue revealed that the distribution of NPY-Y1 receptors was changed on the apical processes at early-symptomatic and late-symptomatic disease stages. Together, our data demonstrate the differential density of NPY-Y1 receptors on upper motor neurons in a familial model of ALS and in ALS cases, indicating a novel pathway that may be targeted to modulate upper motor neuron activity.

Functional role of iNOS-Rac2 interaction in neutrophil extracellular traps (NETs) induced cytotoxicity in sepsis.

BACKGROUND: Recent reports from this lab have demonstrated a higher incidence of NETs, nitrosative, as well as oxidative stress, and have a direct correlation with the severity of sepsis and organ damage. However, the mechanistic perspective of NETs induced organ damage has not been understood at the cellular and molecular level. Interaction of inducible nitric oxide synthase (iNOS) with Rac2 in regulating reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation and its implications in microbial killing has been reported. This study was, therefore, undertaken in neutrophils of sepsis patients to investigate the functional importance of iNOS-Rac2 interaction in ROS/ RNS, peroxynitrite generation, NETs generation, and NETs mediated cell death. METHODS: The study was conducted on 100 patients with sepsis and 50 healthy volunteers. Interaction between iNOS and Rac2 was performed using co-immunoprecipitation and co-immunolabeling assay. Free radicals involving ROS and RNS were evaluated using cytochrome c reduction assay. NETs formation was evaluated by fluorescence microscopy. The cytotoxic effect of NETs was assessed on lung carcinoma cell line (A549) using colorimetric Alamar blue assay. RESULTS: Enhanced interaction between iNOS and Rac2 was found in sepsis neutrophils in comparison with control. This was accompanied by an increased level of superoxide (O2.-), nitric oxide (NO), and peroxynitrite (ONOO-) which were decreased in the presence of NAC, DPI, and 1400 W, signifying the role of iNOS-Rac2 interaction. Enhanced NETs release from activated sepsis neutrophils were abrogated in the presence of DPI. NETs from sepsis neutrophils exert a cytotoxic effect on lung epithelial cells (A549) in a concentration-dependent manner. CONCLUSION: Our findings exhibit the functional role of iNOS-Rac2 interaction in ROS/RNS, peroxynitrite generation, NETs generation, and NETs mediated cell death.

The pathologic outcomes and efficacy of epothilone treatment following traumatic brain injury is determined by age.

Traumatic brain injury (TBI) can affect individuals at any age, with the potential of causing lasting neurologic consequences. The lack of effective therapeutic solutions and recommendations for patients that acquire a TBI can be attributed, at least in part, to an inability to confidently predict long-term outcomes following TBI, and how the response of the brain differs across the life span. The purpose of this study was to determine how age specifically affects TBI outcomes in a preclinical model. Male Thy1-YFPH mice, that express yellow fluorescent protein in the cytosol of a subset of Layer V pyramidal neurons in the neocortex, were subjected to a lateral fluid percussion injury over the right parietal cortex at distinct time points throughout the life span (1.5, 3, and 12 months of age). We found that the degree of neuronal injury, astrogliosis, and microglial activation differed depending on the age of the animal when the injury occurred. Furthermore, age affected the initial injury response and how it resolved over time. Using the microtubule stabilizing agent Epothilone D, to potentially protect against these pathologic outcomes, we found that the neuronal response was different depending on age. This study clearly shows that age must be taken into account in neurologic studies and preclinical trials involving TBI, and that future therapeutic interventions must be tailored to age.

Effectiveness of back massage on pain relief during first stage of labor in primi mothers admitted at a Tertiary care center.

BACKGROUND: Labor pain is one of the most severe pains a woman experiences in her life, causing an increase in the anxiety and stress levels. Massage therapy has proven beneficial for relaxation purposes. AIM: To evaluate the effectiveness of back massage in relieving pain during the first stage of labor in primi mothers. METHODOLOGY: The study included 40 primipara mothers belonging to the age group 22-25 years, equally divided into 2 groups: Experimental (massage therapy) and control (routine care). The socio-demographic data, labor assessment parameters (cervical dilation, status of fetal membranes, frequency and duration of uterine contractions during the latent and active phase of labor, and the total duration of the first stage of labor), and the level of labor pain (numerical rating pain scale) were recorded. Data analysis was performed by one-way ANOVA and two independent samples t-test (P ≤ 0.05 as significant). RESULTS: During the latent and active phase of labor, majority of the mothers experienced 4-5 contractions in a span of 10 min. During the latent phase of labor, uterine contractions for 20-40 s were exhibited by 90% and 75% mothers in the experimental and control group, respectively; and during active phase, contractions of >40 s were exhibited by 85% mothers in both groups. A significant difference in the post-test pain scores was noted between the 2 groups (P < 0.0001). CONCLUSION: Our study proved that back massage was effective in reducing pain during the first stage of labor in primipara mothers in comparison to those who were subjected to routine care.

Description of 'Ca. Methylobacter oryzae' KRF1, a novel species from the environmentally important Methylobacter clade 2.

Members of the genus Methylobacter (Mtb) have been identified to be the most dominant methanotrophs in aquatic as well as terrestrial habitats. Methylobacter shows four species with validly published names and these are grouped in two clades based on phylogenetic and genomic comparisons. Mtb luteus and Mtb marinus (synonym: Mtb whittenburyi) belong to clade 1 Methylobacter. Clade 2 Methylobacter comprises of two species: Mtb tundripaludum and Mtb psychrophilus (type strain, no longer available). We isolated a yellow pigmented, rod-shaped methanotroph, strain (KRF1), from a tropical rice field in India, which might represent a putative novel species within Methylobacter clade 2. The cells are long, thick and motile rods. The strain grows under variable oxygen concentration (5-80% air) and also in nitrogen free media (5-50% air). The morphological, chemotaxonomic and genomic features of KRF1 were investigated in details. The digital DNA-DNA hybridization values and average nucleotide identity (ANI) comparisons with the members of its closest species, Mtb tundripaludum, were in the range of 20-26% and ~ 73-81%, respectively. The fatty acid methyl esters profile of KRF1 was different from the profile of Mtb tundripaludum SV96T. The major cell wall fatty acids of strain KRF1 are 16:1 ω7c/16:1 ω6c summed feature (55.4%) and 16:1 ω5c (28.6%). The draft genome of KRF1 is of 5.04 Mbp in size with a GC content of 49.3% and the whole genome shotgun sequencing project has the accession number RYFG00000000 (version: RYFG02000000). Due to the difficulties in the maintenance and cryopreservation of this culture, it could not be deposited in two international culture collections. We thereby propose KRF1 to be member of a Candidatus species, 'Candidatus Methylobacter oryzae' KRF1. The culture is maintained live in our laboratory and also in our institutional WDCM approved culture collection (MACS Collection of Microorganisms) as MCMB-1471.

Development of Risk Scoring Scale Tool for Prediction of Preterm Birth.

BACKGROUND: Prediction of preterm births in the early stage during pregnancy may reduce prevalence of preterm births by appropriate interventions. AIMS/OBJECTIVE: The aim of the study is to develop an antenatal risk scoring system/scale for prediction of preterm births. SUBJECTS AND METHODS: From a cohort of 1876 and subset of 380 pregnant women attending Krishna Hospital Karad, Maharashtra, routine antenatal and in-depth information on diet, occupation, and the rest were collected and analyzed using SPSS version 16. A scoring system was developed by multivariate analysis based on the relative risk (RR) and tested on separate set of 251 mothers. STATISTICAL ANALYSIS USED: Bivariate analysis by Chi-square test, backward multivariate regression model, receiver operating characteristic curve (ROC) curve analysis, and calculation of RR for identified risk factors. Sensitivity and specificity of newly developed risk scoring scale. RESULTS: Out of six risk factors from whole cohort (n = 1876) and three risk factors from subsample (n = 380) identified by bivariate analysis. Further four and three risk factors were retained after multivariate analysis from whole and part of cohort, respectively, and risk scores of "7" and "9" were assigned based on RR cutoff levels of three and five were identified separately for whole and part data by ROC curve analyses together making it "8" with 75.5% sensitivity and 85.5% specificity when tested on 251 independent patients. Based on the prevalence of preterm births, low-, moderate-, and high-risk grading was done by identifying as second cutoff value. CONCLUSIONS: Identification of low-, moderate-, and high-risk of preterm births was possible at <8, 8, and 9 and equal to ≥10 with high sensitivity at lower cutoff and high specificity at upper cutoff.

Antenatal Risk Scoring Scale for Predication of Low Birth Weight and Its Validity.

BACKGROUND: Prediction of low birth weight (LBW) early during pregnancy may prevent LBW by appropriate interventions. AIMS/OBJECTIVE: The aim of the study is to develop an antenatal risk scoring scale for prediction of LBW. SUBJECT AND METHODS: Routine and in-depth information on diet, occupation, and rest was collected from November 1, 2013, to November 13, 2015. A cohort of 1876 and subset of 380 pregnant women attending Krishna Hospital Karad, Maharashtra, India. STATISTICAL ANALYSIS: Multivariate analysis and relative risks (RRs) were found out by SPSS version 16 and tested on a separate set of 251 mothers. RESULTS: The frequency of meals of <4, hard work <6 h of sleep and illiteracy, antenatal morbidity, <10 kg weight gain, <40 kg maternal weight, and anemia during the first trimester were the risk factors identified from subset and cohort, respectively. Based on their RRs, a new scoring system with a total score of 24 and cutoff "12" was identified by using receiver operating characteristics (ROC) curve analysis with 98.6% sensitivity and 41.1% specificity as tested on 251-independent individuals. The second cutoff of "15" score was identified based on the prevalence of LBW in babies of these 251 mothers. CONCLUSIONS: The identification of low-, moderate-, and high-risk of LBW was possible at <12, between 12 and 15, and >15 scores, respectively, with good sensitivity and specificity.

Nitrosative stress and cytokines are linked with the severity of sepsis and organ dysfunction.

OBJECTIVE: An imbalance in oxidant-antioxidant status may impact the severity of sepsis. We hypothesised links between nitrosative stress and pro-inflammatory cytokines and their correlation with the severity of sepsis and associated organ dysfunction. METHODS: The hypothesis was tested in 110 patients with sepsis (in whom a disease severity score (APACHE II) and assessment of organ failure score (SOFA) were determined) and 55 healthy volunteers. Neutrophil inducible nitric oxide synthase (iNOS) expressions at mRNA and protein levels were estimated by real-time PCR and immuno-precipitation followed by Western blotting, respectively. Nitric oxide (NO) content was assessed in neutrophils by confocal microscopy, plasma nitrite by the Griess reaction and inflammatory cytokines (TNF-α, IFN-γ and IL-8) by ELISA (in plasma) and real-time PCR (in neutrophils). Serum bilirubin and creatinine were determined by routine methods and lung function by the PaO2/FiO2 ratio. RESULTS: Increased neutrophil iNOS expression and NO content, plasma total nitrite content and pro-inflammatory cytokines were present in sepsis patients (all P < 0.001). Plasma nitrite correlated with cytokines, APACHE II, SOFA, PaO2/FiO2 ratio, serum bilirubin and creatinine clearance (all r2 0.63-0.85, P < 0.001). Cytokines correlated with nitrite, APACHE II, SOFA, PaO2/FiO2 ratio, serum bilirubin and creatinine clearance (all r2 0.35-0.85, P < 0.001). CONCLUSION: Neutrophils iNOS expression, NO content, plasma nitrite and cytokines have a role in the assessment of the severity of sepsis and organ toxicity.

The Microtubule-Modulating Drug Epothilone D Alters Dendritic Spine Morphology in a Mouse Model of Mild Traumatic Brain Injury.

Microtubule dynamics underpin a plethora of roles involved in the intricate development, structure, function, and maintenance of the central nervous system. Within the injured brain, microtubules are vulnerable to misalignment and dissolution in neurons and have been implicated in injury-induced glial responses and adaptive neuroplasticity in the aftermath of injury. Unfortunately, there is a current lack of therapeutic options for treating traumatic brain injury (TBI). Thus, using a clinically relevant model of mild TBI, lateral fluid percussion injury (FPI) in adult male Thy1-YFPH mice, we investigated the potential therapeutic effects of the brain-penetrant microtubule-stabilizing agent, epothilone D. At 7 days following a single mild lateral FPI the ipsilateral hemisphere was characterized by mild astroglial activation and a stereotypical and widespread pattern of axonal damage in the internal and external capsule white matter tracts. These alterations occurred in the absence of other overt signs of trauma: there were no alterations in cortical thickness or in the number of cortical projection neurons, axons or dendrites expressing YFP. Interestingly, a single low dose of epothilone D administered immediately following FPI (and sham-operation) caused significant alterations in the dendritic spines of layer 5 cortical projection neurons, while the astroglial response and axonal pathology were unaffected. Specifically, spine length was significantly decreased, whereas the density of mushroom spines was significantly increased following epothilone D treatment. Together, these findings have implications for the use of microtubule stabilizing agents in manipulating injury-induced synaptic plasticity and indicate that further study into the viability of microtubule stabilization as a therapeutic strategy in combating TBI is warranted.

Evaluation of oxidative stress and antioxidant status: Correlation with the severity of sepsis.

Sepsis is a condition caused by infection followed by unregulated inflammatory response which may lead to the organ dysfunction. During such condition, over-production of oxidants is one of the factors which contribute cellular toxicity and ultimately organ failure and mortality. Antioxidants having free radicals scavenging activity exert protective role in various diseases. This study has been designed to evaluate the levels of oxidative and antioxidative activity in sepsis patients and their correlation with the severity of the sepsis. A total of 100 sepsis patients and 50 healthy controls subjects were enrolled in this study from the period October 2016 to June 2017. The investigation included measurements of oxidative enzyme, myeloperoxidase (MPO), antioxidant enzymes including superoxide dismutase activity (SOD) and catalase activity (CAT) and cytokines (TNF-α, IL-8 and IFN-γ). Furthermore, the level of these activities was correlated with severity of sepsis. Augmented levels of oxidants were found in sepsis as demonstrated by DMPO nitrone adduct formation and plasma MPO level activity (1.37 ± 0.51 in sepsis vs 0.405 ± 0.16 in control subjects). Cytokines were also found to be increased in sepsis patients. However, plasma SOD and CAT activities were significantly attenuated (P < .001) in the sepsis patients compared with controls subjects. Moreover, inverse relation between antioxidant enzymes (SOD and CAT) and organ failure assessment (SOFA), physiological score (APACHE II), organ toxicity specific markers have been observed as demonstrated by Pearson's correlation coefficient. This study suggests that imbalance between oxidant and antioxidant plays key role in the severity of sepsis.

Harmonic analysis of peripheral pulse for screening subjects at high risk of diabetes.

Power spectral density (PSD) of peripheral pulses in human has been investigated in the past for its clinical applications. Continuing the efforts, data acquired using Peripheral Pulse Analyser in research projects sponsored by Board of Research in Nuclear Sciences in 207 control subjects, 18 descendants of diabetic patients and 22 patients with systemic hypertension have been subjected to PSD analysis for its study of harmonics. Application software, named Pulse Harmonic Analyser specifically developed for this work, selected 131,072 samples from each data file, obtained PSD, derived 52 PHA parameters and saved them in an Excel sheet. Coefficient of variation in control data was reduced significantly by application of Central Limit Theorem, which enabled use of parametric methods for statistical analysis of the observations. Data in hypertensive patients have shown significant difference in comparison to that of controls in eight parameters at low values of α and ß. Data in offspring of diabetic patients also have shown significant difference in one parameter indicating its usefulness in screening subjects with genetic disposition of acquiring Type-II Diabetes. PHA analysis has also yielded sub-harmonic components, which are related to combined variability in the heart rate, pulse volume and pulse morphology and has a potential to become method of choice for real time variability monitoring.

Mild Traumatic Brain Injury Leads to Decreased Inhibition and a Differential Response of Calretinin Positive Interneurons in the Injured Cortex.

It is clear that even mild forms of traumatic brain injury (TBI) can have lasting cognitive effects; however, the specific cellular changes responsible for the functional deficits remain poorly understood. Previous studies suggest that not all neurons respond in the same way and that changes to neuronal architecture may be subtype specific. The current study aimed to characterize the response of interneurons to TBI. To model TBI in vitro, the neurites of primary cortical neurons were transected at 15 days in vitro. In response, calretinin+ interneurons underwent significant neurite remodeling around the injury site. By examining the response of pyramidal neurons, GAD67-GFP+ interneurons, and calretinin+ interneurons to the injury, we found that this response was specific to the calretinin+ cells. To determine whether calretinin+ interneurons respond in this way to a clinically relevant in vivo model of mild diffuse and focal injury, we subjected mice to the lateral fluid percussion injury model. We found that calretinin+ interneuron density was unaltered by this mild injury, but consistent with our in vitro data, these neurons underwent morphological alterations in their dendrites. These alterations evolved over a 28-day period, and calretinin+ interneurons in the injured mice had a reduction in mean dendrite length and reduced number of secondary dendrites than those in the sham-injured controls by 7 days post-injury. Further, these structural alterations were accompanied by a reduction in the frequency of miniature inhibitory post-synaptic currents in layer V pyramidal neurons. These data suggest that even a mild TBI can lead to an overall change in the excitatory/inhibitory balance of the cortex that may play an important role in the longer-term behavioral pathology associated with mild TBI.

A Case for Microtubule Vulnerability in Amyotrophic Lateral Sclerosis: Altered Dynamics During Disease.

Amyotrophic lateral sclerosis (ALS) is an aggressive multifactorial disease converging on a common pathology: the degeneration of motor neurons (MNs), their axons and neuromuscular synapses. This vulnerability and dysfunction of MNs highlights the dependency of these large cells on their intracellular machinery. Neuronal microtubules (MTs) are intracellular structures that facilitate a myriad of vital neuronal functions, including activity dependent axonal transport. In ALS, it is becoming increasingly apparent that MTs are likely to be a critical component of this disease. Not only are disruptions in this intracellular machinery present in the vast majority of seemingly sporadic cases, recent research has revealed that mutation to a microtubule protein, the tubulin isoform TUBA4A, is sufficient to cause a familial, albeit rare, form of disease. In both sporadic and familial disease, studies have provided evidence that microtubule mediated deficits in axonal transport are the tipping point for MN survivability. Axonal transport deficits would lead to abnormal mitochondrial recycling, decreased vesicle and mRNA transport and limited signaling of key survival factors from the neurons peripheral synapses, causing the characteristic peripheral "die back". This disruption to microtubule dependant transport in ALS has been shown to result from alterations in the phenomenon of microtubule dynamic instability: the rapid growth and shrinkage of microtubule polymers. This is accomplished primarily due to aberrant alterations to microtubule associated proteins (MAPs) that regulate microtubule stability. Indeed, the current literature would argue that microtubule stability, particularly alterations in their dynamics, may be the initial driving force behind many familial and sporadic insults in ALS. Pharmacological stabilization of the microtubule network offers an attractive therapeutic strategy in ALS; indeed it has shown promise in many neurological disorders, ALS included. However, the pathophysiological involvement of MTs and their functions is still poorly understood in ALS. Future investigations will hopefully uncover further therapeutic targets that may aid in combating this awful disease.