Effect of Yoga on the Stress, Anxiety, and Depression of COVID-19-Positive Patients: A Quasi-Randomized Controlled Study.

The spread of COVID-19 has resulted in reports of increase in stress, anxiety, and depression across society, especially in people who have tested positive for COVID-19, which affects their mental health and well-being. This article reports a quasi-randomized controlled study conducted in the COVID wards of a hospital to examine the efficacy of add-on yoga intervention in reducing stress, anxiety, and depression in COVID-affected patients under quarantine. The peripheral capillary oxygen saturation level and heart rate of the COVID-19-affected patients were also measured. A total of 62 COVID-19-positive patients participated in the study. The participants were randomized into a control group (n = 31), which received conventional medical treatment alone, and a yoga intervention group (n = 31), which received 50 minutes of yoga intervention along with the conventional medical treatment. Standardized Hospital Anxiety and Depression Scale, Generalized Anxiety Disorder-7 Item, Patient Health Questionnaire-9, and Perceived Stress Scale were administered at the beginning and end of the quarantine period. A significant decrease in stress, anxiety, and depression was observed in the patients who undertook the add-on yoga intervention. There was also a significant decrease in anxiety in the control group, but the intervention group had a larger decrease compared to the control group. Further significant improvements in oxygen saturation and heart rate levels were observed in the group of patients who were practicing yoga, but no significant improvement was observed in the control group. Findings of this study suggest that yoga intervention can be an effective add-on practice in reducing stress, anxiety, and depression levels of COVID-19 patients.

Intracardiac administration of ephrinA1-Fc preserves mitochondrial bioenergetics during acute ischemia/reperfusion injury.

AIMS: Intracardiac injection of recombinant EphrinA1-Fc immediately following coronary artery ligation in mice reduces infarct size in both reperfused and non-reperfused myocardium, but the cellular alterations behind this phenomenon remain unknown. MAIN METHODS: Herein, 10 wk-old B6129SF2/J male mice were exposed to acute ischemia/reperfusion (30minI/24hrsR) injury immediately followed by intracardiac injection of either EphrinA1-Fc or IgG-Fc. After 24 h of reperfusion, sections of the infarct margin in the left ventricle were imaged via transmission electron microscopy, and mitochondrial function was assessed in both permeabilized fibers and isolated mitochondria, to examine mitochondrial structure, function, and energetics in the early stages of repair. KEY FINDINGS: At a structural level, EphrinA1-Fc administration prevented the I/R-induced loss of sarcomere alignment and mitochondrial organization along the Z disks, as well as disorganization of the cristae and loss of inter-mitochondrial junctions. With respect to bioenergetics, loss of respiratory function induced by I/R was prevented by EphrinA1-Fc. Preservation of cardiac bioenergetics was not due to changes in mitochondrial JH2O2 emitting potential, membrane potential, ADP affinity, efficiency of ATP production, or activity of the main dehydrogenase enzymes, suggesting that EphrinA1-Fc indirectly maintains respiratory function via preservation of the mitochondrial network. Moreover, these protective effects were lost in isolated mitochondria, further emphasizing the importance of the intact cardiomyocyte ultrastructure in mitochondrial energetics. SIGNIFICANCE: Collectively, these data suggest that intracardiac injection of EphrinA1-Fc protects cardiac function by preserving cardiomyocyte structure and mitochondrial bioenergetics, thus emerging as a potential therapeutic strategy in I/R injury.

Brain neurochemistry in unmedicated obsessive-compulsive disorder patients and effects of 12-week escitalopram treatment: 1 H-magnetic resonance spectroscopy study.

AIM: The purpose of this study was to examine treatment-related neurochemical changes in 28 unmedicated obsessive-compulsive disorder (OCD) patients using 1 H-magnetic resonance spectroscopy (1 H-MRS). METHODS: We included subjects diagnosed with OCD (n = 28), each with a total duration of illness of less than 5 years, as a study group and age- and sex-matched healthy controls (n = 26). The inclusion criteria for the OCD group were right-handed individuals aged 18 years or older who had not been on any specific treatment for OCD for the last at least 8 weeks and who had no other psychiatric comorbidity. A pre-post and case-control design was employed in which OCD patients underwent 1 H-MRS at baseline and 12 weeks after treatment with escitalopram (n = 21). Clinical assessment was carried out using a semi-structured pro forma Yale-Brown Obsessive Compulsive Scale and the World Health Organization Disability Assessment Scale 2.0 before and after treatment. Volume-localized 1 H-MRS was carried out with a 3-Tesla Philips MR scanner. RESULTS: Our data suggested higher levels of myoinositol (mI), total choline (tCho), and glutamate+glutamine (Glx) in the medial thalamus at pre-assessment in OCD subjects as compared to healthy controls and a significant reduction in tCho and Glx after treatment in OCD subjects. The mI levels in the caudate nucleus and Glx levels in the anterior cingulate cortex were significantly correlated with disease severity on the Yale-Brown Obsessive Compulsive Scale. CONCLUSION: Our study supports the hypothesis of a hyper-glutaminergic state (as suggested by increased Glx levels) and neurodegeneration (as suggested by increased tCho and mI in the thalamus) in cortico-striato-thalamocortical circuitry in OCD patients as suggested by previous studies using MRS as well as other functional imaging studies.

Multi-functional nanoparticles as theranostic agents for the treatment & imaging of pancreatic cancer.

Theranostics has received considerable attention since both therapy and imaging modalities can be integrated into a single nanocarrier. In this study, fluorescent iron oxide (FIO) nanoparticles and gemcitabine (G) encapsulated poly(lactide-co-glycolide) (PLGA) nanospheres (PGFIO) conjugated with human epidermal growth factor receptor 2, (HER-2) antibody (HER-PGFIO) were prepared and characterized. HER-PGFIO showed the magnetic moment of 10emu/g, relaxivity (r2) of 773mM-1s-1 and specific absorption rate (SAR) of 183W/g. HER-PGFIO showed a sustained release of gemcitabine for 11days in PBS (pH 7.4). In vitro cytotoxicity evaluation of HER-PGFIO in 3D MIAPaCa-2 cultures showed 50% inhibitory concentration (IC50) of 0.11mg/mL. Subcutaneous tumor xenografts of MIAPaCa-2 in SCID mice were developed and the tumor regression study at the end of 30days showed significant tumor regression (86±3%) in the HER-PGFIO with magnetic hyperthermia (MHT) treatment group compared to control group. In vivo MRI imaging showed the enhanced contrast in HER-PGFIO+MHT treated group compared to control. HER-PGFIO showed significant tumor regression and enhanced MRI in treatment groups, which could be an effective nanocarrier system for the treatment of pancreatic cancer. STATEMENT OF SIGNIFICANCE: Combination therapies are best suitable to treat pancreatic cancer. Theranostics are the next generation therapeutics with both imaging and treatment agents encapsulated in a single nanocarrier. The novelty of the present work is the development of targeted nanocarrier that provides chemotherapy, thermotherapy and MRI imaging properties. The present work is the next step in developing the nanocarriers for pancreatic cancer treatment. Different treatment modalities embedding into a single nanocarrier is the biggest challenge that was achieved without compromising the functionality of each other. The surface modification of polymeric nanocarriers for antibody binding and their multifunctional abilities will appeal to wider audience.

Medicinal attributes of major phenylpropanoids present in cinnamon.

BACKGROUND: Excessive production of free radicals has been implicated in many diseases including cancer. They are highly reactive and bring about oxidation of biomolecules i.e., proteins, lipids and nucleic acids which are associated with many degenerative diseases. Natural products acting as antioxidants have ability to neutralize free radicals and their actions and hence they mitigate their harmful effects. The present study was designed to investigate pharmacological properties viz., antioxidant, antibacterial and antiproliferative activities of cinnamaldehyde and eugenol, the two naturally occurring phenylpropanoids present in Cinnamomum spp. and other plants. METHODS: The antioxidant potential of test compounds was evaluated by measuring DPPH free radical scavenging, reducing power and metal ion chelating activities. Protection against membrane damage was assayed by inhibition of lipid peroxidation in rat liver homogenate. Antibacterial activity was measured by Kirby-Bauer disc diffusion method while antiproliferative activity of test compounds was measured by sulforhodamine-B (SRB) assay. RESULTS: Eugenol exhibited noticeable antioxidant potential in DPPH radical scavenging (81 %) and reducing power (1.12) assays at 1.0 µM/ml and 0.1 µM/ml concentrations, respectively. IC50 value of eugenol for radical scavenging activity was found to be 0.495 µM/ml. Cinnamaldehyde demonstrated considerable metal ion chelating ability (75 %) at 50 µM/ml and moderate lipo-protective activity in lipid peroxidation assay at 3 µM/ml. In addition cinnamaldehyde also showed appreciable antibacterial activity (zone of inhibition 32-42 mm) against Bacillus cereus (MTCC 6840), Streptococcus mutans (MTCC 497), Proteus vulgaris (MTCC 7299), Salmonella typhi (MTCC 3917) and Bordetella bronchiseptica (MTCC 6838) while eugenol produced moderate activity at 80 µM/disc. Cinnamaldehyde exhibited comparatively better antiproliferative potential against breast (T47D) and lung (NCI-H322) cancer cell lines than eugenol in SRB assay at 50 µM concentration. CONCLUSION: Cinnamaldehyde possessed metal ion chelating, lipo-protective, antibacterial and antiproliferative activities while eugenol showed potent H-atom donating potential indicating radical quenching and reducing power abilities. Medicinal attributes shown by both the compounds indicated their usefulness in food and pharmaceutical sector.

High resolution 1H NMR-based metabonomic study of the auditory cortex analogue of developing chick (Gallus gallus domesticus) following prenatal chronic loud music and noise exposure.

Proper functional development of the auditory cortex (ACx) critically depends on early relevant sensory experiences. Exposure to high intensity noise (industrial/traffic) and music, a current public health concern, may disrupt the proper development of the ACx and associated behavior. The biochemical mechanisms associated with such activity dependent changes during development are poorly understood. Here we report the effects of prenatal chronic (last 10 days of incubation), 110dB sound pressure level (SPL) music and noise exposure on metabolic profile of the auditory cortex analogue/field L (AuL) in domestic chicks. Perchloric acid extracts of AuL of post hatch day 1 chicks from control, music and noise groups were subjected to high resolution (700MHz) (1)H NMR spectroscopy. Multivariate regression analysis of the concentration data of 18 metabolites revealed a significant class separation between control and loud sound exposed groups, indicating a metabolic perturbation. Comparison of absolute concentration of metabolites showed that overstimulation with loud sound, independent of spectral characteristics (music or noise) led to extensive usage of major energy metabolites, e.g., glucose, ß-hydroxybutyrate and ATP. On the other hand, high glutamine levels and sustained levels of neuromodulators and alternate energy sources, e.g., creatine, ascorbate and lactate indicated a systems restorative measure in a condition of neuronal hyperactivity. At the same time, decreased aspartate and taurine levels in the noise group suggested a differential impact of prenatal chronic loud noise over music exposure. Thus prenatal exposure to loud sound especially noise alters the metabolic activity in the AuL which in turn can affect the functional development and later auditory associated behaviour.

Ethnobotany of religious and supernatural beliefs of the Mising tribes of Assam with special reference to the 'Dobur Uie'.

Assam is very rich in plant biodiversity as well as in ethnic diversity and has a great traditional knowledge base in plant resources. It is inhabited by the largest number of tribes and they lead an intricate life totally dependent on forest plants. The Mising is the major section and second largest tribal community of Assam and have a rich tradition of religion and culture. Their religious practices and beliefs are based on supernaturalism. A study of the plants related to magico religious beliefs in Dobur Uie of Mising is carried out. The results revealed the use of 30 plants belonging to 23 families. All plant species are used both in religious purpose as well as in the treatment of different ailments. Details of the uses of plants and conservational practices employed in Dobur Uie are provided. Our findings on the use of plants in Dobur Uie ritual reflect that some plants are facing problems for survival and they need urgent conservation before their elimination. Because this elimination may threat the rich tradition of Mising culture. Most of the plants that are domesticated for different rituals are almost same in all Mising populated areas.

Composite polymeric magnetic nanoparticles for co-delivery of hydrophobic and hydrophilic anticancer drugs and MRI imaging for cancer therapy.

Exercising complementary roles of polymer-coated magnetic nanoparticles for precise drug delivery and image contrast agents has attracted significant attention in biomedical applications. The objective of this study was to prepare and characterize magnetic nanoparticles embedded in polylactide-co-glycolide matrixes (PLGA-MNPs) as a dual drug delivery and imaging system capable of encapsulating both hydrophilic and hydrophobic drugs. PLGA-MNPs were capable of encapsulating both hydrophobic and hydrophilic drugs in a 2:1 ratio. Biocompatibility, cellular uptake, cytotoxicity, membrane potential, and apoptosis were carried out in two different cancer cell lines (MCF-7 and PANC-1). The molecular basis of induction of apoptosis was validated by Western blotting analysis. For targeted delivery of drugs, targeting ligand such as Herceptin was used, and such a conjugated system demonstrated enhanced cellular uptake and an augmented synergistic effect in an in vitro system when compared with native drugs. Magnetic resonance imaging was carried out both in vitro and in vivo to assess the efficacy of PLGA-MNPs as contrast agents. PLGA-MNPs showed a better contrast effect than commercial contrast agents due to higher T(2) relaxivity with a blood circulation half-life ∼ 47 min in the rat model. Thus, our results demonstrated the dual usable purpose of formulated PLGA-MNPs toward either, in therapeutics by delivering different hydrophobic or hydrophilic drugs individually or in combination and imaging for cancer therapeutics in the near future.

Effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in vitamin D-deficient Asian Indians: a randomized, controlled trial.

CONTEXT: Vitamin D deficiency is prevalent worldwide. Vitamin D supplementation has shown variable effect on skeletal muscle strength in the elderly with hypovitaminosis D. There is a paucity of similar data in young individuals. OBJECTIVE: To study the effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in young individuals. SUBJECTS: Forty healthy volunteers (24 M/16 F, mean age (SD) 31.5 ± 5.0 year) with hypovitaminosis D were randomized to either oral cholecalciferol (60,000 IU D3/week for 8 weeks followed by 60,000 IU/month for 4 months) with 1 g of elemental calcium daily or dual placebos for 6 months. MEASUREMENTS: Handgrip and gastro-soleus dynamometry, pinch-grip strength, respiratory pressures, 6-min walk-test and muscle energy metabolism on (31) P magnetic resonance spectroscopy were assessed at baseline and after 6 months. RESULTS: The mean serum 25(OH)D in the supplemented and placebo groups at baseline, two and 6 months were 25.4 ± 9.9, 94.5 ± 53.8 and 56.0 ± 17.0 nm, and 21.1 ± 9.4, 32.8 ± 14.4 and 29.7 ± 15.0 nm, respectively. The supplemented group gained a handgrip strength of 2.4 kg (95% C.I. = 1.2-3.6); gastro-soleus strength of 3.0 Nm (95% C.I. = 0.1-5.9) and walking distance of 15.9 m (95% C.I. = 6.3-25.5) over the placebo group after adjustment for age, gender and respective baseline parameters. Muscle energy parameters were comparable at 6 months. CONCLUSIONS: Six months of cholecalciferol and calcium supplementation results in enhanced skeletal muscle strength and physical performance despite no change in muscle energy parameters. Cholecalciferol supplementation of 60,000 IU per month could not maintain 25(OH)D levels in the sufficient range.

Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized, placebo-controlled 31P MRS study.

Randomized, placebo-controlled single blinded study was carried out to evaluate the effect of oral creatine supplementation on cellular energetics, manual muscle test (MMT) score and functional status in steroid-naive, ambulatory boys suffering with Duchenne muscular dystrophy (DMD; n=33). Eighteen patients received creatine monohydrate (Cr; 5 g/day for 8 weeks), while 15 received placebo (500 mg of vitamin C). Phosphorus metabolite ratios were determined from the right calf muscle of patients using phosphorus magnetic resonance spectroscopy ((31)P MRS) both prior to (baseline) and after supplementation of Cr or placebo. In addition, metabolite ratios were determined in normal calf muscle of age and sex matched controls (n=8). Significant differences in several metabolite ratios were observed between controls and DMD patients indicating a lower energy state in these patients. Analysis using analysis of covariance adjusted for age and stature showed that the mean phosphocreatine (PCr)/inorganic phosphate (Pi) ratio in patients treated with Cr (4.7; 95% CI; 3.9-5.6) was significantly higher (P=.03) compared to the placebo group (3.3; 95% CI; 2.5-4.2). The mean percentage increase in PCr/Pi ratio was also more in patients <7 years of age compared to older patients after Cr supplementation indicating variation in therapeutic effect with the age. In the placebo group, significant reduction in PCr/Pi (P=.0009), PCr/t-ATP (P=.05) and an increase in phosphodiester (PDE)/PCr ratios was observed after supplementation. Further, in the placebo group, patients <7 years showed reduction of PCr/t-ATP and Pi/t-ATP compared to older patients (>7 years), after supplementation. These results imply that the significant difference observed in PCr/Pi ratio between the Cr and the placebo groups after supplementation may be attributed to a decrease of PCr in the placebo group and an increase in PCr in the Cr group. Changes in MMT score between the two groups was significant (P=.04); however, no change in functional scale (P=.19) was observed. Parents reported subjective improvement on Cr supplementation versus worsening in placebo (P=.02). Our results indicated that Cr was well tolerated and oral Cr significantly improved the muscle PCr/Pi ratio and preserved the muscle strength in short term. However, this study provides no evidence that creatine will prove beneficial after long-term treatment, or have any positive effect on patient lifespan.

Neuroprotective efficacy and therapeutic window of curcuma oil: in rat embolic stroke model.

BACKGROUND: Among the naturally occurring compounds, turmeric from the dried rhizome of the plant Curcuma longa has long been used extensively as a condiment and a household remedy all over Southeast Asia. Turmeric contains essential oil, yellow pigments (curcuminoids), starch and oleoresin. The present study was designed for investigating the neuroprotective efficacy and the time window for effective therapeutic use of Curcuma oil (C. oil). METHOD: In the present study, the effect of post ischemic treatment of C.oil after ischemia induced by occlusion of the middle cerebral artery in the rat was observed. C.oil (500 mg/kg body wt) was given 4 hrs post ischemia. The significant effect on lesion size as visualized by using diffusion-weighted magnetic resonance imaging and neuroscore was still evident when treatment was started 4 hours after insult. Animals were assessed for behavioral deficit scores after 5 and 24 hours of ischemia. Subsequently, the rats were sacrificed for evaluation of infarct and edema volumes and other parameters. RESULTS: C.oil ameliorated the ischemia induced neurological functional deficits and the infarct and edema volumes measured after 5 and 24 hrs of ischemia. After 24 hrs, immunohistochemical and Western blot analysis demonstrated that the expression of iNOS, cytochrome c and Bax/Bcl-2 were altered after the insult, and antagonized by treatment with C.oil. C.oil significantly reduced nitrosative stress, tended to correct the decreased mitochondrial membrane potential, and also affected caspase-3 activation finally apoptosis. CONCLUSION: Here we demonstrated that iNOS-derived NO produced during ischemic injury was crucial for the up-regulation of ischemic injury targets. C.oil down-regulates these targets this coincided with an increased survival rate of neurons.

Curcuma oil: reduces early accumulation of oxidative product and is anti-apoptogenic in transient focal ischemia in rat brain.

Turmeric is a source of numerous aromatic compounds isolated from powdered rhizomes of Curcuma longa Linn. The constituents are present as volatile oil, the Curcuma oil (C.oil), semi-solid oleoresins and non-volatile compounds such as curcumin. A rapidly expanding body of data provides evidence of the anti-cancer action of Curcumin, and most importantly in the present context, its neuroprotective activity. Almost nothing is known about such activity of C.oil. We report that C.oil (500 mg Kg(-1) i.p.) 15 min before 2 h middle cerebral artery occlusion (MCAo) followed by 24 h reflow in rats significantly diminished infarct volume, improved neurological deficit and counteracted oxidative stress. The percent ischemic lesion volume on diffusion-weighted imaging was significantly attenuated. Mitochondrial membrane potential, reactive oxygen species, peroxynitrite levels, caspase-3 activities leading to delayed neuronal death were significantly inhibited after treatment with C.oil. These results suggest that the neuroprotective activity of C.oil against cerebral ischemia is associated with its antioxidant activities and further; there is attenuation of delayed neuronal death via a caspase-dependent pathway. C.oil appears to be a promising agent not only for the treatment of cerebral stroke, but also for the treatment of other disorders associated with oxidative stress.

Potential of magnetic resonance spectroscopy to detect metastasis in axillary lymph nodes in breast cancer.

Focused pathological evaluation of axillary lymph nodes in breast cancer is gaining importance. Nuclear magnetic resonance (NMR) spectroscopy that assesses the whole of the specimen has the potential in evaluating micrometastases. The biochemical changes associated with breast cancer metastases in axillary nodes by in vitro NMR and its use in the detection of axillary metastases in a clinical setting in comparison with conventional histopathology is presented in this study. Eighty-eight lymph nodes obtained from 30 patients with breast cancer were investigated. Histopathology revealed metastases in 20 nodes from 11 patients, while in vitro NMR spectroscopy revealed metastases in 22 nodes. Out of these 22 nodes, 16 were the same, which showed metastases on histopathology, while 6 nodes have shown metastases only on in vitro magnetic resonance spectroscopy (MRS). These 6 nodes with suspicion of metastases on MRS were subjected to reevaluation with serial sectioning and immunohistochemistry, but no additional metastases were revealed. Forty metabolites could be identified from the MR spectrum of lymph nodes. The levels of the glycerophosphocholine-phosphocholine (GPC-PC), choline, lactate, alanine and uridine diphosphoglucose were elevated significantly in nodes with metastases. In addition, the intensity ratio of GPC-PC/threonine (Thr) was higher in nodes with metastases, and using this as marker, MRS detected the axillary metastases with a sensitivity, specificity and accuracy of 80%, 91% and 88%, respectively. Neoadjuvant chemotherapy (NACT) lowered the concentrations of GPC-PC and GPC-PC/Thr ratio. The accuracy of MRS in detecting metastases was 75% in patients who received NACT (n=9) as compared to 96% in those who did not (n=21). Our results demonstrate the potential of in vitro MRS in characterizing the metabolite profile of the axillary nodes with breast cancer metastases. It detected axillary metastases with reasonable accuracy and can be complementary to histopathological evaluation and immunohistochemistry.

Evaluation of Withania somnifera in a middle cerebral artery occlusion model of stroke in rats.

1. Stroke causes brain injury in millions of people worldwide each year. Despite the enormity of the problem, there is currently no approved therapy that can reduce infarct size or neurological disability. One of the approaches that can be used in limiting the neurological damage after stroke is the use of prophylactic treatment in patients with a high-risk of stroke. The present study was undertaken to investigate the effect of the Indian herbal plant Withania somnifera as a prophylactic treatment in the middle cerebral artery (MCA) occlusion model of stroke in rats. 2. Two groups of male Wistar rats were pretreated with a hydroalcoholic extract of W. somnifera (1 g/kg, p.o.) for 15 and 30 days. Thereafter, rats were subjected to focal ischaemia by occlusion of the MCA using an intraluminal thread. After 2 h MCA occlusion, reperfusion was allowed by retracting the thread. Animals were assessed for ischaemic changes using diffusion-weighted imaging 30 min after reperfusion. Twenty-four hours later, rats were subjected to motor performance tests and were subsequently killed for the estimation of the marker of oxidative stress malondialdehyde (MDA). The control group received vehicle and a similar protocol was followed. 3. Significant motor impairment, with elevated levels of MDA, was observed in vehicle-treated MCA-occluded rats. In addition, diffusion-weighted imaging showed increased signal intensity in the right hemisphere compared with the contralateral hemisphere. Treatment with W. somnifera for 15 days did not improve motor performance or decrease the elevated levels of MDA. However, when the pretreatment time of W. somnifera was increased to 30 days, it prevented motor impairment and significantly decreased the raised levels of MDA compared with vehicle-treated rats. In the W. somnifera (30 days)-pretreated group, the percentage hemispheric lesion area in diffusion-weighted imaging was significantly attenuated (17 +/- 2%) compared with the vehicle-treated MCA-occluded group (30 +/- 4%). 4. Because W. somnifera has been documented to have anti-oxidant properties, the protection afforded by W. somnifera could be due to its anti-oxidant effect. The present study provides first evidence of the effectiveness of an Indian herb in focal ischaemia.