Pharmaco-Magnetic Resonance as Tool for Monitoring the Medication-Related Effects in the Brain May Provide Potential Biomarkers for Psychotic Disorders

Psychotic disorders occur as a result of pathobiochemical processes in the brain, which disrupt the central neurotransmission of molecules such as dopamine and glutamate. The dopamine hypothesis, adopted more than 2 decades ago, has repeatedly asserted its position as an etiopathogenetic substrate through the action of psychostimulants and neuroleptics on the mesolimbic and mesocortical systems, giving insight into the origin of positive and negative schizophrenic symptoms. On the other hand, cognitive impairments in schizophrenia remain not fully understood but are thought to be present during all stages of the disease, as well as in the prodromal the interictal and residual phases. Over the last decade, functional magnetic resonance imaging has focused on research of brain networks like the Default mode network, the Salience network and Central executive network, enabling a deeper understanding of cognitive deficits, as well as other phenomena such as disorganization of thought and behavior. The study of the nodes of these networks, such as the precuneus and insula, informs about their complex significant roles as structures responsible for important cognitive domains such as concentration, attention, ability to understand and reproduce information, as well as memory functions. It is suggested that the neurotransmission of dopamine and glutamate play a key role in these processes and their successful modulation in the correct brain regions through psychopharmacological and biomedical instrumental methods may lead to a significant reversal of conventional paradigms. Pharmaco-magnetic resonance imaging is a neuroimaging method that can provide the translation of scientific knowledge about the neural networks and the disruptions in and between different brain regions, into clinically applicable and effective therapeutic results in the management of severe psychotic disorders.

Cumin Prevents 17β-Estradiol-Associated Breast Cancer in ACI Rats

Breast cancer (BC) is a leading cause of cancer deaths in women in less developed countries and the second leading cause of cancer death in women in the U.S. In this study, we report the inhibition of E2-mediated mammary tumorigenesis by Cuminum cyminum (cumin) administered via the diet as cumin powder, as well as dried ethanolic extract. Groups of female ACI rats were given either an AIN-93M diet or a diet supplemented with cumin powder (5% and 7.5%, w/w) or dried ethanolic cumin extract (1%, w/w), and then challenged with subcutaneous E2 silastic implants (1.2 cm; 9 mg). The first appearance of a palpable mammary tumor was significantly delayed by both the cumin powder and extract. At the end of the study, the tumor incidence was 96% in the control group, whereas only 55% and 45% animals had palpable tumors in the cumin powder and extract groups, respectively. Significant reductions in tumor volume (660 ± 122 vs. 138 ± 49 and 75 ± 46 mm3) and tumor multiplicity (4.21 ± 0.43 vs. 1.16 ± 0.26 and 0.9 ± 0.29 tumors/animal) were also observed by the cumin powder and cumin extract groups, respectively. The cumin powder diet intervention dose- and time-dependently offset E2-related pituitary growth, and reduced the levels of circulating prolactin and the levels of PCNA in the mammary tissues. Mechanistically, the cumin powder diet resulted in a significant reversal of E2-associated modulation in ERα, CYP1A1 and CYP1B1. Further, the cumin powder diet reversed the expression levels of miRNAs (miR-182, miR-375, miR-127 and miR-206) that were highly modulated by E2 treatment. We analyzed the composition of the extract by GC/MS and established cymene and cuminaldehyde as major components, and further detected no signs of gross or systemic toxicity. Thus, cumin bioactives can significantly delay and prevent E2-mediated mammary tumorigenesis in a safe and effective manner, and warrant continued efforts to develop these clinically translatable spice bioactives as chemopreventives and therapeutics against BC.

Cognitive impairment reversed by cinacalcet administration in primary hyperparathyroidism

Primary hyperparathyroidism (pHPT) is a common endocrine disorder. Often serum calcium is minimally elevated with few symptoms. In elderly patients with multiple co-morbidities, the decision to “watch and wait” is often most clinically appropriate as operative intervention is associated with high peri-operative risk. We present an elderly patient with mild hypercalcemia secondary to primary hyperparathyroidism. The clinical decision was initially to watch and wait. The patient subsequently developed cognitive impairment and was diagnosed with mixed Alzheimer’s disease/vascular dementia. She became dependent for all care and housebound. A therapeutic trial of cinacalcet was commenced following a further acute rise in serum calcium. Significant reversal of her functional and cognitive deficit occurred. She was no longer fully dependent. Mini mental state examination (MMSE) improved from 8/30 to 21/30. In vulnerable neural systems, even mild elevation in serum calcium may have a profound effect on cognition and function. We propose a therapeutic trial of cinacalcet in such patients.

AZELAIC ACID ATTENUATESROTENONE-INDUCED BEHAVIOURAL ALTERATIONS IN PARKINSON’S DISEASE RAT MODEL

In the current study, we investigated the anti-Parkinson’s effect of azelaic acid (AA; 20 mg/kg, 40mg/kg, 80 mg/kg p.o.) against rotenone (2 mg/kg s.c.) induced Parkinson’s disease (PD) rat model. Rotenone was administered continuously for 35 days and caused behavioural alterations such as catalepsy, rigidity in muscles, posture instability and decrease in body weight, locomotor activity, and rearing behaviour.AAshowed significant (p<0.05) reversal in behavioural alterations induced by rotenone at 80 mg/kg dose on 28th and 35th day of treatment. Administration of azelaic acid along with levodopa-carbidopa (100mg/kg+25mg/kg p.o.) also showed significant reversal of behavioural alterations induced by rotenone and this effect was comparable to the effect of levodopa-carbidopa treatment group. The study proved the ameliorative effect of azelaic acidin rotenone induced PD rat model indicating its possible therapeutic potential for this devastating disease.

Coronavirus Disease 2019 (COVID-19) Transmission in the United States Before Versus After Relaxation of Statewide Social Distancing Measures

Background Weeks after issuing social distancing orders to suppress severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and reduce growth in cases of severe coronavirus disease 2019 (COVID-19), all US states and the District of Columbia partially or fully relaxed these measures. Methods We identified all statewide social distancing measures that were implemented and/or relaxed in the United States between 10 March and 15 July 2020, triangulating data from state government and third-party sources. Using segmented linear regression, we estimated the extent to which relaxation of social distancing affected epidemic control, as indicated by the time-varying, state-specific effective reproduction number (Rt). Results In the 8 weeks prior to relaxation, mean Rt declined by 0.012 units per day (95% confidence interval [CI], −.013 to −.012), and 46/51 jurisdictions achieved Rt &lt; 1.0 by the date of relaxation. After relaxation of social distancing, Rt reversed course and began increasing by 0.007 units per day (95% CI, .006–.007), reaching a mean Rt of 1.16. Eight weeks later, the mean Rt was 1.16 and only 9/51 jurisdictions were maintaining an Rt &lt; 1.0. Parallel models showed similar reversals in the growth of COVID-19 cases and deaths. Indicators often used to motivate relaxation at the time of relaxation (eg, test positivity rate &lt;5%) predicted greater postrelaxation epidemic growth. Conclusions We detected an immediate and significant reversal in SARS-CoV-2 epidemic suppression after relaxation of social distancing measures across the United States. Premature relaxation of social distancing measures undermined the country’s ability to control the disease burden associated with COVID-19.

Nootropic Effect of Fenugreek Seed Extract against Scopolamine Induced Cognitive Decline in Experimental Mice

Background: Alzheimer&rsquo;s disease affecting about 24 million people world-wide. The socio-economic burden on world-economies costing more than 172 billion US $ annually for the US alone. Objectives: To prepare aqueous extract of T. foenum graecum seeds (FSE) to explore the possible treatment for cognitive deficit in experimental animals. Materials and methods: FSE was subjected to preliminary phytochemical evaluation and antioxidant effect using free radical scavenging method (DPPH). All the animal behavior was video recorded with no human intervention during observation and animal groupings were blinded to avoid investigator bias. Different doses of FSE (5%, 10% and 20%), control, standard (Piracetam, 200 mg/kg, IP.) were given for male albino mice a period of 15 days followed by cognitive assessment in elevated plus maze and novel objection recognition tests. Ttransfer latencies and time exploring novel and familiar objects were recorded in respective tests. Retention of this learned-task was examined again 24 h later and inflexion ratio (IR) and discriminative index (DI) were calculated respectively. Next in the second set of experiment same groups and treatments were continued but scopolamine was administered to all the groups except normal control one hour after the last dose and examined similarly. Results: FSE showed potential antioxidant effect and a dose dependent increase in transfer latency and improved DI indicating a nootropic effect. FSE at 20% showed significant reversal of scopolamine induced dementia in the second set of experiment. Conclusion: FSE improved memory as well as reversed the chemically induced memory deficits in experimental mice.

Overpressure Identification Using The Eaton Method on The Gumai Formation of Geragai Graben, Jambi Sub Basin

Geragai graben is located in the South Sumatera Basin. It was formed by mega sequence tectonic process with various stratigraphic sequence from land and marine sedimentation. One of the overpressure indication zones in the Geragai graben is in the Gumai Formation, where the sedimentation is dominated by fine grained sand and shale with low porosity and permeability. The aim of the study is to localize the overpressure zone and to analyze the overpressure mechanism on the Gumai Formation. The Eaton method was used to determine pore pressure value using wireline log data, pressure data (RFT/FIT), and well report. The significant reversal of sonic and porosity log is indicating an overpressure presence. The cross-plot analysis of velocity vs density and fluid type data from well reports were used to analyze the causes of overpressure in the Gumai Formation. The overpressure in Gumai Formation of Geragai graben is divided into two zones, they are in the upper level and lower level of the Gumai Formation. Low overpressure have occurred in the Upper Gumai Formation and mild overpressure on the Lower Gumai Formation. Based on the analyzed data, it could be predicted, that the overpressure mechanism in the Upper Gumai Formation might have been caused by a hydrocarbon buoyancy, whereas in the Lower Gumai Formation, might have been caused by disequilibrium compaction as a result of massive shale sequence.

COVID-19 transmission in the U.S. before vs. after relaxation of state social distancing measures

Background: Weeks after issuing social distancing orders, all U.S. states and the District of Columbia at least partially relaxed these measures. Critical unanswered questions remain about the timing of relaxation, and if and how unregulated social distancing measures can be sustained while effectively maintaining epidemic control. Methods: We identified all statewide social distancing measures that were implemented and/or relaxed in the U.S. between March 10-July 15, 2020, triangulating data from state government and third-party sources. Using segmented linear regression, we evaluated the extent to which social distancing measure relaxation affected epidemic control, as indicated by the time-varying, state-specific effective reproduction number (R[t]). Results: In the eight weeks prior to relaxation, mean R[t] declined by 0.012 units per day (95% CI, -0.013 to -0.012), and 46/51 jurisdictions achieved R[t] < 1.0 by the date of relaxation. After relaxation of social distancing, R[t] reversed course and began increasing by 0.007 units per day (95% CI, 0.006-0.007), reaching a mean R[t] of 1.16 eight weeks later, with only 9/51 jurisdictions maintaining R[t] <1.0. Indicators often used to motivate relaxation at the time of relaxation (e.g. test positivity rate <5%) predicted greater post-relaxation epidemic growth. Conclusions: We detected an immediate and significant reversal in epidemic growth gains after relaxation of social distancing measures across the U.S. These results illustrate the potential pitfalls of premature relaxation of social distancing measures in the U.S.

GABA and 5-HT Receptor Mediated Anxiolytic Effect of Essential Oil of Ferula sumbul Hook. Roots

Background: Ferula sumbul Hook. (Umbelliferae) roots have been traditionally used as sedative in nervous disorders. Objective: The present study identifies the components of essential oil of F. sumbul roots (EOFS) using GC-MS analysis and further evaluates mechanism-based anxiolytic potential of oil. Materials and Methods: EOFS was extracted using Clevenger apparatus, and was screened for anxiolytic activity using an elevated plus maze model. A battery of models was subsequently used to confirm the anxiolytic potential of EOFS. Further, benzodiazepine (BZD) receptor antagonist flumazenil and pentylenetetrazole (PTZ) were used for investigating the possible involvement of GABA receptors. Results: GC-MS analysis of EOFS revealed the presence of 32 components comprising triterpenoids and their derivatives. The oil exhibited significant anxiolytic activity at 50 μl/kg in various models like the elevated plus maze, light/dark, mirror chamber, open-field and mCPP-induced anxiety. The observation that anxiolytic effect of EOFS was completely blocked by benzodiazepine (BZD) receptor antagonist flumazenil, and partially by pentylenetetrazole, clearly demonstrates that anxiolytic activity of the oil is mediated mainly through BZD site on GABA receptors. Further, a significant reversal of mCPP induced anxiety by EOFS strongly indicates the possible involvement of 5-HT receptors in mediating anxiolytic activity of the oil. Conclusion: Results of the present study clearly demonstrates the anxiolytic potential of EOFS and, thus, validates the traditional relevance of the plant. This is the first report not only on multi-model based antianxiety activity of EOFS but also on the possible antianxiety mechanism of the oil.

Do momentum and reversal strategies work in commodity futures? A comprehensive study

PurposeMotivated by the debate on the patterns and sources of commodity futures returns, this paper investigates the performance of three investment trading strategies, namely, the momentum strategy of Jegadeesh and Titman (1993), the 52-week high momentum strategy of George and Hwang (2004) and the pairs trading strategy of Gatev et al. (2006) in the commodity futures market.Design/methodology/approachThe three strategies are those given by Jegadeesh and Titman (1993), George and Hwang (2004) and Gatev et al. (2006), respectively.FindingsThe authors find that there is no significant reversal profit across 189 formation-holding windows for all the three strategies. However, there are statistical and economically significant momentum profits, and the profitability increases with the rising of formation-holding periods. Momentum returns are quite sensitive to market conditions but the crash of momentum returns is partly predictable. Return seasonality, risk and herding also provide partial explanation of the momentum profits.Originality/valueThe authors are the first to compare the performances of the pairs trading strategy of Gatev et al. (2006), the conventional momentum of Jegadeesh and Titman (1993), and the 52-week high momentum of George and Hwang (2004) under 189 formation-holding windows. Also, the authors are the first to investigate the association between herding behaviour and momentum returns in the commodity futures market.