TXA2 mediates LPA1-stimulated uterine contraction in late pregnant mouse.

Lysophosphatidic acid (LPA) is known to increase uterine contraction in the estrus cycle and early pregnancy, however, the effect of LPA in late pregnant uterus and its mechanisms are not clear. In the present study, we show the LPA receptor subtypes expressed and the mechanism of LPA-induced contractions in late pregnant mouse uterus. We determined the relative mRNA expression of LPA receptor genes by quantitative PCR and elicited log concentration-response curves to oleoyl-L-α-LPA by performing tension experiments in the presence and absence of nonselective and selective receptor antagonists and inhibitors of the TXA2 pathway. LPA1 was the most highly expressed receptor subtype in the late pregnant mouse uterus and LPA1/2/3 agonist (Oleoyl-L-α LPA) elicited increased contractions in this tissue that had lesser efficacy compared to oxytocin. LPA1/3 antagonist, Ki-16425, and a potent LPA1 antagonist (AM-095) significantly inhibited the LPA-induced contractions. Further, the nonselective COX inhibitor, indomethacin, and potent thromboxane A2 synthase inhibitor, furegrelate significantly impaired LPA-induced contractions. Moreover, selective thromboxane receptor (TP) antagonist, SQ-29548, and Rho kinase inhibitor, Y-27632 almost eliminated LPA-induced uterine contractions. LPA1 stimulation elicits contractions in the late pregnant mouse uterus using the contractile prostanoid, TXA2 and may be targeted to induce labor in uterine dysfunctions/ dystocia.

Hyperlipidemia impairs uterine ß-adrenergic signaling by reducing cAMP in late pregnant rats.

The aim of the present study was to reveal the effect of hyperlipidemia on ß2- and ß3-adrenergic signaling in late pregnant rat uterus. Hyperlipidemia was induced in female Wistar rats by feeding a high-fat high-cholesterol diet for 8 weeks before and after mating upto the 21st day of gestation. The effect of hyperlipidemia on ß-adrenergic signaling was studied with the help of tension experiments, real-time PCR and cAMP ELISA in 21-day pregnant rat uterus. In tension experiments, hyperlipidemia neither altered the spontaneous contractility nor the oxytocin-induced contractions. However, it decreased the -logEC50 values of ß2-adrenoceptor agonist, salbutamol and ß3-adrenoceptor agonist, BRL37344. It also decreased the efficacy of adenylyl cyclase activator, forskolin. Further, there was a significant decrease in salbutamol and BRL37344-stimulated cAMP content in uterine tissues. However, there was no alteration in mRNA expressions of ß2-adrenoceptor (Adrb2), ß3-adrenoceptor (Adrb3) and Gs protein (Gnas) though there was a significant increase in the mRNA expression of Gi protein (Gnai). In conclusion, reduced cAMP content after beta-adrenergic receptor stimulation, which correlates with an increase in Gnai mRNA, may explain the mechanism of the impairment of uterine ß-adrenergic signaling in hyperlipidemic pregnant rats. The clinical implication of the present study may relate to reduced myometrial relaxant response to ß-adrenergic agonists in high fat-induced uterine dysfunction.

Casein kinase 2 inhibition impairs spontaneous and oxytocin-induced contractions in late pregnant mouse uterus.

NEW FINDINGS: What is the central question of this study? Does the inhibition of the protein kinase casein kinase 2 (CK2) alter the uterine contractility? What is the main finding and its importance? Inhibition of CK2 impaired the spontaneous and oxytocin-induced contractility in late pregnant mouse uterus. This finding suggests that CK2 is a novel pathway mediating oxytocin-induced contractility in the uterus and thus opens up the possibility for this class of drugs to be developed as a new class of tocolytics. ABSTRACT: The protein kinase casein kinase 2 (CK2) is a ubiquitously expressed serine or threonine kinase known to phosphorylate a number of substrates. The aim of this study was to assess the effect of CK2 inhibition on spontaneous and oxytocin-induced uterine contractions in 19 day pregnant mice. The CK2 inhibitor CX-4945 elicited a concentration-dependent relaxation in late pregnant mouse uterus. CX-4945 and another selective CK2 inhibitor, apigenin, also inhibited the oxytocin-induced contractile response in late pregnant uterine tissue. Apigenin also blunted the prostaglandin F2α response, but CX-4945 did not. Casein kinase 2 was located in the lipid raft fractions of the cell membrane, and disruption of lipid rafts was found to reverse its effect. The results of the present study suggest that CK2, located in lipid rafts of the cell membrane, is an active regulator of spontaneous and oxytocin-induced uterine contractions in the late pregnant mouse.

Coleus aromaticus: a therapeutic herb with multiple potentials.

The herb Coleus aromaticus belonging to Lamiaceae family and Coleus genus is known by numerous names in different parts of the world and several language specific vernacular names. The herb has been extensively studied as well as reported in several fields of science. The multiple potential of the herb includes allelopathic potential, antibacterial property, antimicrobial activity, insecticidal property; free radical scavenging and radio-protective components from herb extracts and most recently the appetizing potential of the herb have been reported. The herb has carvacrol and thymol as the major components responsible for the flavour; while chlorogenic acid, rosmarinic acid etc. as the phenolic components. The herb has been used in therapeutic and medicinal applications as well as in culinary preparations.

Heavy metal accumulation analysis using bivalve, sponge, sea urchin, and gastropod species as bioindicators.

A comparative assessment of heavy metal accumulation potential in four distinct marine benthic bioindicators: the bivalve Perna perna, the sponge Callyspongia fibrosa, the sea urchin Tripneustes gratilla, and the gastropod Purpura bufo were conducted. These organisms were collected from the same location, and the concentration of ten heavy metals was analyzed in water, sediment and various body parts of the organisms. The bioaccumulation potential was evaluated using the bio-water accumulation factor and bio-sediment accumulation factor. There was significant variation in the bioaccumulation potential of each organism with respect to different metals. The sponge proved to be a reliable indicator of Cd with a highest concentration of 2.60 µg/g. Sea urchin accumulated high concentrations of Cr (16.98 µg/g) and Pb (4.80 µg/g), whereas Cu was predominant (21.05 µg/g) in gastropod, followed by bivalve (17.67 µg/g). The concentration of metals in hard parts was found to be lower than in the tissues.

Development of an ammonia-biodiesel dual fuel combustion engine's injection strategy map using response surface optimization and artificial neural network prediction.

The study intends to calibrate the compression ignition (CI) engine split injection parameters as efficiently. The goal of the study is to find the best split injection parameters for a dual-fuel engine that runs on 40% ammonia and 60% biodiesel at 80% load and a constant speed of 1500 rpm with the CRDi system. To optimize and forecast split injection settings, the RSM and an ANN model are created. Based on the experimental findings, the RSM optimization research recommends a per-injection timing of 54 °CA bTDC, a main injection angle of 19 °CA bTDC, and a pilot mass of 42%. As a result, in comparison to the unoptimized map, the split injection optimized calibration map increases BTE by 12.33% and decreases BSEC by 6.60%, and the optimized map reduces HC, CO, smoke, and EGT emissions by 15.68%, 21.40%, 18.82, and 17.24%, while increasing NOx emissions by 15.62%. RSM optimization with the most desirable level was selected for map development, and three trials were carried out to predict the calibrated map using ANN. According to the findings, the ANN predicted all responses with R > 0.99, demonstrating the real-time reproducibility of engine variables in contrast to the RSM responses. The experimental validation of the predicted data has an error range of 1.03-2.86%, which is acceptable.

Enhancing automotive cooling systems: composite fins and nanoparticles analysis in radiators.

Composites are driving positive developments in the automobile sector. In this study investigated the use of composite fins in radiators using computational fluid dynamics (CFD) to analyze the fluid-flow phenomenon of nanoparticles and hydrogen gas. Our world is rapidly transforming, and new technologies are leading to positive revolutions in today's society. In this study successfully analyzed the entire thermal simulation processes of the radiator, as well as the composite fin arrangements with stress efficiency rates. The study examined the velocity path, pressure variations, and temperature distribution in the radiator setup. As found that nanoparticles and composite fins provide superior thermal heat rates and results. The combination of an aluminum radiator and composite fins in future models will support the control of cooling systems in automotive applications. The final investigation statement showed a 12% improvement with nanoparticles, where the velocity was 1.61 m/s and the radiator system's pressure volume was 2.44 MPa. In the fin condition, the stress rate was 3.60 N/mm2.

Integrated smart dust monitoring and prediction system for surface mine sites using IoT and machine learning techniques.

The mining industry confronts significant challenges in mitigating airborne particulate matter (PM) pollution, necessitating innovative approaches for effective monitoring and prediction. This research focuses on the design and development of an Internet of Things (IoT)-based real-time monitoring system tailored for PM pollutants in surface mines, specifically PM 1.0, PM 2.5, PM 4.0, and PM 10.0. The novelty of this work lies in the integration of IoT technology for real-time measurement and the application of machine learning (ML) techniques for accurate prediction based on recorded dust pollutants data. The study's findings indicate that PM 1.0 pollutants exhibited the highest concentration in the atmosphere of the ball clay surface mine sites, with the stockyard site registering the maximum levels of PM pollutants (28.45 µg/m3, 27.89 µg/m3, 26.17 µg/m3, and 27.24 µg/m3, respectively) due to the dry nature of clay materials. Additionally, the research establishes four ML models-Decision Tree (DT), Gradient Boosting Regression (GBR), Random Forest (RF), and Linear Regression (LR)-for predicting PM pollutant concentrations. Notably, Random Forest demonstrates superior performance with the lowest Mean Absolute Error (MAE) and Root Mean Squared Error (RMSE) at 1.079 and 1.497, respectively. This comprehensive solution, combining IoT-based monitoring and ML-based prediction, contributes to sustainable mining practices, safeguarding worker well-being, and preserving the environment.

Comparative analysis of temporal variation of heavy metal accumulation by two sea urchin species from a harbour region, including pre and post COVID 19 lock down period.

Sea urchins are marine invertebrates belonging to phylum Echinodermata, recognized as relevant biological tool for assessing environmental pollution. In the present study, we assessed the bioaccumulation potential of different heavy metals by two sea urchin species, Stomopneustes variolaris Lamarck, 1816 and Echinothrix diadema Linnaeus, 1758, collected from a harbour region, along the south west coast of India, during four different sampling periods for 2 years, from the same sea urchin bed. Heavy metals like Pb, Cr, As, Cd, Co, Se, Cu, Zn, Mn and Ni were analysed from water, sediment and different body parts of sea urchins, such as shell, spine, tooth, gut and gonad. The sampling periods also included the pre and post COVID 19 lockdown period during which the harbour activities were closed. The bio-water accumulation factor (BWAF), bio-sediment accumulation factor (BSAF) and the metal content/test weight index (MTWI) were calculated, in order to compare the bioaccumulation of metals by both the species. The results showed that S. variolaris had higher bioaccumulation potential than E. diadema, for metals like Pb, As, Cr, Co and Cd especially in the soft body parts like gut and gonad. The hard parts of S. variolaris like shell, spine, and tooth also accumulated more Pb, Cu, Ni and Mn than E. diadema. Following the lockdown period, there was a decline in the concentration of all heavy metals in water, whereas in sediment, Pb, Cr, and Cu levels were reduced. The gut and gonad tissues of both the urchins showed a decrease in the concentration of most of the heavy metals following the lockdown phase and no significant reduction was observed in the hard parts. This study reveals the use of S. variolaris as an excellent bioindicator of heavy metal contamination in the marine environment which can be employed for coastal monitoring programs.

Dissemination of multidrug resistant bacteria to the polar environment - Role of the longest migratory bird Arctic tern (Sterna paradisaea).

The ever-increasing prevalence of antibiotic-resistant bacteria(ARB), primarily due to the frequent use and misuse of antibiotics, is an issue of serious global concern. Migratory birds have a significant role in dissemination of ARB, as they acquire resistant bacteria from reservoirs and transport them to other environments which are relatively less influenced by anthropogenically. We have investigated the prevalence of ARB in a long-distance migratory bird, the Arctic tern (Sterna paradisaea) captured from the Svalbard Archipelago. The birds were tagged with geolocators to track their extraordinary long migration, and the cloacal samples were collected before the migration and after the migration by recapturing the same birds. The tracking of 12 birds revealed that during the annual cycle they underwent a total of 166 stopovers (11-18, mean = 3.8) and recovery points along the Atlantic Ocean. Twelve major bacterial genera were identified from Arctic tern cloacal samples, which are dominated by Staphylococcus spp. and Aerococcus spp. The bacterial isolates showed resistance against 16 antibiotics (before migration) and 17 antibiotics (after migration) out of 17 antibiotics tested. Resistance to ß-lactam and quinolone class of antibiotics were frequent among the bacteria. The study highlights the potential role of Arctic tern in the dissemination of multidrug resistant bacteria across far and wide destinations, especially to the polar environments.

Could hypertension possibly be adaptive?

1. We believe that the ultimate goal of cardiovascular regulatory mechanisms is not the regulation of arterial blood pressure (BP), but the maintenance of tissue blood flows commensurate with metabolic requirements. Thus, elevated BP can potentially contribute to optimizing tissue blood flows under select circumstances; for example, when there are primary defects in autoregulation of tissue blood flows. 2. The hypothesis that a primary defect in autoregulation of tissue blood flows may be responsible for the development of hypertension is presented. It is argued that, in this context, at least part of the rise in BP may be reflexly driven by a 'metaboreflex', a homeostatic mechanism acting to regulate tissue blood flows. 3. We argue that in the context of primary defects in autoregulation of tissue blood flows, the ability to generate and sustain a hypertensive phenotype increases the lifespan of species (i.e. if it were not for this adaptive hypertensive phenotype, death due to circulatory failure would occur much earlier). 4. Experimental and clinical evidence that indirectly supports the hypothesis is reviewed briefly and a means for testing this hypothesis is suggested.

Effect of antihypertensive drug therapy on short-term heart rate variability in newly diagnosed essential hypertension.

1. Abnormalities of cardiac autonomic regulation are a potential mechanism for morbidity despite blood pressure (BP) lowering in hypertension. Analysis of short-term (5 min) heart rate variability (HRV) provides a non-invasive probe of autonomic regulation of sino-atrial (SA) node automaticity. 2. We hypothesized that antihypertensive drug therapy would be associated with an increase in 5 min overall HRV, along with a decrease in blood pressure (BP), at 8 weeks follow up in subjects with newly diagnosed, never-treated essential hypertension. 3. One hundred and fifty patients (84 men and 66 women; mean (+/-SD) age 48 +/- 10 years) with newly diagnosed essential hypertension were divided to five groups of 30 patients each to receive one of the following antihypertensive drugs (or drug combinations): 5 mg/day amlodipine; 50 mg/day atenolol; 5 mg/day enalapril; 25 mg/day hydrochlorothiazide; or a combination of 5 mg/day amlodipine and 50 mg/day atenolol. 4. The only significant change in HRV indices was an increase in total variability of RR intervals and an increase in high-frequency (HF) RR interval spectral power in the amlodipine + atenolol-treated group (P < 0.05). 5. The results indicate that there is a dissociation between changes in short-term HRV and mean RR interval and BP lowering in patients with newly diagnosed hypertension. 6. We interpret the increase in HF RR interval spectral power in the amlodipine + atenolol-treated group as being due to an increase in vagal modulation of RR intervals and/or diminution in sympathetic restraint of respiratory sinus arrhythmia.

Explicit constructivism: a missing link in ineffective lectures?

This study tested the possibility that interactive lectures explicitly based on activating learners' prior knowledge and driven by a series of logical questions might enhance the effectiveness of lectures. A class of 54 students doing the respiratory system course in the second year of the Bachelor of Medicine and Bachelor of Surgery program in my university was randomized to two groups to receive one of two types of lectures, "typical" lectures (n = 28, 18 women and 10 men) or "constructivist" lectures (n = 26, 19 women and 7 men), on the same topic: the regulation of respiration. Student pretest scores in the two groups were comparable (P > 0.1). Students that received the constructivist lectures did much better in the posttest conducted immediately after the lectures (6.8 +/- 3.4 for constructivist lectures vs. 4.2 +/- 2.3 for typical lectures, means +/- SD, P = 0.004). Although both types of lectures were well received, students that received the constructivist lectures appeared to have been more satisfied with their learning experience. However, on a posttest conducted 4 mo later, scores obtained by students in the two groups were not any different (6.9 +/- 3 for constructivist lectures vs. 6.9 +/- 3.7 for typical lectures, P = 0.94). This study adds to the increasing body of evidence that there is a case for the use of interactive lectures that make the construction of knowledge and understanding explicit, easy, and enjoyable to learners.

Student perceptions regarding the usefulness of explicit discussion of "Structure of the Observed Learning Outcome" taxonomy.

One method of grading responses of the descriptive type is by using Structure of Observed Learning Outcomes (SOLO) taxonomy. The basis of this study was the expectation that if students were oriented to SOLO taxonomy, it would provide them an opportunity to understand some of the factors that teachers consider while grading descriptive responses and possibly develop strategies to improve scores. We first sampled the perceptions of 68 second-year undergraduate medical students doing the Respiratory System course regarding the usefulness of explicit discussion of SOLO taxonomy. Subsequently, in a distinct cohort of 20 second-year medical students doing the Central Nervous System course, we sought to determine whether explicit illustration of SOLO taxonomy combined with some advice on better answering descriptive test questions (to an experimental group) resulted in better student scores in a continuous assessment test compared with providing advice for better answering test questions but without any reference to SOLO taxonomy (the control group). Student ratings of the clarity of the presentation on SOLO taxonomy appeared satisfactory to the authors, as was student understanding of our presentation. The majority of participants indicated that knowledge of SOLO taxonomy would help them study and prepare better answers for questions of the descriptive type. Although scores in the experimental and control group were comparable, this experience nonetheless provided us with the motivation to orient students to SOLO taxonomy early on in the medical program and further research factors that affect students' development of strategies based on knowledge of SOLO taxonomy.

Diabetes mellitus and renal tubular acidosis in primary Sjögren's syndrome.

Sjögren's syndrome is an autoimmune disease with multisystem involvement characterised by lymphocytic infiltration of exocrine glands resulting in keratoconjunctivitis sicca, xerostomia and bilateral parotid gland enlargement. Renal manifestation is characteristically chronic lymphocytic tubulointerstitial nephritis. Diabetes mellitus in Sjogren's syndrome has also been described in literature. In this article we discuss two cases of Sjogren's syndrome with diabetes mellitus and renal manifestations.

Effect of six weeks yoga training on weight loss following step test, respiratory pressures, handgrip strength and handgrip endurance in young healthy subjects.

The present study was designed to test whether yoga training of six weeks duration modulates sweating response to dynamic exercise and improves respiratory pressures, handgrip strength and handgrip endurance. Out of 46 healthy subjects (30 males and 16 females, aged 17-20 yr), 23 motivated subjects (15 male and 8 female) were given yoga training and the remaining 23 subjects served as controls. Weight loss following Harvard step test (an index of sweat loss), maximum inspiratory pressure, maximum expiratory pressure, 40 mm endurance, handgrip strength and handgrip endurance were determined before and after the six week study period. In the yoga group, weight loss in response to Harvard step test was 64 +/- 30 g after yoga training as compared to 161 +/- 133 g before the training and the difference was significant (n = 15 male subjects, P < 0.0001). In contrast, weight loss following step test was not significantly different in the control group at the end of the study period. Yoga training produced a marked increase in respiratory pressures and endurance in 40 mm Hg test in both male and female subjects (P < 0.05 for all comparisons). In conclusion, the present study demonstrates attenuation of the sweating response to step test by yoga training. Further, yoga training for a short period of six weeks can produce significant improvements in respiratory muscle strength and endurance.

What is the ultimate goal in acid-base regulation?

It is common to see chapters on acid-base physiology state that the goal of acid-base regulatory mechanisms is to maintain the pH of arterial plasma and not arterial Pco(2) (Pa(CO(2))) or plasma HCO(3). A hypothetical situation in which the Pa(CO(2)) of arterial plasma is 80 mmHg and the plasma HCO(3) concentration is 48 mM is presented and analyzed to get over this misconception. As per the modified Henderson equation, the pH of arterial plasma would be 7.4; however, we explain that this may be associated with intracellular acidosis due to intracellular hypercapnia and that derangement of homeostasis is evident from the occurrence of respiratory depression and, eventually, coma in the patient described. This suggests that the ultimate goal of acid-base regulatory mechanisms is not just the maintenance of the pH of arterial plasma but the maintenance of the steady-state pH of intracellular fluid as well.

Effect of deep breathing at six breaths per minute on the frequency of premature ventricular complexes.

Although the effect of reflex increase in vagal tone on the frequency of premature ventricular complexes (PVC) is known, the effect of timed deep breathing on the frequency of PVC has not been reported. We serendipitously discovered that deep breathing at six breaths per minute abolished PVC in an 18-year-old female with frequent PVC, anxiety, and palpitations. In five of a series of 10 consecutive patients with frequent (> or = 10/min) unifocal PVC, deep breathing at 6 breaths/min reduced the frequency of PVC by at least 50%. This is possibly due to increased vagal modulation of sinoatrial and atrioventricular node. However, factors predicting the response to deep breathing, and the mechanisms involved need to be studied in a larger number of patients.