Effective Dose of Prophylactic Oxytocin Infusion During Cesarean Delivery in 90% Population of Nonlaboring Patients With Preeclampsia Receiving Magnesium Sulfate Therapy and Normotensives: An Up-Down Sequential Allocation Dose-Response Study.

BACKGROUND: Oxytocin administration during cesarean delivery is the first-line therapy for the prevention of uterine atony. Patients with preeclampsia may receive magnesium sulfate, a drug with known tocolytic effects, for seizure prophylaxis. However, no study has evaluated the minimum effective dose of oxytocin during cesarean delivery in women with preeclampsia. METHODS: This study compared the effective dose in 90% population (ED90) of oxytocin infusion for achieving satisfactory uterine tone during cesarean delivery in nonlaboring patients with preeclampsia who were receiving magnesium sulfate treatment with a control group of normotensives who were not receiving magnesium sulfate. This prospective dual-arm dose-finding study was based on a 9:1 biased sequential allocation design. Oxytocin infusion was initiated at 13 IU/h, on clamping of the umbilical cord, in the first patient of each group. Uterine tone was graded as satisfactory or unsatisfactory by the obstetrician at 4 minutes after initiation of oxytocin infusion. The dose of oxytocin infusion for subsequent patients was decided according to the response exhibited by the previous patient in the group; it was increased by 2 IU/h after unsatisfactory response or decreased by 2 IU/h or maintained at the same level after satisfactory response, in a ratio of 1:9. Oxytocin-associated side effects were also evaluated. Dose-response data for the groups were evaluated using a log-logistic function and ED90 estimates were derived from fitted equations using the delta method. RESULTS: The ED90 of oxytocin was significantly greater for the preeclampsia group (n = 27) than for the normotensive group (n = 40) (24.9 IU/h [95% confidence interval {CI}, 22.4-27.5] and 13.9 IU/h [95% CI, 12.4-15.5], respectively); the difference in dose requirement was 10.9 IU/h (95% CI, 7.9-14.0; P < .001). The number of patients with oxytocin-related hypotension, defined as a decrease in systolic blood pressure >20% from baseline or to <90 mm Hg, was significantly greater in the preeclampsia group (92.6% vs 62.5%; P = .030), while other side effects such as ST-T depression, nausea/vomiting, headache, and flushing, were not significantly different. There was no significant difference in the need for additional uterotonic or uterine massage, estimated blood loss, and need for re-exploration for uncontrolled bleeding. CONCLUSIONS: Patients with preeclampsia receiving preoperative magnesium therapy need a greater intraoperative dose of oxytocin to achieve satisfactory contraction of the uterus after fetal delivery, as compared to normotensives.

Effect of Yoga on Performance and Physical Fitness in Cricket Bowlers.

Cricket-bowling performance is known to be influenced by speed of ball release and accuracy. Currently, training sessions typically involve fielding-specific drills and conditioning exercises. Scientific evidence for inclusion of a comprehensive yoga intervention in daily training and exercise sessions remains unexplored. The present study explored the effect of yoga on bowling performance and physical fitness in cricket bowlers. Sports fitness testing and training were conducted among 60 non-elite recreational-club male cricket players aged 13-25 years. Cricket-bowling speed was e valuated using a speed radar gun, accuracy with a test developed by Portus et al., cardiorespiratory endurance using the yo-yo intermittent recovery test, lower-extremity and trunk strength using a back-leg dynamometer, upper-limb power using a medicine ball-throw test, power using a vertical-jump test, and flexibility using a sit-and-reach test. In addition to bowling practice, the yoga intervention group (n = 30) performed pranayama and standing and prone asana, whereas the control group (n = 30) practiced conventional conditioning exercises, for 45 minutes/day, three times a week, for 12 weeks. Improvement in bowling speed, accuracy, cardiorespiratory endurance, muscle strength, and flexibility were comparable between the two groups. Statistically significant improvements in baseline scores in bowling speed, accuracy, cardiorespiratory endurance, muscle flexibility, strength, and power were comparable between the two groups of non-elite male cricket players. Bowling speed improved by 6.52% in the yoga group and by 5.18% in the control group. Bowling accuracy improved by 35.40% in the yoga group and by 31.29% in the control group. Additional research on long-duration intervention in elite players may help to establish the role of yoga in conventional cricket-bowling training.

Lower extremity joint loading during Bounce rope skip in comparison to run and walk.

BACKGROUND: Bounce rope-skip holds immense scope as an aerobic exercise in space and time constrained urban setting with additional constraints placed by pandemic situations such as Covid 19, wherein adherence to commonly performed weight-bearing, aerobic activities like walking and running is a challenge. Limited knowledge informing biomechanical demands and misconceptions about knee joint loading, confines safe application of bounce rope-skip in health promotion. Thus, present study aimed to explore kinematics and lower-extremity joint loading during rope-skipping compared to walking and running. METHODS: Following ethical approval, 3D motion analysis of bounce rope-skip, walk and run was captured from 22 healthy female participants aged 18-25yr using 12-camera Vicon system and 2AMTI force plates. Three trials for bounce rope-skip were recorded with five skip-jumps on force-plates at a cadence of 105 skips/min. Mid-skip, mid-gait and mid-run data were averaged to compute kinetic and kinematic variables for hip, knee and ankle during loading/initial contact, take-off/push-off and flight/mid-swing phases of rope-skip, walk and run. RESULT: Average time of one rope-skip cycle was 1.2sec; mean foot contact time was 0.55sec and flight time was 0.65sec. In one bounce rope-skip cycle, hip motion ranged between 13.4o-35.3oflexion; knee between 13.6 o-67.9° flexion and ankle between 34.5odorsiflexion to-13.40plantarflexion. Vertical ground reaction force (vGRF) during rope-skip (landing-phase) was lower compared to run; however, it was higher than walk (p < 0.001). In coronal plane, peak hip and knee adductor moment during rope-skip were lower compared to run and higher than walk (p < 0.001). CONCLUSION: Bounce rope-skip generated low lower extremity joint loading compared to run; supporting its prescription as a hip and knee joint-protective aerobic weight-bearing exercise for health promotion in young adults.

Click Biotinylation of PLGA Template for Biotin Receptor Oriented Delivery of Doxorubicin Hydrochloride in 4T1 Cell-Induced Breast Cancer.

PLGA was functionalized with PEG and biotin using click chemistry to generate a biotin receptor targeted copolymer (biotinylated-PEG-PLGA) which in turn was used to fabricate ultrafine nanoparticles (BPNP) of doxorubicin hydrochloride (DOX) for effective delivery in 4T1 cell induced breast cancer. However, adequate entrapment of a hydrophilic bioactive like DOX in a hydrophobic polymer system made of PLGA is not usually possible. We therefore modified a conventional W/O/W emulsion method by utilizing NH4Cl in the external phase to constrain DOX in dissolved polymer phase by suppressing DOX's inherent aqueous solubility as per common ion effect. This resulted in over 8-fold enhancement in entrapment efficiency of DOX inside BPNP, which otherwise is highly susceptible to leakage due to its relatively high aqueous solubility. TEM and DLS established BPNP to be sized below 100 nm, storage stability studies showed that BPNP were stable for one month at 4 °C, and in vitro release suggested significant control in drug release. Extensive in vitro and in vivo studies were conducted to propound anticancer and antiproliferative activity of BPNP. Plasma and tissue distribution study supplemented by pertinent in vivo fluorescence imaging mapped the exact fate of DOX contained inside BPNP once it was administered intravenously. A comparative safety profile via acute toxicity studies in mice was also generated to out rightly establish usefulness of BPNP. Results suggest that BPNP substantially enhance anticancer activity of DOX while simultaneously mitigating its toxic potential due to altered spatial and temporal presentation of drug and consequently deserve further allometric iteration.

Immunotherapeutic vitamin E nanoemulsion synergies the antiproliferative activity of paclitaxel in breast cancer cells via modulating Th1 and Th2 immune response.

Paclitaxel (PTX) is used as first line treatment for metastatic breast cancer but the relief comes at a heavy cost in terms of accompanying adverse effects. The pharmaceutical credentials of PTX are further dampened by the intrinsically low aqueous solubility. In order to sideline such insidious tendencies, PTX was incorporated in a vitamin E nanoemulsion using high pressure homogenization. The encapsulation efficiency of PTX in nanoemulsion was 97.81±2.7% and a sustained drug release profile was obtained. PTX loaded nanoemulsion exhibited higher cytotoxicity in breast cancer cell line (MCF-7) when compared to free PTX and marketed formulation (Taxol). Cell cycle arrest study depicted that MCF-7 cells treated with PTX loaded nanoemulsion showed high arrest in G2-M phase. Moreover blank nanoemulsion induced additional apoptosis in breast cancer cells through G1-S arrest by disrupting mitochondrial membrane potential. Cytokine estimation study in macrophages showed that both PTX loaded nanoemulsion and blank nanoemulsion enhanced secretion of IL-12 and downregulated secretion of IL-4 and IL-10. Results suggest that inclusion of vitamin E in nanoemulsion opened multiple complementary molecular effects which not only magnified the principle antiproliferative activity of PTX but also independently showcased potential in restoring the proactive nature of the breast cancer slackened chronic immune response. In-vivo anticancer activity showed significantly improved efficacy of PTX loaded nanoemlsion compare to Taxol and free PTX. The list of plausible advantages of PTX nanoemulsification was further substantiated by acceptable haemolytic potential, reduced in-vivo toxicity and conveniently modified pharmacokinetic profile in which the AUC and MRT were extended considerably. Overall, there were strong evidences that developed formulation can serve as a viable alternative to currently available PTX options.