Extracellular fluid viscosity enhances cell migration and cancer dissemination.

Cells respond to physical stimuli, such as stiffness1, fluid shear stress2 and hydraulic pressure3,4. Extracellular fluid viscosity is a key physical cue that varies under physiological and pathological conditions, such as cancer5. However, its influence on cancer biology and the mechanism by which cells sense and respond to changes in viscosity are unknown. Here we demonstrate that elevated viscosity counterintuitively increases the motility of various cell types on two-dimensional surfaces and in confinement, and increases cell dissemination from three-dimensional tumour spheroids. Increased mechanical loading imposed by elevated viscosity induces an actin-related protein 2/3 (ARP2/3)-complex-dependent dense actin network, which enhances Na+/H+ exchanger 1 (NHE1) polarization through its actin-binding partner ezrin. NHE1 promotes cell swelling and increased membrane tension, which, in turn, activates transient receptor potential cation vanilloid 4 (TRPV4) and mediates calcium influx, leading to increased RHOA-dependent cell contractility. The coordinated action of actin remodelling/dynamics, NHE1-mediated swelling and RHOA-based contractility facilitates enhanced motility at elevated viscosities. Breast cancer cells pre-exposed to elevated viscosity acquire TRPV4-dependent mechanical memory through transcriptional control of the Hippo pathway, leading to increased migration in zebrafish, extravasation in chick embryos and lung colonization in mice. Cumulatively, extracellular viscosity is a physical cue that regulates both short- and long-term cellular processes with pathophysiological relevance to cancer biology.

Drug resistance among extrapulmonary TB patients: Six years experience from a supranational reference laboratory.

BACKGROUND & OBJECTIVES: There is limited information available about the drug resistance patterns in extrapulmonary tuberculosis (EPTB), especially from high burden countries. This may be due to difficulty in obtaining extrapulmonary specimens and limited facilities for drug susceptibility testing. This study was undertaken to review and report the first and second-line anti-TB drug susceptibility patterns in extrapulmonary specimens received at the National Institute for Research in Tuberculosis (NIRT), Chennai, India, between 2005 and 2012. METHODS: Extrapulmonary specimens received from referring hospitals were decontaminated and cultured using standard procedures. Drug susceptibility testing (DST) for Mycobacterium tuberculosis was done by absolute concentration or resistance ratio methods for the first and the second line anti-TB drugs. RESULTS: Between 2005 and 2012, of the 1295 extrapulmonary specimens, 189 grew M. tuberculosis, 37 (19%) cases were multidrug resistant (MDR) while one was extensively drug resistant (XDR). Specimen-wise MDR prevalence was found to be: CSF-10 per cent, urine-6 per cent, fluids and aspirates-27 per cent, pus-23 per cent, lymph nodes-19 per cent. Resistance to isoniazid and ethionamide was found to be high (31 and 38%, respectively). INTERPRETATION & CONCLUSIONS: Drug resistance including MDR-TB was observed in a significant proportion of extrapulmonary specimens referred for DST. Access to culture and DST for extrapulmonary specimens should be expanded. Guidelines for MDR-TB management should have explicit sections on extra-pulmonary tuberculosis and training on laboratory techniques is urgently required.

Engaging Chief Medical Officers to Improve Multidisciplinary Rounds.

Background: Multidisciplinary rounds (MDRs), a model of care in which multiple members of the care team, representing different disciplines, come together to discuss the care of a patient in real-time. MDRs are a valuable tool for clinical teams to improve patient length of stay (LOS), reduce healthcare-associated infections, and increase care coordination. HCA Healthcare's data science and performance improvement teams created a data visualization tool called Next-gen Analytics for Treatment and Efficiency (NATE) Tempo to support care teams in managing rounds and barriers. Methods: A pilot implementation of MDRs using the NATE Tempo tool was initiated in 10 hospitals, accompanied by a survey for Chief Medical Officers (CMOs) of each of the participating hospitals. Results: Implementation of MDRs using the NATE Tempo tool was associated with an average reduction in LOS ratio from 135% to 114% across the 10 hospitals. CMO survey feedback identified areas of improvement related to MDR participation, and incorporation of NATE Tempo. CMO leadership within each facility and the use of the interactive dashboard facilitated the identification of high performers and areas of opportunity for improvement. Conclusion: CMO engagement can help physicians take steps to decrease variation in practice, leading to compliance with best practice guidelines and decreasing the overall LOS in hospitals. The MDR process can support these efforts. Empowering CMOs through the use of the NATE Tempo tool improved engagement. Through the tool, the CMO promotes coordination of patient care throughout the hospital experience and during the post-discharge phase.

Performance investigation of a modified single-basin solar distiller by augmenting thermoelectric cooler as an external condenser.

Harvesting freshwater from saline and seawater using solar energy has proven a significant impact in recent times. The present study aims to investigate the performance of the solar desalination system by incorporating glass reflectors, heat storage media, and a thermoelectric cooling system with a single-basin-type distiller. Accordingly, the objective of the study is to improve the performance of the solar distiller in terms of freshwater production and efficiency compared to a conventional setup. Moreover, the designed unit was tested under the environment of the Western part of India (Mehsana-23.5880° N, 72.3693° E) for 19 days in the months of May and June 2022. The maximum daily productivity observed during the day was 2.5 l at an average solar radiation of 1200 W/m2, which was 1.23 times higher than its conventional counterpart. Similarly, the energy efficiency showed a maximum improvement of 23.73%. At the middle of the day, i.e., maximum performance condition, the exergy efficiency was doubled with current modifications. Solar radiation and ambient temperature were found to be the most critical parameters that influence performance. Modifications also increase the % off sunshine hour productivity compared to sunshine hour from ~ 10 to 11% to ~ 20.8 to 24%, respectively. The cost of water distillation for the proposed solar still was found as 0.037 $/l/m2,s and the payback period was estimated as 2.27 years. The overall results indicate the positive influence of the modifications; hence, this type of setup is feasible for implementation on the field in harsh and coastal line areas. However, modified single-basin solar still needs extended field study to realize the full potential of the modifications.

Impact of Adherence to a Standardized Oxytocin Induction Protocol on Obstetric and Neonatal Outcomes.

BACKGROUND: Oxytocin protocols are employed to induce uterine contractions and progressive cervical changes, but they are associated with adverse maternal and neonatal outcomes. The aim of this study was to determine whether compliance with a checklist-based protocol for oxytocin administration was associated with changes in neonatal and maternal outcomes. METHODS: A retrospective cohort study of 86,786 pregnant women undergoing term (> 37 weeks) induction of labor between January 2015 and December 2017 was performed. Systemwide training in the use of an oxytocin administration protocol was provided to obstetricians and nurses. Pre-use and in-use oxytocin checklists were incorporated into each unit's policies and procedures. Subsequently, charts were reviewed and individually audited by an obstetric nurse who scored each record based on the documentation of variables in an oxytocin administration protocol and ranked adherence as complete or absent. Primary outcomes were postpartum hemorrhage, neonatal ICU (NICU) admission, and delivery by cesarean section. Bivariate analyses (t-tests) were performed on adherent and nonadherent groups for comparison of selected demographic variables and the primary outcome variables. Logistic regression was completed on the primary outcome variable with eight covariates. RESULTS: Among patients with complete adherence to the oxytocin administration protocol, the rate of cesarean section in the unadjusted analysis was 16.20%, compared to 18.54% for those with incomplete adherence; the rates of postpartum hemorrhage were 2.64% vs. 3.14%, respectively, and the rates of NICU admission were 3.03% vs. 3.86%, respectively. In the multivariable logistic regression, complete protocol adherence was associated with significantly lower odds of postpartum hemorrhage (adjusted odds ratio [OR] 0.85, 95% confidence interval [CI] 0.76-0.94) but higher odds of Cesarean section (adjusted OR 1.07, 95% CI 1.01-1.13); the adjusted OR for NICU admission was 0.90, which did not reach statistical significance (95% CI 0.81-1.00). Among the covariates, nulliparity and elective induction were the strongest predictors of the primary outcomes of cesarean section, postpartum hemorrhage, and NICU admission. CONCLUSION: Adherence to the oxytocin administration protocol was associated with a decrease in postpartum hemorrhage but an increased risk of delivery by cesarean section.

Performance improvement and advancement studies of mixed-mode solar thermal dryers: a review.

Solar thermal dryers are solar-operated gadgets utilized to dehumidify various products, especially food items and rubber sheets. This article provides detailed design, parametric studies, and an in-depth review of mixed-mode solar dryers (MMSD) with a case study of fish drying near coastal lines. Due to several advantages compared to open sun drying and prominent performance index compared to indirect and direct type solar dryers, mixed-mode solar dryers have large adaptability on the field. Moreover, mixed-mode solar thermal dryers with different augmentations are reviewed, for instance, mixed-mode solar dryers with evacuated tube collectors, phase change materials, ultraviolet rays stabilized housing, and dehumidifiers. The case study of fish drying near the coastal line of Gujarat, India has been carried out to study the present scenario of the drying activities. Hence, the objective of this review is to identify the capable mixed-mode solar dryer with heat recovery systems. Substantial reviews within the article suggest an essential need to implement the hybrid mixed-mode solar dryer cum distiller technology for small-scale enterprises that can simultaneously provide potable water near coastal lines along with drying of fishes from the solar dryer. Furthermore, future research demands such hybrid mixed-mode solar drying systems that strongly fulfill the requirements of local communities near coastal lines involved in fish drying activities.

Performance assessment of conventional solar desalination system in Northern part of Gujarat.

Water distillation by utilising free energy from the sun is one of the significant techniques for getting freshwater from salty and seawater. For the remote areas and small societies where freshwater is distant, solar distillation is one of the best explanations for freshwater creation. The main objective of this study is to evaluate the performance of the flat plate collector-assisted conventional solar still incorporating mirror wall and heat storage material, which was tested at Anchor institute of solar energy studies, Mehsana (23.5275311° latitude and 72.3881041° longitude), Gujarat. Moreover, the study captures average productivity with and without FPC which was 1.5 L and 1.0 L respectively during the day time for the entire period of experiments. In this study, the water depth is varied from 1 to 5 cm inside the single basin solar still to obtain the optimum depth. It was observed that when mirror augmented still was operated with the FPC, 3.6L/day productivity was achieved with 30% instantaneous efficiency, at solar radiation of 1122 W/m2 and ambient temperature of 24 °C. Also, the maximum productivity was observed at a water depth of 3 cm and 4 cm. Moreover, improvements in daily and yearly productivity were observed to be 51.515% and 56.6474% respectively, which were estimated on the basis of with and without FPC. An experiment was performed at Anchor Institute of Solar Energy, Mehsana located at the north part of Gujarat where the average annual rain was comparatively less compared to other regions, so this type of solar still can provide potable water to daily workers who work on site. Furthermore, economic study reveals 0.577 INR/litre cost of distiller output for conventional set-up and 0.477 INR/litre for the FPC assisted set-up.

Microfluidics meets 3D cancer cell migration.

An early step of metastasis requires a complex and coordinated migration of invasive tumor cells into the surrounding tumor microenvironment (TME), which contains extracellular matrix (ECM). It is being appreciated that 3D matrix-based microfluidic models have an advantage over conventional in vitro and animal models to study tumor progression events. Recent microfluidic models have enabled recapitulation of key mechanobiological features present within the TME to investigate collective cancer cell migration and invasion. Microfluidics also allows for functional interrogation and therapeutic manipulation of specific steps to study the dynamic aspects of tumor progression. In this review, we focus on recent developments in cancer cell migration and how microfluidic strategies have evolved to address the physiological complexities of the TME to visualize migration modes adapted by various tumor cells.

Visualizing Dynamic Changes During TGF-ß-Induced Epithelial to Mesenchymal Transition.

Epithelial to mesenchymal transition (EMT) is crucial during embryonic development, tissue fibrosis, and cancer progression. Epithelial cells that display a cobblestone-like morphology can undergo a switch to mesenchymal-like phenotype, displaying an elongated spindle shape or a fibroblast-like morphology. EMT is characterized by timely and reversible alterations of molecular and cellular processes. The changes include loss of epithelial and gain of mesenchymal marker expression, loss of polarity, increased cell migratory and invasive properties. Epithelial cells can progress unevenly during this transition and attain hybrid E/M states or metastable EMT states, referred to as epithelial cell plasticity. To gain a deeper insight into the mechanism of EMT, understanding the dynamic aspects of this process is essential. One of the most prominent factors to induce EMT is the cytokine transforming growth factor-ß (TGF-ß). This chapter discusses molecular and cellular techniques to monitor TGF-ß-induced signaling and EMT changes in normal and cancer cell lines. These methods include measuring the TGF-ß-induced activation of its intracellular SMAD effectors proteins and changes in epithelial/mesenchymal marker expression and localization. Moreover, we describe assays of cell migration and dynamic reorganization of the actin cytoskeleton and stress filaments that are frequently part of the TGF-ß-induced EMT cellular response.

COVID-19-Induced New-Onset Diabetes: Trends and Technologies.

The coronavirus disease 2019 (COVID-19) global pandemic continues to spread worldwide with approximately 216 million confirmed cases and 4.49 million deaths to date. Intensive efforts are ongoing to combat this disease by suppressing viral transmission, understanding its pathogenesis, developing vaccination strategies, and identifying effective therapeutic targets. Individuals with preexisting diabetes also show higher incidence of COVID-19 illness and poorer prognosis upon infection. Likewise, an increased frequency of diabetes onset and diabetes complications has been reported in patients following COVID-19 diagnosis. COVID-19 may elevate the risk of hyperglycemia and other complications in patients with and without prior diabetes history. It is unclear whether the virus induces type 1 or type 2 diabetes or instead causes a novel atypical form of diabetes. Moreover, it remains unknown if recovering COVID-19 patients exhibit a higher risk of developing new-onset diabetes or its complications going forward. The aim of this review is to summarize what is currently known about the epidemiology and mechanisms of this bidirectional relationship between COVID-19 and diabetes. We highlight major challenges that hinder the study of COVID-19-induced new-onset of diabetes and propose a potential framework for overcoming these obstacles. We also review state-of-the-art wearables and microsampling technologies that can further study diabetes management and progression in new-onset diabetes cases. We conclude by outlining current research initiatives investigating the bidirectional relationship between COVID-19 and diabetes, some with emphasis on wearable technology.