Tamoxifen modulates nutrition deprivation-induced ER stress through AMPK-mediated ER-phagy in breast cancer cells.

PURPOSE: Rapid proliferation and nutrition starvation in the tumor microenvironment pose significant challenges to cellular protein homeostasis. The accumulation of misfolded proteins in the endoplasmic reticulum lumen induces stress on cells and causes irreversible damage to cells if unresolved. Emerging reports emphasize the influence of the tumor microenvironment on therapeutic molecule efficacy and treatment outcomes. Hence, we aimed to understand the influence of tamoxifen on the cellular adaptation to endoplasmic reticulum stress during metabolic stress in breast cancer cells. METHODS: Nutrition deprivation induces endoplasmic reticulum stress (ER stress), and the unfolded protein response (UPR) in breast cancer cells was confirmed by a Thioflavin B assay and western blotting. Tamoxifen-indued ER-phagy was studied using an MCD assay, confocal microscopy, and western blotting. RESULTS: Nutrition deprivation induces ER stress in breast cancer cells. Interestingly, tamoxifen modulates the nutrition deprivation-induced endoplasmic reticulum stress through enhancing the selective ER-phagy, a specialized autophagy. The tamoxifen-induced ER-phagy is mediated by AMPK activation. The pharmacological inhibition of AMPK blocks tamoxifen-induced ER-phagy and tamoxifen modulatory effect on ER stress during nutrition deprivation. CONCLUSION: Tamoxifen modulates ER stress by inducing ER-phagy through AMPK, thereby, may support breast cancer cell survival during nutrition deprivation conditions.

GPER induces mitochondrial fission through p44/42 MAPK - Drp1 pathway in breast cancer cells.

Understanding GPER biology in breast cancer is rather limited in compassion to the classic estrogen receptors. Mitochondrial dynamics play a critical role in determining cell survival and death under various microenvironmental conditions. We present evidence that GPER-induce mitochondrial fission in breast cancer cells. GPER mediated mitochondrial fission through activating Drp1 by phosphorylating S616 residue and down-regulates fusion proteins Mfn1 and Mfn2 levels. GPER-induced Drp1 activation mediated by p44/42 MAPK and inhibition of this signalling axis completely reverse the mitochondrial fission induced by GPER. Further, mitochondrial fission is required for GPER-induced cell death in breast cancer cells. To conclude, GPER induces mitochondrial fission through p44/42 MAPK - Drp1 signalling, and mitochondrial fission is critical for GPER-induced cell death in breast cancer cells. GENERAL SIGNIFICANCE: First time we report GPER's role in mitochondrial dynamics in cancer cells. Mitochondrial dynamics play a critical role in cancer progression including tamoxifen resistance. Exploring a detailed mechanistic understanding of GPER signalling may help to design new therapy for advanced cancers.

Microplastic pollution in aquatic environments with special emphasis on riverine systems: Current understanding and way forward.

Microplastics (MPs) are emerging as a severe threat in our environment. Their diverse existence in marine environments is being researched globally and thus a widely known fact; however, their presence in the freshwater counterpart has gained attention lately only. Riverine systems, the most critical freshwater resources serve as an essential link between terrestrial and marine environments and their contamination with MPs is going to create severe environmental issues. Because of their small size and unique morphology, these polymers can exhibit variable toxicity to the interacting biota and alter their habitat properties; thus, causing serious impacts on the environment and health of living beings, including humans. These microplastics can also interact with pollutants like heavy metals and organic pollutants, which further augment their harming potential. Inefficient and poor plastic waste disposal practices play an important role in the generation of microplastic pollutants. In the present COVID 19 pandemics, the excessive use of plastic to contain the spread of infection has further added the plastic load in the environment which will eventually lead to the generation of microplastic particles. Also, a significant amount of microplastic pollutants in riverine systems are delivered through wastewater treatment plant effluents. These trade-offs create a distress situation in the environment. The present study connects these key issues for a better understanding of the diverse existence of microplastic pollutants, their sources, and fate, with a special emphasis on riverine systems. A critical appraisal of the knowledge gaps and proposal of suitable solutions through this review might open up avenues for further research and effective management of the microplastics in aquatic environments.

News from Horizons in Binary Black Hole Mergers.

In a binary black hole merger, it is known that the inspiral portion of the waveform corresponds to two distinct horizons orbiting each other and that the merger and ringdown signals correspond to the final horizon being formed and settling down to equilibrium. However, we still lack a detailed understanding of the relation between the horizon geometry in these three regimes and the observed waveform. Here we show that the well-known inspiral chirp waveform has a clear counterpart on black hole horizons, namely, the shear of the outgoing null rays at the horizon. We demonstrate that the shear behaves very much like a compact binary coalescence waveform with increasing frequency and amplitude. Furthermore, the parameters of the system estimated from the horizon agree with those estimated from the waveform. This implies that even though black hole horizons are causally disconnected from us, assuming general relativity to be true, we can potentially infer some of their detailed properties from gravitational wave observations.

Sustainable synthesis of silver nanoparticles using exposed X-ray sheets and forest-industrial waste biomass: Assessment of kinetic and catalytic properties for degradation of toxic dyes mixture.

Silver being the precious metal, its recovery from the waste and utilization is a worthy attempt. The present study represents a very promising sustainable approach for the synthesis of silver nanoparticles (AgNPs), where prime raw materials are waste products (silver metal extracted from waste X-ray sheets and Sal deoiled seed cake (DOC), a plant-based waste as reducing-capping agent). Upon reaction of silver nitrate extracted from waste X-ray sheets and Sal DOC extract at room temperature, the characteristic yellowish-brown color appeared within 30 min. Peak at 485-495 in UV-visible spectrophotometer confirmed the synthesis of AgNPs. X-ray waste synthesized (XRWS) AgNPs were polycrystalline in nature and have face centered cubic (fcc) lattice. Majority of them were polygonal in shape (size range 30-150 nm) with some flower like aggregates as revealed by Transmission Electron Microscope. The XRWS-AgNPs were stabilized by organic groups adhered to their surface and had good stability with a zeta potential of -27.60 mV. These XRWS-AgNPs could work as an efficient catalyst for the reduction of five selected azo dyes individually as well as mixture of these dyes. The degraded products of the individual dyes were identified using Gas Chromatography Mass Spectroscopy. Experimental values obtained for dye degradation study were fitted with first and second order linear kinetic model to know about rate of the reaction.

Alleviation of hexavalent chromium by using microorganisms: insight into the strategies and complications.

Excessive industrialization and anthropogenic activities have resulted in widespread prevalence of heavy metals including hexavalent chromium in the environment. In addition to toxic properties, Cr(VI) possesses high stability and mobility, which in total makes it included in the list of priority heavy metals; thus it needs to be managed urgently. Among different methods available for remediation of Cr(VI), bioremediation is considered as one of the sustainable methods which could effectively be utilized for controlling Cr(VI) pollution. In this aspect, the treatment of Cr(VI)-containing wastewater originating from industries is noteworthy. The present review thus is an attempt to present a systematic overview dealing with studies on remediation of hexavalent chromium by using microorganisms and their application in treatment of Cr(VI)-containing industrial wastewaters. Various factors affecting the Cr(VI) removal and methods to enhance the bio-treatment are highlighted, which might act as a basis for researchers developing Cr(VI) bioremediation techniques.

Impact of heavy metals on inhibitory concentration of Escherichia coli-a case study of river Yamuna system, Delhi, India.

The occurrence of resistant bacteria to specific heavy metals can be associated with increasing load of the metals in the environment. River Yamuna is polluted by various toxic heavy metals discharged by several industrial and agricultural sources. Therefore, the use of heavy metal-resistant bacteria as an indicator of metal pollution was tested in the present study. For the purpose of the study, the heavy metal resistance status of 42 Escherichia coli strains isolated from River Yamuna water from 7 sampling sites within a span of 2 years was determined using growth curves and plate dilution method in terms of minimum inhibitory concentration (MIC) values by comparing with MIC value of control strain. Seasonally, the lowest mean MIC value was observed for bacterial strains isolated in post-monsoon (December) 2013 and highest mean MIC value was observed for bacterial strains isolated in monsoon (August) 2015. Site-wise analysis of the maximum mean MIC values for all the isolated strains showed the highest mean Ni MIC value for the bacterial strains isolated from site S4 (ITO), highest mean Cu MIC, Cr MIC, and Fe MIC values for the bacterial strains isolated from site S2 (Najafgarh drain intermixing zone) and highest mean Cd MIC, Pb MIC, and Zn MIC values for the bacterial strains isolated from site S7 (Shahdara drain intermixing zone). Correlation analysis between mean MIC site-wise results with mean heavy metal site-wise concentrations showed significant positive correlation indicating that the higher the mean concentration of a given heavy metal at a given site, the higher the mean MIC value for the strains isolated from the same site indicating higher level of resistance. Overall, the present study has shown that the presence of heavy metals in River Yamuna caused due to indiscriminate discharge of various effluents from different kind of sources as well as due to insufficient treatment capacity of sewage treatment plants as well as common effluent treatment plants, has serious impacts on its bacterial microflora as it leads to the development of resistant strains.

Degradation of azo dye methyl red by alkaliphilic, halotolerant Nesterenkonia lacusekhoensis EMLA3: application in alkaline and salt-rich dyeing effluent treatment.

Effluents from textile industries are highly colored due to vast use of various azo dyes and color is the first visual indicator of pollution. Biological treatment of textile effluent is often hampered due to the alkaline pH and high salinity; a common characteristic of many textile industrial wastewaters. Considering this, the present study explores the potential of a newly isolated halotolerant and alkaliphilic bacterium Nesterenkonia lacusekhoensis EMLA3 for degradation of methyl red (MR) dye under alkaline condition. Strain EMLA3 showed 97% degradation of 50 mg L-1 MR after 16 h at initial pH of 11.5 in nutrient medium. Dye degradation by the isolate is supported by the formation of low-molecular weight metabolites as divulge through GC-MS & FTIR studies Optimum dye degradation was observed in the pH range of 8.0-11.5 and temperature range of 30-35 °C. Significant MR degrading activity of the strain could be achieved in the presence of very high salt level (100-120 g L-1 NaCl) and in co-presence of different heavy metals. Application of strain to alkaline pH, salt, and heavy metals laden-textile effluent resulted in overall 83% dye removal from the effluent after 120 h of treatment under static condition. Furthermore, the property of microbe to drop-down the pH of wastewater from 11.5 to 8.60 after treatment also lowers the need of additional neutralization treatment. The entire study thus comes out with novel application of N. lacusekhoensis-a less explored extremophilic bacterium-for treatment of alkaline and salt-rich azo dye-containing wastewaters.

Laryngoscope decontamination techniques: A survey.

BACKGROUND AND AIMS: India is a vast country with variable, nonuniform healthcare practices. A laryngoscope is an important tool during general anesthesia and resuscitation. The study aimed to determine the current practices of laryngoscope decontamination in India. MATERIAL AND METHODS: An online survey was conducted amongst 100 anesthesiologists to determine the common methods of laryngoscope decontamination adopted in their settings. The survey was done over 6 months after validating the questionnaire. RESULTS: A total of 73 responses were received out of 100. The result of the survey revealed that there is no uniform technique of laryngoscope decontamination. There is marked variability in techniques followed not only among different institutions, but also within the same institution. CONCLUSION: There are no fixed protocols adopted for laryngoscope decontamination. Thus, there is a need to develop definitive guidelines on this subject, which can be implemented in India.

Efficacy of Acinetobacter sp. B9 for simultaneous removal of phenol and hexavalent chromium from co-contaminated system.

The present study shows the feasibility of a newly isolated strain Acinetobacter sp. B9 for concurrent removal of phenol and Cr (VI) from wastewater. The experiments were conducted in a batch reactor under aerobic conditions. Initially, when mineral salt solution was used as the culture medium, the strain was found to utilize phenol as sole carbon and energy source while no Cr (VI) removal was observed. However, the addition of glucose as co-carbon source resulted in the removal of both toxicants. This co-removal efficiency of the strain was further improved with nutrient-rich media (NB). Optimum co-removal was determined at 188 mg L(-1) of phenol and 3.5 mg L(-1) of Cr (VI) concentrations at pH 7.0. Strain B9 followed the orthometabolic pathway for phenol degradation. Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FT-IR) studies showed sorption of chromium as one of the major mechanisms for Cr (VI) removal by B9 cells. Acinetobacter sp. B9 was later on checked for bioremediation of real tannery wastewater. After 96 h of batch treatment of tannery effluent containing an initial 47 mg L(-1) phenol and 16 mg L(-1) Cr (VI), complete removal of phenol and 87 % reduction of Cr (VI) were attained, showing high efficiency of the bacterial strain for potential application in industrial pollution control.

Accurate, scalable, and fully automated inference of species trees from raw genome assemblies using ROADIES.

Inference of species trees plays a crucial role in advancing our understanding of evolutionary relationships and has immense significance for diverse biological and medical applications. Extensive genome sequencing efforts are currently in progress across a broad spectrum of life forms, holding the potential to unravel the intricate branching patterns within the tree of life. However, estimating species trees starting from raw genome sequences is quite challenging, and the current cutting-edge methodologies require a series of error-prone steps that are neither entirely automated nor standardized. In this paper, we present ROADIES, a novel pipeline for species tree inference from raw genome assemblies that is fully automated, easy to use, scalable, free from reference bias, and provides flexibility to adjust the tradeoff between accuracy and runtime. The ROADIES pipeline eliminates the need to align whole genomes, choose a single reference species, or pre-select loci such as functional genes found using cumbersome annotation steps. Moreover, it leverages recent advances in phylogenetic inference to allow multi-copy genes, eliminating the need to detect orthology. Using the genomic datasets released from large-scale sequencing consortia across three diverse life forms (placental mammals, pomace flies, and birds), we show that ROADIES infers species trees that are comparable in quality with the state-of-the-art approaches but in a fraction of the time. By incorporating optimal approaches and automating all steps from assembled genomes to species and gene trees, ROADIES is poised to improve the accuracy, scalability, and reproducibility of phylogenomic analyses.

Early Clinical and Economic Outcomes for the VELYS Robotic-Assisted Solution Compared with Manual Instrumentation for Total Knee Arthroplasty.

Robotic-assisted total knee arthroplasty (TKA) has been developed to improve functional outcomes after TKA by increasing surgical precision of bone cuts and soft tissue balancing, thereby reducing outliers. The DePuy Synthes VELYS robotic-assisted solution (VRAS) is one of the latest entrants in the robotic TKA market. Currently, there is limited evidence investigating early patient and economic outcomes associated with the use of VRAS. The Premier Healthcare Database was analyzed to identify patients undergoing manual TKA with any implant system compared with a cohort of robotic-assisted TKAs using VRAS between September 1, 2021 and February 28, 2023. The primary outcome was all-cause and knee-related all-setting revisits within 90-day post-TKA. Secondary outcomes included number of inpatient revisits (readmission), operating room time, discharge status, and hospital costs. Baseline covariate differences between the two cohorts were balanced using fine stratification methodology and analyzed using generalized linear models. The cohorts included 866 VRAS and 128,643 manual TKAs that had 90-day follow-up data. The rates of both all-cause and knee-related all-setting follow-up visits (revisits) were significantly lower in the VRAS TKA cohort compared with the manual TKA cohort (13.86 vs. 17.19%; mean difference [MD]: -3.34 [95% confidence interval: -5.65 to -1.03] and 2.66 vs. 4.81%; MD: -2.15 [-3.23 to -1.08], respectively, p-value < 0.01) at 90-day follow-up. The incidence of knee-related inpatient readmission was also significantly lower (53%) for VRAS compared with manual TKA. There was no significant difference between total cost of care at 90-day follow-up between VRAS and manual TKA cases. On average, the operating room time was higher for VRAS compared with manual TKA (138 vs. 134 minutes). In addition, the discharge status and revision rates were similar between the cohorts. The use of VRAS for TKA is associated with lower follow-up visits and knee-related readmission rates in the first 90-day postoperatively. The total hospital cost was similar for both VRAS and manual TKA cohort while not accounting for the purchase of the robot.

Development and In-Vitro Evaluation of Eugenol-Based Nanostructured Lipid Carriers for Effectual Topical Treatment Against C. albicans.

The main objective of the experiment is to develop and evaluate hydrogel-bearing nanostructured lipid carriers (NLCs) loaded with ketoconazole (KTZ) for the effective treatment of candidiasis. The eugenol was used as a liquid lipid (excipient) for the development of KTZ-loaded NLCs and was explored for anti-fungal effect. The production of NLCs involves high energy processes to generate spherical, uniform particles, having a higher percentage of entrapment efficiency (%EE) for KTZ with 89.83 ± 2.31 %. The data from differential scanning calorimeter (DSC), powder x-ray diffraction (PXRD), and attenuated total reflectance (ATR) demonstrated the KTZ dispersion in NLCs. The NLCs loaded hydrogel possessed optimum spreadability and exhibited shear thinning behavior, indicating the ease of application of the final formulation. The 6.41-fold higher transdermal flux (Jss) was governed for KTZ from KTZ-NLC than coarse-KTZ, which explains the usefulness of NLCs. The KTZ-NLCs exhibited significant 2.58 and 6.35-fold higher retention in the stratum corneum and viable epidermis of the skin. The cell cytotoxicity studies using human dermal fibroblast cell (HDFS) lines depicted the usefulness of NLCs in reducing cell toxicities for KTZ. The KTZ-NLCs were found to inhibit planktonic growth and hyphal transition and showed a larger zone of inhibition against C. albicans strains with a MIC-50 value of 0.39 µg/mL. The antibiofilm activity of KTZ-NLCs at lower concentrations, in contrast to plain KTZ, explained the interaction of developed NLCs with fungal membranes. The overall results depicted the effectiveness of the loading KTZ in the lipid matrix to achieve antifungal activity against C. albicans.

Halo-alkaliphilic microbes as an effective tool for heavy metal pollution abatement and resource recovery: challenges and future prospects.

The current study presents an overview of heavy metals bioremediation from halo-alkaline conditions by using extremophilic microorganisms. Heavy metal remediation from the extreme environment with high pH and elevated salt concentration is a challenge as mesophilic microorganisms are unable to thrive under these polyextremophilic conditions. Thus, for effective bioremediation of extreme systems, specialized microbes (extremophiles) are projected as potential bioremediating agents, that not only thrive under such extreme conditions but are also capable of remediating heavy metals from these environments. The physiological versatility of extremophiles especially halophiles and alkaliphiles and their enzymes (extremozymes) could conveniently be harnessed to remediate and detoxify heavy metals from the high alkaline saline environment. Bibliometric analysis has shown that research in this direction has found pace in recent years and thus this review is a timely attempt to highlight the importance of halo-alkaliphiles for effective contaminant removal in extreme conditions. Also, this review systematically presents insights on adaptive measures utilized by extremophiles to cope with harsh environments and outlines the role of extremophilic microbes in industrial wastewater treatment and recovery of metals from waste with relevant examples. Further, the major challenges and way forward for the effective applicability of halo-alkaliphilic microbes in heavy metals bioremediation from extremophilic conditions are also highlighted.

Approach to the Patient: Preventing Adrenal Crisis Through Patient and Clinician Education.

Adrenal crisis continues to be an important cause of death despite being a preventable condition. Significant deficits in patient education in the prevention of adrenal crisis have been identified as a contributor to adrenal crisis risk, despite the importance of patient education being highlighted in international guidelines. Deficits in clinician education have also been identified as risk factors for adrenal crisis although they have not been addressed. We use 3 clinical cases to highlight the role of both patient and clinician education in the prevention of adrenal crisis, review what is known about education related to adrenal insufficiency and provide a possible approach to addressing education deficits with the aim of reducing the risk of adrenal crisis through both patient and clinician education.

A broad-based probe-free qPCR assay for detection and discrimination of three human herpes viruses.

Primary infection or reactivation of latent human cytomegalovirus (HCMV) or herpes simplex viruses (HSV) 1 or 2 during pregnancy can transmit the virus in utero or during natural childbirth to the fetus. The majority of these infections are asymptomatic at birth but may present later with potentially lethal disseminated infection or meningitis (HSV), or long-term neurodevelopmental sequelae including sensorineural hearing loss or neurodevelopmental impairments (HCMV). Unfortunately, early signs and symptoms of disseminated viral infections may be misdiagnosed as bacterial sepsis. Therefore, immediate testing for viral etiologies may not be ordered or even considered by skilled clinicians. In asymptomatic HCMV infections, early detection is necessary to monitor for and treat future neurologic sequelae. In acutely ill-appearing infants, specific detection of viruses against other disease-causing agents is vital to inform correct patient management, including early administration of the correct antimicrobial(s). An ideal test should be rapid, inexpensive, require low sample volumes, and demonstrate efficacy in multiple tissue matrices to aid in timely clinical decision-making for neonatal infections. This work discusses the development of a rapid probe-free qPCR assay for HSV and HCMV that enables early and specific detection of these viruses in neonates. The assay's probe free chemistry would allow easier extension to a broad-based multiplexed pathogenic panel as compared to assays utilizing sequence-specific probes or nested PCR.

Readmission rate and healthcare utilization outcomes of computer-assisted fluoroscopy-based hip navigation versus manual total hip arthroplasty.

INTRODUCTION: The study evaluates the technology of fluoroscopy-based hip navigation that has shown to improve implant positioning in total hip arthroplasty (THA). METHODS: Premier Healthcare data for patients undergoing manual THA or fluoroscopy-based hip navigation THA between 1 January 2016-30 September 2021, were analyzed 90- and 365-day post-THA. The primary outcome was inpatient readmission. Secondary outcomes were operating room (OR) time, length of stay, discharge status, and hospital costs. Baseline covariate differences were balanced using fine stratification and analyzed using generalized linear models. RESULTS: Among 4,080 fluoroscopy-based hip navigation THA and 429,533 manual THA balanced patients, hip-related readmission rates were statistically significantly lower for the fluoroscopy-based hip navigation THA cohort vs. manual THA for both 90-day (odd ratio [95% CI]: 0.69 [0.52 to 0.91] and 365-day (0.63 [0.49 to 0.81] follow-up. OR time was higher with fluoroscopy-based hip navigation THA vs. manual THA (134.65 vs. 132.04 minutes); however, fluoroscopy-based hip navigation THA patients were more likely to be discharged to home (93.73% vs. 90.11%) vs. manual THA. Hospital costs were not different between cohorts at 90- and 365-day post-operative. CONCLUSIONS: Fluoroscopy-based hip navigation THA resulted in fewer readmissions, greater discharge to home, and similar hospital costs compared to manual THA.

Computer-assisted solutions are becoming more ubiquitous in surgical procedures. However, most of the current research is limited to small sample size and limited economic endpoints. The current study utilizes hospital billing data and fine stratification methodology to address the issue around sample size and covariate balancing. Hospital billing data provide a large sample across the US along with hospital costs that can be broken into different categories. Fine stratification methodology allows for covariate balancing while keeping all the samples. It is particularly advantageous when the treated or exposed group represents less than 5% of the entire cohort for a given study, as was observed in this study. Covariate balancing was done on patient, provider (hospital) and surgeon characteristics to minimize confounding. Furthermore, a generalized linear model was utilized to minimize any residual confounding. The study evaluated both short term (3-month) and long term (1-year) outcomes. Study suggested clinical benefits in using computer-assisted fluoroscopy-based hip navigation system in THA compared to manual THA as well as showed cost parity between computer-assisted fluoroscopy-based hip navigation system in THA and manual THA.

Resource utilization and costs for robotic-assisted and manual total knee arthroplasty - a premier healthcare database study.

INTRODUCTION: The impact of robotic-assisted total knee arthroplasty (rTKA) vs. traditional, manual TKA (mTKA) on hospital costs is not well documented and is analyzed herein. RESEARCH DESIGN AND METHODS: Patients in the Premier billing Healthcare Database undergoing elective rTKA or mTKA ("index') in the in- or outpatient setting for knee osteoarthritis between Oct 1st, 2015, to September 30th, 2021, were identified. Variables included patient demographics and comorbidities and hospital characteristics. Matched rTKA vs. mTKA cohorts were created using direct (on provider characteristics, age, gender, race and Elixhauser index) and propensity score matching (fixation type, comorbidities). Index and 90-day inflation-adjusted costs and healthcare utilization (HCU) were analyzed for both cohorts, using generalized linear models. RESULTS: 16,714 rTKA patients were matched to 51,199 mTKA patients. Average 90-day hospital cost reached $17,932 and were equivalent for both cohorts (rTKA vs. mTKA: $132 (95% confidence interval; -$19 to $284). There was a 2.7% (95%CI: 2.2%-3.3%) increase in home or home health discharge, and a 0.4% (95%CI: 0%-0.8%) decrease in 90-day hospital knee related re-visit in the rTKA vs. mTKA group. CONCLUSIONS: Cost-neutrality of rTKA vs. mTKA was observed, with a potential for lowered immediate post-operative HCU in the rTKA vs. mTKA cohorts.

Practice Variation among Pediatric Endocrinologists in the Dosing of Glucocorticoids in Young Children with Congenital Adrenal Hyperplasia.

A Pediatric Endocrine Society (PES) Drugs and Therapeutics Committee workgroup sought to determine the prescribing practices of pediatric endocrinologists when treating children <10 years of age with congenital adrenal hyperplasia (CAH). Our workgroup administered a 32-question online survey to PES members. There were 187 respondents (88.9% attending physicians), mostly from university-affiliated clinics (~80%). Ninety-eight percent of respondents prescribed the short-acting glucocorticoid hydrocortisone to treat young children, as per the Endocrine Society CAH Guidelines, although respondents also prescribed long-acting glucocorticoids such as prednisolone suspension (12%), prednisone tablets (9%), and prednisone suspension (6%). Ninety-seven percent of respondents indicated that they were likely/very likely to prescribe hydrocortisone in a thrice-daily regimen, as per CAH Guidelines, although 19% were also likely to follow a twice-daily regimen. To achieve smaller doses, using a pill-cutter was the most frequent method recommended by providers to manipulate tablets (87.2%), followed by dissolving tablets in water (25.7%) to create a daily batch (43.7%) and/or dissolving a tablet for each dose (64.6%). Thirty-one percent of providers use pharmacy-compounded hydrocortisone suspension to achieve doses of <2.5 mg. Our survey shows that practices among providers in the dosing of young children with CAH vary greatly and sometimes fall outside of the CAH Guidelines-specifically when attempting to deliver lower, age-appropriate hydrocortisone doses.

A Randomized Control Trial of Three Intravenous Dexmedetomidine Doses for Procedural Sedation in Patients Undergoing Minor Gynaecological Surgery.

BACKGROUND: Minor gynaecological procedures are usually done in outpatient settings. Early discharge with minimal haemodynamic compromise is an essential requirement of these procedures. Many sedative drugs are being used for outpatient surgeries. Of the sedative agents available, dexmedetomidine, which has sedative and analgesic sparing effects, has the best safety profile in the cardiorespiratory system. Therefore, we evaluated the optimum dexmedetomidine dose for providing better procedural sedation. METHODOLOGY: This randomized, double-blinded study included 120 ASA grade I and II patients aged 18-45 years who were undergoing short gynaecological procedures in a tertiary care hospital. Patients were randomly allocated into three groups of 40 each. After a loading dose of 1 µg/kg over 10 min, group A received dexmedetomidine infusion at a rate of 0.2 µg/kg/hr, group B at a rate of 0.4 µg/kg/hr, and group C at a rate of 0.6 µg/kg/hr. Perioperative hemodynamic changes, intraoperative adjuvant drug requirements, and postoperative recovery were also compared in the three different dexmedetomidine groups. RESULTS: Heart rate, blood pressure, oxygen saturation, and respiratory rate remained within the normal physiological range in all three groups at most perioperative time points. The time to achieve the Modified Aldrete Score and the post-anesthetic discharge scoring system was maximum in group C and minimum in group A. Ketamine had to be supplemented in almost half of the patients in group A and less than a quarter of the patients in group B. In group C, surgery was completed without any drug supplementation. Two patients in group B and four patients in group C had an episode of bradycardia. Oxygen saturation decreased in one patient in group C, necessitating oxygen supplementation. CONCLUSIONS: Dexmedetomidine, at a dose of 0.4 µg/kg/hr with ketamine supplementation, provides the most appropriate procedural sedation and analgesia (PSA) without any significant hemodynamic compromise.