Accuracy of Anatomical Depictions in Cone Beam Computed Tomography (CBCT)-Reconstructed Panoramic Projections Compared to Conventional Panoramic Radiographs: A Clinical Risk-Benefit Analysis.

INTRODUCTION: Two-dimensional (2D) radiographs are the standard of care for diagnosis and treatment planning in the day-to-day practice of dentistry. With the growing popularity of cone beam computed tomography (CBCT), it is now becoming the standard of care in many areas of general dentistry due to its ability to create non-linear projections from volumetric data. The CBCT-generated non-orthogonal radiographs can serve as easy-to-use 2D and three-dimensional (3D) diagnostic tools and offer a similar experience for diagnosis as conventional 2D images. The aim of this study is to compare the accuracy of conventional radiographs and CBCT-generated projections to identify relevant anatomic landmarks and their associated variants. METHODS: Thirty-two patients referred to the University of Connecticut School of Dental Medicine's Advanced Imaging Center were selected for this retrospective analysis. Nineteen anatomical landmarks were retrospectively assessed on conventional panoramic and CBCT scans generated panoramic radiographs using two different digital imaging and communications in medicine viewers. A total of 1,216 anatomical landmarks were evaluated by two oral and maxillofacial radiologists to assess the accuracy and consistency of the depiction of radiographic anatomy. RESULTS: There was a very good agreement between the two evaluators with a Cohen's kappa value of 0.934. McNemar change test concluded that the anatomical assessment values compared between conventional panoramic and CBCT-generated panoramic radiographs are similar. CONCLUSION: This study showed that CBCT-generated panoramic images are comparable to conventional panoramic radiographs in identifying anatomical landmarks typically evaluated using a conventional panoramic projection. In addition, they have the added advantage of having 3D information in the acquired volume to better evaluate the area of interest. In clinical situations where a mid- to large-volume CBCT scan is available, a simulated panoramic image can be generated using the CBCT volume, leaving exposure of the patient to the additional radiation of a panoramic image unnecessary.

Aggressive Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Review.

Non-melanoma skin cancer of the head and neck (NMSCHN) is one of the most common malignancies worldwide, and its incidence is growing at a significant rate. It has been found to be aggressive in its spread and has the capacity to metastasize to regional lymph nodes. Cutaneous squamous cell carcinoma (cSCC) has a considerably high mortality rate. It has remarkable characteristics: diameter >2 cm, depth >5 mm, high recurrence, perineural invasion, and locoregional metastases. Aggressive cSCC lesions most commonly metastasize to the parotid gland. Also, immunocompromised patients have a higher risk of developing this aggressive cancer along with the worst prognostic outcomes. It is very important to discuss and assess the risk factors, prognostic factors, and outcomes of patients with cSCC, which will give clinicians future directives for making modifications to their treatment plans. The successful treatment of aggressive cSCC of the head and neck includes early detection and diagnosis, surgery alone or adjuvant chemotherapy, and radiotherapy as required. Multimodal therapy options should be considered by clinicians for better outcomes of aggressive cSCC of the head and neck.

Massage therapy for children, adolescents, and young adults: Clinical delivery and effectiveness in hematology and oncology.

BACKGROUND: Children, adolescents, and young adults with hematologic and/or oncologic conditions experience multiple, significant symptoms (e.g., pain, stress, and anxiety), which may be addressed by nonpharmacologic approaches such as massage therapy (MT). The purpose of this study was to describe the clinical delivery of MT provided by a certified pediatric massage therapist and assess effectiveness in two patient groups: those with sickle cell disease (SCD) or hematologic and/or oncologic conditions excluding SCD (HemOnc). METHODS: Investigators conducted a retrospective review of MT sessions provided to patients 0-39 years with hematologic and/or oncologic conditions at a large pediatric academic medical center. RESULTS: Between October 2019 and December 2021, 3015 MT sessions were provided to 243 patients (171 HemOnc; 72 SCD) and documented in the electronic health record. Patients (mean age: 12.21 ± 7.19 years) were generally White (49.4%) or Black/African American (43.2%), non-Hispanic (94.2%), and 52.3% female. Patients in the SCD group (vs. patients in the HemOnc group) reported significantly higher (p < .05) pretreatment pain (6.95 vs. 4.46), stress (6.47 vs. 4.58), and anxiety (6.67 vs. 4.59). All patients reported clinically and statistically significant (p < .001) mean reductions in pain (-2.25 ± 1.87), stress (-2.50 ± 1.73), and anxiety (-2.52 ± 1.69), with patients in the HemOnc group reporting greater mean pain change (-2.54 vs. -1.87) than patients in the SCD group. CONCLUSIONS: This study supports the clinical effectiveness of MT for addressing acute pain, stress, and anxiety among youth with hematologic and/or oncologic conditions. Future research is needed to identify optimal MT utilization.

Sorafenib Loaded Resealed Erythrocytes for the Treatment of Hepatocellular Carcinoma.

BACKGROUND: This study aims to formulate and characterize sorafenib-loaded resealed erythrocytes (SoRE) and investigate their anticancer activity in a rat model of hepatocellular carcinoma. METHODS: SoRE were prepared by hypotonic dialysis of red blood cells obtained from Wistar rats using a range of drug-containing dialysis mediums (2-10 mg/ml) and osmosis time (30-240 mins). Optimized SoRE (8 mg/mL and 240 mins) were characterized for size, morphology, stability, entrapment efficiency, in vitro release profiles, and in vivo efficacy evaluations. For efficacy studies, optimized SoRE were intravenously administered to Wistar rats having hepatocellular lesions induced by aflatoxin B and monitored for in vivo antineoplastic activity. RESULTS: The amount of sorafenib entrapped was directly proportional to the drug concentration in the dialysis medium and duration of osmosis; highest for 10 mg/mL and 240 minutes and lowest for 2 mg/mL and 30 minutes, respectively. Optimized SoRE were biconcave with a size of 112.7 nm and zeta potential of -11.95 ± 2.25 mV. Osmotic and turbulence fragility were comparable with native erythrocytes. CONCLUSION: Drug release follows the first-order pattern. In vivo investigations reveal better anticancer activity of SoRE formulation compared to sorafenib standard preparation. Resealed erythrocytes loaded with sorafenib displayed first-order in vitro release and promising anticancer activity in a rat model of hepatocellular carcinoma.

Case report: Daratumumab treatment in pre-transplant alloimmunization and severe hemolytic anemia.

Daratumumab, a CD38 monoclonal antibody that has been FDA-approved to treat multiple myeloma, has acquired popularity and is used off-label for both auto- and alloantibody mediated disorders, particularly in refractory/resistant circumstances. Much of the published data for its use in pediatric blood disorders has been in post-transplant autoimmune cytopenias. Here we describe three patients in whom daratumumab was used outside of post-transplant autoimmune cytopenias, highlighting further potential uses of this medication.

Synthesis of Hollow Gold Nanoparticles - Impact of Variables on Process Optimization.

Hollow gold nanoparticles (HAuNPs) are gold nanostructures with hollow interior. These particles have attracted a lot of interest due their excellent physicochemical and optical properties and their potential applications in diagnostics, sensing, imaging and assisting in tumor tracing and evaluating the effect of chemotherapy on tumor size, drug delivery and photothermal therapy. Sacrificial galvanic replacement using cobalt core is the most commonly used method for synthesis of HAuNPs. However, lack of reproducibility in synthesizing particles with desired surface plasmon resonance (SPR) is one of the major concerns for clinical application of these particles. In this work, we have identified and categorized various factors that could affect uniformity of cobalt core and subsequent formation of gold shell. Using slight modifications in the method, we have been able to synthesize HAuNPs with SPR in near infrared region at 808 nm with size of particles around 50-80 nm. HAuNPs can be further functionalized with suitable ligands like glutathione, polyethylene glycol, nucleic acids, sugars, fatty acids, proteins and peptides to promote enhanced permeability and retention in cancer cells and thus can serve as potential candidates in treatment of cancer.

Therapeutic benefits of natural oils along with permeation enhancing activity.

The skin is the largest organ of the integumentary system with a multifunctional purpose to protect the body from heat and microbes, regulate body temperature, and act as a sensory organ. A topical dosage form applied on the skin will have to cross the stratum corneum, which would then allow the dosage form to traverse the subsequent layers of the skin. The drug with poor solubility and short half-life would serve as an ideal candidate for its delivery via the transdermal route. This review reports the role of natural oils in enhancing the permeation of drugs through skin as they possess different features like natural origin, favorable penetration enhancement, and partitioning action in the skin. Chemical penetration enhancers have been used widely but are associated with toxicities. Thus, more research should be channelized in the area of extraction of oils from natural sources, along with their active constituents, which can serve as therapeutic alternatives to various disorders and diseases. Natural oils are obtained from leaves, fruits, flowers, seeds, bark, and roots, which have a therapeutic potential as well as penetration enhancing activity. The demerits of oral drug delivery include degradation of drugs in the gastrointestinal tract, addition of taste masking, and coating of tablets, which can be overcome by delivering the drug via the transdermal route. Natural oil contains lipids, flavonoids, and terpenes, which play a significant role in anti-inflammatory and penetration enhancing activity.

Formulation Development and In-vitro/Ex-vivo Evaluation for a Polysaccharide-based Colon Targeted Matrix Tablet.

OBJECTIVE: The objective of this study was to develop and optimize a microflora-triggered colon targeted sustained-release dosage form using Gum Ghatti (GG) and Hydroxypropyl Methylcellulose (HPMC K100). METHODS: GG and HPMC K100 were used to prepare microflora triggered colon targeted sustained- release dosage form. For evaluation, two different tablets comprising metoprolol succinate and mesalamine as an active ingredient were used with the objective of developing a platform technology for various categories of drugs. The tablets were coated with Eudragit® L100 and Eudragit® S100 to provide enteric coating and evaluated for hardness, thickness, friability, weight variation, disintegration, and drug content. in vitro release studies for the prepared tablets were carried out mimicking the physiological transit time. Further, the effects of microflora were evaluated using rat cecal content. RESULTS: The in vitro dissolution profile of coated matrix tablets showed that 86.03±0.43% of metoprolol succinate and 80.26±0.67% of mesalamine were released at the end of 12 h. The ex vivo dissolution profile of coated matrix tablets showed that 96.50±0.27% of metoprolol succinate and 92.58±0.39% of mesalamine were released at the end of 12 h in the presence of rat ceacal content. The developed formulation was stable when subjected to the standard ICH stability study conditions. CONCLUSION: The result of this study showed that gum ghatti together with hydroxypropyl methylcellulose could be successfully used for the preparation of microflora-triggered colon targeted matrix tablets.

Surviving the surge: Evaluation of early impact of COVID-19 on inpatient pharmacy services at a community teaching hospital.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has presented novel challenges to healthcare systems; however, an analysis of the impact of the pandemic on inpatient pharmacy services has not yet been conducted. METHODS: Results of an observational assessment of operational and clinical pharmacy services at a community teaching hospital during the first weeks of the COVID-19 pandemic are presented. Service outcomes of the inpatient pharmacy were evaluated from February 1 to April 8, 2020. Outcomes during the weeks preceding the first COVID-19 admission (February 1 to March 11, 2020) and during the pandemic period (March 12 to April 8, 2020) were compared. Evaluated outcomes included daily order verifications, clinical interventions, and usage of relevant medications. An exploratory statistical analysis was conducted using Student's t test. RESULTS: During the pandemic period, the number of new order verifications decreased from approximately 5,000 orders per day to 3,300 orders per day (P < 0.01), a reduction of 30% during the first 4 weeks of the pandemic compared to the weeks prior. Average daily pharmacokinetic dosing consults were reduced in the pandemic period (from 82 to 67; P < 0.01) compared to the prepandemic period; however, total daily pharmacist interventions did not differ significantly (473 vs 456; P = 0.68). Dispensing of hydroxychloroquine, azithromycin, enoxaparin, and sedative medications increased substantially during the pandemic period (P < 0.01 for all comparisons). CONCLUSION: The operational and clinical requirements of an inpatient pharmacy department shifted considerably during the first weeks of the COVID-19 pandemic. Pharmacy departments must be adaptable in order to continue to provide effective pharmaceutical care during the pandemic.

Colon targeted bioadhesive pellets of curcumin and cyclosporine for improved management of inflammatory bowel disease.

The objective of the present work was to develop and optimize multiparticulate pH-dependent bioadhesive pellets of curcumin and cyclosporine for the management of intestinal bowel disease (IBD). The bioadhesive sustained release pellets were intended for targeting the affected site for an improved therapeutic effect. Bioadhesive pellet cores of curcumin and cyclosporine were formulated using Carbopol 940 (CP940) and hydroxypropyl cellulose (HPC-H) by the extrusion/spheronization method, and drug delivery to the colon was controlled by the pH-sensitive polymer Eudragit® S100. Microcrystalline cellulose (Avicel PH101) was found to be the best forming agent for pellet core. The ratio of CP940 to HPC-H was kept at 1:1 to achieve 100% bioadhesion. The in vitro dissolution profiles of coated pellets depicted that 12.327 ± 0.342% of curcumin and 14.751 ± 0.112% of cyclosporine were released at the end of 6 h (at pH 6.8), whereas 71.278 ± 0.100% of curcumin and 76.76 ± 0.195% of cyclosporine were released at the end of 24 h (at pH 7.4). The drug release profile was found to follow zero-order kinetics for both drugs. The selected formulation was evaluated on an acetic acid-induced ulcerative colitis in the rat model to evaluate the efficiency of drug-loaded pellets coated with Eudragit®S100. The pharmacodynamic study revealed the therapeutic efficacy of Eudragit®S100-coated pellets of curcumin and cyclosporine in alleviating the conditions of the acetic acid-induced colitis model as reflected by weight gain as well as improvement of clinical, macroscopic and microscopic parameters of induced colitis, as compared with free curcumin and cyclosporine. The combination of curcumin and cyclosporine has been proven to have a synergistic effect for the successful management of IBD when used in a low dose as compared with individual drugs with high doses. Hence, curcumin- and cyclosporine-loaded bioadhesive pellets may act as a promising targeted drug delivery system in the management of IBD. Graphical abstract.

Society of Onco-Anaesthesia and Perioperative Care consensus guidelines for perioperative management of patients for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for primary peritoneal malignancies or peritoneal spread of malignant neoplasm is being done at many centres worldwide. Perioperative management is challenging with varied haemodynamic and temperature instabilities, and the literature is scarce in many aspects of its perioperative management. There is a need to have coalition of the existing evidence and experts' consensus opinion for better perioperative management. The purpose of this consensus practice guideline is to provide consensus for best practice pattern based on the best available evidence by the expert committee of the Society of Onco-Anaesthesia and Perioperative Care comprising perioperative physicians for better perioperative management of patients of CRS-HIPEC.

MicroRNA-124-3p suppresses mouse lip mesenchymal cell proliferation through the regulation of genes associated with cleft lip in the mouse.

BACKGROUND: Cleft lip (CL), one of the most common congenital birth defects, shows considerable geographic and ethnic variation, with contribution of both genetic and environmental factors. Mouse genetic studies have identified several CL-associated genes. However, it remains elusive how these CL-associated genes are regulated and involved in CL. Environmental factors may regulate these genes at the post-transcriptional level through the regulation of non-coding microRNAs (miRNAs). In this study, we sought to identify miRNAs associated with CL in mice. RESULTS: Through a systematic literature review and a Mouse Genome Informatics (MGI) database search, we identified 55 genes that were associated with CL in mice. Subsequent bioinformatic analysis of these genes predicted that a total of 33 miRNAs target multiple CL-associated genes, with 20 CL-associated genes being potentially regulated by multiple miRNAs. To experimentally validate miRNA function in cell proliferation, we conducted cell proliferation/viability assays for the selected five candidate miRNAs (miR-124-3p, let-7a-5p, let-7b-5p, let-7c-5p, and let-7d-5p). Overexpression of miR-124-3p, but not of the others, inhibited cell proliferation through suppression of CL-associated genes in cultured mouse embryonic lip mesenchymal cells (MELM cells) isolated from the developing mouse lip region. By contrast, miR-124-3p knockdown had no effect on MELM cell proliferation. This miRNA-gene regulatory mechanism was mostly conserved in O9-1 cells, an established cranial neural crest cell line. Expression of miR-124-3p was low in the maxillary processes at E10.5, when lip mesenchymal cells proliferate, whereas it was greatly increased at later developmental stages, suggesting that miR-124-3p expression is suppressed during the proliferation phase in normal palate development. CONCLUSIONS: Our findings indicate that upregulated miR-124-3p inhibits cell proliferation in cultured lip cells through suppression of CL-associated genes. These results will have a significant impact, not only on our knowledge about lip morphogenesis, but also on the development of clinical approaches for the diagnosis and prevention of CL.

MicroRNA-655-3p and microRNA-497-5p inhibit cell proliferation in cultured human lip cells through the regulation of genes related to human cleft lip.

BACKGROUND: The etiology of cleft lip with or without cleft palate (CL/P), a common congenital birth defect, is complex and involves the contribution of genetic and environmental factors. Although many candidate genes have been identified, the regulation and interaction of these genes in CL/P remain unclear. In addition, the contribution of microRNAs (miRNAs), non-coding RNAs that regulate the expression of multiple genes, to the etiology of CL/P is largely unknown. METHODS: To identify the signatures of causative biological pathways for human CL/P, we conducted a systematic literature review for human CL/P candidate genes and subsequent bioinformatics analyses. Functional enrichment analyses of the candidate CL/P genes were conducted using the pathway databases GO and KEGG. The miRNA-mediated post-transcriptional regulation of the CL/P candidate genes was analyzed with miRanda, PITA, and TargetScan, and miRTarbase. Genotype-phenotype association analysis was conducted using GWAS. The functional significance of the candidate miRNAs was evaluated experimentally in cell proliferation and target gene regulation assays in human lip fibroblasts. RESULTS: Through an extensive search of the main biomedical databases, we mined 177 genes with mutations or association/linkage reported in individuals with CL/P, and considered them as candidate genes for human CL/P. The genotype-phenotype association study revealed that mutations in 12 genes (ABCA4, ADAM3A, FOXE1, IRF6, MSX2, MTHFR, NTN1, PAX7, TP63, TPM1, VAX1, and WNT9B) were significantly associated with CL/P. In addition, our bioinformatics analysis predicted 16 microRNAs (miRNAs) to be post-transcriptional regulators of CL/P genes. To validate the bioinformatics results, the top six candidate miRNAs (miR-124-3p, miR-369-3p, miR-374a-5p, miR-374b-5p, miR-497-5p, and miR-655-3p) were evaluated by cell proliferation/survival assays and miRNA-gene regulation assays in cultured human lip fibroblasts. We found that miR-497-5p and miR-655-3p significantly suppressed cell proliferation in these cells. Furthermore, the expression of the predicted miRNA-target genes was significantly downregulated by either miR-497-5p or miR-655-3p mimic. CONCLUSION: Expression of miR-497-5p and miR-655-3p suppresses cell proliferation through the regulation of human CL/P-candidate genes. This study provides insights into the role of miRNAs in the etiology of CL/P and suggests possible strategies for the diagnosis of CL/P.

Pharmacokinetics and investigation of optimal dose ertapenem in intermittent hemodialysis patients.

BACKGROUND: Previous pharmacokinetic studies demonstrated an increase in serum ertapenem concentrations with decreasing kidney function, including patients receiving renal replacement therapy. This study evaluated the pharmacokinetic parameters of ertapenem in patients receiving hemodialysis. METHODS: This prospective, single-center, open-label study examined the pharmacokinetics of a single intravenous (IV) dose of ertapenem 1 g in seven hospitalized noninfected patients undergoing hemodialysis. Blood samples were collected prior to ertapenem administration and at 0.5, 1, 2, 6, 12 and 48 hours (h) after administration. Ertapenem concentrations were determined by validated liquid chromatography mass spectrometry assay. RESULTS: Following an IV bolus of 1 g ertapenem, plasma concentrations declined relatively slowly with a mean ±standard deviation (SD) elimination half-life of 19.3 ±6.6 h. Plasma concentrations were similar in all subjects, with maximum mean plasma concentration observed of 343±48 µg/mL postdose. The mean ±SD values for systemic plasma clearance (CL) and volume of distribution at steady state (Vss) were 2±0.5 mL/min and 3295±1187 mL, respectively. The area under the curve for 0 h-∞ (AUCinf) was 7494 ±1424 h•µg/mL. No gender effect was observed and no serious adverse events were reported. CONCLUSIONS: Ertapenem half-life was prolonged in hemodialysis patients. Considering the nonrenal clearance and the expected 70% removal with high-efficacy hemodialysis, the dose of 1 g ertapenem, three times weekly, after hemodialysis may produce pharmacodynamically sufficient exposure for potential antimicrobial efficacy. Further studies are warranted to assess the clinical efficacy and safety of this dose with prolonged duration of therapy.

Surfactant mediated synthesis of bismuth selenide thin films for photoelectrochemical solar cell applications.

In the present report, nanostructured bismuth selenide (Bi2Se3) thin films have been successfully deposited by using arrested precipitation technique (APT) at room temperature. The effect of three different surfactants on the optostructural, morphological, compositional and photoelectrochemical properties of Bi2Se3 thin films were investigated. Optical absorption data indicates direct and allowed transition with a band gap energy varied from 1.4 eV to 1.8 eV. The X-ray diffraction pattern (XRD) revealed that Bi2Se3 thin films are crystalline in nature and confirmed rhombohedral crystal structure. SEM micrographs shows morphological transition from interconnected mesh to nanospheres like and finally granular morphology. Surface topography of Bi2Se3 thin films was determined by AFM. Compositional analysis of all samples was carried out by energy dispersive X-ray spectroscopy (EDS). Finally, all Bi2Se3 thin films shows good PEC performance with highest photoconversion efficiency 1.47%. In order to study the stability of Bi2Se3 thin films four cycles are repeated after gap of one week each. Further PEC performance of all Bi2Se3 thin films are also supported by electrochemical impedance (EIS) measurement study.

Complications, hospital length of stay, and readmission after total laryngectomy.

BACKGROUND: The purpose of this study was to describe the 30-day incidence of complications after total laryngectomy (TL) in a high-volume institution and their impact on the hospital length of stay (LOS) and readmission rates. METHODS: A retrospective cohort study of all patients who underwent TL at The University of Texas MD Anderson Cancer Center from January 1, 2010 through June 30, 2013 was conducted. The patient demographics, treatment history, LOS, and 30-day post-TL complications and readmissions were extracted from the medical record. Univariate associations were analyzed, and stepwise backward selection methods were used to fit multivariate models. RESULTS: Two hundred forty-five patients were included. Complications occurred in 83 patients (33.9%) and included 3 deaths (1.2%). Wound complications occurred in 53 patients (21.6%), and 34 were pharyngocutaneous fistulas (PCFs; 13.9% overall). Thirty-four patients (13.9%) were readmitted within 30 days. A multivariate analysis revealed the following: wound complications were associated with former (odds ratio [OR], 5.1; P = .03) and current smokers (OR, 5.8; P = .02), PCFs were associated with prior wide-field radiation (OR, 3.1; P = .01) but not prior narrow-field (larynx-only) radiation (OR, 1.4; P = .61), LOS was associated with the type of flap (P = .002) and postoperative hematomas (P = .05), and readmissions were associated with preoperative hypoalbuminemia (P = .003) and postoperative wound complications (P < .001). CONCLUSIONS: Complications occurred in approximately one-third of TL patients and particularly in patients with poor wound-healing risk factors such as prior smoking and radiation. As expected, LOS was longer among reconstructed patients. Readmission was associated with hypoalbuminemia and postoperative wound complications. These data can inform quality improvement efforts and the counseling of high-risk patients undergoing TL. Cancer 2017;123:1760-1767. © 2016 American Cancer Society.

Comparison of ultrasound imaging in transverse median and parasagittal oblique planes for thoracic epidurals: A pilot study.

BACKGROUND AND AIMS: The use of ultrasound (US) scanning to assess the depth of epidural space to prevent neurological complications is established in current practice. In this study, we hypothesised that pre-puncture US scanning for estimating the depth of epidural space for thoracic epidurals is comparable between transverse median (TM) and paramedian sagittal oblique (PSO) planes. METHODS: We performed pre-puncture US scanning in 32 patients, posted for open abdominal surgeries. The imaging was done to detect the depth of epidural space from skin (ultrasound depth [UD]) and needle insertion point, in parasagittal oblique plane in PSO group and transverse median plane in TM group. Subsequently, epidural space was localised through the predetermined insertion point by 'loss of resistance' technique and needle depth (ND) to the epidural space was marked. Correlation between the UD and actual ND was calculated and concordance correlation coefficient (CCC) was used to determine the degree of agreement between UD and ND in both the planes. RESULTS: The primary outcome, i.e., the comparison between UD and ND, done using Pearson correlation coefficient, was 0.99 in both PSO and TM groups, and the CCC was 0.93 (95% confidence interval [95% CI]: 0.81-0.97) and 0.90 (95% CI: 0.74-0.96) in PSO and TM groups respectively, which shows a strong positive association between UD and ND in both groups. CONCLUSION: The use of pre-puncture US scanning in both PSO and TM planes for estimating the depth of epidural space at the level of mid- and lower-thoracic spine is comparable.

Mechanics of severing for large microtubule complexes revealed by coarse-grained simulations.

We investigate the mechanical behavior of microtubule (MT) protofilaments under the action of bending forces, ramped up linearly in time, to provide insight into the severing of MTs by microtubule associated proteins (MAPs). We used the self-organized polymer model which employs a coarse-grained description of the protein chain and ran Brownian dynamics simulations accelerated on graphics processing units that allow us to follow the dynamics of a MT system on experimental timescales. Our study focused on the role played in the MT depolymerization dynamics by the inter-tubulin contacts a protofilament experiences when embedded in the MT lattice, and the number of binding sites of MAPs on MTs. We found that proteins inducing breaking of MTs must have at least three attachment points on any tubulin dimer from an isolated protofilament. In contrast, two points of contact would suffice when dimers are located in an intact MT lattice, in accord with experimental findings on MT severing proteins. Our results show that confinement of a protofilament in the MT lattice leads to a drastic reduction in the energy required for the removal of tubulin dimers, due to the drastic reduction in entropy. We further showed that there are differences in the energetic requirements based on the location of the dimer to be removed by severing. Comparing the energy of tubulin dimers removal revealed by our simulations with the amount of energy resulting from one ATP hydrolysis, which is the source of energy for all MAPs, we provided strong evidence for the experimental finding that severing proteins do not bind uniformly along the MT wall.

Standard versus prolonged doripenem infusion for treatment of gram-negative infections.

BACKGROUND: Doripenem is the most recently introduced carbapenem, with a broad spectrum of antimicrobial activity. Preliminary data indicated that activity is optimized by maximizing the time that serum concentration remains above the minimum inhibitory concentration; however, limited clinical data are available to support this approach. OBJECTIVE: To compare clinical outcomes before and after implementation of a hospital-wide initiative extending the duration of infusion for doripenem from 1 hour (standard) to 4 hours (prolonged). METHODS: This retrospective, quasi-experimental study compared clinical outcomes associated with doripenem administered as a 1-hour infusion versus a 4-hour infusion for treatment of suspected or documented infections caused by gram-negative organisms. Outcomes were assessed for the entire cohort, as well as for the subpopulation of patients admitted to the intensive care unit. RESULTS: Two hundred patients were included; 106 patients received doripenem via standard infusion and 94 patients via prolonged infusion. No significant differences were noted between the treatment groups in clinical success, length of stay, or duration of treatment when the entire cohort was evaluated. In the critically ill subgroup, pneumonia, standard-infusion doripenem, and concomitant bacteremia were independent predictors of clinical failure (adjusted odds ratio [95% CI] 7.8 [2.4-25.6], 5.5 [1.6-18.7], and 7.0 [1.6-31.3], respectively). Additionally, critically ill patients who received doripenem via standard infusion were significantly more likely to experience recurrence of infection or death within 90 days. No significant differences were noted in length of stay or duration of bacteremia. CONCLUSIONS: The duration of infusion did not significantly impact outcomes when the entire cohort was compared; however, prolonged infusion of doripenem was associated with significantly improved clinical outcomes among critically ill patients. These findings support the use of prolonged infusion of doripenem for critically ill patients.