Combinatorial cetuximab targeted polymeric nanocomplexes reduce PRC1 level and abrogate growth of metastatic hepatocellular carcinoma in vivo with efficient radionuclide uptake.

Hepatocellular carcinoma (HCC) is the most aggressive form of cancer with poor drug responses. Developing an effective drug treatment remains a major unmet clinical need for HCC. We report a comprehensive study of combinatorial Cetuximab (Cet) targeted polymeric poly(D, L-lactide-co-glycolide)-b-poly(ethylene glycol) nanocomplexes delivery of Combretastatin A4 (CA4) and 2-Methoxyestradiol (2ME) (Cet-PLGA-b-PEG-CA4 NP + Cet-PLGA-b-PEG-2ME NP) against metastatic HCC in SCID mice. 125I-Cet-PLGA-b-PEG NP showed potent accumulation and retention in HCC tumors with longer circulation time up to 48 h (18 ±â€¯1.0% ID/g, P < .0001). Combinatorial treatment with targeted polymeric nanocomplexes presented significant tumor growth inhibition (85%, P < .0001) than the free drug combinatorial counterpart, effectively inhibited orthotopic HCC and prevented lung metastasis. Combinatorial nanocomplexes treatment significantly blocked PRC1, a novel target of therapeutic response against HCC. Thus, the combinatorial cetuximab-targeted polymeric nanocomplexes possess superior antitumor activity against metastatic HCC and provide supports for the clinical translation ahead.

Hepatocellular Carcinoma: Intra-arterial Delivery of Doxorubicin-loaded Hollow Gold Nanospheres for Photothermal Ablation-Chemoembolization Therapy in Rats.

Purpose To determine if combretastatin A-4 phosphate disodium (CA4P) can enhance the tumor uptake of doxorubicin (Dox)-loaded, polyethylene glycol (PEG)-coated hollow gold nanospheres (HAuNS) mixed with ethiodized oil for improved photothermal ablation (PTA)-chemoembolization therapy (CET) of hepatocellular carcinoma (HCC) in rats. Materials and Methods Animal experiments were approved by the institutional animal care and use committee and performed from February 2014 to April 2015. Male Sprague-Dawley rats (n = 45; age, 12 weeks) were inoculated with N1S1 HCC cells in the liver, and 8 days later, were randomly divided into two groups of 10 rats. Group 1 rats received intrahepatic arterial injection of PEG-HAuNS and ethiodized oil alone; group 2 received pretreatment with CA4P and injection of PEG-HAuNS and ethiodized oil 5 minutes later. The gold content of tumor and liver tissue at 1 hour or 24 hours after injection was quantified by using neutron activation analysis (n = 5 per time point). Five rats received pretreatment CA4P, PEG-copper 64-HAuNS, and ethiodized oil and underwent micro-positron emission tomography (PET)/computed tomography (CT). In a separate study, three groups of six rats with HCC were injected with saline solution (control group); CA4P, Dox-loaded PEG-coated HAuNS (Dox@PEG-HAuNS), and ethiodized oil (CET group); or CA4P, Dox@PEG-HAuNS, ethiodized oil, and near-infrared irradiation (PTA-CET group). Temperature was recorded during laser irradiation. Findings were verified at postmortem histopathologic and/or autoradiographic examination. Wilcoxon rank-sum test and Pearson correlation analyses were performed. Results PEG-HAuNS uptake in CA4P-pretreated HCC tumors was significantly higher than that in non-CA4P-pretreated tumors at both 1 hour (P < .03) and 24 hours (P < .01). Mean ± standard deviation of tumor-to-liver PEG-HAuNS uptake ratios at 1 hour and 24 hours, respectively, were 5.63 ± 3.09 and 1.68 ± 0.77 in the CA4P-treated group and 1.29 ± 2.40 and 0.14 ± 0.11 in the non-CA4P-treated group. Micro-PET/CT allowed clear delineation of tumors, enabling quantitative imaging analysis. Laser irradiation increased temperature to 60°C and 43°C in the tumor and adjacent liver, respectively. Mean HCC tumor volumes 10 days after therapy were 1.68 cm3 ± 1.01, 3.96 cm3 ± 1.75, and 6.13 cm3 ± 2.27 in the PTA-CET, CET, and control groups, respectively, with significant differences between the PTA-CET group and other groups (P < .05). Conclusion CA4P pretreatment caused a higher concentration of Dox@PEG-HAuNS to be trapped inside the tumor, thereby enhancing the efficacy of anti-HCC treatment with PTA-CET in rats. © RSNA, 2016 Online supplemental material is available for this article.

Epidermal electronics with advanced capabilities in near-field communication.

Epidermal electronics with advanced capabilities in near field communications (NFC) are presented. The systems include stretchable coils and thinned NFC chips on thin, low modulus stretchable adhesives, to allow seamless, conformal contact with the skin and simultaneous capabilities for wireless interfaces to any standard, NFC-enabled smartphone, even under extreme deformation and after/during normal daily activities.

Effect of Transcatheter Intra-Arterial Therapies on Tumor Interstitial Fluid Pressure and Its Relation to Drug Penetration in a Rabbit Liver Tumor Model.

PURPOSE: To determine the change in tumor interstitial fluid pressure (IFP) after transcatheter intra-arterial (IA) therapies and its relation to drug penetration in liver cancer. MATERIALS AND METHODS: VX2 tumors were grown in the livers of 16 rabbits. The rabbits were treated with intravenous injection of doxorubicin (group 1; n = 4), hepatic IA injection of doxorubicin (group 2; n = 4), hepatic IA injection of doxorubicin followed by embolization with polyvinyl alcohol particles (group 3; n = 4), or hepatic IA injection of doxorubicin mixed with Lipiodol followed by polyvinyl alcohol embolization (group 4; n = 4). Tumor IFP was measured with a Mikro-Tip pressure catheter before and 1 hour after treatment. Doxorubicin penetration was evaluated by immunofluorescence. RESULTS: Tumor IFP after treatment decreased by 5.0% ± 2.8, 3.9% ± 9.0, 27.1% ± 5.2, and 31.8% ± 7.4 in groups 1-4, respectively. The difference in IFP reduction between embolization-treated groups (groups 3 and 4) and nonembolized groups (groups 1 and 2) was significant (P < .001). Doxorubicin penetration distances were 20.3 µm ± 3.7, 45.7 µm ± 10.5, 69.5 µm ± 9.3, and 47.9 µm ± 6.4 in groups 1-4, respectively. IFP reduction was significantly correlated with doxorubicin penetration distance (r = .671, P = .004). CONCLUSIONS: A greater reduction of tumor IFP was associated with embolization in a preclinical liver tumor model, and embolization may indirectly contribute to increased drug penetration.

Development of poly(aspartic acid-co-malic acid) composites for calcium carbonate and sulphate scale inhibition.

Polyaspartic acid (PSI) is suitable for the inhibition of inorganic scale deposition. To enhance its scale inhibition efficiency, PSI was modified by reacting aspartic acid with malic acid (MA) using thermal polycondensation polymerization. This reaction resulted in poly(aspartic acid-co-malic acid) (PSI-co-MA) dual polymer. The structural, chemical and thermal properties of the dual polymers were analysed by using scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and gel permeation chromatography. The effectiveness of six different molar ratios of PSI-co-MA dual polymer for calcium carbonate and calcium sulphate scale inhibition at laboratory scale batch experiments was evaluated with synthetic brine solution at selected doses of polymer at 65-70°C by the static scale test method. The performance of PSI-co-MA dual polymer for the inhibition of calcium carbonate and calcium sulphate precipitation was compared with that of a PSI single polymer. The PSI-co-MA exhibited excellent ability to control inorganic minerals, with approximately 85.36% calcium carbonate inhibition and 100% calcium sulphate inhibition at a level of 10 mg/L PSI-co-MA, respectively. Therefore, it may be reasonably concluded that PSI-co-MA is a highly effective scale inhibitor for cooling water treatment applications.

Towards an optimal design of a functionally graded porous uncemented acetabular component using genetic algorithm.

Generation of polyethylene wear debris and peri­prosthetic bone resorption have been identified as potential causes of acetabular component loosening in Total Hip Arthroplasty. This study was aimed at optimization of a functionally graded porous acetabular component to minimize peri­prosthetic bone resorption and polyethylene liner wear. Porosity levels (porosity values at acetabular rim, and dome) and functional gradation exponents (radial and polar) were considered as the design parameters. The relationship between porosity and elastic properties were obtained from numerical homogenization. The multi-objective optimization was carried out using a non-dominated sorting genetic algorithm integrated with finite element analysis of the hemipelvises subject to various loading conditions of common daily activities. The optimal functionally graded porous designs (OFGPs -1, -2, -3, -4, -5) exhibited less strain-shielding in cancellous bone compared to solid metal-backing. Maximum bone-implant interfacial micromotions (63-68 µm) for OFGPs were found to be close to that of solid metal-backing (66 µm), which might facilitate bone ingrowth. However, OFGPs exhibited an increase in volumetric wear (3-10 %) compared to solid metal-backing. The objective functions were found to be more sensitive to changes in polar gradation exponent than radial gradation exponent, based on the Sobol' method. Considering the common failure mechanisms, OFGP-1, having highly porous acetabular rim and less porous dome, appears to be a better alternative to the solid metal-backing.

Contribution of Anatomy in Forensic Age Evaluation: A Systematic Review.

The field of forensic anthropology is characterised by its ongoing development and growth. Forensic anatomy is a burgeoning discipline that focuses on the analysis and identification of both preserved and unpreserved human body parts, both in deceased individuals and the living. This subject plays a crucial role in establishing the four key factors of forensic anthropology, namely sex, age, race, and height. The objective of this research endeavour was to evaluate the significance of anatomical information in the process of forensic age estimation. The researchers established the inclusion criteria in accordance with the globally recognised Population, Intervention, Comparison, Outcome (PICOS) framework, as advised by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The research included many methodologies in order to ascertain the age. Upon conducting a comprehensive review of the existing literature pertaining to anatomical knowledge in the field of forensic age estimate, we have identified many notable applications. These include the utilisation of various anatomical features such as the dental pulp chamber, fingerprints, acetabulum, sternal end of the fourth rib, as well as hand and wrist bones for the purpose of age estimation. It is important for anatomists and other forensic scientists to engage in collaborative efforts to facilitate the exchange of ideas and ensure thorough investigations. This cooperation is particularly crucial in areas where anatomical sciences play a significant role in forensic science and investigation. Nevertheless, in order to mitigate the potential for estimating error, it is still advisable to use a multi-factorial evaluation approach that involves examining many body areas.

Effects of Smokeless Tobacco on Oral Health: A Cross-Sectional Study.

BACKGROUND: Smokeless tobacco (SLT) consumption poses a significant global public health challenge because of its adverse effects on oral health. Although the detrimental impact of SLT on oral tissues is well-documented, understanding its multifaceted effects is essential for effective prevention and intervention strategies. OBJECTIVE: This study aimed to comprehensively assess the impact of SLT on oral health, focusing on various clinical parameters and their differences between placement and non-placement sites of SLT. METHODS: A cross-sectional study involving 528 habitual users of SLT was conducted. Clinical parameters included the plaque index (PI), gingival index (GI), gingival bleeding index (GBI), gingival recession (GR), and probing depth (PD). Oral mucosal changes at SLT placement sites have also been reported. Statistical analysis was performed to compare parameters between the placement and non-placement sites. RESULTS:  The study involved 528 subjects, mostly male (82%) and aged 21-40 years (mean±SD=31.14±9.10), habitual users of SLT. Prevalent SLT types included tobacco with betel nuts/masala/gutkha (59.9%) and tobacco with lime (54.5%). Significant differences were observed between SLT placement and non-placement sites: higher gingival inflammation (GI) at placement sites (1.54±0.61 vs. 1.45±0.54, p=0.01), lower GBI at placement sites (40.0% vs. 84.3%, p=0.001), and more prevalent GR (65.7% vs. 34.3%, p=0.03) at placement sites. Probing depths ≥ 3 mm were also less frequent at placement sites (2.67±0.72) than non-placement sites (3.37±1.03, p=0.001). These results highlight the detrimental impact of SLT on periodontal health, emphasizing the need for targeted interventions among SLT users. CONCLUSION: SLT use is associated with adverse effects on oral health, including GI, plaque accumulation, gingival bleeding, GR, and changes in the oral mucosa. Targeted interventions and public health policies are needed to address these issues effectively.

Clinical Evaluation of Coronally Advanced Flap with or without a Platelet-Rich Fibrin Membrane for the Root Coverage.

Aim: To evaluate "coronally advanced flap" with or without "a platelet-rich fibrin membrane for the root coverage." Materials and Methods: All the clinical parameters were assessed at different time intervals (at baseline, 1, 3, and 6 months) in both experimental and control group. Following "clinical parameters" were recorded using "UNC-15" "Probe-Plaque Index (PI)" (Silness and Loe, 1964), "Gingival Index" (GI) (Loe and Silness, 1963), "Recession depth (RD)," "Recession width (RW)," "Clinical attachment level (CAL)," and "Width of keratinized gingiva (WKG)". Results: At final evaluation (i.e., mean change from baseline to 6 months), "the decrease in Plaque Index was 2.5% higher in Group B (66.0%) as compared to Group A (63.5%). The decrease in Gingival Index was 6.1% higher in Group B (91.4%) as compared to Group A (85.3%), and the decrease in recession width was 4.0% higher in Group B (75.2%) as compared to Group A (71.2%). The decrease in clinical attachment level was 4.4% higher in Group B (53.2%) as compared to Group A (48.4%). The increase in width of keratinized gingiva was 1.9% higher in Group A (28.8%) as compared to Group B (26.9%)." Conclusion: The controlled, randomized, split mouth design showed that CAF surgery, either by alone or in combination with PRF, is an efficient treatment method for covering denuded roots. "This design was used to treat bilateral isolated Miller's class I and II recessions in gingival part. When compared to the CAF approach, the results from a combination of CAF and PRF after a 6-month period showed additional advantages in addition to mean root coverage in the treatment of Miller's classes I and II recessions in gingival part."

The effect of high dose antibiotic impregnated cement on rate of surgical site infection after hip hemiarthroplasty for fractured neck of femur: a protocol for a double-blind quasi randomised controlled trial.

BACKGROUND: Mortality following hip hemiarthroplasty is in the range of 10-40% in the first year, with much attributed to post-operative complications. One such complication is surgical site infection (SSI), which at the start of this trial affected 4.68% of patients in the UK having this operation. Compared to SSI rates of elective hip surgery, at less than 1%, this figure is elevated. The aim of this quasi randomised controlled trial (RCT) is to determine if high dose antibiotic impregnated cement can reduce the SSI in patients at 12-months after hemiarthroplasty for intracapsular fractured neck of femur. METHODS: 848 patients with an intracapsular fractured neck of femur requiring a hip hemiarthroplasty are been recruited into this two-centre double-blind quasi RCT. Participants were recruited before surgery and quasi randomised to standard care or intervention group. Participants, statistician and outcome assessors were blind to treatment allocation throughout the study. The intervention consisted of high dose antibiotic impregnated cement consisting of 1 gram Clindamycin and 1 gram of Gentamicin. The primary outcome is Health Protection Agency (HPA) defined deep surgical site infection at 12 months. Secondary outcomes include HPA defined superficial surgical site infection at 30 days, 30 and 90-day mortality, length of hospital stay, critical care stay, and complications. DISCUSSION: Large randomised controlled trials assessing the effectiveness of a surgical intervention are uncommon, particularly in the speciality of orthopaedics. The results from this trial will inform evidence-based recommendations for antibiotic impregnated cement in the management of patients with a fractured neck of femur undergoing a hip hemiarthroplasty. If high dose antibiotic impregnated cement is found to be an effective intervention, implementation into clinical practice could improve long-term outcomes for patients undergoing hip hemiarthroplasty. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN25633145.

An Orthodontic Approach for the Correction of Transposition along with Multiple Impacted Teeth.

Impaction of teeth affects patients' esthetics, speech, and masticatory efficiency. In addition, the transposition of teeth makes a case difficult to manage. This case report describes a case of a 14-year-old boy with the impaction of the maxillary right central incisor and canine along with the transposition of the right canine and lateral incisor. The impacted teeth were surgically exposed and guided into the arch using orthodontic traction. Likewise, the transposition was corrected orthodontically by moving the teeth to their desired position without any detrimental effect on the adjacent teeth. The patient's esthetics and occlusion improved substantially after the orthodontic intervention.

Association of Serum Interleukin-10 Level with Glycemic Status to Predict Glycemic Alteration with Periodontitis: A Cross-Sectional, Observational Study.

Background and Aim: Studies showed bidirectional relationship between chronic periodontitis (CPD) and diabetes. This study was conducted to estimate the levels of serum interleukin (IL)-10 in patients with CPD and type 2 diabetes mellitus (T2DM) to evaluate the association of serum IL-10 levels with glycemic status and to evaluate the influence of periodontal inflammation on glycemic control. Setting and Design: A cross-sectional observational study. Materials and Methods: Eighty patients were divided into four groups consisting of 20 patients in each group. Group 1: healthy control, Group 2: T2DM without chronic periodontitis, Group 3: chronic periodontitis only (CPD), and Group 4: T2DM with chronic periodontitis (CPD). Plaque index, gingival index, pocket probing depth, clinical attachment loss, random blood sugar, and glycated hemoglobin (HbA1c) level were recorded for categorizing patients into aforestated groups. Serum IL-10 level was measured by ELISA kit. Statistical Analysis Used: ANOVA statistics and post hoc Tukey's test were performed for comparing individual groups. Results: IL-10 was detected lowest in Group 3 followed by Group 4. Highest level of IL-10 was found in the healthy group then in Group 2. Conclusion: IL-10 levels have an inverse relationship with HbA1c. Lowest level of IL-10 in CPD dictates periodontal inflammation itself influences in regulating serum IL-10 level and poor glycemic control. Serum IL-10 level may be one of the predictors of glycemia.

Injectable Synthetic Beta-Tricalcium Phosphate/Calcium Sulfate (GeneX) for the Management of Contained Defects Following Curettage of Benign Bone Tumours.

Benign and low-grade malignant bone tumours are often treated with curettage and filling of the resultant defect using any of a number of materials, including autologous bone grafts, allografts, or synthetic materials. The objective of this study was to report our experience using a synthetic bone graft substitute in these patients. Ten consecutive cases (four males, six females; mean age, 36 years) of benign bone tumours were treated surgically at a tertiary musculoskeletal oncology centre, between 2019 and 2021. Following curettage, the contained defects were managed with injectable beta-tricalcium phosphate/calcium sulfate (GeneX; Biocomposites Ltd., Keele, UK). The desired outcomes were early restoration of function and radiographic evidence of healing. No other graft materials were used in any of the patients. The mean follow-up was 24 months (range, 20-30 months). All patients in this series (100%) demonstrated radiographic evidence of healing and resumed their daily living activities. There were no tumour recurrences and no complications were encountered with the use of GeneX. In patients with contained defects following curettage of benign bone tumours, we found GeneX to be a safe and effective filling agent. These findings contrast with some existing studies that have reported local complications with the use of injectable beta-tricalcium phosphate/calcium sulfate.

Clinical efficacy of ozonated water and photodynamic therapy in non-surgical management of chronic periodontitis: A clinico- microbial study.

BACKGROUND: Periodontitis is a chronic multifactorial inflammatory disease associated with dysbiotic plaque biofilms and characterized by progressive destruction of the tooth-supporting apparatus. Treatment of the periodontitis is a key challenge since the disease occurs due to microbial biofilm which is extremely resistant to host response and antimicrobials. Among non-surgical methods, scaling and root planning (SRP) is considered as the fundamental method and results in the utmost improvements. However, complete elimination of subgingival calculus is difficult. A substitute treatment in inhibition of subgingival microbiota can be attained by ozonated water at a concentration of 0.5-4 mg/L. Lately, laser light therapy has been proposed in periodontal therapy in an endeavor to improve the efficiency and effectiveness of bacterial elimination and root surface debridement. MATERIALS AND METHODS: 26 patients with chronic periodontitis were selected. The selected arches were randomly divided into two groups: Group-A was subjected to SRP + Ozone-Therapy and Group-B to SRP + Photodynamic-Therapy. Clinical parameters were recorded at baseline, 1&2months. Microbial parameters were recorded at baseline and 2-months. RESULTS: For both the groups significant decrease in clinical parameters were seen from baseline to 1 month and further in 2 months. On intergroup comparison of clinical parameters no significant result was found. Both the groups showed significant decrease in microbial parameters was seen from baseline to 2 months. On intergroup comparison of microbial parameters no significant result was found. CONCLUSION: Clinically and microbiologically, there was significant difference in both the groups between all time periods (P < 0.001), however there was no significant difference between the two groups at all periods (P > 0.05).

Glucose-Responsive Chitosan Nanoparticle/Poly(vinyl alcohol) Hydrogels for Sustained Insulin Release In Vivo.

Stimuli-responsive hydrogels (HGs) with a controlled drug release profile are the current challenge for advanced therapeutic applications. Specifically, antidiabetic drug-loaded glucose-responsive HGs are being investigated for closed-loop insulin delivery in insulin-dependent diabetes patients. In this direction, new design principles must be exploited to create inexpensive, naturally occurring, biocompatible glucose-responsive HG materials for the future. In this work, we developed chitosan nanoparticle/poly(vinyl alcohol) (PVA) hybrid HGs (CPHGs) for controlled insulin delivery for diabetes management. In this design, PVA and chitosan nanoparticles (CNPs) are cross-linked with a glucose-responsive formylphenylboronic acid (FPBA)-based cross-linker in situ. Leveraging the structural diversity of FPBA and its pinacol ester-based cross-linkers, we fabricate six CPHGs (CPHG1-6) with more than 80% water content. Using dynamic rheological measurements, we demonstrate elastic solid-like properties of CPHG1-6, which are dramatically reduced under low-pH and high-glucose environments. An in vitro drug release assay reveals size-dependent glucose-responsive drug release from the CPHGs under physiological conditions. It is important to note that the CPHGs show appreciable self-healing and noncytotoxic properties. Promisingly, we observe a significantly slower insulin release profile from the CPHG matrix in the type-1 diabetes (T1D) rat model. We are actively pursuing scaling up of CPHGs and the in vivo safety studies for clinical trial in the near future.

Comparative evaluation of a patient-specific customised plate designs and screws for partial mandibular reconstruction.

Mandibles with odontogenic tumors are often partially reconstructed with a metallic bone graft analogue with dental roots, crowns, along with a customized plate fixed with monocortical or bicortical screws, following resection of the tumor. In this study, two different designs of patient specific customized Ti reconstruction plates, solid and plate with holes, were considered. Fixation through both bicortical and monocortical screw types were investigated. FE models of the reconstructed mandibles were developed to analyse the influence of the plate-screw type combination on the load transfer across the mandibles under a mastication cycle. The effective homogenized orthotropic material properties of the lattice structures with 0.6 mm fibre diameter with 0.5 mm inter-fibre space were assigned to material properties for the bone graft analogue. The study shows that the combination of plate and screw types influences the state of stresses in the reconstructed mandible. Based on the results of this patient specific study, following resection of the tumor, either solid Ti plate with bicortical screws or Ti plate with holes along with monocortical screws may be used for partial mandibulectomy. It should also be noted that stresses in none of the plates or screws exceeded the yield limit for Ti under the mastication cycle indicating that the components are safe for mandibular reconstruction. However, the choice of this combination of reconstruction plates and screws is dependant on the condition and severity of the tumor in the diseased mandible.

Characterization of Recombinantly-Expressed Hydrolytic Enzymes from Chinese Hamster Ovary Cells: Identification of Host Cell Proteins that Degrade Polysorbate.

Enzymatic hydrolysis of polysorbate in drug products is a major challenge for the biopharmaceutical industry. Polysorbate hydrolysis caused by host cell proteins (HCPs) co-purified during bioprocessing can reduce the protective effects of the surfactant for the active pharmaceutical ingredient and cause the accumulation of low-solubility degradation products over the long-term storage. The identities of such HCPs are elusive due to their extremely low concentrations after the efficient purification processes of most biopharmaceuticals. In this work, 20 enzymes-selected for their known or putative hydrolytic activity and potential to degrade polysorbate-were recombinantly expressed, purified, and characterized via orthogonal methods. First, these recombinant HCPs were assessed for hydrolytic activity against a fluorogenic esterase substrate in a recently-developed, high-throughput assay. Second, these HCPs were screened for hydrolytic activity against polysorbate in a representative mAb formulation. Third, HCPs that displayed hydrolytic activities in the first two assays were subjected to more detailed characterization of their enzyme kinetics against polysorbates. Finally, these HCPs were evaluated for substrate specificity towards different sub-species of polysorbates. This work provides critical new insights for targeted LC-MS/MS approaches for identification of relevant polysorbate-degrading enzymes and supports improvements to remove such HCPs, including knockouts or targeted removal during purification.

A fast and sensitive high-throughput assay to assess polysorbate-degrading hydrolytic activity in biopharmaceuticals.

Hydrolysis of polysorbate in biopharmaceutical products has been ascribed to the enzymatic activity from trace levels of residual host cell proteins. In recent years, significant efforts to identify the causative enzymes typically used elaborate, material-intensive and time-consuming approaches. Therefore, the lack of fast and sensitive assays to monitor their activity remains a major bottleneck for supporting process optimization and troubleshooting activities where time and sample throughput are crucial constraints. To address this bottleneck, we developed a novel Electrochemiluminescence-based Polysorbase Activity (EPA) assay to measure hydrolytic activities in biotherapeutics throughout the drug substance manufacturing process. By combining the favorable features of an in-house designed surrogate substrate with a well-established detection platform, the method yields fast (∼36 h turnaround time) and highly sensitive readouts compatible with high-throughput testing. The assay capability for detecting substrate conversion in a precise and reliable manner was demonstrated by extensive qualification studies and by employing a number of recombinant hydrolases associated with polysorbate hydrolysis. In addition, high assay sensitivity and wide applicability were confirmed for in-process pool samples of three different antibody products by performing a head-to-head comparison between this method and an established liquid chromatography - mass spectrometry based assay for the quantification of free fatty acids. Overall, our results suggest that this new approach is well-suited to resolve differences in hydrolytic activity through all stages of purification.

Experimental validation of finite element models of intact and implanted composite hemipelvises using digital image correlation.

A detailed understanding of the changes in load transfer due to implantation is necessary to identify potential failure mechanisms of orthopedic implants. Computational finite element (FE) models provide full field data on intact and implanted bone structures, but their validity must be assessed for clinical relevance. The aim of this study was to test the validity of FE predicted strain distributions for the intact and implanted pelvis using the digital image correlation (DIC) strain measurement technique. FE models of an in vitro hemipelvis test setup were produced, both intact and implanted with an acetabular cup. Strain predictions were compared to DIC and strain rosette measurements. Regression analysis indicated a strong linear relationship between the measured and predicted strains, with a high correlation coefficient (R = 0.956 intact, 0.938 implanted) and a low standard error of the estimate (SE = 69.53 µÎµ, 75.09 µÎµ). Moreover, close agreement between the strain rosette and DIC measurements improved confidence in the validity of the DIC technique. The FE model therefore was supported as a valid predictor of the measured strain distribution in the intact and implanted composite pelvis models, confirming its suitability for further computational investigations.

Mean Mesiodistal Width of Canine in Patients Visiting a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: The measurement of the teeth is one of the most reliable method of identification. The teeth represent the most durable, resilient, and chemically stable part of the skeleton. The comparison of tooth dimensions is one of the tools of sex determination. Canines, in particular, are found to have the greatest degree of sexual dimorphism. The aim of the study was to determine the mean mesiodistal width of canines in patients visiting a tertiary care centre. Methods: This descriptive cross-sectional study was done among patients visiting a tertiary care centre from 25 August 2021 to 28 December 2021. The ethical approval was taken from the Institutional Review Committee [Reference number: 61 (6-11)E2 078/079]. The maximum mesiodistal width of the permanent maxillary canine was measured by a digital vernier caliper. The formula given by Garn and Len was used to calculate sexual dimorphism. Convenience sampling was used. Point estimate and 95% Confidence Interval were calculated. Results: Among 104 maxillary casts studied, the mean mesiodistal width of the maxillary canine was 7.85±0.45 mm (7.76-7.93, 95% Confidence Interval). The mean mesiodistal width of the right maxillary canine in males and females were 7.90±0.48 mm and 7.83±0.45 mm respectively and that of the left maxillary canines in males and females were 7.92±0.44 mm and 7.75±0.45 mm respectively. The sexual dimorphism in the right and left maxillary canine was seen in 10 (0.96%) and 22 (2.12%) respectively. Conclusions: The mean mesiodistal width of the maxillary canine was similar to other studies done in similar settings. Keywords: canine teeth; maxillary bone; sexual dimorphism.