Search

Small molecule-driven JNK activation has been found to induce apoptosis and paraptosis in cancer cells. Herein pharmacological effects of synthetic oxazine (4aS, 7aS)-3-((4-(4‑chloro-2-fluorophenyl)piperazin-1-yl)methyl)-4-phenyl-4, 4a, 5, 6, 7, 7a-hexahydrocyclopenta[e] [1,2]oxazine (FPPO; BSO-07) on JNK-driven apoptosis and paraptosis has been demonstrated in human breast cancer (BC) MDA-MB231 and MCF-7 cells respectively. BSO-07 imparted significant cytotoxicity in BC cells, induced activation of JNK, and increased intracellular reactive oxygen species (ROS) levels. It also enhanced the expression of apoptosis-associated proteins like PARP, Bax, and phosphorylated p53, while decreasing the levels of Bcl-2, Bcl-xL, and Survivin. Furthermore, the drug altered the expression of proteins linked to paraptosis, such as ATF4 and CHOP. Treatment with N-acetyl-cysteine (antioxidant) or SP600125 (JNK inhibitor) partly reversed the effects of BSO-07 on apoptosis and paraptosis. Advanced in silico bioinformatics, cheminformatics, density Fourier transform and molecular electrostatic potential analysis further demonstrated that BSO-07 induced apoptosis and paraptosis via the ROS/JNK pathway in human BC cells.

Pure and Fe-doped TiO2 nanoparticles were synthesized through green synthesis route for wastewater remediation application. Pure and Fe-doped TiO2 nanoparticles were further characterised through various techniques like XRD, SEM, and EDS. The XRD patterns indicate pure anatase phase with space group I 41/a m d through the Rietveld refinement. The average crystalline size of Fe-doped TiO2 nanoparticles decreases with the increment in the concentration of doping. The high agglomeration of pure and Fe-doped TiO2 nanoparticles is observed through SEM. EDS analysis conforms the presence of Fe, Ti, and O elements in the nanoparticles. The photo catalytic activities of pure and Fe-doped TiO2 under ultraviolet (UV) light with different concentration were investigated. The dissolved oxygen in the water increases with the increment of Fe doping and time of exposer of UV light.

Paper based point-of-care (PoC) detection platforms applying lateral flow assays (LFAs) have gained paramount approval in the diagnostic domain as well as in environmental applications owing to their ease of utility, low cost, and rapid signal readout. It has centralized the aspect of self-evaluation exhibiting promising potential in the last global pandemic era of Covid-19 implementing rapid management of public health in remote areas. In this perspective, the present review is focused towards landscaping the current framework of LFAs along with integration of components and characteristics for improving the assay by pushing the detection limits. The review highlights the synergistic aspects of assay designing, sample enrichment strategies, novel nanomaterials-based signal transducers, and high-end analytical techniques that contribute significantly towards sensitivity and specificity enhancement. Various recent studies are discussed supporting the innovations in LFA systems that focus upon the accuracy and reliability of rapid PoC testing. The review also provides a comprehensive overview of all the possible difficulties in commercialization of LFAs subjecting its applicability to pathogen surveillance, water and food testing, disease diagnostics, as well as to agriculture and environmental issues.

The present study involves the use of combined network pharmacology and molecular modelling approach for identifying important phytoconstituents that could modulate the functions of multiple therapeutic targets in Alzheimer’s disease. A list of botanicals reported in the literature for their efficacy in Alzheimer’s disease, the phytochemicals present in the botanicals were identified with the help of network pharmacology approach. The pharmacokinetic properties like blood brain barrier penetration and Lipinski’s rule of five for the selected phytoconstituents were analyzed. The major targets involved in the pathogenesis of Alzheimer’s disease were collected from the DisGeNET database. The selected proteins were subjected to topological analysis using Cytoscape software to identify the important targets in the network. The top 7 phytoconstituents and 5 proteins were subjected to molecular docking, MM-GBSA and molecular dynamics studies. A total of 15 plants and 1443 phytoconstituents were identified through a literature survey and from several databases. The pharmacokinetics study revealed that 7 phytoconstituents - glycyrrhisoflavone, eugenol, ferulic acid, methyl jasmonate, geranyl formate, formononetin, and elemicin- exhibited favourable pharmacokinetic properties. Five targets, HMOX1, CNR1, STAT3, HDAC2, and MAOB were found to be important in the network of 3300 proteins based on degree centrality and betweenness centrality. Among the seven phytoconstituents, glycyrrhisoflavone exhibited good dock scores and free energy value. Based on this, the stability of glycyrrhisoflavone with the five selected targets were analyzed using molecular dynamics study. Glycyrrhisoflavone showed good stability with most of the selected therapeutic targets. The current study reveals that the selected phytoconstituents i.e glycyrrhisoflavone, eugenol, ferulic acid, methyl jasmonate, geranyl formate, formononetin, and elemicin could serve as good lead molecules in treatment and management of Alzheimer’s disease through modulation of multiple targets.

Irradiation-induced defects and the precipitates in the wrapper material of the Indian Fast Breeder Test Reactor (FBTR), SS 316 are analyzed using the synchrotron source-based Angle Dispersive X-Ray Diffraction (ADXRD) technique with X-rays of energy 17.185 keV (wavelength ∼0.72146 Å). The differences and similarities in the high displacement damage samples as a function of dpa (displacement per atom) and dpa rate in the range of 2.9 × 10−7- 9 × 10−7 dpa/s are studied. Ferrite and M23C6 are commonly observed in the present set of high displacement damage 40–74 dpa SS 316 samples irradiated at temperatures in the range of 400–483 °C. Also, the dislocation density has increased as a function of the irradiation dose. The X-ray diffraction peak profile parameters quantified such as peak shift and asymmetry show that the irradiation-induced defects are sensitive to the dpa rate-irradiation temperature combinations. The increase in yield strength as a function of displacement damage is also correlated to the dislocation density.

Despite being widely used for high-resolution spectral analysis and quantifying low activity in natural samples, the operations and data analysis of High Purity Germanium (HPGe) gamma-ray detectors are seldom fully automated due to the excessive costs associated with commercially available automatic sample changing systems. This paper introduces the design and implementation of a cost-effective, customized remote gamma-ray spectra collection system centered around the HPGe detector coupled to a cosmic-ray veto background reduction device. The HPGe detector system, equipped with a Lynx DSA, is seamlessly integrated with an economically viable automatic sample changer. This sample vial changer is controlled by a high-torque NEMA 34 stepper servo motor from Vention. Web control of the rotary actuator is facilitated through a CAD-based programming tool. The remote-controlled sample pick-and-place procedure is executed using a robotic arm (Trossen Robotics, Viper X 250). The DYNAMIXEL servomotors of the robotic arm are programmed using Python software supported by the Robotic Operating System. Beyond its technical construction, this system is uniquely fashioned for academic research, providing invaluable hands-on experience in gamma spectrometry to both junior researchers and students.

The current study describes composite membranes that utilise exfoliated graphitic carbon nitride (Eg-C3N4) as a promising membrane additive for oily-water separation, owing to its hydrophilic nature and high functionality. The integrated membranes have been discovered to have outstanding properties when Eg-C3N4 is used as a composite material in polysulphone (PSf) membranes. The study provides provide insights into the usage of such nanosheets to achieve good chemical interaction with the membrane matrix, enabling both Eg-C3N4 and PSf synergistic characteristics. The well-planned exfoliated g-C3N4-PSf composite demonstrated promising oil-water separation with an oil rejection capacity of >99 %. Furthermore, these exfoliated laminar planes interacted well with the polymer, resulting in membranes that were both thermally and mechanically stable. The membrane also has a high porosity range of 46.13 % to 76.03 % and a high-water uptake range of 42.23 + 1.68 % to 71.34 + 1.24 %, which explains the membrane's enhanced hydrophilicity and appropriate oily-water treatment capacity. Furthermore, the addition of Eg-C3N4 lowers surface roughness, which explains for the great antifouling capacity exhibited by the composite membrane, demonstrating a remarkable flux recovery ratio of about 99.1 % with no compromise in oil rejection during subsequent cycles.

ABSTRACT: Objective: The aim of this research was to evaluate peri-implant health status in patients infected with COVID-19 and control patients (individuals without COVID-19). Methods: This observational investigation was performed in adults with (test group) and without (control group) COVID-19 infection having at least 1 functional dental implant. Self-reported education status and daily frequency of toothbrushing and flossing was determined. A questionnaire was administered to record demographic data, brushing/flossing frequency, and education status. Periodontal examination comprised full-mouth assessment of clinical attachment loss (CAL), plaque index (PI), probing depth (PD), and gingival index (GI). Peri-implant PD, modified PI, and modified gingival index were recorded. Loss of marginal and crestal bone around teeth and implants was also measured. Significance level was established for P < .05. Results: Seventy-three (41 males) and 71 (44 males) individuals were included in the test and control groups, respectively. Average ages of patients and controls were 44.6 ± 5.2 and 40.1 ± 3.1 years, respectively. University-level education was attained by 52 (75.3%) and 50 (70.4%) individuals in the test and control groups, respectively. Seventy (95.9%) and 68 (95.7%) patients and controls were brushing twice a day. Once-daily interproximal flossing was reported by 44 (60.3%) and 48 (67.6%) individuals in test and control groups. All participants had healthy periodontal and peri-implant tissues. Conclusions: The study indicated that there are no short-term adverse effects on the peri-implant tissues due to acute COVID-19 infection, and further well-controlled longitudinal studies are needed to evaluate the long-term effect of the infection on these tissues.

The optical and surface morphological properties of thin films are profoundly influenced by the deposition technique and the various process parameters employed. In present work, several tantalum penta oxide thin films have been fabricated using reactive electron beam evaporation at varying oxygen (O2) pressures, ranging from 3 × 10−3 Pa to 8 × 10−2 Pa. Refractive index, extinction coefficient, and voids in thin film microstructure were determined through the analysis of spectroscopic ellipsometric measurements. The refractive index, which exhibits a decreasing trend, varies between 1.859 and 2.067, with the exception being the lowest O2 pressure. The variation has been explained in terms of varying oxygen content and voids in the thin films. The extinction coefficient exhibits a decreasing trend due to the increasing oxidation of tantalum, except at O2 pressure of 8 × 10−2 Pa. Increase in the extinction coefficient at this pressure could be due to porous film microstructure, resulting in dominant light scattering. Variation of film density which is similar to that of refractive index, has been attributed to the varying oxidation of tantalum (Ta) and film porosity. Surface root mean square (rms) roughness, correlation length and Hurst parameter, have been derived from suitable analysis of atomic force microscopy measurements. Variations of correlation length and rms roughness have been explained in terms of varying surface shadowing effects and oxidation of Ta with varying O2 pressure.

ABSTRACT: Objective: There are no studies that have evaluated the effect of Alveogyl with and without adjunct photobiomodulation therapy (PBMT) in reducing self-rated post-operative pain (SPP) in patients with alveolar osteitis (AO; dry socket). The aim of the present randomised controlled trial was to assess the effectiveness of Alveogyl with and without PBMT for the management of SPP in patients with AO. Methods: Adult nonsmokers with diagnosed AO were included. Patients were randomly divided into 4 groups. In Group 1, patients underwent mechanical curettage (MC) with copious normal saline irrigation. In Group 2, patients underwent MC + Alveogyl dressings in extraction sites which were changed every 48 hours until cessation of pain. In Group 3, patients underwent MC + Alveogyl followed by PBMT using a 660-nm indium-gallium-aluminum-phosphide diode laser. In Group 4, patients were treated solely with PBMT. The visual analogue scale was used up to 3 postoperative days to assess SPP up to 3 days at 6- (T0) and 12-hour (T1) intervals. Statistical analyses were performed using the analysis of variance and Bonferroni post hoc adjustment tests. Correlation between SPP scores and age, sex, and eruption status of teeth was assessed using logistic regression models. P values

ABSTRACT: Objective: The aim of this research was to assess the effect of 0.12% chlorhexidine (CHX) and a Salvadora persica–based mouthwash on whole salivary tumour necrosis factor-alpha (TNF-α) levels and periodontal inflammation in patients with type 2 diabetes mellitus (T2DM). Methods: Patients with and without medically diagnosed T2DM were included. Patients’ medical records were evaluated to confirm the diagnosis of T2DM. All patients underwent nonsurgical periodontal therapy (NSPT). Patients were divided into 2 subgroups. In the test and control group, patients were advised to rinse with an S persica–based mouthwash and a non-alcoholic 0.12% CHX after NSPT twice daily for 2 weeks, respectively. Demographic data were collected. Full-mouth plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment loss (AL) were measured, and whole salivary TNF-α levels were gauged at baseline and at 3-month follow-up. Haemoglobin A1c (HbA1c) levels were measured in all patients at baseline and at 3-month follow-up. Sample size estimation was done, and group comparison was performed. Level of significance was set at P < .01. Results: Twenty-one nondiabetic individuals and 21 patients with T2DM were included. At baseline, there was no significant difference in clinical and radiographic periodontal parameters amongst in patients with and without T2DM. At 3-month follow-up, HbA1c, TNF-α, PI, PD, and clinical AL were comparable with their respective baseline values in the test and control groups amongst patients with T2DM. In nondiabetic individuals, there was a significant reduction in PI (P < .01), GI (P < .01), and PD (P < .01), and TNF-α (P < .01) at 3-month follow-up in the test and control groups compared with their respective baseline scores. Conclusions: In the short term, NSPT with 0.12% CHX or S persica–based mouthwashes is more effective in reducing periodontal inflammation and whole salivary TNF-α levels in nondiabetic individuals than in patients with T2DM with periodontal inflammation.

Background and objectives: In spite of bone’s healing capacity, critical-size bone defect regeneration and peri-implant osseointegration are challenging. Tissue engineering provides better outcomes, but requires expensive adjuncts like stem cells, growth factors and bone morphogenic proteins. Vitamin D (Vit.D) regulates calcium and phosphorus metabolism, and helps maintain bone health. Vit.D supplements in deficient patients, accentuates bone healing and regeneration. Therefore the aim of this systematic review was to evaluate the role of adjunctive Vit.D on bone defect regeneration. Methods: Comprehensive database search of indexed literature, published between January 1990 and June 2022, was carried out. English language articles fulfilling inclusion criteria (clinical/in vivo studies evaluating bone regeneration including osseointegration and in vitro studies assessing osteogenic differentiation, with adjunct Vit.D) were identified and screened. Results: Database search identified 384 titles. After sequential title, abstract and full-text screening, 23 studies (in vitro – 9/in vivo – 14) were selected for review. Vit.D as an adjunct with stem cells and osteoblasts resulted in enhanced osteogenic differentiation and upregulation of genes coding for bone matrix proteins and alkaline phosphatase. When used in vivo, Vit.D resulted in early and increased new bone formation and mineralization within osseous defects, and better bone implant contact and osseointegration, around implants. Adjunct Vit.D in animals with induced systemic illnesses resulted in bone defect regeneration and osseointegration comparable to healthy animals. While systemic and local administration of Vit.D resulted in enhanced bone defect healing, outcomes were superior with systemic route. Conclusions: Based on this review, adjunct Vit.D enhances bone defect regeneration and osseointegration. In vitro application of Vit.D to stem cells and osteoblasts enhances osteogenic differentiation. Vit.D is a potentially non-invasive and inexpensive adjunct for clinical bone regeneration and osseointegration. Long term clinical trials are recommended to establish protocols relating to type, dosage, frequency, duration and route of administration.

Background & Aims: The reported burden of multidrug-resistant organism (MDRO) infections is highest in patients with cirrhosis from India. We evaluated whether colonisation at multiple barriers predisposes to such infections and poor outcomes in patients with cirrhosis. Methods: We prospectively performed swab cultures, antimicrobial susceptibility testing (AST), and genotype testing for MDROs from various sites (rectum, nose, composite-skin, and central-line) in patients with cirrhosis (2020–2021) on admission and follow-up at a tertiary institute. We analysed clinical data, risk factors for MDROs, and patient outcomes. Results: Of 125 patients aged 49 years, 85.6% males, 60.8% with acute-on-chronic liver failure, 99 (79.2%) were identified as ‘colonisers’. MDRO-colonisation at rectum, nose, skin, or central line was observed in 72.7% (88/121), 30.0% (36/120), 14.9% (18/121), and 3.3% (4/121) patients, respectively. Patients were colonised with the following types of bacteria: extended-spectrum beta-lactamase (71/125), carbapenem-resistant Enterobacterales (67/125), MDR-Enterococcus (48/125), MDR-Acinetobacter (21/125), or methicillin-resistant Staphylococcus aureus (4/125). Multiple precipitants of acute-decompensation (odds ratio [OR]: 3.4, p = 0.042), norfloxacin prophylaxis (OR: 3.9, p = 0.008), and MDRO infection at admission (OR: 8.9, p = 0.041) were the independent predictors of colonisation. Colonisation increased the risk of infection by MDROs at admission (OR: 8.5, p = 0.017) and follow up (OR: 7.5, p

Dyes are considered as a major pollutant released in industrial (leather, textile, and paper) effluents. In this study, the ability of Clinoptilolite in adsorbing an industrial dye (Violet 5BN) was assessed. Clinoptilolite was characterized by Scanning Electron Microscopy, Energy Dispersive analysis using X-ray and Brunauer, Emmett and Teller analysis. Batch studies at varying adsorbent dosage, pH, temperature, and time revealed that 96% of the dye was adsorbed with an adsorbent mass of 1.5 g at 30 °C, pH 5 and reaction time of 90 min. Both Langmuir and Freundlich isotherms were found to be fit, which proves the process to be heterogeneous. The experimental and calculated values of adsorption capacity were almost similar, with correlation coefficients greater than 0.9, thus implying pseudo-second order and intraparticle diffusion as the favorable models. Negative values of ΔG° indicate strong binding energy between the adsorbent and adsorbate, while negative ΔS° values prove less randomness of the process and higher adsorbate concentration on the adsorbent surface due to ion-exchange interaction. The exothermic nature of adsorption is evident from the negative ΔH° recorded. Thermodynamic studies showed the system was a spontaneous and enthalpy driven process, with chemisorption as the predominant mode of adsorption at 30 °C and physisorption at elevated temperatures. The study demonstrates the significance of natural clinoptilolite in environmental protection, as an adsorbent for remediation of dyes.

Earlier, prior to the development of effective systemic therapy, monotherapy with whole-brain radiotherapy (WBRT) was widely used to treat primary central nervous system lymphoma (PCNSL). Recently, chemotherapy, especially with high dose methotrexate (HDMTX), has largely replaced WBRT as upfront treatment, and the most accepted standard of care is induction with a combination drug therapy followed by consolidation therapy with either autologous stem-cell transplantation (ASCT) or radiation. Whilst WBRT is an effective component of treatment, it is occasionally associated with risk of permanent, irreversible neurotoxicity when doses of more than 30 Gy are used. Hence, there has been a strong focus on the optimization of radiotherapy (RT) which includes dose reduction in the consolidation phase. In this comprehensive review, we have summarized the progress on clinical results and evidence considering the role and use of radiation including combined treatment modalities, low-dose radiotherapy, and neurotoxicity. Finally, we present a practical approach to low-dose WBRT and boosting higher doses to the gross tumor that can be integrated into clinical practice.

Abstract Background Autoinflammatory disorders are the group of inherited inflammatory disorders caused due to the genetic defect in the genes that regulates innate immune systems. These have been clinically characterized based on the duration and occurrence of unprovoked fever, skin rash, and patient’s ancestry. There are several autoinflammatory disorders that are found to be prevalent in a specific population and whose disease genetic epidemiology within the population has been well understood. However, India has a limited number of genetic studies reported for autoinflammatory disorders till date. The whole genome sequencing and analysis of 1029 Indian individuals performed under the IndiGen project persuaded us to perform the genetic epidemiology of the autoinflammatory disorders in India. Results We have systematically annotated the genetic variants of 56 genes implicated in autoinflammatory disorder. These genetic variants were reclassified into five categories (i.e., pathogenic, likely pathogenic, benign, likely benign, and variant of uncertain significance (VUS)) according to the American College of Medical Genetics and Association of Molecular pathology (ACMG-AMP) guidelines. Our analysis revealed 20 pathogenic and likely pathogenic variants with significant differences in the allele frequency compared with the global population. We also found six causal founder variants in the IndiGen dataset belonging to different ancestry. We have performed haplotype prediction analysis for founder mutations haplotype that reveals the admixture of the South Asian population with other populations. The cumulative carrier frequency of the autoinflammatory disorder in India was found to be 3.5% which is much higher than reported. Conclusion With such frequency in the Indian population, there is a great need for awareness among clinicians as well as the general public regarding the autoinflammatory disorder. To the best of our knowledge, this is the first and most comprehensive population scale genetic epidemiological study being reported from India.

Background: Due to the high prevalence of oral and maxillofacial (OMF) trauma in city of Riyadh, a special focus on pediatric trauma is needed. The purpose of this audit was to assess the protocol followed by the OMF unit at King Khalid University Hospital (KKUH) on pediatric trauma patients. The trauma incidence, mechanism of injury, volume, the type of pediatric trauma operated and dental management were analyzed. Materials and Methods: A quantitative retrospective review of 223 patients, at pediatric emergency unit of KKUH, Riyadh, KSA from January 2017 to July 2018, was done. The data retrieved included variables such as, age, gender, and cause of injury, site of injury, type of injury, and assessment of jaws, and teeth. Data regarding the type of investigations, treatment protocol, follow up visit, and dental management, were extracted from the medical records. Results: Of the 223 pediatric patients presenting to the emergency unit, 116 (52%) were under the age of 5 years. A total of 64.4% of patients reported “self-fall” as the cause of injury. Soft-tissue injuries were common in 63 (56.8%) of patients in the form of lacerations 87 (41.2%). Involvement of the teeth in the injury was observed in 57 patients, in which 33 (57.9%) patients were reported to have tooth/teeth avulsions, 15 (26.3%) patients had luxation and 9 (15.8%) patients had crown fractures. 27 (47%) patients were referred to the pedodontist for a follow-up visit. Conclusions: It can concluded that clinicians facing maxillofacial trauma in an emergency department need to have access to useful and practice guidelines. The study also showed the need for more manpower-oriented training such as a pedodontist and a general dentist to join the OMFS team to manage pediatric patients. The regional referral hospitals should be equipped to decentralize the management of these patients to the Dental University Hospital.

3-Hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency is a rare mitochondrial disorder of valine metabolism which may present with motor delay, hypotonia, ataxia, dystonia, seizures poor feeding, and organic aciduria. Neuroimaging findings include signal abnormalities of the deep gray matter, particularly the globus pallidi, and cerebral peduncles. We report a 15-month-old male patient with HIBCH deficiency who presented with paroxysmal tonic upgaze of infancy, motor delay, and hypotonia. MRI revealed characteristic bilateral, symmetric signal abnormalities in the basal ganglia and a mutation in HIBCH was confirmed with whole exome sequencing. HIBCH should be a consideration in patients with Leigh-like features, especially if neuroimaging changes primarily affect the globus pallidi. Recognition of this pattern may help guide targeted testing and expedite the diagnosis and treatment of this rare disease.

In December of 2019, several cases of atypical pneumonia caused by an unknown agent were reported in Wuhan, the capital city of Hubei Province in China. In early January 2020, it was announced that these cases were caused by a novel coronavirus. The virus was later named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes a disease associated with atypical pneumonia termed Corona virus disease 2019 (COVID-19). Several respiratory viruses, including coronaviruses and influenza viruses tend to have prominent peaks of infection during colder seasons, especially in temperate regions. The cold temperatures, along with accompanying dry conditions can drive respiratory tract infections by assisting with viral transmission, weakening the human immune system, and increasing viral molecular stability. Though the topic of SARS-CoV-2 transmission and warm weather has been associated with misinformation campaigns, it is worth investigating since an informative answer may give an indication of the future behavior of SARS-CoV-2.

Introduction: Osteoporosis is a global burden with the prevelance ranging from 15 to 20% in women and 4–7% in men across the globe. This is the age group which most commonly presents in spine clinic with pathologies requiring pedicle screw fixation. Pedicle screw fixation in osteoporotic spine is a challenge pertaining to the poor bone quality leading to various complication like screw backout, loosening and pedicle breach. With the advent of O arm and navigation, it is now possible to place pedicle screw with reported accuracy of 96%. Here, in this one of a kind study, we study the accuracy of O arm guided pedicle screw insertion in osteoporotic spine. Materials and method: This is a retrospective study of patients operated between July 2020 to December 2020 for pedicle screw fixation at a tertiary care center by a single senior spine surgeon using O arm (O2) Navigation. All patients, over the age of 55 years having osteoporosis; defined by Singh’s index; who were operated for lumbar pedicle screw fixation were included in the study. All patients under the age of 55 or having Singh’s index of more than 3 were excluded. Results: All the patients operated at a tertiary care center by a single senior spine surgeon was considered in our study. Of 67 patients operated between July 2020 to December 2020 using O arm navigation, 32 patients fit into our criteria. Total 172 pedicle screws were inserted in osteoporotic spine. One of the patients had one pedicle breach in our group intra operatively which needed reinsertion of screw. Conclusion: O arm guided pedicle screw placement is a novel technique which seems to be the most accurate technique till date. With an accuracy of 99.5% in osteoporotic spine, this should be the method of choice when using pedicle screws, whenever available.

In the current scenario, the emergence of drug resistance in Mycobacterium tuberculosis is the consequence of the failure of conventional diagnostic and treatment approaches. To combat this global emergence of drug resistance, alternative approaches such as pathogen-centric (use of repurposed drugs, novel analogues of existing anti-TB drugs and novel compounds with a different mechanism of action), host-centric (immunomodulatory agents, therapeutic vaccines, immune and cellular therapies) and nano-based drug/vaccine delivery should be used singly or in combination. Diverse types of nano-carriers have assessed as auspicious diagnostic and drug delivery systems. In this focused review, we have suggested a long-term solution for combating antimicrobial resistance and also an attractive means to increase patient compliance and reduce treatment duration.

Purpose: We report the clinical outcomes of patients with soft tissue sarcomas (STS) arising in extremities treated with image-guided intensity modulated radiotherapy (IG-IMRT) at our institute. Local control of the tumors treated with RT was the primary end point of this study. Analyzing overall survival and long-term toxicities were the secondary objectives. Methods and materials: The database of the patients with STS who received wide local excision and IG-IMRT at our institution from January 2012 to December 2020 was reviewed. Radiation was offered either preoperatively or postoperatively as part of multi-modality treatment. Results: Thirty-three consecutive patients were identified and included for analysis. Twenty-eight patients (84.8%) received postoperative adjuvant radiotherapy. Dedicated MRI simulation studies were performed in 31 patients (93.9%) in the treatment position. RapidArc IMRT technique was used in 31 patients (93.9%). A total of 2954 images were acquired during 991 treatment sessions. Errors exceeding 1 mm in the x, y and z directions were corrected online before the treatment. With a median follow-up of 36 months, two patients (6.1%) developed local recurrence. The 3-year local control was 90.9% (95% CI, 0.76 - 0.98), and the 5-year overall survival was 71.7% (95% CI, 0.44 – 0.88). One patient (3.03%) sustained a pathological fracture during the follow-up period. Conclusion: Our results showed that IMRT with daily imaging offered excellent local control with acceptable long-term toxicity, as well as being feasible and practical to implement in our routine clinical practice.

Purpose:: It is imperative to spare functioning kidneys from high radiation doses when they are near enough to radiotherapy (RT) target volumes in patients with polycystic kidney disease (PKD). To achieve this intent, we designed the unique approach that we report here. Methods and materials:: The patient who has PKD, presented with B-cell lymphoma involving paraaortic lymph nodes. After completing chemotherapy, RT was planned to the residual nodal disease. The diagnostic positron emission tomography computed tomography (PETCT) scan was fused with the RT planning CT scan. 18F-2-deoxy-2(F)-fluro-d-glucose (FDG) avid active kidneys were contoured separately, and the treatment plan was optimized to avoid these volumes. Results:: The functional volume was 17.52% of the right kidney whereas it was 7.44% of the left. The mean doses were 4.61 Gy and 4.2 Gy, respectively. The baseline estimated glomerular filtration rate (eGFR) was >60 mL/min; at 18 months follow-up, it was 62 mL/min. Conclusions:: Delineation of functional nephrons was feasible while utilizing the staging FDG-PETCT scan for radiotherapy contouring in our patient, which aided to achieve the optimal dose-volume constraints. Further studies are warranted to analyze and quantify the benefit of this easily accessible method in the future.

Summary: Sequencing of SARS-CoV-2 genomes is crucial for understanding the genetic epidemiology of the COVID-19 pandemic. It is also critical for understanding the evolution of the virus and also for the rapid development of diagnostic tools. The present protocol is a modification of the Illumina COVIDSeq test. We describe an amplicon-based next-generation sequencing approach with short turnaround time, adapted for bench-top sequencers like MiSeq, iSeq, and MiniSeq.For complete details on the use and execution of this protocol, please refer to Bhoyar et al. (2021).

Summary: Swarming in Pseudomonas aeruginosa is a coordinated movement of bacteria over semisolid surfaces (0.5%–0.7% agar). On soft agar, P. aeruginosa exhibits a dendritic swarm pattern, with multiple levels of branching. However, the swarm patterns typically vary depending upon the experimental design. In the present study, we show that the pattern characteristics of P. aeruginosa swarm are highly environment dependent. We define several quantifiable, macroscale features of the swarm to study the plasticity of the swarm, observed across different nutrient formulations. Furthermore, through a targeted screen of 113 two-component system (TCS) loci of the P. aeruginosa strain PA14, we show that forty-four TCS genes regulate swarming in PA14 in a contextual fashion. However, only four TCS genes—fleR, fleS, gacS, and PA14_59770—were found essential for swarming. Notably, many swarming-defective TCS mutants were found highly efficient in biofilm formation, indicating opposing roles for many TCS loci. : Pathogenic Organism; Biological Sciences; Microbiology Subject Areas: Pathogenic Organism, Biological Sciences, Microbiology

Presented in this article are systematic microstructural and mechanical property data for anisotropic collagen scaffolds made by freeze casting. Three applied cooling rates (10 °C/min, 1 °C/min, 0.1 °C/min) and two freezing directions (longitudinal and radial) were used during scaffold manufacture. Utilizing a semi-automated image analysis technique applied to confocal micrographs of fully hydrated scaffolds, pore area, long and short pore axes, and pore aspect ratio were determined. Compression testing was performed to determine scaffold modulus, yield strength, and toughness.

Introduction: Vallecular varices are easy to overlook because of their small size and intermittent bleeding pattern, but they can cause dramatic blood loss. Here we describe our novel method of treating a bleeding vallecular varix using the Ethicon Endopath 5mm bipolar forceps with macro jaw (Endopath), a tool originally designed for use during laparoscopic surgery. Case description: A healthy 59-year-old female presented to the emergency department with a week of hemoptysis, postnasal drip, and occasional epistaxis. Labs were notable for hemoglobin 7.5g/dL. Nasopharyngolaryngoscopy revealed a pedunculated, vascular-appearing lesion in the left vallecula that bled sluggishly during a Valsalva maneuver. The patient underwent direct laryngoscopy and operative excision. The stalk was cauterized using Endopath and the varix was separated from the surrounding vallecular tissues with a combination of Endopath bipolar forceps and sharp dissection using microlaryngoscopy scissors. Results: The patient had no further bleeding episodes and was discharged on post-operative day one. Final pathology confirmed the vallecular lesion was a varix. Seven weeks post-operatively, her hemoglobin was stable at 14.8 g/dL. Conclusion: A vallecular varix should be considered in patients with significant bleeding from the oral cavity when history is not suggestive of pulmonary, gastrointestinal, or nasal source. Thermal cauterization with the Endopath and excision with microlaryngoscopy scissors is a successful treatment for a bleeding vallecular varix. The Endopath bipolar forceps are a useful new addition to the otolaryngologist's armamentarium.

Electrocution injuries, particularly high voltage, are uncommon, but can be devastating. Thermal burns, arrhythmias and myonecrosis are commonly known and monitored complications of electrical injuries. Direct thermal trauma to internal viscera is also known and almost all internal organs have been reported to be affected, bowel being the most common. However, bowel perforation occurring in a delayed fashion is one rare, dreaded and erratic complication of electrocution, making it a dangerous pitfall if missed. Alimentary tract perforations can present on a delayed basis in high voltage electrocution injuries; advise for clinical follow up must incorporate this possibility at the time of discharge. Presentation of delayed visceral injuries is subtle & atypical, and post burn immunosuppression may play a part for such presentation. We suggest that all victims of high voltage electrocution with abdominal wall burns receive diagnostic laparoscopy and/or CECT abdomen as part of workup of their injuries. Any non-enhancing segment of bowel on CECT, howsoever small, should be prudently evaluated with laparoscopy.

Purpose: To describe a case of anterior ischemic optic neuropathy as a presenting sign of granulomatosis with polyangiitis. Observations: A previously healthy 50-year-old female developed right eye, then left eye, redness and pruritis and was diagnosed with allergic versus viral conjunctivitis. Five days later, she noted an acute decline in vision in the right eye, corresponding with a decrease on Snellen testing from 20/30 to 20/100 with correction. She was noted to have a right relative afferent pupillary defect, 2+ pallid disc edema, and OCT (Spectralis, Heidelberg Engineering, Carlsbad, CA) findings of significant retinal nerve fiber thickening. Review of systems revealed a three-month history fatigue, right-sided headaches, jaw claudication, bronchitis, cough without hemoptysis, and epistaxis, as well as interval development of a petechial rash across her body, migratory polyarthralgias, fevers, and tachycardia. ESR and CRP were markedly elevated, and the patient was admitted to the hospital for a systemic vasculitis workup. She was started on IV methylprednisolone. Her vision improved dramatically with steroids, measuring 20/50 with correction in the right eye after 24 hours and returning to baseline after five days. An extensive workup including imaging, bloodwork, and biopsies led to a diagnosis of granulomatosis with polyangiitis, with PR3-positive ANCA. Conclusions: Ocular findings, including anterior ischemic optic neuropathy, may be the presenting signs for patients with granulomatosis with polyangiitis. Prompt recognition and treatment with high-dose steroids and immunomodulatory therapy is important for visual recovery. Importance: Prompt recognition of potential vasculitis-related vision loss can lead to timely initiation of vision-saving treatment.

Summary: Background: Intravenous iron sucrose is a promising therapy for increasing haemoglobin concentration; however, its effect on clinical outcomes in pregnancy is not yet established. We aimed to assess the safety and clinical effectiveness of intravenous iron sucrose (intervention) versus standard oral iron (control) therapy in the treatment of women with moderate-to-severe iron deficiency anaemia in pregnancy. Methods: We did a multicentre, open-label, phase 3, randomised, controlled trial at four government medical colleges in India. Pregnant women, aged 18 years or older, at 20–28 weeks of gestation with a haemoglobin concentration of 5–8 g/dL, or at 29–32 weeks of gestation with a haemoglobin concentration of 5–9 g/dL, were randomly assigned (1:1) to receive intravenous iron sucrose (dose was calculated using a formula based on bodyweight and haemoglobin deficit) or standard oral iron therapy (100 mg elemental iron twice daily). Logistic regression was used to compare the primary maternal composite outcome consisting of potentially life-threatening conditions during peripartum and postpartum periods (postpartum haemorrhage, the need for blood transfusion during and after delivery, puerperal sepsis, shock, prolonged hospital stay [>3 days following vaginal delivery and >7 days after lower segment caesarean section], and intensive care unit admission or referral to higher centres) adjusted for site and severity of anaemia. The primary outcome was analysed in a modified intention-to-treat population, which excluded participants who refused to participate after randomisation, those who were lost to follow-up, and those whose outcome data were missing. Safety was assessed in both modified intention-to-treat and as-treated populations. The data safety monitoring board recommended stopping the trial after the first interim analysis because of futility (conditional power 1·14% under the null effects, 3·0% under the continued effects, and 44·83% under hypothesised effects). This trial is registered with the Clinical Trial Registry of India, CTRI/2012/05/002626. Findings: Between Jan 31, 2014, and July 31, 2017, 2018 women were enrolled, and 999 were randomly assigned to the intravenous iron sucrose group and 1019 to the standard therapy group. The primary maternal composite outcome was reported in 89 (9%) of 958 patients in the intravenous iron sucrose group and in 95 (10%) of 976 patients in the standard therapy group (adjusted odds ratio 0·95, 95% CI 0·70–1·29). 16 (2%) of 958 women in the intravenous iron sucrose group and 13 (1%) of 976 women in the standard therapy group had serious maternal adverse events. Serious fetal and neonatal adverse events were reported by 39 (4%) of 961 women in the intravenous iron sucrose group and 45 (5%) of 982 women in the standard therapy group. At 6 weeks post-randomisation, minor side-effects were reported by 117 (16%) of 737 women in the intravenous iron sucrose group versus 155 (21%) of 721 women in the standard therapy group. None of the serious adverse events was found to be related to the trial procedures or the interventions as per the causality assessment made by the trial investigators, ethics committees, and regulatory body. Interpretation: The study was stopped due to futility. There is insufficient evidence to show the effectiveness of intravenous iron sucrose in reducing clinical outcomes compared with standard oral iron therapy in pregnant women with moderate-to-severe anaemia. Funding: WHO, India.

Artemether (ARM) is a poorly water soluble and poorly permeable drug effective against acute and severe falciparum malaria, hence there is a strong need to improve its solubility. The objective of the study was to enhance the solubility and dissolution rate of ARM by preparation of solid dispersions using spray-drying technique. Solid dispersions of ARM were prepared with Soluplus, Kollidon VA 64, HPMC and Eudragit EPO at weight ratios of 1:1, 1:2, 1:3 using spray drying technology, and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and X-ray powder diffraction (XRD) to identify the physicochemical interaction between drug and carrier, as well as effect on dissolution. The prepared solid dispersion of ARM with polymers showed reduced crystallinity as compared to neat ARM, which was confirmed by DSC and XRD. Drug/polymer interactions were studied in-silico by docking and molecular dynamics which indicated formation of van der Waals type of interactions of ARM with the polymers. Based on solubility studies, the optimum drug/Soluplus ratio was found to be 1:3. The dissolution studies of formulation SD3 showed highest drug release up to 82% compared to neat ARM giving only 20% at 60 minutes. The spray-dried products were free of crystalline ARM; possessed higher dissolution rates, and were stable over a period according to ICH guidelines. These findings suggest that an amorphous solid dispersion of ARM could be a viable option for enhancing the dissolution rate of ARM.

Human immunodeficiency virus-1 (HIV-1) enters the brain early during infection and leads to severe neuronal damage and central nervous system impairment. HIV-1 envelope glycoprotein 120 (gp120), a neurotoxin, undergoes intracellular trafficking and transport across neurons; however mechanisms of gp120 trafficking in neurons are unclear. Our results show that mannose binding lectin (MBL) that binds to the N-linked mannose residues on gp120, participates in intravesicular packaging of gp120 in neuronal subcellular organelles and also in subcellular trafficking of these vesicles in neuronal cells. Perinuclear MBL:gp120 vesicular complexes were observed and MBL facilitated the subcellular trafficking of gp120 via the endoplasmic reticulum (ER) and Golgi vesicles. The functional carbohydrate recognition domain of MBL was required for perinuclear organization, distribution and subcellular trafficking of MBL:gp120 vesicular complexes. Nocodazole, an agent that depolymerizes the microtubule network, abolished the trafficking of MBL:gp120 vesicles, suggesting that these vesicular complexes were transported along the microtubule network. Live cell imaging confirmed the association of the MBL:gp120 complexes with dynamic subcellular vesicles that underwent trafficking in neuronal soma and along the neurites. Thus, our findings suggest that intracellular MBL mediates subcellular trafficking and transport of viral glycoproteins in a microtubule-dependent mechanism in the neurons.

Tensile properties of directionally freeze-cast biopolymer scaffolds are rarely reported, even though they are of interest from a fundamental science perspective and critical in applications such as scaffolds for the regeneration of nerves or when used as ureteral stents. The focus of this study is on collagen scaffolds freeze-cast with two different applied cooling rates (10 °C/min and 1 °C/min) in two freezing directions (longitudinal and radial). Reported are the results of a systematic structural characterization of dry scaffolds by scanning electron microscopy and the mechanical characterization in tension of both dry and fully hydrated scaffolds. Systematic structure-property-processing correlations are obtained for a comparison of the tensile performance of longitudinally and radially freeze-cast collagen scaffolds with their performance in compression. Collated, the correlations, obtained both in tension in this study and in compression for collagen and chitosan in two earlier reports, not only enable the custom-design of freeze-cast biopolymer scaffolds for biomedical applications but also provide new insights into similarities and differences of scaffold and cell-wall structure formation during the directional solidification of "smooth" and "fibrillar" biopolymers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Nutritional status may be impaired in patients with head and neck cancer undergoing surgical treatment, often necessitating gastrostomy tube (G-tube) placement. Identifying which patients will require a G-tube remains a challenge. This study identifies predictors of G-tube requirement in patients undergoing tumor resection and reconstruction with pedicled or free flaps., Methods: Systematic review of the PubMed, Cochrane, and Scopus databases was performed of English language articles, discussing risk factors of perioperative G-tube placement among patients >18 years. Data on patient, tumor, and treatment factors, as well as need for G-tube, were collected. Univariable meta-analysis was conducted to identify predictors for G-tube placement., Results: Eleven studies (1,112 patients) met inclusion criteria. Overall pooled prevalence of postoperative G-tube placement was 25%. Patients with advanced cancer stage IV/recurrence were more likely to require a G-tube (OR 2.81 [CI 1.03-7.69]; p<0.05), as were those who had undergone preoperative radiation (OR 3.55 [CI 2.03-6.20], p<0.05). Reconstruction with a radial forearm free flap was associated with a lower need for G-tube versus rectus abdominis (OR 0.25 [CI 0.08-0.83], p=0.02) and latissimus dorsi flap (OR 0.21 [CI 0.04-1.09], p=0.06). There was no difference in G-tube placement between those receiving pedicled flaps versus free flaps (OR 1.54 [CI 0.38-6.20], p=0.54)., Conclusions: Among patients with head and neck cancer undergoing resection with immediate pedicled or free flap reconstruction, advanced tumor stage and history of prior radiation therapy are associated with increased likelihood of G-tube placement. More randomized controlled trials are needed to develop a decision-making algorithm., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest and all authors contributed to the development of this research., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: The pathogenesis of thymic epithelial tumors remains largely unknown. We previously identified GTF2I L424H as the most frequently recurrent mutation in thymic epithelial tumors. Nevertheless, the precise role of this mutation in tumorigenesis of thymic epithelial cells is unclear., Methods: To investigate the role of GTF2I L424H mutation in thymic epithelial cells in vivo, we generated and characterized a mouse model in which the Gtf2i L424H mutation was conditionally knocked-in in the Foxn1+ thymic epithelial cells. Digital spatial profiling was performed on thymomas and normal thymic tissues with GeoMx-mouse whole transcriptome atlas. Immunohistochemistry staining was performed using both mouse tissues and human thymic epithelial tumors., Results: We observed that the Gtf2i mutation impairs development of the thymic medulla and maturation of medullary thymic epithelial cells in young mice and causes tumor formation in the thymus of aged mice. Cell cycle-related pathways, such as E2F targets and MYC targets, are enriched in the tumor epithelial cells. Results of gene set variation assay analysis revealed that gene signatures of cortical thymic epithelial cells and thymic epithelial progenitor cells are also enriched in the thymomas of the knock-in mice, which mirrors the human counterparts in The Cancer Genome Atlas database. Immunohistochemistry results revealed similar expression pattern of epithelial cell markers between mouse and human thymomas., Conclusions: We have developed and characterized a novel thymoma mouse model. This study improves knowledge of the molecular drivers in thymic epithelial cells and provides a tool for further study of the biology of thymic epithelial tumors and for development of novel therapies., (Copyright © 2022 International Association for the Study of Lung Cancer. All rights reserved.)

Introduction: Despite the clinical efficacy of immune checkpoint inhibitors (ICIs) in NSCLC, only approximately 20% of patients remain disease-free at 5 years. Here, we use digital spatial profiling to find candidate biomarker proteins associated with ICI resistance., Methods: Pretreatment samples from 56 patients with NSCLC treated with ICI were analyzed using the NanoString GeoMx digital spatial profiling method. A panel of 71 photocleavable oligonucleotide-labeled primary antibodies was used for protein detection in four molecular compartments (tumor, leukocytes, macrophages, and immune stroma). Promising candidates were orthogonally validated with quantitative immunofluorescence. Available pretreatment samples from 39 additional patients with NSCLC who received ICI and 236 non-ICI-treated patients with operable NSCLC were analyzed to provide independent cohort validation., Results: Biomarker discovery using the protein-based molecular compartmentalization strategy allows 284 protein variables to be assessed for association with ICI resistance by univariate analysis using continuous log-scaled data. Of the 71 candidate protein biomarkers, CD66b in the CD45+CD68 molecular compartment (immune stroma) predicted significantly shorter overall survival (OS) (hazard ratio [HR] 1.31, p = 0.016) and was chosen for validation. Orthogonal validation by quantitative immunofluorescence illustrated that CD66b was associated with resistance to ICI therapy but not prognostic for poor outcomes in untreated NSCLC (discovery cohort [OS HR 2.49, p = 0.026], validation cohort [OS HR 2.05, p = 0.046], non-ICI-treated cohort [OS HR 1.67, p = 0.06])., Conclusions: Using the technique, we have discovered that CD66b expression is indicative of resistance to ICI therapy in NSCLC. Given that CD66b identifies neutrophils, further studies are warranted to characterize the role of neutrophils in ICI resistance., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Surprisingly little clarity exists concerning effects of biomaterial properties on spatially localized protein expression, which drives implant success. Wound healing and tissue regeneration must be optimally supported by the implant, adsorbed proteins, immune cells, and fibroblasts; cells determine repair and functional recovery through protein production and regulation. However, not yet fully understood is how implants differentially drive spatial quantities of individual proteins both within the implant interior and the tissue surrounding it. Here we apply GeoMx Ⓡ digital spatial profiling to site-specifically investigate protein production in porous implants. Data is collected on the location and quantity of 40+ proteins from formalin-fixed, paraffin-embedded tissue slides of anisotropic tissue scaffolds (n = 18) with differing pore sizes (35 µm, 53 µm) and implantation durations (2, 14, 28 days); matching bulk gene expression data (700+ genes) is measured for identical implants. Notably, we discover fundamental spatial relationships in protein localization that in both the implant interior and the exterior are either uniquely independent or dependent of implant microstructure: dendritic cell marker CD11c and fibronectin significantly dominate the scaffold interior, while cell-to-cell adhesion marker CD34 and anti-inflammatory M2 polarization marker CD163 localize in the exterior. Lastly, collating spatial and bulk information, unique spatiotemporal expression patterns are identified for markers such as fibronectin, which are only uncoverable through spatial profiling and are otherwise hidden in bulk expression results. Together, these discoveries illustrate the critical importance of quantifying spatial expression patterns for implants, facilitating a paradigm shift in the iterative design, mechanistic understanding, and rapid assessment of biomaterials. STATEMENT OF SIGNIFICANCE: Spatial localization and expression of proteins, which determine implant success, are not fully understood because quantitative high-plex profiling is challenging. Applying GeoMx Ⓡ digital spatial profiling to site-specifically investigate protein production in porous implants, data is collected on the location and quantity of 40+ protein targets from tissue scaffolds with differing pore sizes (35 µm, 53 µm) and implantation durations (2, 14, 28 days). Collecting in parallel matched bulk gene expression data (700+ genes) for identical implants, we discover significant spatiotemporal expression patterns that remain otherwise hidden in differential bulk results. This new approach for the rapid assessment of biomaterials offers an enhanced mechanistic understanding and enables the tailoring of implants for superior regenerative outcomes., Competing Interests: Declaration of Competing Interest PD, JR, and JG are employees and stockholders of NanoString Technologies, Inc., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Needed for the custom-design of longitudinally freeze-cast chitosan scaffolds for biomedical applications are systematic structure-property-processing correlations. Combining mechanical testing in compression with both scanning electron microscopy and semiautomated confocal microscopy for a quantitative structural characterization of fully hydrated chitosan scaffolds, robust correlations were determined. Decreasing the applied cooling rate from 10 °C/min to 0.1 °C/min, the short and long axes of the pore cross-sections, the pore aspect ratio, and the pore area were found to increase from 68.0 μm to 120.5 μm, from 189.2 μm to 401.2 μm, from 2.64 to 3.52, and from 8,922 μm 2 to 35,596 μm 2 , respectively. Values for the scaffolds' modulus, yield strength, and toughness range from 1,067 kPa to 3,209 kPa, from 37.7 kPa to 75.5 kPa, and from 20.3 kJ/m 3 to 35.3 kJ/m 3 , respectively. Because of additional structural features, such as cell wall stiffening ridges, affecting the mechanical properties, not linear but more complex correlation with modulus, yield strength, and toughness were observed. Contrasting the results of this study with those obtained in an earlier study of dry and fully hydrated collagen scaffolds, we were able to identify features that are important and peculiar to each material system. Highlighted in this study are newly determined robust structure-property-processing correlations as well as processing conditions and features that are critical for the mechanical performance of chitosan and other biopolymer scaffolds made by freeze casting for biomedical applications., (Copyright © 2021. Published by Elsevier Ltd.)

Few systematic structure-property-processing correlations for directionally freeze-cast biopolymer scaffolds are reported. Such correlations are critical to enable scaffold design with attractive structural and mechanical cues in vivo. This study focuses on freeze-cast collagen scaffolds with three different applied cooling rates (10, 1, and 0.1 °C/min) and two freezing directions (longitudinal and radial). A semi-automated approach for the structural characterization of fully hydrated scaffolds by confocal microscopy is developed to facilitate an objective quantification and comparison of structural features. Additionally, scanning electron microscopy and compression testing are performed longitudinally and transversely. Structural and mechanical properties are determined on dry and fully hydrated scaffolds. Longitudinally frozen scaffolds have aligned and regular pores while those in radially frozen ones exhibit greater variations in pore geometry and alignment. Lamellar spacing, pore area, and cell wall thickness increase with decreasing cooling rate: in longitudinally frozen scaffolds from 25 µm to 83.5 µm, from 814 µm 2 to 8452 µm 2 , and from 4.21 µm to 10.4 µm, and in radially frozen ones, from 69 µm to 116 µm, from 7679 µm 2 to 25,670 µm 2 , and from 6.18 µm to 13.6 µm, respectively. Both longitudinally and radially frozen scaffolds possess higher mechanical property values, when loaded parallel rather than perpendicular to the ice-crystal growth direction. Modulus and yield strength range from 779 kPa to 4700 kPa and from 38 kPa to 137 kPa, respectively, as a function of cooling rate and freezing direction. Collated, the correlations obtained in this study enable the custom-design of freeze-cast collagen scaffolds, which are ideally suited for a large variety of tissue regeneration applications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

As a new strategy for improved urinary drainage, in parallel to the potential for additional functions such as drug release and self-removal, highly porous chitosan stents are manufactured by radial, bi-directional freeze-casting. Inserting the porous stent in to a silicone tube to emulate its placement in the ureter shows that it is shape conforming and remains safely positioned in place, also during flow tests, including those performed in a peristaltic pump. Cyclic compression tests on fully-hydrated porous stents reveal high stent resilience and close to full elastic recovery upon unloading. The drainage performance of the chitosan stent is evaluated, using effective viscosity in addition to volumetric flow and flux; the porous stent's performance is compared to that of the straight portion of a commercial 8 Fr double-J stent which possesses, in its otherwise solid tube wall, regularly spaced holes along its length. Both the porous and the 8 Fr stent show higher effective viscosities, when tested in the silicone tube. The performance of the porous stent improves considerably more (47.5%) than that of the 8 Fr stent (30.6%) upon removal from the tube, illustrating the effectiveness of the radially aligned porosity for drainage. We conclude that the newly-developed porous chitosan ureteral stent merits further in vitro and in vivo assessment of its promise as an alternative and complement to currently available medical devices. STATEMENT OF SIGNIFICANCE: No papers, to date, report on porous ureteral stents, which we propose as a new strategy for improved urinary drainage. The highly porous chitosan stents of our study are manufactured by radial, bi-directional freeze casting. Cyclic compression tests on fully-hydrated porous stents revealed high stent resilience and close to full recovery upon unloading. The drainage performance of the chitosan is evaluated, using effective viscosity in addition to volumetric flow and flux, and compared to that of the straight portion of a commercial 8 Fr double-J stent. The performance of the porous stent improves considerably more (47.5%) than that of the 8 Fr stent (30.6%) upon removal from the tube, illustrating the effectiveness of the radially aligned porosity for drainage. While further studies are required to explore other potential benefits of the porous stent design such as antimicrobial behavior, drug release, and biodegradability, we conclude that the newly-developed porous chitosan ureteral stent has considerable potential as a medical device., (Copyright © 2018. Published by Elsevier Ltd.)