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Liver fibrosis (LF) occurs when the liver tissue responds to injury or inflammation by producing excessive amounts of scar tissue, known as the extracellular matrix. This buildup stiffens the liver tissue, hinders blood flow, and ultimately impairs liver function. Various factors can trigger this process, including bloodborne pathogens, genetic predisposition, alcohol abuse, non-steroidal anti-inflammatory drugs, non-alcoholic steatohepatitis, and non-alcoholic fatty liver disease. While some existing small-molecule therapies offer limited benefits, there is a pressing need for more effective treatments that can truly cure LF. RNA therapeutics have emerged as a promising approach, as they can potentially downregulate cytokine levels in cells responsible for liver fibrosis. Researchers are actively exploring various RNA-based therapeutics, such as mRNA, siRNA, miRNA, lncRNA, and oligonucleotides, to assess their efficacy in animal models. Furthermore, targeted drug delivery systems hold immense potential in this field. By utilizing lipid nanoparticles, exosomes, nanocomplexes, micelles, and polymeric nanoparticles, researchers aim to deliver therapeutic agents directly to specific biomarkers or cytokines within the fibrotic liver, increasing their effectiveness and reducing side effects. In conclusion, this review highlights the complex nature of liver fibrosis, its underlying causes, and the promising potential of RNA-based therapeutics and targeted delivery systems. Continued research in these areas could lead to the development of more effective and personalized treatment options for LF patients., (© 2024. Controlled Release Society.)

Cystic fibrosis (CF) is a genetic disorder affecting nearly 105,000 patients worldwide and is characterized by poor respiratory function due to accumulation of thick mucus in the lungs, which not just acts as a physical barrier, but also provides a breeding ground for bacterial infections. These infections can be controlled with the help of antibiotics which can be delivered directly into the lungs for amplifying the local anti-bacterial effect. More than 50 % of CF patients are associated with Pseudomonas aeruginosa infection in their lungs which requires antibiotics such as Aztreonam (AZT). In this study, we prepared inhalable AZT-loaded lipid nanoparticles using Hot-melt extrusion (HME) coupled with probe sonication to target Pseudomonas aeruginosa infection in the lungs. The optimized nanoparticles were tested for physicochemical properties, stability profile, in-vitro aerosolization, and antimicrobial activity against Pseudomonas aeruginosa. The optimized nanoparticles with a PEI concentration of 0.1 % demonstrated a uniform particle size of <50 nm, a spherical shape observed under a transmission electron microscope, and >70 % drug entrapment. Incorporating cationic polymer, PEI, resulted in sustained drug release from the lipid nanoparticles. The in-vitro aerosolization studies exhibited a mass median aerodynamic diameter (MMAD) of <4.3 μm, suggesting deposition of the nanoparticles in the respirable airway. The antimicrobial activity against Pseudomonas aeruginosa showed the minimum inhibitory concentration of the formulation is 2-fold lower than plain AZT. Stability profile showed the formulations are stable after exposure to accelerated conditions. In conclusion, hot-melt extrusion in combination with probe sonication can be used as a potential method for the continuous production of AZT-loaded lipid nanoparticles with enhanced anti-bacterial activity., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with a high mortality rate due to limited treatment options. Current therapies cannot effectively reverse the damage caused by IPF. Research suggests that promoting programmed cell death (apoptosis) in myofibroblasts, the key cells driving fibrosis, could be a promising strategy. However, inducing apoptosis in healthy cells like epithelial and endothelial cells can cause unwanted side effects. This project addresses this challenge by developing a targeted approach to induce apoptosis specifically in myofibroblasts. We designed liposomes (LPS) decorated with peptides that recognize VCAM-1, a protein highly expressed on myofibroblasts in fibrotic lungs. These VCAM1-targeted LPS encapsulate Venetoclax (VNT), a small molecule drug that inhibits BCL-2, an anti-apoptotic protein. By delivering VNT directly to myofibroblasts, we hypothesize that VCAM1-VNT-LPS can selectively induce apoptosis in these cells, leading to reduced fibrosis and improved lung function. We successfully characterized VCAM1-VNT-LPS for size, surface charge, and drug loading efficiency. Additionally, we evaluated their stability over three months at different temperatures. In vitro and in vivo studies using a bleomycin-induced mouse model of lung fibrosis demonstrated the therapeutic potential of VCAM1-VNT-LPS. These studies showed a reduction in fibrosis-associated proteins (collagen, α-SMA, VCAM1) and BCL-2, while simultaneously increasing apoptosis in myofibroblasts. These findings suggest that VCAM1-targeted delivery of BCL-2 inhibitors using liposomes presents a promising and potentially selective therapeutic approach for IPF., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Continuous and aberrant activation of myofibroblasts is the hallmark of pathological fibrosis (e.g., abnormal wound healing). The deposition of excessive extracellular matrix (ECM) components alters or increases the stiffness of tissue and primarily accounts for multiple organ dysfunctions. Among various proteins, Cadherin-11 (CDH11) has been reported to be overexpressed on myofibroblasts in fibrotic tissues. Anti-apoptotic proteins such as (B cell lymphoma-2) (BCL-2) are also upregulated on myofibroblasts. Therefore, we hypothesize that CDH11 could be a targeted domain for cell-specific drug delivery and targeted inhibition of BCL-2 to ameliorate the development of fibrosis in the skin. To prove our hypothesis, we have developed liposomes (LPS) conjugated with CDH11 neutralizing antibody (antiCDH11) to target cell surface CDH11 and loaded these LPS with a BCL-2 inhibitor, Navitoclax (NAVI), to induce apoptosis of CDH11 expressing fibroblasts. The developed LPS were evaluated for physicochemical characterization, stability, in vitro therapeutic efficacy using dermal fibroblasts, and in vivo therapeutic efficacy in bleomycin-induced skin fibrosis model in mice. The findings from in vitro and in vivo studies confirmed that selectivity of LPS was improved towards CDH11 expressing myofibroblasts, thereby improving therapeutic efficacy with no indication of adverse effects. Hence, this novel research work represents a versatile LPS strategy that exhibits promising potential for treating skin fibrosis., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Trigonocephaly is a craniofacial malformation caused by premature fusion of the metopic suture. Surgical correction frequently results in the need for blood transfusion. Transfusion complications include transfusion-transmitted infections (TTIs), immune-mediated reactions, and volume overload. Donor exposure (DE) describes the number of blood products from unique donors with increasing DE equating to an increased risk of TTI. We evaluate data on 204 trigonocephaly patients covering 20 years of practice with respect to blood transfusions and DE. This represents the largest series from a single unit to date. A protocol based on our experiences has been devised that summarizes the key interventions we recommend to minimize blood transfusions and DE in craniofacial surgery. Patients operated on between 2000 and 2020 were included. DE and a range of values were calculated including estimated red cell loss (ERCL) and estimated red cell volume transfused (ERCVT). Groups were established by relevant interventions and compared using the Mann-Whitney U test. Mean DE fell from 1.46 at baseline to 0.85 ( P <0.05). Median allogenic transfusion volume fell from 350 mL at baseline to 250 mL ( P <0.05). Median ERCL fell from 15.05 mL/kg at baseline to 12.39 mL/kg and median ERCVT fell from 20.85 to 15.98 mL/kg. Changes in ERCL and ERCVT did not reach statistical significance. DE can be minimized with the introduction of key interventions such as a restrictive transfusion policy, preoperative iron, cell saver, tranexamic acid, and use of a matchstick burr for osteotomies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Pulmonary fibrosis (PF) is a progressive, and life-threatening interstitial lung disease which causes scarring in the lung parenchyma and thereby affects architecture and functioning of lung. It is an irreversible damage to lung functioning which is related to epithelial cell injury, immense accumulation of immune cells and inflammatory cytokines, and irregular recruitment of extracellular matrix. The inflammatory cytokines trigger the differentiation of fibroblasts into activated fibroblasts, also known as myofibroblasts, which further increase the production and deposition of collagen at the injury sites in the lung. Despite the significant morbidity and mortality associated with PF, there is no available treatment that efficiently and effectively treats the disease by reversing their underlying pathologies. In recent years, many therapeutic regimens, for instance, rho kinase inhibitors, Smad signaling pathway inhibitors, p38, BCL-xL/ BCL-2 and JNK pathway inhibitors, have been found to be potent and effective in treating PF, in preclinical stages. However, due to non-selectivity and non-specificity, the therapeutic molecules also result in toxicity mediated severe side effects. Hence, this review demonstrates recent advances on PF pathology, mechanism and targets related to PF, development of various drug delivery systems based on small molecules, RNAs, oligonucleotides, peptides, antibodies, exosomes, and stem cells for the treatment of PF and the progress of various therapeutic treatments in clinical trials to advance PF treatment., 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 B.V. All rights reserved.)

Gout, calcium pyrophosphate deposition disease, and apatite calcifications, the three main crystal disorders, may involve the spine. These disorders can be completely asymptomatic or associated with various clinical symptoms, such as acute flares and more chronic manifestations. This article presents the typical and more unusual imaging features encountered in these disorders., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To conduct a randomized controlled trial (RCT) on the efficacy of immediate lymphatic reconstruction (ILR) for decreasing the incidence of breast cancer-related lymphedema (BCRL) after axillary lymph node dissection (ALND)., Background: Despite encouraging results in small studies, an appropriately powered RCT on ILR has not been performed., Methods: Women undergoing ALND for breast cancer were randomized in the operating room 1:1 to either ILR, if technically feasible, or no ILR (control). The ILR group underwent lymphatic anastomosis to a regional vein using microsurgical techniques; control group had no repair and cut lymphatics were ligated. Relative volume change (RVC), bioimpedance, quality of life (QoL), and compression use were evaluated at baseline and every 6 months postoperatively up to 24 months. Indocyanine green (ICG) lymphography was performed at baseline and 12 and 24 months postoperatively. The primary outcome was the incidence of BCRL, defined as ≥10% RVC from baseline in the affected extremity at 12-, 18-, or 24-month follow-up., Results: Of 72 patients randomized to ILR and 72 to control from January 2020 to March 2023, our preliminary analysis includes 99 patients with 12-month follow-up, 70 with 18-month follow-up, and 40 with 24-month follow-up. The cumulative incidence of BCRL was 9.5% in the ILR group and 32% in the control group ( P =0.014). The ILR group had lower bioimpedance values, decreased compression usage, better lymphatic function on ICG lymphography, and better QoL than the control group., Conclusions: Preliminary results of our RCT show that ILR after ALND decreases BCRL incidence. Our goal is to finish the accrual of 174 patients with 24-month follow-up., Competing Interests: B.M. is the recipient of investigator-initiated research awards from Regeneron Corp and Pfizer and royalty payments from PureTech and is a consultant with Mediflix Corp. J.D. is an advisor to Stryker Corporation, is on the board of Welwaze Medical LLC, and has a royalty agreement with Springer publishers for the book, Multimodal Treatment of Upper and Lower Extremity Lymphedema. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Solid tumors are abnormal mass of tissue, which affects the organs based on its malignancy and leads to the dysfunction of the affected organs. The major problem associated with treatment of solid tumors is delivering anticancer therapeutics to the deepest layers/core of the solid tumor. Deposition of excessive extracellular matrix (ECM) hinders the therapeutics to travel towards the core of the tumor. Therefore, conventional anticancer therapeutics can only reduce the tumor size and that also for a limited duration, and tumor recurrence occurs once the therapy is discontinued. Additionally, by the time the cancer is diagnosed, the cancer cells already started affecting the major organs of the body such as lung, liver, spleen, kidney, and brain, due to their ability to metastasize and lung is the primary site for them to be infiltrated. To facilitate the anticancer therapeutics to penetrate the deeper layers of tumor, and to provide concurrent treatment of both the solid tumor and metastasis, we have designed and developed a Bimodal Light Assisted Skin Tumor and Metastasis Treatment (BLAST), which is a combination of photothermal and chemotherapeutic moieties. The BLAST is composed of 2D boron nitride (BN) nanosheet with adsorbed molecules of BCL-2 inhibitor, Navitoclax (NAVI) on its surface, that can breakdown excessive ECM network and thereby facilitate dissociation of the solid tumor. The developed BLAST was evaluated for its ability to penetrate solid tumors using 3D spheroids for the uptake, cytotoxicity, growth inhibition, reactive oxygen species (ROS) detection, penetration, and downregulation of proteins upon laser irradiation. The in vivo therapeutic studies on a skin cancer mice model revealed that the BLAST with and without laser were able to penetrate the solid tumor, reduce tumor volume in mice, dissociate the protein network, and prevent lung metastasis as confirmed by immunohistochemistry and western blot analysis. Post analysis of serum and blood components revealed the safety and efficacy of BLAST in mice. Hence, the developed BLAST holds strong promise in solid tumor treatment and metastasis prevention simultaneously., Competing Interests: Declaration of Competing Interest Md Nurunnabi serves as Scientific Advisory Board member for KB BioMed Inc., and Filament LLC (Dunatech), and owns equity for DunaTech LLC. Md Nurunnabi and Himanshu Bhatt is an inventor on patents related to the tools and methods reported in this manuscript (owned and managed by University of Texas at El Paso)., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pseudoaneurysms are frequent vascular anomalies. This review article aims to describe the unique specific aspect of pseudoaneurysm (PSA) that allows to make the diagnosis using different modalities: colour Doppler ultrasound, computed tomographic angiography, magnetic resonance angiography and conventional angiography. It is essential to know the various aetiologies of PSA: iatrogenic, traumatic, dissecting and anastomotic; different locations and the possible complications, information to help clinicians choose the best treatment. Our review is supported by illustrated series of cases., Competing Interests: The authors have no conflicts of interest to declare and were not recipients of research funding relevant to this study., (© 2023 Australasian Society for Ultrasound in Medicine.)

The oral route is considered the most convenient route of drug administration for both systemic and local delivery. Besides stability and transportation, another unmet but important issue regarding oral medication is retention duration within the specific region of the gastrointestinal (GI) tract. We hypothesize that an oral vehicle that can adhere and maintain retention within the stomach for a longer duration can be more effective to treat stomach-related diseases. Therefore, in this project, we developed a carrier that is highly specific to the stomach and maintains its retention for a longer duration. We developed a vehicle composed of β- G lucan A nd D ocosahexaenoic A cid ( GADA ) to observe its affinity and specificity to the stomach. GADA forms a spherical-shaped particle with negative zeta potential values that vary based on the feed ratio of docosahexaenoic acid. Docosahexaenoic acid is an omega-3 fatty acid that has transporters and receptors throughout the GI tract, such as CD36, plasma membrane-associated fatty acid-binding protein (FABP (pm)), and a family of fatty acid transport proteins (FATP1-6). The in vitro studies and characterization data showed that GADA has the capability to carry a payload of hydrophobic molecules and specifically deliver the payload to the GI tract, exert its therapeutic effects, and help to maintain stability for more than 12 h in the gastric and intestinal fluid. The particle size and surface plasmon resonance (SPR) data showed that GADA has a strong binding affinity with mucin in the presence of simulated gastric fluids. We observed a comparatively higher drug release of lidocaine in gastric juice than that in intestinal fluids, demonstrating the influence of the pH values of the media on drug-release kinetics. In vivo and ex vivo imaging of mice demonstrated that GADA maintains its retention within the stomach for at least 4 hr. This stomach-specific oral vehicle holds strong promise to translate various injectable therapeutic drugs to oral form upon further optimizations.

Anatomical variants are frequently encountered when assessing the sacroiliac joints (SIJ) using magnetic resonance imaging. When not located in the weight-bearing part of the SIJ, variants associated with structural and edematous changes can be misinterpreted as sacroiliitis. Their correct identification is necessary to avoid radiologic pitfalls. This article reviews five SIJ variants involved in the dorsal ligamentous space (accessory SIJ, iliosacral complex, semicircular defect, bipartite iliac bony plate, and crescent iliac bony plate) and three SIJ variants involved in the cartilaginous part of the SIJ (posterior dysmorphic SIJ, isolated synostosis, and unfused ossification centers)., Competing Interests: None declared., (Thieme. All rights reserved.)

Over the last decades, photomedicine has made a significant impact and progress in treating superficial cancer. With tremendous efforts many of the technologies have entered clinical trials. Photothermal agents (PTAs) have been considered as emerging candidates for accelerating the outcome from photomedicine based cancer treatment. Besides various inorganic and organic candidates, 2D materials such as graphene, boron nitride, and molybdenum disulfide have shown significant potential for photothermal therapy (PTT). The properties such as high surface area to volume, biocompatibility, stability in physiological media, ease of synthesis and functionalization, and high photothermal conversion efficiency have made 2D nanomaterials wonderful candidates for PTT to treat cancer. The targeting or localized activation could be achieved when PTT is combined with chemotherapies, immunotherapies, or photodynamic therapy (PDT) to provide better outcomes with fewer side effects. Though significant development has been made in the field of phototherapeutic drugs, several challenges have restricted the use of PTT in clinical use and hence they have not yet been tested in large clinical trials. In this review, we attempted to discuss the progress, properties, applications, and challenges of 2D materials in the field of PTT and their application in photomedicine.

Background and Aims: This study intended to analyse the effectiveness of compression-only life support cardiopulmonary resuscitation (COLS CPR) training based on training knowledge acquired among non-medical staffs., Methods: The study was conducted among 300 non-medical staffs. Study design: It is an observational study where the effect of COLS CPR training was evaluated based on the pre-training and post-training assessment score. Google Forms questionnaire was used as an interventional tool. Participants in our study included security guards, ambulance drivers, housekeeping and facility staff of our hospital. Training was conducted for seven days through lecture, audio-visual display, demonstration and then hands-on session conducted at the end of each training. The Google Form questionnaires consisted of COLS meaning, rate, depth of compression, usefulness, etc. Corrective action preventive action (CAPA) analysis report was prepared along with corrective and preventive action, and onsite debriefing was also done., Results: Paired t -test was applied. For pre-test questions, 1,2,3,4,5 and 6 correct answers were 82.8%, 20.2%, 15%, 5%, >80% and <10%, respectively. In post-test, correct answers were 98.8%, 95%, 92.8%, 67%, 99.6% and 99.3%, respectively. P value 0.0022 suggested that training is highly effective and made statistically significant difference in knowledge of the participants., Conclusion: Among non-medical staff, this study emphasises the cognitive approach to the general perception and skill of COLS. Hence, formal refresher training and experience enhance the knowledge of CPR., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Anaesthesia.)

The vast majority of non-Achilles ankle tendinopathies are related to overuse. This article discusses the clinical aspect, imaging appearance, and management of tendinopathies of the lateral, medial, and the anterior compartments with a focus on presurgical perspective and postsurgical evaluation., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme. All rights reserved.)

Magnetic resonance imaging of the sacroiliac joints is now frequently performed to help identify patients with early axial spondyloarthritis. However, differential diagnoses exist and should be recognized. The aim of this article is to review the most frequent differential diagnoses that may mimic inflammatory sacroiliitis in clinical practice.

Cilnidipine (CND), an anti-hypertensive drug, possesses low oral bioavailability due to its poor aqueous solubility, low dissolution rate, and high gut wall metabolism. In the present study, an attempt has been made to prepare CND loaded polycaprolactone based nanoparticles (CND-PCL-NPs) by nanoprecipitation method applying the concepts of Design of Experiments. Critical factors affecting particle size and loading efficiency (LE%) were assessed by a hybrid design approach, comprising of Mini Run Resolution IV design followed by Box-Behnken design. Particle size, PDI, zeta potential and LE% of optimized formulations of CND-PCL-NPs were 220.3 ± 2.6 nm, 0.25 ± 0.1, -19.5 ± 0.9 mV, and 46.4 ± 1.8%, respectively. No significant changes were observed in the physical stability of nanoparticles when stored at 25 °C/60% RH over a period of 3 months. Oral pharmacokinetic studies revealed that F abs of CND-PCL-NPs (0.55) were significantly higher than the CND suspension (0.26). Pharmacodynamic studies have revealed that the mean percent reduction in systolic blood pressure (% ΔSBP) was significantly higher in the case of CND-PCL-NPs (42%) as compared to CND suspension (24%). Optimized CND-PCL-NPs offer great potential in providing higher and sustained antihypertensive effect compared to conventional formulations of CND.

Cilnidipine (CND) is known to have low oral bioavailability due to its poor aqueous solubility, low dissolution rate, and high gut wall metabolism. In the present study, CND-loaded PLGA nanoparticles (CND-PLGA-NPs) were prepared with two different grades of PLGA (50:50 and 75:25) by design of experiment. Critical factors affecting particle size and entrapment efficiency (EE%) were assessed by mixed design approach, comprising of Plackett-Burman design followed by rotatable central composite design. Particle size, PDI, zeta potential, and EE% of optimized formulations of CND-PLGA(50:50)-NPs and CND-PLGA(75:25)-NPs were 211.6 ± 1.8 nm, 0.21 ± 0.05, - 15.1 ± 1.6 mV, and 85.9 ± 1.5% and 243.5 ± 2.4 nm, 0.23 ± 0.06, -19.6 ± 1.3 mV, and 92.0 ± 1.2% respectively. No significant changes were observed in physical stability of NPs when stored at 25 °C/60% RH over a period of 3 months. Pharmacokinetic studies revealed that F abs of CND-PLGA(50:50)-NPs (1.15) and CND-PLGA(75:25)-NPs (2.23) were significantly higher than the free CND (0.26). The C max and AUC 0-∞ of CND-PLGA(50:50)-NPs (787.42 ± 27.38 ng/mL and 9339.37 ± 252.38 ng/ml × h) and CND-PLGA(75:25)-NPs (803.49 ± 19.63 ng/mL and 18,153.34 ± 543.05 ng/ml × h) were significantly higher (p ˂ 0.0001) compared with free CND (367.69 ± 47.22 ng/mL and 2107.95 ± 136.40 ng/ml × h). MRT Oral of CND-PLGA(50:50)-NPs (33.36 ± 0.48 h) and CND-PLGA(75:25)-NPs (48.37 ± 0.61 h) were significantly higher (p ˂ 0.0001) compared with free CND (4.69 ± 0.58 h). CND-PLGA-NPs can provide higher and sustained plasma drug levels of CND and be effective in antihypertensive therapy. Graphical abstract.

Cilnidipine (CND), an anti-hypertensive drug, is known to have low oral bioavailability due to its poor aqueous solubility, low dissolution rate and high gut wall metabolism. In the present study, CND loaded compritol based nanoparticles (CND-CMP-NPs) were prepared by emulsification-solvent evaporation method applying the concepts of design of experiments. Critical factors affecting particle size and loading efficiency (LE%) were assessed by hybrid design approach, comprising of Mini Run Resolution IV design followed by Box-Behnken design. Particle size, PDI, zeta potential and LE% of optimized formulations of CND-CMP-NPs were 207.1 ± 2.9 nm, 0.27 ± 0.1, -22.2 ± 1.9 mV and 15.9 ± 1.3% respectively. No significant changes were observed in physical stability of NPs when stored at 25 °C/60% RH over a period of three months. Pharmacokinetic studies revealed that F abs of CND-CMP-NPs (0.66) was significantly higher than the free CND (0.27). The C max and AUC 0-∞ of CND-CMP-NPs (572.4 ± 25.3 ng/mL and 5588.6 ± 229.5 ng/mL × h) were significantly higher (P cal < 0.0001) as compared to free CND (363.6 ± 23.5 ng/mL and 2316.1 ± 163.6 ng/mL × h). MRT of CND-CMP-NPs (9.8 ± 0.9 h) was significantly higher (P cal < 0.0001) as compared to free CND (5.7 ± 0.5 h). Pharmacodynamic studies showed a maximum of 38% decrease in systolic blood pressure with more than 20% drop in systolic blood pressure sustained for a total duration of 64 h in the case of CND-CMP-NPs as compared to free CND. CND-CMP-NPs not only provide higher and sustained plasma levels of CND but also higher and sustained antihypertensive therapy as compared to free CND., 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 © 2020 Elsevier B.V. All rights reserved.)

This pictorial essay aims to generate attention and inform sonographers and clinicians by remembering the "longitudinal pulsatility" as an evocative B-mode echographic sign of arterial occlusion, when the artery exhibits a systolic axial motion instead of its normal radial pulsatility., (© 2018 Wiley Periodicals, Inc.)

Background: Atherosclerotic disease of the superficial femoral artery (SFA) is frequently seen and can be treated with percutaneous interventions, traditionally via femoral artery access. There are limited reports of transpedal artery access for peripheral artery interventions, but none to date describing routine primary transpedal artery approach for SFA stenting., Methods: In this preliminary study, we report 4 patients who underwent successful endovascular SFA stenting using a single transpedal artery access via a new ultra-low profile 6 Fr sheath (Glidesheath Slender; Terumo Corporation)., Results: All patients underwent successful SFA stenting without complication. Procedure time varied from 51 to 72 minutes. The mean contrast amount used was 56 mL; mean fluoroscopy time was 21 minutes; mean radiation dose was 91 mGy. At 1-month follow-up, duplex ultrasonography showed that all pedal arteries had remained patent., Conclusions: Transpedal artery approach as a primary approach to SFA stenting appears feasible and safe. Comparative trials with standard percutaneous femoral approach are warranted.

Technological innovations have enabled higher success rates with percutaneous coronary intervention (PCI) of complex coronary lesions via the transradial approach. The orbital atherectomy system (OAS; Cardiovascular Systems, Inc) is the most recent innovation that abrades plaque using a rotation device for the facilitation of stent placement in heavily calcified lesions. Fifty patients with classic anginal symptoms and an abnormal stress test demonstrating ischemia underwent PCI using the coronary OAS. In all, 46 out of 50 patients received stents in the target lesion after orbital atherectomy. At follow-up, there were no major adverse cardiovascular events, including cardiac death, myocardial infarction, and need for target-vessel revascularization. Radial artery occlusion rate was 6% at 30 days. The use of the OAS via the radial approach may be a safe and feasible option to assist in the treatment of heavily calcified coronary lesions.

A group of marine dinoflagellates (Alveolata, Eukaryota), consisting of ∼10 species of the genus Alexandrium, Gymnodinium catenatum and Pyrodinium bahamense, produce the toxin saxitoxin and its analogues (STX), which can accumulate in shellfish, leading to ecosystem and human health impacts. The genes, sxt, putatively involved in STX biosynthesis, have recently been identified, however, the evolution of these genes within dinoflagellates is not clear. There are two reasons for this: uncertainty over the phylogeny of dinoflagellates; and that the sxt genes of many species of Alexandrium and other dinoflagellate genera are not known. Here, we determined the phylogeny of STX-producing and other dinoflagellates based on a concatenated eight-gene alignment. We determined the presence, diversity and phylogeny of sxtA, domains A1 and A4 and sxtG in 52 strains of Alexandrium, and a further 43 species of dinoflagellates and thirteen other alveolates. We confirmed the presence and high sequence conservation of sxtA, domain A4, in 40 strains (35 Alexandrium, 1 Pyrodinium, 4 Gymnodinium) of 8 species of STX-producing dinoflagellates, and absence from non-producing species. We found three paralogs of sxtA, domain A1, and a widespread distribution of sxtA1 in non-STX producing dinoflagellates, indicating duplication events in the evolution of this gene. One paralog, clade 2, of sxtA1 may be particularly related to STX biosynthesis. Similarly, sxtG appears to be generally restricted to STX-producing species, while three amidinotransferase gene paralogs were found in dinoflagellates. We investigated the role of positive (diversifying) selection following duplication in sxtA1 and sxtG, and found negative selection in clades of sxtG and sxtA1, clade 2, suggesting they were functionally constrained. Significant episodic diversifying selection was found in some strains in clade 3 of sxtA1, a clade that may not be involved in STX biosynthesis, indicating pressure for diversification of function., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To demonstrate the feasibility and safety of transpedal arterial access for lower-extremity angiography and intervention., Background: Traditionally, the femoral artery is chosen for the initial access site in symptomatic peripheral artery disease (PAD), but this approach carries a substantial portion of the entire procedural complication risk., Methods: 80 patients were prospectively evaluated for the treatment of PAD between May and July 2014. All patients underwent peripheral angiography, and intervention if necessary. A pedal artery was the initial access site for all patients. Under ultrasound guidance, one of the pedal arteries was visualized and accessed, and a 4 Fr Glidesheath was inserted. Retrograde orbital atherectomy and balloon angioplasty were performed with a 4 Fr sheath or upsizing to a 6 Fr Glidesheath Slender (Terumo) for stenting as needed. Clinical and ultrasound assessment of the pedal arteries were performed before the procedure and at 1-month follow-up., Results: Diagnostic transpedal peripheral angiography was performed in all 80 patients. 43 out of 51 patients (84%) who required intervention were successful using a pedal artery as the sole access site. No immediate or delayed access-site complications were detected. Clinical follow-up was achieved in 77 patients (96%) and access artery patency was demonstrated by ultrasound at 1 month in 100% of patients., Conclusion: The routine use of a transpedal approach for the treatment of PAD may be feasible and safe. Pedal artery access may also avoid many of the complications associated with the traditional femoral approach, but further study is needed.

Objectives: To provide new strategies and techniques for the successful recanalization of chronic total occlusions (CTOs) with the sole use of the CrossBoss catheter. In addition, some common CTO scenarios are illustrated in detail., Background: CTOs are one of the most challenging complex coronary lesion subsets to intervene upon. Even with the innovation of specialized catheters, the success rate of antegrade recanalization remains low., Methods: Between June and December 2013, a retrospective analysis of 50 consecutive patients who presented with a planned percutaneous intervention (PCI) of a CTO was performed. In all patients, the CrossBoss catheter was used. No additional reentry devices were necessary. Procedural success was defined as <20% residual stenosis and TIMI-3 distal blood flow of the treated vessel at the end of the procedure., Results: The majority of the patients were male (72%), with an average age of 68 years. Thirty percent of patients presented with prior CTO-PCI failure. The average fluoroscopy time was 45.9 minutes and the average amount of contrast use was 273.8 mL. No patient suffered a coronary perforation from the CrossBoss catheter., Conclusions: With increased experience using the CrossBoss catheter, the antegrade success rate of CTOs can be improved. Some tips include identifying the likely course of the artery with the aid of retrograde injection, proper guidewire selection and manipulation, and redirecting the CrossBoss catheter if there is substantial deviation from the original path.

Objectives: To evaluate the use of extension catheters in transradial intervention of complex coronary lesions., Background: Complex percutaneous coronary intervention (PCI) via transradial approach remains a challenge for many interventionalists, primarily due to the difficulty in obtaining adequate guide catheter support., Methods: A retrospective case series identified 54 patients who presented for PCI of complex coronary lesions. A lesion was defined as complex if it contained severe calcification, proximal tortuosity, chronic total occlusion, or was located distal to a previously implanted stent. After identifying the complex lesions, a conversion to femoral approach was considered, but an attempt via the transradial approach with the use of an extension catheter was chosen as the initial strategy. Specific cases highlighting this approach are illustrated in detail., Results: The average age of the patients was 72 years old, with male predominance (55%). The success rate of completing the transradial intervention with the help of an extension catheter was 96%. Stent delivery failed due to severe tortuosity and calcification in only 2 cases. The coronary artery involved was either the left anterior descending (n = 25), the left circumflex (n = 10), the right coronary artery (n = 14), or a saphenous vein graft (n = 5). There were no coronary dissections evident from use of the extension catheter., Conclusion: In the treatment of complex coronary lesions via the transradial approach, the use of an extension catheter may assist in improving successful intervention and decrease the frequency of crossover to a femoral approach.

Background and Aims: Intubation is often a challenge for anaesthesiologists. Many parameters assist to predict difficult intubation. The present study was undertaken to assess the validity of different parameters in predicting difficult intubation for general anaesthesia (GA) in adults and effect of combining the parameters on the validity., Methods: The anaesthesiologist assessed oropharynx of 135 adult patients. Modified Mallampati test (MMT) was used and the thyromental distance (TMD) and sternomental distances (SMD) for each of the patients were also measured. The Cormack and Lehane laryngoscopic grading was assessed following laryngoscopy. The validity parameters such as sensitivity, specificity, false positive and negatives values, positive and negative predictive values were calculated. The effect of combining different measurements on the validity was also studied. Univariate analysis was performed using the parametric method., Results: The study group comprised of 135 patients. The sensitivity and specificity of MMT were 28.6% and 93%, respectively. The TMD (<6.5 CM) had sensitivity and specificity of 100% and 75.8%, respectively. The SMD (<12.5 CM) had sensitivity and specificity of 91% and 92.7%, respectively. Combination of MMT grading and TMD and SMD measurements increased the validity (sensitivity of 100% and specificity of 92.7%)., Conclusion: MMT had high specificity. The validity of combination of MMT, SMD and TMD as compared to MMT alone was very high in predicting difficult intubation in adult patients. All parameters should be used in assessing an adult patient for surgery under GA.

Species of the PST producing planktonic marine dinoflagellate genus Alexandrium have been intensively scrutinised, and it is therefore surprising that new taxa can still be found. Here we report a new species, Alexandrium diversaporum nov. sp., isolated from spherical cysts found at two sites in Tasmania, Australia. This species differs in its morphology from all previously reported Alexandrium species, possessing a unique combination of morphological features: the presence of 2 size classes of thecal pores on the cell surface, a medium cell size, the size and shape of the 6″, 1', 2⁗ and Sp plates, the lack of a ventral pore, a lack of anterior and posterior connecting pores, and a lack of chain formation. We determined the relationship of the two strains to other species of Alexandrium based on an alignment of concatenated SSU-ITS1, 5.8S, ITS2 and partial LSU ribosomal RNA sequences, and found A. diversaporum to be a sister group to Alexandrium leei with high support. A. leei shares several morphological features, including the relative size and shapes of the 6″, 1', 2⁗ and Sp plates and the fact that some strains of A. leei have two size classes of thecal pores. We examined A. diversaporum strains for saxitoxin production and found them to be non-toxic. The species lacked sequences for the domain A4 of sxtA, as has been previously found for non-saxitoxin producing species of Alexandrium., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: This study aims to investigate the etiological relationship among hepatitis B virus (HBV), hepatitis C virus (HCV), and alcohol as risk factors in a cohort of hepatocellular carcinoma (HCC) patients from India. The clinical and biochemical profiles and tumor characteristics in the HCC cases were also evaluated., Methods: A total of 357 consecutive cases of HCC fulfilling the diagnostic criteria from the Barcelona-2000 EASL conference were included in the study. The blood samples were evaluated for serological evidence of HBV and HCV infection, viral load, and genotypes using serological tests, reverse transcription-polymerase chain reaction, and restriction fragment length polymorphism., Results: The male/female ratio for the HCC cases was 5.87:1. Majority of the HCC patients (33.9%) were 50 to 59 years of age, with a mean age of 4±13.23 years. More than half the cases (60.8%) had underlying cirrhosis at presentation. Among the HCC patients, 68.9% were HBV related, 21.3% were HCV related, 18.8% were alcoholic, and 18.2% were of cryptogenic origin. The presence of any marker positive for HBV increased the risk for developing HCC by almost 27 times [OR: 27.33; (12.87-60.0)]. An increased risk of 10.6 times was observed for HCC development for cases positive for any HCV marker [OR: 10.55; (3.13-42.73)]. Heavy alcohol consumption along with HCV RNA positivity in cirrhotic patients was found to be a risk for developing HCC by 3 folds [OR: 3.17; (0.37-70.71)]., Conclusions: Patients of chronic HBV infection followed by chronic HCV infection were at higher risk of developing HCC in India. Chronic alcohol consumption was found to be a risk factor in cirrhotic cases only when it was associated with HCV RNA positivity. Most of the patients had a large tumor size (>5 cm) with multiple liver nodules, indicating an advanced stage of the disease thus making curative therapies difficult.

The influence of the polyamines putrescine (Put), spermine (Spr) and spermidine (Spd) on growth and furanocoumarin production was investigated by exogenous addition, at different concentrations, to shoot cultures of Ruta graveolens at different phases of growth. Preliminary studies indicated that addition of Put (20 microM) and Spr (80 microM) had a promotive effect on shoot multiplication rate and number of multiple shoots formed. Spd was toxic, even at lower concentrations. The growth-phase of the culture at the time of exogenous addition of polyamines was found to be an important factor. Put was most effective when added at the lag phase, while Spr was most effective when added in the log phase. Time course studies of growth and furanocoumarin content were carried out for each polyamine and phase of addition. It was seen that maximum production of furanocoumarins (256.8 mg/10 g DW) occurred in the second week when Put was added in the lag phase and 260.5 mg/10 g DW in the fourth week when Spr was added in the log phase. Put addition resulted in a 3.10 fold increase in psoralen, 6.12 in xanthotoxin and 1.46 fold in bergapten production. Spr addition resulted in a 1.31 fold increase in psoralen, 4.11 fold in xanthotoxin and 1.49 fold in bergapten production. Results indicate that alteration of growth and furanocoumarin production kinetics is a combined outcome of choice of polyamine and the phase of culture at the time of exogenous addition. Polyamine addition enabled significant enhancement in production of pharmaceutically important bergapten and xanthotoxin in shoot cultures of Ruta graveolens, which could be explored for commercial production.

Effect of various abiotic (methyl jasmonate, salicylic acid) and biotic (yeast extract, Aspergillus niger) elicitors on furanocoumarin production and in situ product removal was studied using shoot cultures of Ruta graveolens L. Elicitation by yeast extract (1% w/v) on day 15 was most effective. It led to 7.8-fold higher furanocoumarin production that was attained 24 h after elicitation and 43% of the product was released into the medium. Changes in the relative concentration of furanocoumarins produced depend on the elicitor used. Molar ratio of bergapten increased to 93% in response to yeast extract. With the perspective of developing a commercially feasible process, an approach for preserving viability of biomass and its reuse needs to be developed. For this, medium renewal strategy was investigated. Removal of the spent medium 48 h after elicitation allowed in situ product removal and proved effective in revival of cultures, allowing reuse of biomass. A week after medium renewal, the revived biomass was re-elicited and a second furanocoumarin production peak was obtained. A perfusion-based bioprocess optimization approach, employing elicitation coupled with medium renewal with subsequent re-elicitation, as a new strategy for improved furanocoumarin production, has been suggested.

A 56 year old male with a past medical history of hypertension and dyslipidemia presented with recurrent dizziness. Routine EKG was performed, which suggested frequent junctional extra systoles with compensatory pauses. During telemetry periods of 2:1 block with effective ventricular rate of 34 bpm was observed. His bundle study suggested frequent His extra systoles causing functional AV block. Treatment with anti-arrhythmic medication, paradoxically improved AV block and symptoms in our patient.

Background: ST-segment depression in lead aVR in acute inferior wall ST-segment elevation myocardial infarction (STEMI) has recently been suggested as a predictor of left circumflex (LCx) artery involvement. The purpose of this study is to evaluate the clinical significance of aVR depression during inferior wall STEMI., Methods: This study included 106 consecutive patients who presented with inferior wall STEMI and underwent urgent coronary angiogram. Clinical and angiographic findings were compared between patients with and without aVR depression > or = 0.1 mV., Results: The sensitivity and specificity of aVR depression as a predictor of LCx infarction were 53% and 86%, respectively. In patients with right coronary artery infarction, aVR depression was associated with increased cardiac enzymes and the involvement of a large posterolateral branch, which may explain the larger infarction., Conclusions: ST-segment depression in lead aVR in inferior wall STEMI predicts LCx infarction or larger RCA infarction involving a large posterolateral branch., (2010 Elsevier Inc. All rights reserved.)

Topoisomerase I inhibitors from Ruta graveolens are reported for the first time. Potent topoisomerase I inhibitory activity from in vitro culture extracts R. graveolens were observed. Stabilization of DNA-topoisomerase covalent complex was observed in all the tested extracts. The mechanism of topoisomerase inhibition was determined by preincubation studies. The irreversible topoisomerase I mediated relaxation of plasmid in enzyme-substrate preincubation study, indicated that the observed inhibitory activity of extract constituents was not mediated through conformational changes in the DNA. Furthermore, the affinity of inhibitors with the enzyme was tested by enzyme-extract preincubation study. Increase in inhibition of topoisomerase activity and promotion of DNA-enzyme complex was observed after enzyme-extract preincubation. The activity could be assigned to furanocoumarins-psoralen, bergapten and xanthotoxin, identifying them as novel, potent topoisomerase I inhibitors.

Wide applications of Ruta graveolens L. in pharmaceutical industry has led to increased interest in large-scale plant production, with emphasis on use of in vitro cultures. Earlier reports describe use of in vitro germinated seedlings for raising shoot cultures and not regeneration. There is only a single regeneration protocol of R. graveolens; however, it employs conventional labour intensive techniques deterring automation. The aim of present investigation was to establish a cost effective protocol for large-scale plant production. We report for the first time a one-step protocol with improved regeneration efficiency for multiple shoots induction employing liquid culture systems. Effect of polyamines (putrescine and spermine) on growth and furanocoumarin was studied. Addition of spermine enhanced the number of multiple shoots formed (2.5-fold) and reduced the time taken by half. Spermine addition resulted in 1.47-fold in furanocoumarin production. The selected shoot line, RS2 was successfully scaled up to 5L in culture vessels, with 1.53-fold increase in biomass without affecting the productivity of these cultures. This proves to be a commercially feasible alternative to bioreactors for large-scale biomass and furanocoumarin production.

Background: Optimized functional results are difficult to achieve following hand injuries. This prospective study was undertaken to evaluate the functional outcome after surgical stabilization of metacarpal and phalangeal fractures., Materials and Methods: Forty-five fractures of digits of hand in 31 patients were managed by surgical stabilization. Five fractures were fixed with closed reduction and percutaneous Kirschner wire fixation; 10 with external fixator; 26 with open reduction and Kirschner wire fixation; and four with open reduction and plate and screw or screw fixation., Results: Final evaluation of the patients was done at the end of three months. It was based on total active range of motion for digital functional assessment as suggested by the American Society for surgery of hand. Overall results were excellent to good in 87%. Better total active range of motion (excellent grade) was observed in metacarpal fractures (47%) versus phalanx fractures (31%); closed fractures (57%) versus open fractures (27%); and single digit involvement (55%) versus multiple digits (29%). Excellent total active range of motion was observed with all four plate and screw/ screw fixation technique (100%) and closed reduction and percutaneous kirschner wire fixation (60%). Twenty-two complications were observed in 10 patients with finger stiffness being the most common., Conclusion: Surgical stabilization of metacarpal and phalangeal fractures of hand seems to give good functional outcome. Closed fractures and fractures with single digit involvement have shown a better grade of total active range of motion.

Background: Malaria remains one of the leading causes of morbidity and mortality. A definitive and early diagnosis remains the biggest challenge world-wide. Light microscopy of blood smears has been the gold standard in diagnosis of malaria for decades. This routine microscopic diagnosis is often unreliable and may not be available at many peripheral health centers. Hence newer diagnostic techniques have been developed based on antigen detection., Method: Microscopy and Non-radioactive Malaria Detection System (NOMADS) to diagnose falciparum malaria were compared. Specificity and sensitivity of this technique and applicability of the kit for rapid and reliable malaria diagnosis were evaluated. 2579 samples of blood were processed. Both thick and thin blood smear examination and NOMADS was carried out on each of them. All smear positive samples and highly suspicious clinical cases were also subjected to detection of HRP-2 antigen by ICT Malaria Pf test., Results: The detection rate for malaria on smear examination (both vivax and falciparum) was highest at Dimapur (7.41%), followed by Tezpur (7.13%), Kolkata (7%), Guwahati (6%) and Changsari (3.6%). All centers had greater incidence of falciparum compared to vivax except Kolkata where only vivax was detected. The sensitivity of NOMADS was 0%, 4.8%, 13.5%, 42.9% and 52.8% at Kolkata, Tezpur, Guwahati, Changsari and Dimapur respectively. The specificity of the test ranged between 91.8% at Changsari to 95.9% at Dimapur. The specificity at Tezpur, Kolkata and Guwahati was 92.3%, 94% and 95.3% respectively., Conclusion: The study revealed that the test kit developed needs to be standardised as regards calculation of cut off values for each of the test runs and reproductibility of optical density readings. Immuno-Chromatography Test (ICT) is helpful in early diagnosis, management and follow-up of cases of malignant malaria.

Over ordering blood is a common practice in medicine. This can be corrected by a simple means of changing the blood ordering pattern. A retrospective study was carried out in a tertiary care hospital of Armed Forces for a three year period to study the blood ordering strategies in the hospital. The total units demanded and the corresponding units issued were estimated. Thereafter, transfusion probability and ratio of units cross-matched to actual units transfused (C/T ratio) was calculated. In this study, using Mead's criterion, transfusion probability and C/T ratio, transfusion guidelines for all cases requiring transfusion is proposed. The study also identifies the common cases where 'Type and Screen' (T&S) procedure could be introduced in cases where the transfusion probability is low. The other group where transfusion probability is high, a maximum surgical blood ordering schedule (MSBOS) has been determined to identify the number of units to be cross-matched and kept ready before the procedure. The implementation of this proposal will avoid over-ordering of blood and will promote maximum utilization.

In renal transplantation, a good HLA-DR match is associated with higher success rate of graft outcome. It is particularly so In high risk recipients. Serological HLA-DR typing is not always easy due to a number of technical problems. In view of this, a comparison of serological and molecular typing was done in our institutions. A total of 64 live related donor patients of renal transplantation were studied. Serological typing was done by conventional methods. Molecular HLA class II typing was done by polymerase chain reaction (PCR) based sequence specific oligonucleotide probe (SSOP) hybridization technique. An overall discrepancy of 19.5% was observed in the DR typing obtained by serology and PCR-SSOP of all the recipients and donors. 14.5% of cases showed discrepancy in the results of only one DR antigen. Serological typing failure was seen in 10.9% of total cases. In 19.5% cases, only one DR antigen was assigned by PCR-SSOP as compared to two antigens by serological methods. Maximum number of discrepancies were seen in DR 2 antigens. There was no appreciable difference of graft survival shown in the patients typed by both methods. However, higher incidence of acute graft rejection episodes were seen in patients with 1 antigen mismatch as compared to zero mismatch. It is concluded that HLA-DR typing should be carried out by molecular methods as these have been found to be more specific and accurate.

Implications: In congenital lobar emphysema, positive pressure ventilation can expand the emphysematous lobe, compressing the normal lung during anesthesia induction. We managed the dual challenges of safe induction and analgesia for thoracotomy by placing thoracic epidural catheters via the caudal insertion site and retaining spontaneous ventilation until thoracotomy.

Eosinophilic gastroenteritis is a rare entity. We report a 41-year-old man who presented with features of gastric outlet obstruction due to a submucosal lesion in the distal end of the stomach. Distal gastrectomy with Billroth II reconstruction was done. Histology showed eosinophilic gastritis infiltrating the muscular and serosal layers of the pylorus and antrum.

We report the use of continuous regional block with light general anaesthesia in epidermolysis bullosa simplex. A 4-year-old girl suffering from florid epidermolysis bullosa simplex was scheduled for external fixator (JESS) for manus valgus deformity of the left forearm. Haemoglobin was 7.6 g.dl(-1) and blood chemistry was normal. She had no history of oral bullae, although a younger sibling had died of Bart syndrome with oral lesions. She was sedated with nasal midazolam 0.5 mg.kg(-1). All pressure points were cushioned. Inhalational anaesthesia was given by holding a mask above her face. Only oximetry and capnography were monitored. ECG and noninvasive blood pressure monitoring were avoided. The intravenous cannula was fixed by sutures. An epidural catheter of 0.63 mm OD (21-G) was passed into the axilla for continuous axillary block. Intra- and postoperative course was uneventful with slight bullae at the i.v. site and at the fixator which healed without further damage. The axilla remained free of problems. Continuous peripheral plexus or nerve blocks can be an option in these difficult patients, and can minimize the amount of general anaesthesia along with problems of airway handling and potential subsequent mucosal lesions. The postoperative period was pain free and comfortable.

Experiments have been carried out on the curing of poly(methyl methacrylate) denture base material in a microwave oven, using conventional dental flasks and flask clamps. It has been shown that it is important (a) to maintain sufficient pressure on the materials, (b) to avoid gaseous porosity by not heating too rapidly initially, and (c) to ensure that all metal is protected from exposure to microwaves. When the appropriate conditions of polymerisation were used, microwave-cured samples had satisfactory physical and mechanical properties according to American Dental Association specification number 12.

Retinoids profoundly affect the normal growth and differentiation of epithelial tissues. Retinoic acid receptor-gamma (RAR-gamma) is a member of a family of retinoid receptors, and has been shown to be expressed almost exclusively in skin. However, little is known about the cellular localization of this receptor in human skin. The authors studied the expression of RAR-gamma in normal skin and human skin tumors by Northern blot analysis and in situ hybridization. RAR-gamma mRNA was detected in normal skin as well as in cultures of neonatal keratinocytes. Using an oligonucleotide specific for the RAR-gamma cDNA isoform 1 (RAR-gamma 1), RAR-gamma 1 mRNA was localized to all layers of the epidermis, the outer root sheath of hair follicles, follicular hair bulbs, eccrine and sebaceous glands. Basal cell carcinoma constitutively expressed gamma-1 mRNA and one of seven squamous cell carcinomas showed loss of gamma-1 mRNA expression, relative to adjacent epithelium. By contrast, normal melanocytic nevi and tumor-associated lymphocytes expressed little or no RAR-gamma mRNA. These results suggest that RAR-gamma 1 may play an important role in the maintenance and differentiation of normal epidermis and skin appendages.