Bridging Tradition and Modernity: Embracing the Bipaddled Pectoralis Major Myocutaneous Flap for Challenging Oral Cavity Defects in the Free Flap Era.

Oral squamous cell carcinoma is a serious global issue, with the prognosis decreasing as the disease severity increases. The implications of this condition are so disastrous that they cause a lot of suffering for the individual. Early diagnosis has proven to improve patients' overall survival and quality of life. Surgery remains the mainstay in treating oral carcinoma. It is aimed at the complete removal of the cancerous lesion along with the management of cervical nodal metastasis. Larger defects call for reconstruction with bulky flaps. In our case, we had a composite defect postresection of the cancerous lesion, which was reconstructed using a bipaddled pectoralis major myocutaneous flap.

A Case of Advanced Oral Submucous Fibrosis Management: Beyond Conventional Approach.

A chronic, persistent, possibly cancerous condition that mostly affects the oral cavity is called oral submucous fibrosis (OSMF) and causes severe functional impairment. Due to its complex nature, OSMF requires a comprehensive strategy that includes both surgical and medication therapies. Multidisciplinary treatment was started, which included a complete stoppage of habit, dental hygiene precautions, dietary counselling, surgical intervention, supportive medicinal therapy, and physiotherapy. Following surgery and adjunct therapy, the patient's mouth opening and functional results were improved. The patient is kept for regular follow-up to assess the recurrence of fibrosis or any incidence of malignant transformation. This case emphasizes the difficulties in treating advanced OSMF and emphasizes how crucial it is to improve patient outcomes by early detection, stopping betel nut chewing, and thorough multidisciplinary care.

Rehabilitation Techniques Before and After Total Knee Arthroplasty for a Better Quality of Life.

The most important gold standard treatment following advanced knee osteoarthritis is total knee arthroplasty. Following surgery of total knee replacement, the majority of patients report decreased pain and successful long-term results, but recovery is unpredictable, and most patients continue to exhibit muscle weakness in their lower limbs and functional limitations in comparison to similarly aged control individuals. The goal of this review article was to systematically review different articles containing controlled and randomized studies to find out the effectiveness of outpatient care postoperatively on short- and long-term functional recovery. The purpose of this review article is to investigate the possible advantages of pre- and postoperative rehabilitation as well as the value of exercise regimen recommendations following total knee replacement. The following interventions after total knee arthroplasty are discussed in this review article: preoperative education and exercises, continuous passive movement, strengthening interventions, aquatic therapy, balanced training, tourniquet exposure, use of alignment and implants, role of apps in phones and different wearable devices, influence of postoperative protocols, knee bracing, neuromuscular electrical stimulation, and clinical environment. Strengthening and intense functional exercises for patients above 45 years of age, in land or water programs like aquatic activities, with the increasing intensity of the exercises in accordance with the patient's progress, should be included in the best outpatient physical therapy protocols. Because these exercises are so precisely personalized, the best long-term effects after surgery may come from outpatient physiotherapy performed in a clinical setting under the supervision of a registered physiotherapist or medical professional. This review article also includes the change in the quality and well-being of a patient's life who has undergone total knee arthroplasty and practiced the rehabilitation techniques.

Codon Optimization Using a Recurrent Neural Network.

Codon optimization of a DNA sequence can significantly increase efficiency of protein expression, reducing the cost to manufacture biologic pharmaceuticals. Although directed methods based on such factors as codon usage bias and GC nucleotide content are often used to optimize protein expression, undirected optimization using machine learning could further improve the process by capitalizing on undiscovered patterns that exist within real DNA sequences. To explore this hypothesis, Chinese hamster DNA sequences were used to train a recurrent neural network (RNN) model of codon optimization. The model was used to generate optimized DNA sequence based on an input amino acid sequence for the example receptor programmed death-ligand 1 and for an example monoclonal antibody. When RNN-optimized sequences were transfected transiently or stably into Chinese hamster ovary cells, the resulting protein expression was as high or higher than that produced by DNA sequences optimized by conventional algorithms.

Differential expression of complement receptors CR1/2 and CR4 by murine M1 and M2 macrophages.

Macrophages polarize into functionally divergent phenotypes - M1 and M2 - which express distinct receptors. These cells are known to express complement receptors, including CR1, CR3, and CR4. However, whether these complement receptors are differentially expressed on M1 and M2 macrophages is not yet known. Herein, we have examined the expression of CR1 to CR4 on murine bone marrow-derived M1 (stimulated with IFN-γ or LPS) and M2 (stimulated with IL-4 or IL-4 + IL-13) macrophages. We show that M1 cells exhibit increased expression of CR1/2, whereas M2 cells display the higher expression of CR4; CR3 is equally expressed on both the phenotypes. Thus, M1 cells are CR1/2+CR4+, and M2 are CR1/2-CR4+. Functional probing of these cells for their phagocytic ability indicates that M1 cells, which express higher CR1/2, internalize a significantly greater number of C3b-opsonized erythrocytes. Both M1 and M2 cells, on the other hand, internalize iC3b-opsonized erythrocytes to a similar extent. Interestingly, the phagocytic receptor involved in phagocytosis of iC3b-opsonized erythrocytes is only CR3 with no contribution of CR4. We, thus, propose that complement receptor expression can be used in combination with the expression of other known polarization markers to better locate a macrophage along its phenotypic spectrum.

Structural Constraint of Osteopontin Facilitates Efficient Binding to CD44.

Since the original description in 1996, the interaction between the cytokine osteopontin (OPN) and the homing receptor CD44 has been extensively studied in cancer, inflammation, bone remodeling, and various other conditions. Alternative splicing and extensive posttranslational modifications by both binding partners, as well as the possibility for lateral recruitment of additional membrane receptors or soluble co-ligands into a complex have left the exact molecular requirements for high-affinity OPN-CD44 binding unresolved. We now report that there is a moderate engagement between the unmodified molecules, which results in curved double-reciprocal plots for OPN titration, suggesting the existence of two binding sites or two binding conformations. Structural constraint of OPN, by immobilization or by addition of heparin, is required for its strong ligation of CD44. Prior literature provides evidence that heparin binding to OPN prompts the unfolding of a core element in the protein. This conformational adjustment may be essential for efficient CD44 interaction. The integrin α9ß1 seems to compete with the OPN-CD44 engagement, while the integrin αVß3 reflects additive binding, suggesting that the CD44 contact sites on OPN are downstream of the RGD motif but overlap with the SVVYGLR domain. Hyaluronate has no effect, placing the relevant domain on CD44 downstream of the N-terminus.

The imitation game: a viral strategy to subvert the complement system.

Viruses are obligate parasites of cellular hosts and therefore are constantly confronted with the host immune system. Evasion of innate immunity mechanisms by viruses is paramount for the establishment of their infection. The complement system can directly neutralize viruses and also augments adaptive immune responses against them. This system, therefore, is central to host innate immune surveillance, and viruses have evolved a multitude of ways to escape its assault. A major strategy employed by viruses is the molecular mimicry of human complement regulators, namely regulators of complement activation (RCA) proteins and CD59. Herein, we outline up-to-date information on the structure, function and role of viral homologs of the human complement regulators in viral pathogenesis.

Autophagy-related protein PfATG18 participates in food vacuole dynamics and autophagy-like pathway in Plasmodium falciparum.

Plasmodium falciparum has a limited repertoire of autophagy-related genes (ATGs), and the functions of various proteins of the autophagy-like pathway are not fully established in this protozoan parasite. Studies suggest that some of the autophagy proteins are crucial for parasite growth. PfATG18, for example, is essential for parasite replication and has a noncanonical role in apicoplast biogenesis. In this study, we demonstrate the conserved functions of PfATG18 in food vacuole (FV) dynamics and autophagy. Intriguingly, the P. falciparum FV is found to undergo fission and fusion and PfATG18 gets enriched at the interfaces of the newly generated multilobed FV during the process. In addition, expression of PfATG18 is induced upon starvation, both at the mRNA and protein level indicating its participation in the autophagy-like pathway, which is independent of its role in apicoplast biogenesis. The study also shows that PfATG18 is transported to the FV via the haemoglobin trafficking pathway. Overall, this study establishes the conserved functions of Atg18 in this important apicomplexan.

Amalgamation of Stem Cells with Nanotechnology: A Unique Therapeutic Approach.

In the last few years, the stem cell therapy has gained much popularity among researchers and scientists of biomedical field. It became an effective and alternative approach for the treatment of various physiological conditions (like accidental injuries, burn damage, organ failure, bone marrow transfusion, etc.) and chronic disorders (diabetes, cancer, neurodegenerative disorders, periodontal diseases, etc.). Due to the unique ability of cellular differentiation and regeneration, stem cell therapy serves as the last hope for various incurable conditions and severe damages. The amalgamation of stem cell therapy with nanotechnology brings new prospects to the stem cell research, as it improves the specificity of the treatment and controls the stem cell proliferation and differentiation. In this review article, we have discussed various nanocarrier systems such as carbon nanotubes, quantum dots, nanofibers, nanoparticles, nanodiamonds, nanoparticle scaffold, etc. utilized for the delivery of stem cell inside the body.

Basal and starvation-induced autophagy mediates parasite survival during intraerythrocytic stages of Plasmodium falciparum.

The precise role of autophagy in P. falciparum remains largely unknown. Although a limited number of autophagy genes have been identified in this apicomplexan, only PfAtg8 has been characterized to a certain extent. On the basis of the expression levels of PfAtg8 and the putative PfAtg5, we report that the basal autophagy in this parasite is quite robust and mediates not only the intraerythrocytic development but also fresh invasion of red blood cells (RBCs) in the subsequent cycles. We demonstrate that the basal autophagy responds to both inducers and inhibitors of autophagy. In addition, the parasite survival upon starvation is temporally governed by the autophagy status. Brief periods of starvation, which induces autophagy, help survival while prolonged starvation decreases autophagy leading to stalled parasite growth and reduced invasion. Thus, starvation-induced autophagy is context dependent. Importantly, we report characterization of another autophagy marker in this parasite, the putative PfAtg5 (Pf3D7_1430400). PfAtg5 is expressed in all the intraerythrocytic stages and partially colocalizes with ER, mitochondria, apicoplast and PfAtg8. It is also present on the double membrane bound vesicles. Altogether, these studies pave way for the detailed dissection of P. falciparum autophagy machinery and insights into molecular and functional characterization of its players for developing new therapeutics as antimalarials.

Complement Evasion Strategies of Viruses: An Overview.

Being a major first line of immune defense, the complement system keeps a constant vigil against viruses. Its ability to recognize large panoply of viruses and virus-infected cells, and trigger the effector pathways, results in neutralization of viruses and killing of the infected cells. This selection pressure exerted by complement on viruses has made them evolve a multitude of countermeasures. These include targeting the recognition molecules for the avoidance of detection, targeting key enzymes and complexes of the complement pathways like C3 convertases and C5b-9 formation - either by encoding complement regulators or by recruiting membrane-bound and soluble host complement regulators, cleaving complement proteins by encoding protease, and inhibiting the synthesis of complement proteins. Additionally, viruses also exploit the complement system for their own benefit. For example, they use complement receptors as well as membrane regulators for cellular entry as well as their spread. Here, we provide an overview on the complement subversion mechanisms adopted by the members of various viral families including Poxviridae, Herpesviridae, Adenoviridae, Flaviviridae, Retroviridae, Picornaviridae, Astroviridae, Togaviridae, Orthomyxoviridae and Paramyxoviridae.