Utilizing a Second Flap to Address the Effect of Postradiotherapy Soft Tissue Fibrosis in Head and Neck Malignancy.

Background Late effects of adjuvant radiation therapy (RT) on soft tissues can lead to hair loss, pigmentary changes, loss of tissue volume, and fibrosis, which appear months to years after the treatment. These changes are often progressive and are because of tissue hypoxia due to radiation-induced capillary endothelial damage. Tissue hypoxia may be compounded by subclinical infection following minor trauma, exposed hardware, or associated osteoradionecrosis. The combined effect of these factors causes significant deformities in soft tissue, affecting both function and appearance. Such changes are also seen in primarily transferred flaps, which have been radiated, resulting in severe, progressive soft tissue fibrosis, compromising function and aesthetics. In selected cases, a second flap may be needed to restore function and volume. Methods Data of patients who underwent secondary soft tissue transfers for postradiotherapy-related soft tissue changes were collected from the hospital electronic medical records, from January 2019 to 2023. Details regarding the primary surgery, dose, duration of adjuvant RT, time interval between adjuvant RT and secondary soft tissue transfer, indications, and the choice of the second flap were analyzed. Results Twenty-one patients had undergone secondary soft tissue transfer for extensive soft tissue fibrosis. In addition, associated compounding features like exposed implant and volume loss were observed. Two patients with osteoradionecrosis also had associated extensive soft tissue fibrosis necessitating replacement. Out of these 21 patients, 13 had undergone free tissue transfers, while 7 locoregional tissue transfers. Conclusion Late sequelae of adjuvant RT changes usually present from 6 months onwards. The radiated hypoxic tissue, due to capillary damage, leads to a chronic progressive fibrotic stage, causing loss of soft tissue volume and fibrosis. Replacing this tissue with a vascularized flap helps to restore volume and correct these secondary changes, improving overall quality of life.

Internal mammary artery perforator flap in the management of tracheoesophageal fistulae.

BACKGROUND: A pathological communication between the trachea and oesophagus - a tracheoesophageal fistula - may be congenital or acquired, benign or malignant, necessitating a multidisciplinary approach. Conservative attempts at closure of this abnormal connection are ineffective; the interposition of healthy vascular tissue offers the least chance of recurrence. METHODS: Outcomes of an islanded fasciocutaneous internal mammary artery perforator flap applied for tracheoesophageal fistula management were assessed in four radiated patients with laryngeal carcinoma using retrospective records. RESULTS: Four male patients, with an average age of 60.75 years, underwent tracheoesophageal fistula closure between September 2017 and February 2021. A left-sided second internal mammary artery perforator flap was used in all cases, with an average dimension of 10.5 × 4.5 cm. There were no complications of tracheoesophageal leak, flap issues or donor site morbidity on follow up. CONCLUSION: Recent advances in angiosomal territory mapping and microvascular dissection techniques, combined with an understanding of tracheoesophageal fistula pathology, have changed management perspectives in these difficult-to-treat patients.

EGCG inactivates a pore-forming toxin by promoting its oligomerization and decreasing its solvent-exposed hydrophobicity.

Natural proteinaceous pore-forming agents can bind and permeabilize cell membranes, leading to ion dyshomeostasis and cell death. In the search for antidotes that can protect cells from peptide toxins, we discovered that the polyphenol epigallocatechin gallate (EGCG) interacts directly with melittin from honeybee venom, resulting in the elimination of its binding to the cell membrane and toxicity by markedly lowering the extent of its solvent-exposed hydrophobicity and promoting its oligomerization into larger species. These physicochemical parameters have also been shown to play a key role in the binding to cells of misfolded protein oligomers in a host of neurodegenerative diseases, where oligomer-membrane binding and associated toxicity have been shown to correlate negatively with oligomer size and positively with solvent-exposed hydrophobicity. For melittin, which is not an amyloid-forming protein and has a very distinct mechanism of toxicity compared to misfolded oligomers, we find that the size-hydrophobicity-toxicity relationship also rationalizes the pharmacological attenuation of melittin toxicity by EGCG. These results highlight the importance of the physicochemical properties of pore forming agents in mediating their interactions with cell membranes and suggest a possible therapeutic approach based on compounds with a similar mechanism of action as EGCG.

Possible Contribution of Alternative Transcript Isoforms in Mature Biofilm Growth Phase of Candida glabrata.

Expression of genome-wide alternative transcript isoforms and differential transcript isoform usage in different biological conditions (isoform switching) are responsible for the varied proteomic functional diversity in higher eukaryotic organisms. However, these mechanisms have not been studied in Candida glabrata, which is a potent eukaryotic opportunistic pathogen. Biofilm formation is an important virulence factor of C. glabrata that withstands antifungal drug stress and overcomes the host-immune response. Here, we present the genome-wide differential transcript isoform expression (DTE) and differential transcript isoform usage (DTU) in a mature biofilm growth phase of C. glabrata (clinical isolate; NCCPF 100,037) using the RNA sequencing approach. The DTE analysis generated 7837 transcript isoforms from the C. glabrata genome (5293 genes in total), and revealed that transcript isoforms generated from 292 genes showed significant DTU in the mature biofilm cells. Gene ontology, pathway analysis and protein-protein interactions of significant transcript isoforms, further substantiated that their specific expression and differential usage is required for transitioning the planktonic cells to biofilm in C. glabrata. The present study reported the possible role of expression of alternative transcript isoforms and differential transcript isoform usage in the mature biofilms of C. glabrata. The observation derived from the study may prove to be beneficial for making future antifungal therapeutic strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01036-7.

Bi-directional elucidation of Lactiplantibacillus plantarum (RTA 8) intervention on the pathophysiology of gut-brain axis during Salmonella brain infection.

BACKGROUND: There have been reports of patients suffering from typhoid fever, particularly those involving infants and immunocompromised patients, which at times present with Salmonella induced brain infection. Although rare, it has frequently been associated with adverse neurological complications and increased mortality. In this context, the gut-brain axis, involving two-way communication between the gut and the brain, holds immense significance as various gut ailments have been associated with psychiatric complications. In turn, several neurodegenerative diseases have been associated with an altered gut microbiota profile. Given the paucity of effective antimicrobials and increasing incidence of multi-drug resistance in pathogens, alternate treatment therapies such as probiotics have gained significant attention in the recent past. RESULTS: In the current study, prophylactic effect of Lactiplantibacillus plantarum (RTA 8) in preventing neurological complications occurring due to Salmonella brain infection was evaluated in a murine model. Along with a significant reduction in bacterial burden and improved histoarchitecture, L. plantarum (RTA 8) administration resulted in amelioration in the level of neurotransmitters such as serotonin, norepinephrine and dopamine in the gut as well as in the brain tissue. Simultaneously, increased gene expression of physiologically essential molecules such as mucin (MUC1 and MUC3) and brain-derived neurotrophic factor (BDNF) was also observed in this group. CONCLUSION: Present study highlights the potential benefits of a probiotic supplemented diet in improving various aspects of host health due to their multi-targeted approach, thereby resulting in multi-faceted gains.

Software system to predict the infection in COVID-19 patients using deep learning and web of things.

Since the end of 2019, computed tomography (CT) images have been used as an important substitute for the time-consuming Reverse Transcriptase polymerase chain reaction (RT-PCR) test; a new coronavirus 2019 (COVID-19) disease has been detected and has quickly spread through many countries across the world. Medical imaging such as computed tomography provides great potential due to growing skepticism toward the sensitivity of RT-PCR as a screening tool. For this purpose, automated image segmentation is highly desired for a clinical decision aid and disease monitoring. However, there is limited publicly accessible COVID-19 image knowledge, leading to the overfitting of conventional approaches. To address this issue, the present paper focuses on data augmentation techniques to create synthetic data. Further, a framework has been proposed using WoT and traditional U-Net with EfficientNet B0 to segment the COVID Radiopedia and Medseg datasets automatically. The framework achieves an F-score of 0.96, which is best among state-of-the-art methods. The performance of the proposed framework also computed using Sensitivity, Specificity, and Dice-coefficient, achieves 84.5%, 93.9%, and 65.0%, respectively. Finally, the proposed work is validated using three quality of service (QoS) parameters such as server latency, response time, and network latency which improves the performance by 8%, 7%, and 10%, respectively.

Management of patients with allergy to local anesthetics: two case reports.

Lidocaine is the most commonly used local anesthetic (LA) agent in various dental as well as oral and maxillofacial procedures. Although rare, adverse effects and allergic reactions to lidocaine have been reported. In patients with suspected allergy to LA or a history of such reaction, careful history-taking and allergy testing should be performed to choose an alternative LA agent to avoid any adverse effects. Here, we present two cases of delayed hypersensitivity reaction to lidocaine, wherein the patients presented with erythema, edema, and itching. Intradermal testing confirmed allergic reaction to lidocaine, and the patients underwent successful dental treatment using an alternative LA agent. This report highlights the importance of allergy testing prior to LA use considering the serious consequences of allergy to these agents and describes the management of such patients using an alternative LA agent.

Correction: Förster resonance energy transfer (FRET) and applications thereof.

Correction for 'Förster resonance energy transfer (FRET) and applications thereof' by Amrita Kaur et al., Anal. Methods, 2020, 12, 5532-5550, DOI: 10.1039/D0AY01961E.

Covid-19 fallout: Interplay between stressors and support on academic functioning of Malaysian university students.

Covid-19 has impacted the lives of everyone around the world, including university students. The pandemic has wreaked havoc on all economies, resulting in a huge loss of employment. As a result, university students are anxious about their job prospects upon graduation. The purpose of this study was to identify the effects of two stressors - employment anxiety and financial anxiety and two supports - university support and lecturer support on dropout intention and academic performance on university students with well-being and purpose in life being the mediators. This quantitative was carried out in Malaysia using 436 final-year undergraduate students. The full mediation model indicated that the university and lecturer support mitigates the two stressors' effects through well-being and purpose in life. Students who reported better support systems reported lower academic concerns and were less likely to drop out than those who reported less support from their university and lectures. The significance of this study and its implications are discussed, along with the findings.

Förster resonance energy transfer (FRET) and applications thereof.

FRET is a nonradiative process of energy transfer that is based on the dipole-dipole interactions between molecules that are fluorescent. Transfer of energy takes place rapidly from a donor molecule to an acceptor molecule in juxtaposition such as 0 to 10 nm without photonic radiation. FRET has occupied a center stage in biotechnology and biological studies. It is used to gain information on conformation changes in single molecules. The pharmaceutical industry has also developed large fluorescence detection systems with very small sample sizes, at the level of single molecules, using fluorescence correlation spectroscopy.

Salmonella Strain Specificity Determines Post-typhoid Central Nervous System Complications: Intervention by Lactiplantibacillus plantarum at Gut-Brain Axis.

Neurological complications occurring due to Salmonella infection in some typhoid patients remain a relatively unexplored serious complication. This study firstly aimed to explore whether disseminative ability of Salmonella from gut to brain is strain specific or not and on the basis of bacterial load, histopathology, and behavioral changes, it was observed that Salmonella enterica serovar Typhimurium NCTC 74 did not cause brain infection in murine model in contrast to Salmonella Typhimurium SL1344. Simultaneously, alarming escalation in antimicrobial resistance, making the existing antibiotics treatment inefficacious, prompted us to evaluate other bio-compatible strategies as a potential treatment option. In this context, the role of gut microbiota in influencing behavior, brain neurochemistry, and physiology by modulating key molecules associated with gut-brain axis has captured the interest of the scientific community. Followed by in vitro screening of potential probiotic strains for beneficial attributes, efficacy of the selected strain was systematically evaluated at various levels of gut-brain axis against Salmonella induced brain infection. Analysis of behavioral (depression, anxiety, and locomotor), neurochemical [gamma amino butyric acid and acetylcholinesterase (AChE)], neuropathological (brain and intestinal histology; bacterial burden), and immunohistochemical studies (tight junction proteins expression) revealed its role in preventing serious manifestations and proving its potential as "psychobiotic." To the best of our knowledge, this is the first report elaborating strain specificity of Salmonella in causing post-typhoidal neurological manifestations and simultaneous use of probiotic in managing the same by influencing the pathophysiology at gut-brain axis.

Recombinant expression, purification and PEGylation of Paneth cell peptide (cryptdin-2) with value added attributes against Staphylococcus aureus.

Cryptdins are disulfide-rich cationic antimicrobial peptides secreted by mouse Paneth cells and are known to exhibit potent antimicrobial activity against various deadly pathogens. Keeping in view the extremely low yield obtained from mouse Paneth cells and high cost of synthetic peptide(s), herein, we have attempted to produce cryptdin-2 in Escherichia coli using recombinant technology. To avoid lethal effects of peptide on the host cells, cryptdin-2 was expressed as a fusion protein with thioredoxin as fusion partner which yielded 40 mg/L protein in the soluble fraction. Subsequently, mature cryptdin-2 was cleaved from the fusion partner and purified by cation exchange chromatography. Since conjugation of poly(ethylene) glycol (PEG) has been known to improve the biological properties of biomolecules, therefore, we further attempted to prepare PEG-conjugated variant of cryptdin-2 using thiol specific PEGylation. Though the antimicrobial activity of PEGylated cryptdin-2 was compromised to some extent, but it was found to have enhanced serum stability for longer duration as compared to its un-modified forms. Also, it was found to exhibit reduced toxicity to the host cells. Further, its synergism with gentamicin suggests that PEGylated cryptdin-2 can be used with conventional antibiotics, thereby indicating its possibility to be used as an adjunct therapy.

Efficacy of designer K11 antimicrobial peptide (a hybrid of melittin, cecropin A1 and magainin 2) against Acinetobacter baumannii-infected wounds.

Due to emergence of multidrug resistance in pathogens, the attention of the scientific community is now directed towards strengthening the reservoir of antimicrobial compounds. Prior to in vivo studies, the interaction and penetration of a hybrid peptide K11 in bacterial cells using confocal microscopy was assessed which was observed as early as 10 min after incubation with the peptide. Cell lysis along with leakage of cytoplasmic content was confirmed by electron microscopy. To evaluate the in vivo performance of the peptide, it was contained in carbopol hydrogel. Efficacy of the hydrogel formulation was then evaluated against Acinetobacter baumannii-infected wounds using a murine excision model. Treatment resulted in restoration of body weight, complete clearance of infection from the wound by day 7 and 99% wound enclosure by day 21, in contrast to the persistence of infection and 70% wound enclosure in the infected group. Further, this treatment resulted in a 2.6-fold decrease in the levels of malondialdehyde along with a 4.5-fold increase in the levels of catalase on day 3. Appearance of normal histo-architecture was observed in the treatment group. Based on these results, the peptide hydrogel can be exploited in future as one of the strategies for developing a topical anti-infective therapeutic agent.

Management of Staphylococcus Mediated Systemic Infection by Enhancing the Resurging Activity of Co-trimoxazole in Presence of Cryptdin-2.

Resurgence of sensitivity of the antibiotics, to which the pathogen had developed resistance in the past, requires special attention for strengthening the reservoir of antimicrobial compounds. Reports in the recent past have suggested that co-trimoxazole (COT) has regained its activity against methicillin resistant Staphylococcus aureus (MRSA). The present study exploited the use of COT in the presence of an antimicrobial peptide (AMP), cryptdin-2 (a murine Paneth cell alpha defensin), in order to reduce the selective pressure of the antibiotic on the pathogen. In vitro antibacterial activity and in vivo efficacy of the combination was ascertained against MRSA induced systemic infection using a murine model. Observations of the present study might help in restoring the regained activity of conventional antibiotics, such as COT, when used in combination with novel antimicrobial molecules like AMPs. This might prove as a viable strategy to eliminate the chances of re-occurrence of resistance due to their multi-prong targeting and synergistically combating infections caused by these resistant pathogens.

The interplay of socio-psychological factors on school engagement among early adolescents.

The study examined a conceptual model integrating existing knowledge on the linkages between life satisfaction, affect, purpose in life, and resilience with school engagement. This model posits direct relationships between all the social psychological variables and school engagement, and also indirect relationships between life satisfaction and school engagement as mediated by all the other variables in the study. The participants were 2381 students (1119 boys and 1262 girls) with average age of 15 years, from 40 national secondary schools in Malaysia. The findings supported the theoretical conceptualization. All variables were positively associated with school engagement. The strongest relationship was observed between overall life satisfaction and school engagement. The mediating model was partially supported. The study reiterates the adage that "it takes a village to raise a child". Implications for practice and future research are discussed in the context of engagement in school learning.

Is ectopic pregnancy possible after hysterectomy?

OBJECTIVE: To determine whether ectopic pregnancy should be suspected in young women with abdominal pain even after hysterectomy. DESIGN: Case report. SETTING: The patient presenting with abdominal pain in the emergency department was referred to a tertiary care center. PATIENT(S): A young woman who had had a subtotal hysterectomy 3 years prior for atonic postpartum hemorrhage during her last caesarean section presented with acute abdominal pain. INTERVENTION(S): Urgent ultrasound showed a gestational sac of 9 weeks + 3 days. Emergency laparotomy was done for suspected ectopic pregnancy. MAIN OUTCOME MEASURE(S): Ultrasound, operative findings, and histopathology. RESULT(S): Tubal ectopic pregnancy was confirmed on laparotomy and histopathology. CONCLUSION(S): Early suspicion can avoid missing early and treatable ectopic gestation before life-threatening complications develop.