Protective Role of Nanoceria-Infused Nanofibrous Scaffold toward Bone Tissue Regeneration with Senescent Cells.

The presence of oxidative stress in bone defects leads to delayed regeneration, especially in the aged population and patients receiving cancer treatment. This delay is attributed to the increased levels of reactive oxygen species (ROS) in these populations due to the accumulation of senescent cells. Tissue-engineered scaffolds are emerging as an alternative method to treat bone defects. In this study, we engineered tissue scaffolds tailored to modulate the adverse effects of oxidative stress and promote bone regeneration. We used polycaprolactone to fabricate nanofibrous mats by using electrospinning. We exploited the ROS-scavenging properties of cerium oxide nanoparticles to alleviate the high oxidative stress microenvironment caused by the presence of senescent cells. We characterized the nanofibers for their physical and mechanical properties and utilized an ionization-radiation-based model to induce senescence in bone cells. We demonstrate that the presence of ceria can modulate ROS levels, thereby reducing the level of senescence and promoting osteogenesis. Overall, this study demonstrates that ceria-infused nanofibrous scaffolds can be used for augmenting the osteogenic activity of senescent progenitor cells, which has important implications for engineering bone tissue scaffolds for patients with low regeneration capabilities.

4D hydrogels: fabrication strategies, stimulation mechanisms, and biomedical applications.

Shape-morphing hydrogels have emerged as a promising biomaterial due to their ability to mimic the anisotropic tissue composition by creating a gradient in local swelling behavior. In this case, shape deformations occur due to the non-uniform distribution of internal stresses, asymmetrical swelling, and shrinking of different parts of the same hydrogel. Herein, we discuss the four-dimensional (4D) fabrication techniques (extrusion-based printing, dynamic light processing, and solvent casting) employed to prepare shape-shifting hydrogels. The important distinction between mono- and dual-component hydrogel systems, the capabilities of 3D constructs to undergo uni- and bi-directional shape changes, and the advantages of composite hydrogels compared to their pristine counterparts are presented. Subsequently, various types of actuators such as moisture, light, temperature, pH, and magnetic field and their role in achieving the desired and pre-determined shapes are discussed. These 4D gels have shown remarkable potential as programmable scaffolds for tissue regeneration and drug-delivery systems. Finally, we present futuristic insights into integrating piezoelectric biopolymers and sensors to harvest mechanical energy from motions during shape transformations to develop self-powered biodevices.

Advanced 3D In Vitro Lung Fibrosis Models: Contemporary Status, Clinical Uptake, and Prospective Outlooks.

Fibrosis has been characterized as a global health problem and ranks as one of the primary causes of organ dysfunction. Currently, there is no cure for pulmonary fibrosis, and limited therapeutic options are available due to an inadequate understanding of the disease pathogenesis. The absence of advanced in vitro models replicating dynamic temporal changes observed in the tissue with the progression of the disease is a significant impediment in the development of novel antifibrotic treatments, which has motivated research on tissue-mimetic three-dimensional (3D) models. In this review, we summarize emerging trends in preparing advanced lung models to recapitulate biochemical and biomechanical processes associated with lung fibrogenesis. We begin by describing the importance of in vivo studies and highlighting the often poor correlation between preclinical research and clinical outcomes and the limitations of conventional cell culture in accurately simulating the 3D tissue microenvironment. Rapid advancement in biomaterials, biofabrication, biomicrofluidics, and related bioengineering techniques are enabling the preparation of in vitro models to reproduce the epithelium structure and operate as reliable drug screening strategies for precise prediction. Improving and understanding these model systems is necessary to find the cross-talks between growing cells and the stage at which myofibroblasts differentiate. These advanced models allow us to utilize the knowledge and identify, characterize, and hand pick medicines beneficial to the human community. The challenges of the current approaches, along with the opportunities for further research with potential for translation in this field, are presented toward developing novel treatments for pulmonary fibrosis.

Assessment of factors affecting response of direct-acting antivirals in chronic hepatitis C patients.

Background: Hepatitis C virus (HCV) is a universally prevalent pathogen and a major cause of liver-related morbidity and mortality worldwide. The evolution of antiviral therapy for HCV has rapidly progressed from interferon (IFN)-based therapies to IFN-free combinations of direct-acting antivirals (DAAs). Aims: This study aims to assess the response of DAAs in chronic hepatitis C (CHC) patients and to study the various factors affecting the response of DAAs in CHC. Settings and Design: This longitudinal observational study spanning over a year was conducted in the Medicine department of a tertiary care teaching hospital. Materials and Methods: The study was conducted on 400 adult CHC patients, diagnosed by a positive anti-HCV antibody test and a detectable viral load (HCV RNA) by real time polymerase chain reaction (RT-PCR), registered for treatment with DAAs. The first 400 patients satisfying the eligibility criteria were enrolled by non-probability consecutive sampling. All the participants were treated as per the National Viral Hepatitis Control Programme (NVHCP) guidelines. Repeat HCV viral load was done at or after 12 weeks of completion of anti-viral therapy to ascertain sustained virological response (SVR). Various factors which might predict treatment response were analyzed. Statistical Analysis Used: The continuous variables were expressed as mean and standard deviation, while the categorical variables were summarized as frequencies and percentages. The Student's independent t-test was employed for the comparison of continuous variables. The Chi-square or Fisher's exact test, whichever is appropriate, was employed for the comparison of categorical variables. Multivariate Logistic Regression was used to identify the independent predictors of treatment nonresponse. A P < 0.05 was considered statistically significant. Results: The mean age of the subjects was 42.3 ± 15.23 years with a male-to-female ratio of 1.96:1. Most of the patients (80.5%) were non-cirrhotic; among 19.5% cirrhotic, 13% were compensated while 6.5% were decompensated cirrhotic. The overall SVR done at or after 12 weeks of completion of treatment was 88.75%. Age, gender distribution, occupation, socioeconomic status, educational status, body mass index, treatment regimen, duration of treatment, and baseline viral load did not alter the treatment response. Among comorbidities, only diabetes mellitus (DM) and human immunodeficiency virus (HIV) co-infection adversely affected the treatment response (P = 0.009 and P < 0.001, respectively). Intravenous (IV) drug abuse was significantly associated with treatment failure (P < 0.001). The presence of liver cirrhosis (P < 0.001), thrombocytopenia (P < 0.001), elevated transaminases (alanine transaminase: P = 0.021, aspartate transaminase: P < 0.001), and previous treatment experience (P = 0.038) were other significant predictors of treatment failure. Conclusions: DAAs are highly efficacious drugs in the treatment of CHC with a high rate of treatment response. Significant predictors of CHC treatment failure included comorbidities especially DM and HIV co-infection, IV drug abuse, presence of liver cirrhosis, thrombocytopenia, elevated transaminases, and previous treatment experience. However, independent predictors of treatment nonresponse observed in this study were thrombocytopenia, IV drug abuse, and liver cirrhosis.

Résumé Contexte: Le virus de l'hépatite C (VHC) est un agent pathogène universellement répandu et une cause majeure de morbidité et de mortalité liées au foie dans le monde. L'évolution de la thérapie antivirale pour le VHC a rapidement progressé des thérapies à base d'interféron (IFN) à des combinaisons sans IFN de médicaments à action directe antiviraux (AAD). Objectifs: Cette étude vise à évaluer la réponse des AAD chez les patients atteints d'hépatite C chronique (HCC) et à étudier les différents facteurs affectant la réponse des AAD dans les CHC. Cadres et conception : Cette étude observationnelle longitudinale s'étalant sur un an a été menée dans le département de médecine d'un hôpital universitaire de soins tertiaires. Matériels et méthodes: L'étude a été menée sur 400 patients adultes atteints d'HCC, diagnostiqués par un test d'anticorps anti-VHC positif et une charge virale détectable (ARN du VHC) par réaction en chaîne par polymérase en temps réel, inscrit pour le traitement par DAA. Les 400 premiers patients répondant aux critères d'éligibilité ont été enrôlés par échantillonnage consécutif non probabiliste. Tous les participants étaient traités conformément aux directives du programme national de contrôle de l'hépatite virale. La charge virale répétée du VHC a été effectuée à ou après 12 semaines d'achèvement traitement antiviral pour déterminer la réponse virologique soutenue (RVS). Divers facteurs susceptibles de prédire la réponse au traitement ont été analysés. Analyse statistique utilisée: les variables continues ont été exprimées sous forme de moyenne et d'écart-type, tandis que les variables catégorielles ont été résumés sous forme de fréquences et de pourcentages. Le test t indépendant de Student a été utilisé pour la comparaison des variables continues. Le chi carré ou Le test exact de Fisher, selon le cas, a été utilisé pour la comparaison des variables catégorielles. La régression logistique multivariée a été utilisée identifier les prédicteurs indépendants de la non-réponse au traitement. A P < 0.05 était considéré comme statistiquement significatif. Résultats: L'âge moyen des sujets était de 42.3 ± 15.23 ans avec un ratio hommes-femmes de 1.96:1. La plupart des patients (80.5%) étaient non cirrhotiques ; parmi 19.5% de cirrhose, 13% étaient compensés alors que 6.5% étaient cirrhotiques décompensés. La RVS globale effectuée à 12 semaines ou après la fin du traitement était 88.75%. Âge, répartition par sexe, profession, statut socio-économique, niveau d'instruction, indice de masse corporelle, schéma thérapeutique, durée du traitement, et la charge virale de base n'a pas modifié la réponse au traitement. Parmi les comorbidités, seuls le diabète sucré (DM) et l'immunodéficience humaine la co-infection par le virus (VIH) a affecté négativement la réponse au traitement (P = 0.009 et P < 0.001, respectivement). L'abus de drogues par voie intraveineuse (IV) a été significativement associée à l'échec du traitement (P < 0.001). La présence de cirrhose du foie (P < 0.001), thrombocytopénie (P < 0.001), élévation les transaminases (alanine transaminase: P = 0.021, aspartate aminotransférase: P < 0.001) et l'expérience de traitement antérieure (P = 0.038) étaient d'autres facteurs prédictifs significatifs d'échec thérapeutique. Conclusions: les AAD sont des médicaments très efficaces dans le traitement de l'HCC avec un taux de traitement élevé réponse. Les facteurs prédictifs significatifs d'échec du traitement des CHC comprenaient les comorbidités, en particulier la co-infection par le diabète et le VIH, l'abus de drogues par voie intraveineuse, la presence de cirrhose du foie, de thrombocytopénie, d'élévation des transaminases et d'antécédents de traitement. Cependant, des prédicteurs indépendants du traitement les non-réponses observées dans cette étude étaient la thrombocytopénie, l'abus de drogues intraveineuses et la cirrhose du foie. Mots-clés: Cirrhose, antiviraux à action directe, virus de l'hépatite C, toxicomanie par voie intraveineuse, réponse virologique soutenue, thrombocytopénie.

Customer Centricity in Medical Affairs Needs Human-centric Artificial Intelligence.

The evolution of healthcare, together with the changing behaviour of healthcare professionals, means that medical affairs functions of pharmaceutical organisations are constantly reinventing themselves. The emergence of digital ways of working, expedited by the COVID-19 pandemic, means that pharmaceutical-healthcare relationships are evolving to operate in an increasingly virtual world. The value of the pharmaceutical medical affairs function is dependent on understanding customers' needs and providing the right knowledge at the right time to physicians. This requires a human-centric artificial intelligence (AI) approach for medical affairs, which allows the function to query internal and external data sets in a conversational format and receive timely, accurate and concise intelligence on their customers.

Midfacial leprosy.

Leprosy is a chronic bacterial disease that has many clinical presentations. We are reporting a patient who presented with an erythematous plaque over the nose, which was proved to be due to leprosy. We think that this type of clinical feature is not a common presentation for leprosy.

Blood transfusion and dermatology.

Blood transfusion is an accepted therapeutic procedure in all specialties of medicine. In dermatology, specialized techniques like plasmapheresis and extracorporeal photochemotherapy have provided a good treatment option in immune-mediated disorders like bullous dermatoses, collagen vascular diseases and cutaneous lymphomas. Other anecdotal and less substantiated reports point to its use in chronic disorders like atopic dermatitis and psoriasis. Untoward dermatological manifestations include mainly purpuric rash and GVHD. Since planned studies may not be possible, pertinent observations from chance situations on the effect of blood transfusion in dermatoses would add valuable information.