Dual-Function Antibody Conjugate-Enabled Photoimmunotherapy Complements Fluorescence and Photoacoustic Imaging of Head and Neck Cancer Spheroids.

Several molecular-targeted imaging and therapeutic agents are in clinical trials for image-guided surgery and photoimmunotherapy (PIT) for head and neck cancers. In this context, we have previously reported the development, characterization, and specificity of a dual-function antibody conjugate (DFAC) for multimodal imaging and photoimmunotherapy (PIT) of EGFR-overexpressing cancer cells. The DFAC reported previously and used in the present study comprises an EGFR-targeted antibody, cetuximab, conjugated to benzoporphyrin derivative (BPD) for fluorescence imaging and PIT and a Si-centered naphthalocyanine dye for photoacoustic imaging. We report here the evaluation and performance of DFAC in detecting microscopic cancer spheroids by fluorescence and photoacoustic imaging along with their treatment by PIT. We demonstrate that while fluorescence imaging can detect spheroids with volumes greater than 0.049 mm3, photoacoustic imaging-based detection was possible even for the smallest spheroids (0.01 mm3) developed in the study. When subjected to PIT, the spheroids showed a dose-dependent response, with smaller spheroids (0.01 and 0.018 mm3) showing a complete response with no recurrence when treated with 100 J/cm2. Together our results demonstrate the complementary imaging and treatment capacity of DFAC. This potentially enables fluorescence imaging to assess the presence of tumor on a macroscopic scale, followed by photoacoustic imaging for delineating tumor margins guiding surgical resection and elimination of any residual microscopic disease by PIT, in a single intraoperative setting.

Optimizing Axial and Peripheral Substitutions in Si-Centered Naphthalocyanine Dyes for Enhancing Aqueous Solubility and Photoacoustic Signal Intensity.

Photoacoustic imaging using external contrast agents is emerging as a powerful modality for real-time molecular imaging of deep-seated tumors. There are several chromophores, such as indocyanine green and IRDye800, that can potentially be used for photoacoustic imaging; however, their use is limited due to several drawbacks, particularly photostability. There is, therefore, an urgent need to design agents to enhance contrast in photoacoustic imaging. Naphthalocyanine dyes have been demonstrated for their use as photoacoustic contrast agents; however, their low solubility in aqueous solvents and high aggregation propensity limit their application. In this study, we report the synthesis and characterization of silicon-centered naphthalocyanine dyes with high aqueous solubility and near infra-red (NIR) absorption in the range of 850-920 nm which make them ideal candidates for photoacoustic imaging. A series of Silicon-centered naphthalocyanine dyes were developed with varying axial and peripheral substitutions, all in an attempt to enhance their aqueous solubility and improve photophysical properties. We demonstrate that axial incorporation of charged ammonium mesylate group enhances water solubility. Moreover, the incorporation of peripheral 2-methoxyethoxy groups at the α-position modulates the electronic properties by altering the π-electron delocalization and enhancing photoacoustic signal amplitude. In addition, all the dyes were synthesized to incorporate an N-hydroxysuccinimidyl group to enable further bioconjugation. In summary, we report the synthesis of water-soluble silicon-centered naphthalocyanine dyes with a high photoacoustic signal amplitude that can potentially be used as contrast agents for molecular photoacoustic imaging.

Assessment and Correlation of Salivary Ca, Mg, and pH in Smokers and Non-Smokers with Generalized Chronic Periodontitis.

Background and Objectives: Diagnostic evaluation with the aid of biomarkers has reached newer heights to assess disease activity. Salivary calcium, magnesium, and pH are one of the biochemical parameters which can be helpful in assessing the progression of periodontal disease. Smokers are at topnotch threat for having oral diseases, predominantly periodontal diseases. The aim of this study was to assess the salivary calcium, magnesium, and pH levels in smokers compared with non-smokers with chronic periodontitis. Materials and Methods: The current study was conducted on 210 individuals affected with generalized chronic periodontitis, with the age group between 25 and 55 years. Based on their smoking habit, an equal number of patients were categorized into two groups; namely, group I consisted of non-smokers and group II consisted of smokers. The clinical parameters that were measured included Plaque Index (PI), Gingival Index (GI), Probing Pocket Depth (PPD), and Clinical Attachment Loss (CAL). The biochemical variables that were evaluated in the current study included salivary calcium, magnesium, and pH using an AVL9180 electrolyte analyzer (Roche, Germany). The gathered data were analyzed with an unpaired t test was using SPSS 20.0. Results: A statistically significant higher PPD (p < 0.01), CAL (p < 0.05), and salivary calcium levels (p < 0.001) were observed in the smokers' compared with their non-smoking counterparts. Among the biochemical parameters, calcium showed a significantly (p < 0.001) higher level in smokers (5.79 ± 1.76) in contrast to non-smokers (3.87 ± 1.03). Additionally, a significant negative correlation (p < 0.05) between calcium and PPD was observed in non-smokers, whereas a non-significant inverse relation (p > 0.05) was seen in smokers. Conclusions: The present study indicates that the salivary calcium level can be a potential biochemical parameter to assess the progression of periodontal disease in smokers and non-smokers. Within the limitations of the current study, the salivary biomarkers appear to have an essential role in the identification and indication of the status of periodontal diseases.

Spotlight on Photoactivatable Liposomes beyond Drug Delivery: An Enabler of Multitargeting of Molecular Pathways.

The potential of photoactivating certain molecules, photosensitizers (PS), resulting in photochemical processes, has long been realized in the form of photodynamic therapy (PDT) for the management of several cancerous and noncancerous pathologies. With an improved understanding of the photoactivation process and its broader implications, efforts are being made to exploit the various facets of photoactivation, PDT, and the associated phenomenon of photodynamic priming in enhancing treatment outcomes, specifically in cancer therapeutics. The parallel emergence of nanomedicine, specifically liposome-based nanoformulations, and the convergence of the two fields of liposome-based drug delivery and PDT have led to the development of unique hybrid systems, which combine the exciting features of liposomes with adequate complementation through the photoactivation process. While initially liposomes carrying photosensitizers (PSs) were developed for enhancing the pharmacokinetics and the general applicability of PSs, more recently, PS-loaded liposomes, apart from their utility in PDT, have found several applications including enhanced targeting of drugs, coloading multiple therapeutic agents to enhance synergistic effects, imaging, priming, triggering drug release, and facilitating the escape of therapeutic agents from the endolysosomal complex. This review discusses the design strategies, potential, and unique attributes of these hybrid systems, with not only photoactivation as an attribute but also the ability to encapsulate multiple agents for imaging, biomodulation, priming, and therapy referred to as photoactivatable multiagent/inhibitor liposomes (PMILS) and their targeted versions─targeted PMILS (TPMILS). While liposomes have formed their own niche in nanotechnology and nanomedicine with several clinically approved formulations, we try to highlight how using PS-loaded liposomes could address some of the limitations and concerns usually associated with liposomes to overcome them and enhance their preclinical and clinical utility in the future.

Photoimmunotherapy Retains Its Anti-Tumor Efficacy with Increasing Stromal Content in Heterotypic Pancreatic Cancer Spheroids.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by increased levels of desmoplasia that contribute to reduced drug delivery and poor treatment outcomes. In PDAC, the stromal content can account for up to 90% of the total tumor volume. The complex interplay between stromal components, including pancreatic cancer-associated fibroblasts (PCAFs), and PDAC cells in the tumor microenvironment has a significant impact on the prognoses and thus needs to be recapitulated in vitro when evaluating various treatment strategies. This study is a systematic evaluation of photodynamic therapy (PDT) in 3D heterotypic coculture models of PDAC with varying ratios of patient-derived PCAFs that simulate heterogeneous PDAC tumors with increasing stromal content. The efficacy of antibody-targeted PDT (photoimmunotherapy; PIT) using cetuximab (a clinically approved anti-EGFR antibody) photoimmunoconjugates (PICs) of a benzoporphyrin derivative (BPD) is contrasted with that of liposomal BPD (Visudyne), which is currently in clinical trials for PDT of PDAC. We demonstrate that both Visudyne-PDT and PIT were effective in heterotypic PDAC 3D spheroids with a low stromal content. However, as the stromal content increases above 50% in the 3D spheroids, the efficacy of Visudyne-PDT is reduced by up to 10-fold, while PIT retains its efficacy. PIT was found to be 10-, 19-, and 14-fold more phototoxic in spheroids with 50, 75, and 90% PCAFs, respectively, as compared to Visudyne-PDT. This marked difference in efficacy is attributed to the ability of PICs to penetrate and distribute homogeneously within spheroids with a higher stromal content and the mechanistically different modes of action of the two formulations. This study thus demonstrates how the stromal content in PDAC spheroids directly impacts their responsiveness to PDT and proposes PIT to be a highly suited treatment option for desmoplastic tumors with particularly high degrees of stromal content.

Parents' linguistic strategies in interaction with their children with history of cleft lip and/or palate.

BACKGROUND: Cleft lip and/or palate (CL/P) presents a rather complex challenge that requires understanding beyond biological or clinical perspective. Even though inaccuracies in speech articulation are the common consequences of CL/P, individuals with repaired CL/P are likely to experience other language-associated issues. Studies on social interaction have generally reported the children to be passive interlocutors, despite having their surgical treatment at the early stages of life. AIMS: This study aims to describe the linguistic strategies that parents employ when interacting with their repaired CL/P child. How parents allocate the next turn of speaking to their repaired CL/P child will be specifically examined. METHODS & PROCEDURES: Three parent-child pairs with each child having repaired CL/P were selected to participate in the study. Guided by the principles of Conversation Analysis, their everyday interactions in their homes were video-recorded and transcribed according to the Jefferson System of Transcription Notation (2004). The transcriptions were subsequently analysed in order to highlight the linguistic strategies. OUTCOMES & RESULTS: Three main linguistic strategies are identified in the parents' turns when they allocate the next turn of speaking to their repaired CL/P child. Specifically, parents' turns are constructed through interrogative sentences in addition to using emphasis words and repeated elicitation of responses from their child. CONCLUSION & IMPLICATIONS: Parents' linguistic strategies are found to be restrictive as they limit children's active participation. Consequently, the interaction becomes asynchronous rather than synchronous, which could otherwise benefit children's language development. Findings provide information on how parents can be supported in order to foster a positive growth of the children's language development through everyday interactions. WHAT THIS PAPER ADDS: What is already known on the subject Even after repair surgery, children with CL/P may experience poor language performance that is not limited to inaccuracies in speech articulation. Studies within the area of pragmatics have consistently shown the CL/P children to be passive interlocutors. What this paper adds to existing knowledge This study describes the linguistic strategies employed by parents when they allocate the next turn of speaking to their repaired CL/P child. Parents are found to employ three main strategies: framing the turn into an interrogative sentence, deploying emphasis words and repeatedly eliciting responses. The findings suggest that such strategies limit the interactions, making them asynchronous and potentially unconducive to the positive growth of the child's language development. What are the potential or actual clinical implications of this work? In addition to providing speech treatment to children affected with CL/P, parents, especially those belonging to collectivist groups that are sympathetic to authoritarian parenting styles, can also be informed or trained on other ways to communicate with such individuals.

Nanoparticle-Protein Interaction: The Significance and Role of Protein Corona.

The physico-chemical properties of nanoparticles, as characterized under idealized laboratory conditions, have been suggested to differ significantly when studied under complex physiological environments. A major reason for this variation has been the adsorption of biomolecules (mainly proteins) on the nanoparticle surface, constituting the so-called "biomolecular corona". The formation of biomolecular corona on the nanoparticle surface has been reported to influence various nanoparticle properties viz. cellular targeting, cellular interaction, in vivo clearance, toxicity, etc. Understanding the interaction of nanoparticles with proteins upon administration in vivo thus becomes important for the development of effective nanotechnology-based platforms for biomedical applications. In this chapter, we describe the formation of protein corona on nanoparticles and the differences arising in its composition due to variations in nanoparticle properties. Also discussed is the influence of protein corona on various nanoparticle activities.

New sites of localisation of Pasteurella multocida B:2 in buffalo surviving experimental haemorrhagic septicaemia.

BACKGROUND: Haemorrhagic septicaemia (HS) is an acute septicaemic disease of buffalo and cattle caused by Pasteurella multocida B:2 and E:2. Field outbreaks of HS are known to result in localisation of bacteria in the tonsils of surviving buffalo, confirming that animals can become carriers and the role of respiratory tract in the transmission of the disease. This report describes additional sites of localisation of P. multocida B:2 in surviving buffalo following experimental induction of HS. RESULTS: Following P. multocida B:2 infection, all calves in group 1 and one calf in group 2 that was allowed to commingle with infected calves from group 1 were euthanised within 48 h. Pasteurella multocida B:2 was detected from the nasal and rectal swab samples on days 5 and 6 from the remaining calves in group 2. The first injection of dexamethasone into the carrier animals resulted in reemergence in samples from the nose, rectum and vagina. However, subsequent dexamethasone injections failed to re-activate P. multocida B:2. When surviving carrier calves in group 2 were euthanised at the end of the experiment, P. multocida B:2 was detected in the lungs and various organs of the respiratory, gastrointestinal and urinary tracts. CONCLUSIONS: Commingling naive buffalo calves with calves acutely infected with P. multocida B:2 resulted in carriers among surviving buffalo. Pasteurella was found in various organs of the respiratory, gastrointestinal and urinary tracts, suggesting their role in the pathogenesis of HS.

Methods for assessing and removing non-specific photoimmunotherapy damage in patient-derived tumor cell culture models.

Tumor-targeted, activatable photoimmunotherapy (taPIT) has been shown to selectively destroy tumor in a metastatic mouse model. However, the photoimmunoconjugate (PIC) used for taPIT includes a small fraction of non-covalently associated (free) benzoporphyrin derivative (BPD), which leads to non-specific killing in vitro. Here, we report a new treatment protocol for patient-derived primary tumor cell cultures ultrasensitive to BPD photodynamic therapy (BPD-PDT). Based on free BPD efflux dynamics, the updated in vitro taPIT protocol precludes non-specific BPD-PDT by silencing the effect of free BPD. Following incubation with PIC, incubating cells with PIC-free medium allows time for expulsion of free BPD whereas BPD covalently bound to PIC fragments is retained. Administration of the light dose after the intracellular free BPD drops below the threshold for inducing cell death helps to mitigate non-specific damage. In this study, we tested two primary ovarian tumor cell lines that are intrinsically chemoresistant, yet ultrasensitive to BPD-PDT such that small amounts of free BPD (a few percent of the total BPD dose) lead to potent induction of cell death upon irradiation. The modifications in the protocol suggested here improve in vitro taPIT experiments that lack in vivo mechanisms of free BPD clearance (i.e., lymph and blood flow).

Knowledge, Attitudes, and Practices of Nurses toward Risk Factors and Prevention of Falls in Older Adult Patients in a Large-Sized Tertiary Care Setting.

The objective was to assess the knowledge, attitudes, and practices of nurses toward the prevention of falls in older hospitalized patients. A cross-sectional study employing a 54-item questionnaire was conducted on 370 nurses at a tertiary care referral center. The mean age of the study population was 36.3 ± 7.7 years, with the majority being females (282; 76.8%). Most of them had attended fall prevention training (335; 90.5%). More than 98% knew fall prevention policies and safety goals, according to their response to a fall and risk assessment, but were less aware of the risk factors of falls, such as recurrent falls (61%), depression (44%), and lower-extremity numbness (40.5%). Similarly, 99% had positive attitudes toward risk assessment, fall prevention intervention, and response to a fall. Around 55% thought they were responsible for patients' falls, and 96% felt the need to undergo more training on fall prevention. Furthermore, 92% strictly followed fall prevention policies and 85.4% followed the color-coding system for high-risk patients. Despite the preventive measures in place, 33% encountered patient falls, and 82.2% experienced unwitnessed patient fall incidents in their units. Although the nurses had higher levels of knowledge about the policies, they lacked information on the risk factors. There is a significant scope that warrants great attention concerning the adherence to guidelines and the provision of fall prevention training programs, with a focus on the intrinsic causative factors of falls.

Efficacy and safety of micro-needling combined with topical 5-fluorouracil and excimer light vs. excimer light alone in treatment of non-segmental vitiligo: A comparative study.

BACKGROUND/PURPOSE: Vitiligo is one of the most challenging dermatological diseases with little improvement promises. Various modalities of treatment both medical and surgical have been used in the treatment of vitiligo. Some proved to be effective, others with controversial results and the rest were effective less. The aim of the present study was to evaluate the additional effect of topical 5-fluorouracil after micro-needling to excimer light (308 nm) in treatment of non-segmental vitiligo. METHODS: Fifty patients were included in the present study, only 33 patients continued the treatment for 6 months. Two patches were selected in every patient to be treated, one patch with micro-needling then application of 5 FU and excimer (Group A), and the other with excimer only (Group B). RESULTS: The treatment with the combination of micro-needling then application of 5 FU and excimer showed significant earlier response versus excimer alone. Also, the percentage of re-pigmentation was higher in the patches treated with the combination especially in the face and trunk. The combination of 5 FU after micro-needling and Excimer is more suitable for localized and focal vitiligo. CONCLUSION: Topical 5 FU after micro-needling is a promising, rapid, and cost-effective therapeutic strategy for treatment of non-segmental vitiligo It had limited side effects, and the best response was reported for lesions affecting face and trunk.

A Dual Function Antibody Conjugate Enabled Photoimmunotherapy Complements Fluorescence and Photoacoustic Imaging of Head and Neck Cancer Spheroids.

Several molecular-targeted imaging and therapeutic agents are in clinical trials for image-guided surgery and photoimmunotherapy (PIT) of head and neck cancers. In this context, we have previously reported the development, characterization, and specificity of a dual function antibody conjugate (DFAC) for multi-modal imaging and photoimmunotherapy (PIT) of EGFR over-expressing cancer cells. The DFAC reported previously and used in the present study, comprises of an EGFR targeted antibody - Cetuximab conjugated to Benzoporphyrin derivative (BPD) for fluorescence imaging and PIT, and a Si-centered naphthalocyanine dye for photoacoustic imaging. We report here the evaluation and performance of DFAC in detecting microscopic cancer spheroids by fluorescence and photoacoustic imaging along with their treatment by PIT. We demonstrate that while fluorescence imaging can detect spheroids with volumes greater than 0.049 mm3, photoacoustic imaging-based detection was possible even for the smallest spheroids (0.01 mm3), developed in the study. When subjected to PIT, the spheroids showed a dose-dependent response with smaller spheroids (0.01 and 0.018 mm3) showing a complete response with no recurrence when treated with 100 J/cm2. Together our results demonstrate the complementary imaging and treatment capacity of DFAC. This potentially enables fluorescence imaging to assess tumor presence on a macroscopic scale followed by photoacoustic imaging for delineating tumor margins guiding surgical resection and elimination of any residual microscopic disease by PIT, in a single intra-operative setting.

An Audit of Preoperative Informed Consent in Surgical Patients at a Tertiary Care Hospital in Lahore, Pakistan.

Informed consent plays a crucial role in modern clinical practice, representing a fundamental aspect of patient rights and medical ethics. The purpose of informed consent is to ensure that patients fully comprehend the procedures to which they are providing consent and the recognition that the surgeon is not guilty of battery. Moreover, clinicians safeguard themselves against potential repercussions by documenting the risks adequately conveyed to patients before performing surgery. Therefore, the significance of informed consent cannot be overstated. This survey encompassed patients from various surgical departments who underwent surgery in April 2023 at a tertiary care hospital. For the survey participants above the age of 18 were selected undergoing either emergency or elective surgical procedures. The survey employed a structured questionnaire for interviews, assessing whether patients had given informed consent before surgery. The questionnaire also inquired whether patients received information about the diagnosis, proposed surgical procedure, associated risks, and any available alternative treatment options. Furthermore, patients were asked about the proposed anesthesia type and whether the associated risks were communicated to them before the surgery. A random selection of 50 patients was done for this study, and the process of block randomization was used with the help of a computer app to reduce bias and allow the representation of the various surgical subspecialties present in the tertiary care hospital. No evidence of consent being taken was present in two patients(4%) or the document on which the consent was signed was not present in the file. Only 48% of the patients acknowledged that they fully understood the provided information. While 60% of the patients were informed about the type of anesthesia proposed, a mere 8% were provided information regarding anesthesia risks. None of the patients in the emergency setting signed the consent form themselves, regardless of their capability to do so. Conversely, only 24% of the patients in the elective setting signed the consent form themselves. The study revealed that the quality of informed consent signing in this tertiary care hospital is below average. Healthcare professionals, including doctors and staff, need education regarding the importance of informed consent and the patient's right to comprehend any procedure or intervention to which they are subjected. A shift in the paradigm of decision-making about a patient's health needs to emphasize that the patient is the most critical entity in these decisions. The main aim of the study is twofold, primarily we want to analyze the existing method of taking informed consent by comparison with the guidelines and check whether the current practice of informed consent achieves its goal of involving the patients in their treatment. Secondarily, we want to discuss the effect that patient-doctor communication might have on the delivery of the above-mentioned information.

Using COVID-19 Vaccine Attitudes on Twitter to Improve Vaccine Uptake Forecast Models in the United States: Infodemiology Study of Tweets.

BACKGROUND: Since the onset of the COVID-19 pandemic, there has been a global effort to develop vaccines that protect against COVID-19. Individuals who are fully vaccinated are far less likely to contract and therefore transmit the virus to others. Researchers have found that the internet and social media both play a role in shaping personal choices about vaccinations. OBJECTIVE: This study aims to determine whether supplementing COVID-19 vaccine uptake forecast models with the attitudes found in tweets improves over baseline models that only use historical vaccination data. METHODS: Daily COVID-19 vaccination data at the county level was collected for the January 2021 to May 2021 study period. Twitter's streaming application programming interface was used to collect COVID-19 vaccine tweets during this same period. Several autoregressive integrated moving average models were executed to predict the vaccine uptake rate using only historical data (baseline autoregressive integrated moving average) and individual Twitter-derived features (autoregressive integrated moving average exogenous variable model). RESULTS: In this study, we found that supplementing baseline forecast models with both historical vaccination data and COVID-19 vaccine attitudes found in tweets reduced root mean square error by as much as 83%. CONCLUSIONS: Developing a predictive tool for vaccination uptake in the United States will empower public health researchers and decisionmakers to design targeted vaccination campaigns in hopes of achieving the vaccination threshold required for the United States to reach widespread population protection.

Role of jargon in the patient-doctor communication in the dental healthcare sector-A systematic review and meta-analysis.

Medical terminology is useful for better communication between medical and dental professionals. Overzealous use of this terminology and use of medical terms during patient interaction hamper the complete understanding of the doctor's explanation about their health status. Nowadays, the usage of abbreviations or short terminology in health sectors has become common during all stages like the patient's initial visit, during the diagnosis, and even during the treatment plan stage. The objective was to know the commonly used jargon in the dental profession and to know the effect of the commonly used jargon on patient-doctor communication and treatment outcomes. Three major scientific databases were used as search engines PubMed, Web of Science, and Scopus by following three main search criteria, the common use of jargon in the dental profession, effect of jargon on patient-doctor communication, and treatment outcomes. An approach to meta-synthesis was used in the qualitative research methodology. With the Sandelowski and Barroso approach, meta-synthesis was carried out. Following database searches, during the years 2001 to 2022, 424 studies were gathered. Ten sources were then chosen and used in the analysis stage. Usage of jargon in dental professions has an effect on patient-doctor communication, and to an extent, it also has an effect on the treatment plan which further has its effect on treatment outcome.The correlation ratio (COR) of frequency of jargon is 0.46 (0.34; 0.57), with P value <0.0001, which indicates the presence of these issues in dental healthcare sector. The cautious use of jargon within the health profession will be beneficial in terms of professional communication with the patients and also helps in rendering better treatment to the patients.

Extranodal Diffuse Large B-Cell Lymphoma (DLBCL) Presenting as Diffuse Joint Pain: A Diagnostic Dilemma.

Diffuse Large B-Cell Lymphoma (DLBCL) of bone is a rare presentation of Non-Hodgkin Lymphoma (NHL), which remains asymptomatic or present late in clinical course as bone pain or pathological fracture. We report a case of a 15-year-old male child presenting with diffuse joint pain and swelling over his left shoulder and elbow, associated with B symptoms. Radiological examination revealed lytic lesions in multiple bones along with collection along the left iliopsoas and hip joint, suggestive of infective etiology. The diagnostic dilemma was resolved on biopsy, which confirmed DLBCL involving bones and soft tissue.

Photodynamic augmentation of oncolytic virus therapy for central nervous system malignancies.

Oncolytic viruses (OVs) have emerged as a clinical therapeutic modality potentially effective for cancers that evade conventional therapies, including central nervous system malignancies. Rationally designed combinatorial strategies can augment the efficacy of OVs by boosting tumor-selective cytotoxicity and modulating the tumor microenvironment (TME). Photodynamic therapy (PDT) of cancer not only mediates direct neoplastic cell death but also primes the TME to sensitize the tumor to secondary therapies, allowing for the combination of two potentially synergistic therapies with broader targets. Here, we created G47Δ-KR, clinical oncolytic herpes simplex virus G47Δ that expresses photosensitizer protein KillerRed (KR). Optical properties and cytotoxic effects of G47Δ-KR infection followed by amber LED illumination (peak wavelength: 585-595 nm) were examined in human glioblastoma (GBM) and malignant meningioma (MM) models in vitro. G47Δ-KR infection of tumor cells mediated KR expression that was activated by LED and produced reactive oxygen species, leading to cell death that was more robust than G47Δ-KR without light. In vivo, we tested photodynamic-oncolytic virus (PD-OV) therapy employing intratumoral injection of G47Δ-KR followed by laser light tumor irradiation (wavelength: 585 nm) in GBM and MM xenografts. PD-OV therapy was feasible in these models and resulted in potent anti-tumor effects that were superior to G47Δ-KR alone (without laser light) or laser light alone. RNA sequencing analysis of post-treatment tumor samples revealed PD-OV therapy-induced increases in TME infiltration of variable immune cell types. This study thus demonstrated the proof-of-concept that G47Δ-KR enables PD-OV therapy for neuro-oncological malignancies and warrants further research to advance potential clinical translation.

Variations of Serum CRP Levels in Periodontal Health and Diseases: A Clinico-Biochemical Study.

This study aimed to quantify serum C-reactive protein (CRP) values in periodontally healthy people and explore the relationship between serum CRP levels and chronic periodontitis, and the influence of scaling as well as root planing (SRP) on serum CRP levels. The study included 100 systemically healthy adults (n = 100; 50 males and 50 females) who were separated into two groups: Group A (control) n = 50; periodontally healthy subjects and Group B (test) n = 50; subjects with chronic periodontitis. The test group (group B) was further separated randomly into two groups: B1 (n = 25) and B2 (n = 25). The clinical parameters and serum CRP levels were measured only once in Group A and before SRP in Group B1 subjects. In Group B2 subjects the clinical parameters and serum CRP levels were measured only after two months following SRP. For group A, B1, and B2 (the readings recorded after SRP) the mean gingival index scores were 0.146, 2.437, and 1.052, respectively, while the plaque index was 0.414, 2.499, and 0.954, respectively. Probing pocket depth (PPD) and clinical attachment loss (CAL) showed statistically significant differences between three groups, with higher values in patients with periodontitis before intervention (2.196 ± 0.49; 1.490 ± 0.23), respectively. Healthy controls (Group A) had a C-reactive protein level of 0.04820 mg/dL, while group B1 (test) had 1.678 mg/dL and 0.8892 mg/dL (group B2). C-reactive protein levels were observed to be greater in the test group (groups B1 and B2), and these differences were statistically significant (p < 0.001). Chronic periodontitis enhances blood levels of systemic inflammatory markers like CRP, which has been reduced by periodontal treatment with SRP.

Dual Function Antibody Conjugates for Multimodal Imaging and Photoimmunotherapy of Cancer Cells.

Precision imaging, utilizing molecular targeted agents, is an important tool in cancer diagnostics and guiding therapies. While there are limitations associated with single mode imaging probes, multimodal molecular imaging probes enabling target visualization through complementary imaging technologies provides an attractive alternative. However, there are several challenges associated with designing molecular probes carrying contrast agents for complementary multimodal imaging. Here, we propose a dual function antibody conjugate (DFAC) comprising an FDA approved photosensitizer Benzoporphyrin derivative (BPD) and a naphthalocyanine-based photoacoustic dye (SiNc(OH)) for multimodal infrared (IR) imaging. While fluorescence imaging, through BPD, provides sensitivity, complementing it with photoacoustic imaging, through SiNc(OH), provides a depth-resolved spatial resolution much beyond the optical diffusion limits of fluorescence measurements. Through a series of in vitro experiments, we demonstrate the development and utilization of DFACs for multimodal imaging and photodynamic treatment of squamous cell carcinoma (A431) cell line. The proposed DFACs have potential use in precision imaging applications such as guiding tumor resection surgeries and photodynamic treatment of residual microscopic disease thereby minimizing local recurrence. The data demonstrated in this study merits further investigation for its preclinical and clinical translation.

Differences in Outcomes between Patellar Dislocations Managed in Emergent versus Non-Emergent Care Settings.

Patellar dislocations occur at a much higher rate in military than civilian populations. Past population-level studies have shown that surgical management is as good as or superior to conservative care and may reduce future reoccurrences. Although in acute cases and in civilian clinics, patellar dislocations are usually managed first in an emergent care setting, previous work suggests this can lead to increased costs. This study compared differences in downstream care type and intensity of services based on whether initial care occurred in emergent or non-emergent care settings. In our sample of 1,523 Military Health System (MHS) beneficiaries with patellar dislocation and 2-year follow-up, we found non-significant differences in costs, intensity of services, and rates of surgical repair regardless of whether the patient was initially seen in an emergent versus non-emergent care setting. Although we found significant increases in the use of imaging, patellar dislocation-related medical visits, and frequency of closed treatment approaches in emergent care settings, these values were very small and likely not clinically significant. These findings, which included all the patellar dislocations reported across the entire MHS in a 24-month period, suggest that neither emergent nor non-emergent care settings are likely to influence the long-term care received by the individual.