Oxygen-defect bismuth oxychloride nanosheets for ultrasonic cavitation effect enhanced sonodynamic and second near-infrared photo-induced therapy of breast cancer.

Sonodynamic therapy (SDT) relies heavily on the presence of oxygen to induce cell death. Its effectiveness is thus diminished in the hypoxic regions of tumor tissue. To address this issue, the exploration of ultrasound-based synergistic treatment modalities has become a significant research focus. Here, we report an ultrasonic cavitation effect enhanced sonodynamic and 1208 nm photo-induced cancer treatment strategy based on thermoelectric/piezoelectric oxygen-defect bismuth oxychloride nanosheets (BNs) to realize the high-performance eradication of tumors. Upon ultrasonic irradiation, the local high temperature and high pressure generated by the ultrasonic cavitation effect combined with the thermoelectric and piezoelectric effects of BNs create a built-in electric field. This facilitates the separation of carriers, increasing their mobility and extending their lifetimes, thereby greatly improving the effectiveness of SDT and NIR-Ⅱ phototherapy on hypoxia. The Tween-20 modified BNs (TBNs) demonstrate ∼88.6 % elimination rate against deep-seated tumor cells under hypoxic conditions. In vivo experiments confirm the excellent antitumor efficacy of TBNs, achieving complete tumor elimination within 10 days with no recurrences. Furthermore, due to the high X-ray attenuation of Bi and excellent NIR-Ⅱ absorption, TBNs enable precise cancer diagnosis through photoacoustic (PA) imaging and computed tomography (CT).

Tumor microenvironment ameliorative and adaptive nanoparticles with photothermal-to-photodynamic switch for cancer phototherapy.

The notorious tumor microenvironment (TME) usually becomes more deteriorative during phototherapeutic progress that hampers the antitumor efficacy. To overcome this issue, we herein report the ameliorative and adaptive nanoparticles (TPASIC-PFH@PLGA NPs) that simultaneously reverse hypoxia TME and switch photoactivities from photothermal-dominated state to photodynamic-dominated state to maximize phototherapeutic effect. TPASIC-PFH@PLGA NPs are designed by incorporating oxygen-rich liquid perfluorohexane (PFH) into the intraparticle microenvironment to regulate the intramolecular motions of AIE photosensitizer TPASIC. TPASIC exhibits a unique aggregation-enhanced reactive oxygen species (ROS) generation feature. PFH incorporation affords TPASIC the initially dispersed state, thus promoting active intramolecular motions and photothermal conversion efficiency. While PFH volatilization leads to nanoparticle collapse and the formation of tight TPASIC aggregates with largely enhanced ROS generation efficiency. As a consequence, PFH incorporation not only currently promotes both photothermal and photodynamic efficacies of TPASIC and increases the intratumoral oxygen level, but also enables the smart photothermal-to-photodynamic switch to maximize the phototherapeutic performance. The integration of PFH and AIE photosensitizer eventually delivers more excellent antitumor effect over conventional phototherapeutic agents with fixed photothermal and photodynamic efficacies. This study proposes a new nanoengineering strategy to ameliorate TME and adapt the treatment modality to fit the changed TME for advanced antitumor applications.

Engineering Two-dimensional tungsten-doped molybdenum selenide transformed conformational nanoarchitectonics: Trimodal therapeutic nanoagents for enhanced synergistic Photothermal/Chemodynamic/Chemotherapy of breast carcinoma.

Two-dimensional transition metal dichalcogenides (TMDCs) exhibit promising photothermal therapy (PTT) and chemodynamic therapy (CDT) for anti-tumour treatment. Herein, we proposed an engineering strategy to regulate the lattice structure of tungsten-doped molybdenum selenide (MoxW1-xSe2) transformed conformational nanoarchitectonics using a microwave-assisted solvothermal method for enhancing peroxidase (POD)-like catalytic performance by adjusting the ratio of molybdenum (Mo) and tungsten (W). Furthermore, the optimised Mo0.8W0.2Se2 nanoflakes surface was modified with chitosan (CHI) for improved biocompatibility and nanocatalytic efficacy, then the obtained CHI-Mo0.8W0.2Se2 subsequently loaded the chemotherapeutic drug mitoxantrone (MTO) for enhanced 4 T1 cells killing ability, shortly denoted as CHI-Mo0.8W0.2Se2-MTO for PTT-augmented CDT and chemotherapy (CT). A series of performance validations successfully showed that electrons tend to transfer from W to Mo in CHI-Mo0.8W0.2Se2, which resulted in superior POD-like activity (Km = 0.038 mM) of CHI-Mo0.8W0.2Se2 compared with that of horseradish peroxidase. Furthermore, CHI-Mo0.8W0.2Se2-MTO with excellent photothermal conversion efficiency (PCE=63.2 %) in the near-infrared (NIR) region could further promote endogenous •OH generation and MTO controlled release within solid tumours. In vivo studies confirmed the successful achievement of synergistic therapeutic effects (tumour inhibition rate of over 90 %) with minimised side effects. Versatile therapeutic nanoagents hold great potential for personalised therapy of breast cancer and will find their way to the pharmaceutical field.

Photothermal and enhanced chemodynamic reinforced anti-tumor therapy based on PDA@POM nanocomposites.

Chemodynamic therapy (CDT) and photothermal therapy (PTT) have both demonstrated considerable efficacy in the tumor treatment individually, owing to their non-invasive nature and excellent selectivity. However, due to the propensity of tumors for metastasis and recurrence, a singular therapeutic approach falls short of achieving optimal treatment outcomes. Polydopamine (PDA) has excellent photothermal conversion ability and polyoxometalates (POMs) possess diverse enzymatic activities. Here, we synthesized PDA@POM nanospheres comprising polydopamine-coated Tungsten-based polyoxometalate (W-POM). These nanospheres leverage dual enzymatic activities that synergistically enhance both chemodynamic and photothermal therapies for tumor treatment. The PDA-mediated PTT effect enables precise tumor cell destruction, while the W-POM nanozymes catalyzes the generation of highly toxic reactive oxygen species (ROS) from hydrogen peroxide within tumor cells through a Fenton-like reaction, which mitigates tumor hypoxia and induces tumor cell death. This synergistic photothermal catalytic therapy shows enhanced efficacy in tumor suppression, providing a promising new approach for tumor treatment.

Fe-doped biodegradable dendritic mesoporous silica nanoparticles for starvation therapy and photothermal-enhanced cascade catalysis in tumor therapy.

Combination therapies have attracted significant attention because they address the limitations of monotherapy while improving overall efficacy. In this study, we designed a novel nanoplatform, named GOx@Fe-DMSN@PDA (GFDP), by integrating Fe2+ into dendritic mesoporous silica nanoparticles (DMSN) and selecting glucose oxidase (GOx) as the model drug loaded into the DMSN pores. Additionally, we coated the surface of the DMSN with polydopamine (PDA) to confer pH/near infrared (NIR) light-responsive controlled-release behavior and photothermal therapy (PTT). The introduction of Fe2+ into the DMSN framework greatly improved biodegradability and enhanced the peroxidase (POD)-like activity of GFDP. In addition, GOx could consume glucose and generate hydrogen peroxide (H2O2) within tumor cells to facilitate starvation therapy and enhance cascade catalysis. The PDA coating provided the DMSN with an intelligent response release ability, promoting efficient photothermal conversion and achieving the PTT effect. Cellular tests showed that under NIR light irradiation, GFDP exhibited a synergistic effect of PTT-enhanced starvation therapy and cascade catalysis, with a half-maximal inhibitory concentration (IC50) of 2.89 µg/mL, which was significantly lower than that of GFDP without NIR light irradiation (18.29 µg/mL). The in vivo anti-tumor effect indicated that GFDP could effectively accumulate at the tumor site for thermal imaging and showed remarkable synergistic therapeutic effects. In summary, GFDP is a promising nanoplatform for multi-modal combination therapy that integrates starvation therapy, PTT, and cascade catalysis.

Targeted nanoprobe for magnetic resonance imaging-guided enhanced antitumor via synergetic photothermal/immunotherapy.

Synergistic photothermal/immunotherapy has garnered significant attention for its potential to enhance tumor therapeutic outcomes. However, the fabrication of an intelligent system with a simple composition that simultaneously exerts photothermal/immunotherapy effect and imaging guidance function still remains a challenge. Herein, a glutathione (GSH)-responsive theranostic nanoprobe, named HA-MnO2/ICG, was elaborately constructed by loading photothermal agent (PTA) indocyanine green (ICG) onto the surface of hyaluronic acid (HA)-modified manganese dioxide nanosheets (HA-MnO2) for magnetic resonance (MR) imaging-guided synergetic photothermal/immuno-enhanced therapy. In this strategy, HA-MnO2 nanosheets were triggered by the endogenous GSH in tumor microenvironment to generate Mn2+ for MR imaging, where the longitudinal relaxation rate of HA-MnO2/ICG was up to 14.97 mM-1s-1 (∼24 times than that found in a natural environment), demonstrating excellent intratumoral MR imaging. Moreover, the HA-MnO2/ICG nanoprobe demonstrates remarkable photothermal therapy (PTT) efficacy, generating sufficient heat to induce immunogenic cell death (ICD) within tumor cells. Meanwhile the released Mn2+ ions from the nanosheets function as potent immune adjuvants, amplifying the immune response against cancer. In vivo experiments validated that HA-MnO2/ICG-mediated PTT was highly effective in eradicating primary tumors, while simultaneously enhancing immunogenicity to prevent the growth of distal metastasis. This hybrid HA-MnO2/ICG nanoprobe opened new avenues in the design of MR imaging-monitored PTT/immuno-enhanced synergistic therapy for advanced cancer.

Enzymatic interlocking aptamer-micelles for enhanced cellular internalization and nucleus-targeted cancer phototherapy.

Multifunctional micelles that permit both diagnosis and treatment present enormous advantage and potential for precision medicine. However, the inherent complexities and structural instability of these systems often cause unsatisfactory targeting and therapeutic performances. Herein, by ingenious design of a 2,5-bis(2-thienyl)pyrrole (SNS) modifier to covalently link with AS1411 aptamer and lipid segment, a simple strategy is proposed for one-step enzymatic preparation of interlocked aptamer-micelle (IApM) under bio-friendly conditions. The interlocked poly(SNS) skeleton in IApM can not only stabilize the micelle structure but also enhance near-infrared (NIR) absorption ability, thus further enhancing cellular internalization and photothermal therapy. In addition, the multivalent AS1411 aptamers tethered in the hydrophilic shell can simultaneously increase the specific binding affinity of DNA micelles and induce nucleus-targeted accumulation for DNA damage-triggered apoptosis. This DNA micelle achieves "best of both worlds" with enhanced biostability for cellular internalization and improved NIR photothermal conversion efficiency for nucleus-targeted therapy, which provides a promising formulation strategy for precision cancer treatment.

Mild near-infrared laser-triggered photo-immunotherapy potentiates immune checkpoint blockade via an all-in-one theranostic nanoplatform.

One of the primary challenges for immune checkpoint blockade (ICB)-based therapy is the limited infiltration of T lymphocytes (T cells) into tumors, often referred to as immunologically "cold" tumors. A promising strategy to enhance the anti-tumor efficacy of ICB is to increase antigen exposure, thereby enhancing T cell activation and converting "cold" tumors into "hot" ones. Herein, we present an innovative all-in-one therapeutic nanoplatform to realize local mild photothermal- and photodynamic-triggered antigen exposure, thereby improving the anti-tumor efficacy of ICB. This nanoplatform involves conjugating programmed death-ligand 1 antibody (aPD-L1) with gadolinium-doped near-infrared (NIR)-emitting carbon dots (aPD-L1@GdCDs), which displays negligible cytotoxicity in the absence of light. But under controlled NIR laser irradiation, the GdCDs produce combined photothermal and photodynamic effects. This not only results in tumor ablation but also induces immunogenic cell death (ICD), facilitating enhanced infiltration of CD8+ T cells in the tumor area. Importantly, the combination of aPD-L1 with photothermal and photodynamic therapies via aPD-L1@GdCDs significantly boosts CD8+ T cell infiltration, reduces tumor size, and improves anti-metastasis effects compared to either GdCDs-based phototherapy or aPD-L1 alone. In addition, the whole treatment process can be monitored by multi-modal fluorescence/photoacoustic/magnetic resonance imaging (FLI/PAI/MRI). Our study highlights a promising nanoplatform for cancer diagnosis and therapy, as well as paves the way to promote the efficacy of ICB therapy through mild photothermal- and photodynamic-triggered immunotherapy.

Combined Photothermal Chemotherapy for Effective Treatment Against Breast Cancer in Mice Model.

Introduction: Breast cancer ranks among the most prevalent cancers in women, characterized by significant morbidity, disability, and mortality. Presently, chemotherapy is the principal clinical approach for treating breast cancer; however, it is constrained by limited targeting capability and an inadequate therapeutic index. Photothermal therapy, as a non-invasive approach, offers the potential to be combined with chemotherapy to improve tumor cellular uptake and tissue penetration. In this research, a mesoporous polydopamine-coated gold nanorod nanoplatform, encapsulating doxorubicin (Au@mPDA@DOX), was developed. Methods: This nanoplatform was constructed by surface coating mesoporous polydopamine (mPDA) onto gold nanorods, and doxorubicin (DOX) was encapsulated in Au@mPDA owing to π-π stacking between mPDA and DOX. The dynamic diameter, zeta potential, absorbance, photothermal conversion ability, and drug release behavior were determined. The cellular uptake, cytotoxicity, deep penetration, and anti-tumor effects were subsequently investigated in 4T1 cells. After that, fluorescence imaging, photothermal imaging and pharmacodynamics studies were utilized to evaluate the anti-tumor effects in tumor-bearing mice model. Results: This nanoplatform exhibited high drug loading capacity, excellent photothermal conversion and, importantly, pH/photothermal dual-responsive drug release behavior. The in vitro results revealed enhanced photothermal-facilitated cellular uptake, drug release and tumor penetration of Au@mPDA@DOX under near-infrared irradiation. In vivo studies confirmed that, compared with monotherapy with either chemotherapy or photothermal therapy, the anti-tumor effects of Au@mPDA@DOX are synergistically improved. Conclusion: Together with good biosafety and biocompatibility, the Au@mPDA@DOX nanoplatform provides an alternative method for safe and synergistic treatment of breast cancer.

Dermatologic Procedures for the Treatment of Seborrheic Dermatitis.

BACKGROUND: This paper examines alternative procedural interventions for Seborrheic Dermatitis (SD), aiming to offer clinicians more treatment options and encourage further research. METHOD: A search was conducted on PubMed using specific search terms related to SD and various dermatological procedures. Studies in English, focusing on SD in human patients, and in-office treatments were included. Data were analyzed for procedure type, effectiveness, and side effects. RESULTS: Nine studies were reviewed, covering phototherapy, indole-3-acetic acid photodynamic therapy (IAA-PDT), Picosecond Nd:YAG laser, botulinum toxin (BoNT) injections, triamcinolone injections, hair growth factor therapy, and precision cryotherapy. Most showed significant efficacy in small cohorts with high patient satisfaction. Hair growth factor therapy had long-term benefits, while narrow-band ultraviolet B phototherapy showed relapse within one month. Intense pulsed light with supramolecular salicylic acid, IAA-PDT, and laser therapy reduced sebum output and Malassezia furfur. Triamcinolone injections were effective against SD's immunological aspects. Hair growth factor therapy and precision cryotherapy have been successfully used to treat scalp SD. The role of BoNT in SD is still being explored; however, current evidence does not support its use. CONCLUSION: Limited data reveal the need for further research on dermatological procedures for SD. These methods show promise for better patient compliance but face challenges such as cost, variable effectiveness, and unknown long-term safety. Future research should focus on protocol standardization and comprehensive evaluation of long-term outcomes. J Drugs Dermatol. 2024;23(10):819-824. doi:10.36849/JDD.8116.

Duration of a standard phototherapy course in jaundiced newborns with no neurotoxicity risk.

In this study, we aimed to determine an ordinary/empiric/standard phototherapy treatment protocol for duration without controlling total serum bilirubin (TSB) levels after initiating phototherapy in early-term and full-term jaundiced newborns who had no hyperbilirubinemia neurotoxicity risk factors. We compared two groups, each receiving either 24 h (Group I) or 18 h (Group II) of continuous phototherapy in terms of demographic characteristics and efficacy (rate of decrease in TSB levels with phototherapy). No control TSB measurements were performed in the study groups until the end of phototherapy for the predetermined durations. Declines in TSB after phototherapy were significantly greater in Group I than in Group II, both in terms of mg/dl (11.81 ± 2.93 mg/dl vs. 10.75 ± 2.48 mg/dl, P = .0008) and percentage (56.71 ± 9.06% vs. 52.86 ± 8.37%, P = .0002). However, the rate of TSB reduction after phototherapy in mg/dl/h (0.59 ± 0.13 mg/dl/h vs. 0.49 ± 0.12 mg/dl/h, P = <.0001) and percentage per hour (2.93 ± 0.37% vs. 2.36 ± 0.46%, P = <.0001) were significantly higher in Group II than in Group I. This indicates an inverse time-response relationship between the duration of phototherapy and the response rate in the study groups. Although the 24-h phototherapy course showed greater efficacy concerning the primary bilirubin outcome measures (decline in TSB in mg/dl and %), the 18-h course of phototherapy treatment provided better hourly outcomes and reached its saturation point around the 18th hour. Therefore, an 18-h phototherapy without TSB monitoring until the end of the phototherapy should be considered for jaundiced newborns lacking neurotoxicity risk factors.

Spacer Twisting Strategy to Realize Ultrabright Near-Infrared II Polymer Nanoparticles for Fluorescence Imaging-Guided Tumor Phototheranostics.

Conjugated polymers are becoming popular near-infrared II (NIR-II) phototheranostic agents (PTAs) due to their numerous advantages, such as high photostability, large molar extinction coefficients, and excellent photothermal properties. However, the strong π-π interactions between the chains of the conjugated polymers resulted in their generally low NIR-II emission quantum yields (QY). Therefore, the synthesis of conjugated polymers with high QY is an interesting but challenging task. Herein, we proposed a spacer twisting strategy to realize ultrabright NIR-II polymer nanoparticles for fluorescence imaging-guided tumor phototheranostics. Theoretical calculations indicated that the polymer PY-IT has the largest dihedral angle between the largely π-conjugated skeleton and the spacer, which can effectively inhibit intermolecular π-π stacking, resulting in an improved QY as high as 16.5% in nanoparticles. In addition, PY-IT NPs can effectively perform NIR-II imaging and photothermal treatment of tumors. The work presents some valuable guides for achieving ultrabright NIR-II polymeric PTAs with high QY.

Stable triangle: nanomedicine-based synergistic application of phototherapy and immunotherapy for tumor treatment.

In recent decades, cancer has posed a challenging obstacle that humans strive to overcome. While phototherapy and immunotherapy are two emerging therapies compared to traditional methods, they each have their advantages and limitations. These limitations include easy metastasis and recurrence, low response rates, and strong side effects. To address these issues, researchers have increasingly focused on combining these two therapies by utilizing a nano-drug delivery system due to its superior targeting effect and high drug loading rate, yielding remarkable results. The combination therapy demonstrates enhanced response efficiency and effectiveness, leading to a preparation that is highly targeted, responsive, and with low recurrence rates. This paper reviews several main mechanisms of anti-tumor effects observed in combination therapy based on the nano-drug delivery system over the last five years. Furthermore, the challenges and future prospects of this combination therapy are also discussed.

Symmetrically Fluorinated D-π-A Structured Cyanine Dye for Highly Efficient NIR-II Imaging-Guided Cancer Phototheranostics.

Near-infrared-II (NIR-II) fluorescence imaging-guided photothermal therapy (PTT) represents a cutting-edge approach for precise tumor diagnosis and treatment, providing real-time therapeutic efficacy evaluation. However, a significant challenge lies in the creation of phototheranostic agents that provide robust imaging and efficient photothermal conversion. To address this, a donor-π-acceptor (D-π-A) structure heptamethine cyanine derivative, IR1116, that confers a strong intramolecular charge transfer effect is developed. To enhance its applicability, IR1116 is formulated with DSPE-PEG to create a water-dispersible NIR-II phototheranostic nanoheater, NPIR1116. This nanoheater benefits from the incorporation of an electron-withdrawing group, leading to reduced photooxidation activity and significantly improved photostability. NPIR1116 exhibits strong NIR-II absorption and fluorescence, peaking at 1004 and 1116 nm, respectively, as well as a photothermal conversion efficiency of 79% under 1064 nm lasers. In vitro and in vivo studies showed the efficacy of NPIR1116 in tumor imaging via NIR-II fluorescence and its ability to effectively induce tumor cell apoptosis under 1064 nm laser irradiation. These findings underscore the potential of NPIR1116 in NIR-II fluorescence imaging-guided PTT for tumor treatment, paving the way for further advancements in NIR-II dye development and bioimaging technologies.

2023 guidelines on the management of psoriasis by the Dermatological Society of Singapore.

Introduction: Psoriasis is a multisystem, chronic, inflammatory dermatological disease. In routine clinical practice, the management of psoriasis varies significantly. The current study aimed to develop a set of practice guidelines relevant to dermatology practice in Singapore. Method: The Psoriasis Therapeutic Guidelines Workgroup, comprising members of the Dermato-logical Society of Singapore with a subspecialisation in psoriasis, was convened to develop the guidelines. Clinical questions on selected topics were generated and refined by the workgroup. A literature search using PubMed was performed on their assigned topics from June 2013 to December 2023. The articles were included and graded based on the level of evidence. Results: The guidelines address topics ranging from clinical assessment to practical considerations in the management of mild, moderate and severe psoriasis, including delivery of care, referrals to specialists and adherence to treatment. The recommended therapies include phototherapy, methotrexate, acitretin, cyclosporine; apremilast; topical corticoste-roids, calcipotriol, topical calcineurin inhibitors; and biologics (i.e. adalimumab, infliximab, secukinumab, ixekizumab, ustekinumab, etanercept) either in combina-tion or as monotherapy. Common therapeutic concerns relating to biologic use were addressed. Recommendations on generalised pustular psoriasis, palmoplantar pustular psoriasis and psoriatic arthritis were also made. Patients on systemic therapy would receive appropriate vaccine counselling. Therapeutic implica-tions in special populations, such as pregnant/ lactating women, children, the elderly, those undergo-ing surgery and those suffering from specific infections and cancer were addressed. Conclusion: These guidelines were developed for dermatologists, family physicians, rheumatologists and other specialists to support their selection of appropriate management options.

Rate of glucose-6-phosphate dehydrogenase deficiency in neonatal indirect hyperbilirubinemia at a private tertiary centre.

OBJECTIVES: To investigate the rate of hospitalized neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency presented with indirect hyperbilirubinemia at a private tertiary center in Al-Ahsa, Saudi Arabia, over 4 years and to compare the characteristics of G6PD-deficient and normal neonates admitted for indirect hyperbilirubinemia. METHODS: The retrospective case control study was carried out at Almoosa Specialist Hospital, Al-Ahsa, Saudi Arabia. Data were collected from Yassasi Medical System from 2018-2021 and finalized in 2024. The study included 2 groups: G6PD-normal and G6PD-deficient neonates with indirect hyperbilirubinemia not having recognizable triggers of hemolysis. The analysis focused on serum bilirubin levels, direct bilirubin levels, hematocrit levels, hemoglobin levels, reticulocyte percentage, G6PD levels, duration of phototherapy, and the need for exchange transfusion. RESULTS: The study enrolled 3200 neonates with hyperbilirubinemia, of whom 274 met inclusion criteria. A total of 103 (37.6%) neonates were G6PD-deficient, with 77 (74.8%) being male and 26 (25.2%) female. Glucose-6-phosphate dehydrogenase-deficient neonates exhibited significantly higher initial total bilirubin levels and earlier sampling times. There was no significant correlation between G6PD deficiency and hematocrit or hemoglobin levels in hyperbilirubinemic neonates, but 4 neonates required exchange transfusion, demonstrating statistical significance (p=0.009). CONCLUSION: High rate of G6PD deficiency in neonates with indirect hyperbilirubinemia, requiring close monitoring to prevent exchange transfusions, with no significant differences in hematocrit or hemoglobin levels.

Trends in Phototherapy Utilization, Payments, and Geographic Distribution: An Analysis of United States Medicare Part B From 2000 to 2021.

BACKGROUND: Trends in phototherapy utilization in the context of new therapeutics have not been evaluated. OBJECTIVE: This study aimed to evaluate phototherapy utilization, payments, and geographic distribution for Medicare beneficiaries from 2000 to 2021. PATIENTS/METHODS: A longitudinal analysis of the Medicare Part B National Summary Data Files was conducted to obtain phototherapy utilization and payment amounts. Medicare Physician & Other Practitioners by Provider and Service datasets were used to determine provider type and geographic distribution. RESULTS: Between 2000 and 2021, total Medicare phototherapy volume increased from 335,152 to 621,850, correlating with a 3.0% annual growth rate (5.0% between 2000 and 2015, -3.1% between 2016 and 2021). Ultraviolet B phototherapy represented the majority of use, rising from 68.1% in 2000 to 78.0% in 2021. Psoralens plus ultraviolet A decreased by 11.3% annually, while laser treatments increased by 17.3%. Between 2013 and 2021, the number of clinics offering phototherapy declined; facilities were available in only 9.9% of counties, mainly clustered along both coasts and east of the Mississippi. CONCLUSIONS: Overall, phototherapy continues to be an important therapeutic option. Limited access in non-urban areas remains a significant challenge, and further work is necessary to both evaluate this impact and reduce disparities.

Photoimmunotherapy using indocyanine green-loaded Codium fragile polysaccharide and chitosan nanoparticles suppresses tumor growth and metastasis.

Metastasis and recurrence are the main challenges in cancer treatment. Among various therapeutic approaches, immunotherapy holds promise for preventing metastasis and recurrence. In this study, we evaluated the efficacy of treating primary cancer and blocking metastasis and recurrence with photo-immunotherapeutic nanoparticles, which were synthesized using two types of charged polysaccharides. Codium fragile polysaccharide (CFP), which exhibits immune-stimulating properties and carries a negative charge, was combined with positively charged chitosan to synthesize nanoparticles. Additionally, indocyanine green (ICG), a photosensitizer, was loaded inside these particles and was referred to as chitosan-CFP-ICG (CC-ICG). Murine colon cancer cells (CT-26) internalized CC-ICG, and subsequent 808-nanometer laser irradiation promoted apoptotic/necrotic cell death. Moreover, intratumoral injection of CC-ICG, with 808-nanometer laser irradiation eliminated CT-26 tumors in mice. Rechallenged lung metastases of CT-26 cancer were inhibited by dendritic cell activation-mediated cytotoxic T lymphocyte stimulation in mice cured by CC-ICG. These results demonstrated that CC-ICG is a natural tumor therapeutic with the potential to treat primary tumors and suppress metastasis and recurrence.

Circadian re-set repairs long-COVID in a prodromal Parkinson's parallel: a case series.

BACKGROUND: In this case series, results from daily visual exposure to intense polychromatic light of 2000 to 4000 LUX is presented. Bright light treatment is a standard procedure for treating seasonal affective disorder and prodromal Parkinson's disease with high success. With the post-encephalitic symptoms of long-COVID closely approximating those of prodromal Parkinson's disease, we treated insomnia and sleep-related parameters in these patients, including total sleep, number of awakenings, tendency to fall back to sleep, and fatigue, to determine whether mending sleep could improve quality of life. CASE PRESENTATION: We present three female and two male Caucasian patients aged 42-70 years with long-COVID that persisted from 12 weeks to 139 weeks after contracting coronavirus disease. CONCLUSION: A light presentation protocol was adapted for long-COVID that not only restored sleep in all patients, but also unexpectedly repaired the depression, anxiety, and cognitive changes (brain fog) as well. A robust pattern of recovery commencing 4-5 days after treatment and was maintained for weeks to months without relapse. These preliminary findings represent a novel, minimally invasive approach for managing the most debilitating symptoms of long-COVID, making it an ideal candidate for the drug hypersensitive, post-encephalitic brain. That a compromised circadian mechanism seen in Parkinson's disease may also underlie post-encephalitic long-COVID implicates a compromised role of the circadian system in these disorders.