Severe Hyperkalemia Masquerading as Acute Ischemic Stroke: A Case Report.

Severe hyperkalemia usually presents as cardiac or neurologic manifestations. We report a case of a 63-year-old Caucasian woman, who was admitted to Namazi Hospital, affiliated with Shiraz University of Medical Sciences (Shiraz, Iran) in August 2019. The patient suffered from left-sided weakness and slurred speech for one hour prior to admission. Initially, the patient was treated for acute ischemic stroke, and an intravenous recombinant tissue plasminogen activator (IV-rTPA) was prescribed. However, further investigations showed severe hyperkalemia. Hemiparesis and slurred speech improved significantly with appropriate management of hyperkalemia. To the best of our knowledge, this is the first case of hyperkalemia masquerading as acute ischemic stroke without evidence of concomitant central nervous system malignancies, large vessel atherosclerosis, or recreational drug abuse. Stroke mimics due to hyperkalemia should be considered in any patient with simultaneous sudden onset of focal neurologic deficits and tall peaked T waves, particularly in the context of renal failure and a history of potassium-sparing drug use.

Clinical characteristics, radiological features and prognostic factors of transverse myelitis following COVID-19 vaccination: A systematic review.

BACKGROUND: Since introducing COVID-19 vaccines, many neurological complications such as acute transverse myelitis have been reported in the literature. This study aims to identify the clinical characteristics, radiological findings, and prognostic factors in patients with COVID-19 vaccine-associated transverse myelitis (TM). METHODS: We systematically reviewed Scopus, Pubmed, Cochrane library, Google Scholar, and preprint databases using appropriate keywords from inception till 8th April 2022. Besides, we manually searched the reference lists of the included studies and relevant previous reviews. RESULTS: We included 28 studies identifying 31 post-COVID-19 vaccination myelitis patients (17 female and 14 male). The mean age of the included patients was 52±19 years. ChAdOx1 nCoV-19 vaccine (Oxford-AstraZeneca) was the most common type of vaccine in association with myelitis (12 out of 31), followed by Pfizer (8 out of 31), Moderna (7 out of 31), Sinopharm (3 out of 31), and Janssen vaccine (1 out of 31). The myelitis occurred in 24 and 7 patients after administering the first and second dose of the vaccine, respectively. 21 and 10 patients had good recovery (Modified Rankin Score (MRS) <3 at the follow-up) and poor recovery (MRS≥3 at the follow-up) from myelitis, respectively. Age (OR 1.09, 95%CI 1.01-1.18, pvalue 0.02), and MRS at admission (OR 17.67, 95%CI 1.46-213.76, pvalue 0.024) were two independent risk factors for poor recovery from myelitis. CONCLUSION: The patients with higher age and MRS at admission had a worse prognosis and needed timely and more aggressive therapeutic strategies.

Surface enhanced deep Raman detection of cancer tumour through 71 mm of heterogeneous tissue.

Detection of solid tumours through tissue- from depths relevant to humans- has been a significant challenge for biomedical Raman spectroscopy. The combined use of surface enhanced Raman scattering (SERS) imaging agents with deep Raman spectroscopy (DRS), i.e., surface enhanced deep Raman spectroscopy (SEDRS), offer prospects for overcoming such obstacles. In this study, we investigated the maximum detection depth through which the retrieval of SERS signal of a passively targeted biphenyl-4-thiol tagged gold nanoparticle (NP) imaging agent, injected subcutaneously into a mouse bearing breast cancer tumour, was possible. A compact 830 nm set-up with a hand-held probe and the flexibility of switching between offset, transmission and conventional Raman modalities was developed for this study. In vivo injection of the above SERS NP primary dose allowed surface tumour detection, whereas additional post mortem NP booster dose was required for detection of deeply seated tumours through heterogeneous animal tissue (comprising of proteins, fat, bone, organs, blood, and skin). The highest detection depth of 71 mm was probed using transmission, translating into a ~40% increase in detection depth compared to earlier reports. Such improvements in detection depth along with the inherent Raman chemical sensitivity brings SEDRS one step closer to future clinical cancer imaging technology.

Nanoparticle-Mediated Photothermal Therapy Limitation in Clinical Applications Regarding Pain Management.

The development of new effective cancer treatment methods has attracted much attention, mainly due to the limited efficacy and considerable side effects of currently used cancer treatment methods such as radiation therapy and chemotherapy. Photothermal therapy based on the use of plasmonically resonant metallic nanoparticles has emerged as a promising technique to eradicate cancer cells selectively. In this method, plasmonic nanoparticles are first preferentially uptaken by a tumor and then selectively heated by exposure to laser radiation with a specific plasmonic resonant wavelength, to destroy the tumor whilst minimizing damage to adjacent normal tissue. However, several parameters can limit the effectiveness of photothermal therapy, resulting in insufficient heating and potentially leading to cancer recurrence. One of these parameters is the patient's pain sensation during the treatment, if this is performed without use of anesthetic. Pain can restrict the level of applicable laser radiation, cause an interruption to the treatment course and, as such, affect its efficacy, as well as leading to a negative patient experience and consequential general population hesitancy to this type of therapy. Since having a comfortable and painless procedure is one of the important treatment goals in the clinic, along with its high effectiveness, and due to the relatively low number of studies devoted to this specific topic, we have compiled this review. Moreover, non-invasive and painless methods for temperature measurement during photothermal therapy (PTT), such as Raman spectroscopy and nanothermometry, will be discussed in the following. Here, we firstly outline the physical phenomena underlying the photothermal therapy, and then discuss studies devoted to photothermal cancer treatment concerning pain management and pathways for improved efficiency of photothermal therapy whilst minimizing pain experienced by the patient.

Spatially Offset Raman Spectroscopy-How Deep?

Spatially offset Raman spectroscopy (SORS) is a technique for interrogating the subsurface composition of turbid samples noninvasively. This study generically addresses a fundamental question relevant to a wide range of SORS studies, which is how deep SORS probes for any specific spatial offset when analyzing a turbid sample or, in turn, what magnitude of spatial offset one should select to probe a specific depth. This issue is addressed by using Monte Carlo simulations, under the assumption of negligible absorption, which establishes that the key parameter governing the extent of the probed zone for a point-like illumination and point-like collection SORS geometry is the reduced scattering coefficient of the medium. This can either be deduced from literature data or directly estimated from a SORS measurement by evaluating the Raman intensity profile from multiple spatial offsets. Once this is known, the extent of the probed zone can be determined for any specific SORS spatial offset using the Monte Carlo simulation results presented here. The proposed method was tested using experimental data on stratified samples by analyzing the signal detected from a thin layer that was moved through a stack of layers using both non-absorbing and absorbing samples. The proposed simple methodology provides important additional information on SORS measurements with direct relevance to a wide range of SORS applications including biomedical, pharmaceutical, security, forensics, and cultural heritage.

Estimating the Reduced Scattering Coefficient of Turbid Media Using Spatially Offset Raman Spectroscopy.

We propose a new method for estimating the reduced scattering coefficient, µs', of turbid homogeneous samples using Spatially Offset Raman Spectroscopy (SORS). The concept is based around the variation of Raman signal with SORS spatial offset that is strongly µs'-dependent, as such, permitting the determination of µs'. The evaluation is carried out under the assumptions that absorption is negligible at the laser and Raman wavelengths and µs' is approximately the same for those two wavelengths. These conditions are often satisfied for samples analyzed in the NIR region of the spectrum where SORS is traditionally deployed. Through a calibration procedure on a PTFE model sample, it was possible to estimate the µs' coefficient of different turbid samples with an error (RMSEP) below 18%. The knowledge of µs' in the NIR range is highly valuable for facilitating accurate numerical simulations to optimize illumination and collection geometries in SORS, to derive in-depth information about the properties of SORS measurements or in other photon applications, dependent on photon propagation in turbid media with general impact across fields such as biomedical, pharmaceutical, security, forensic, and cultural sciences.

Treatment of Breast Cancer-Bearing BALB/c Mice with Magnetic Hyperthermia using Dendrimer Functionalized Iron-Oxide Nanoparticles.

The development of novel nanoparticles for diagnostic and therapeutic applications has been one of the most crucial challenges in cancer theranostics for the last decades. Herein, we functionalized iron oxide nanoparticles (IONPs) with the fourth generation (G4) of poly amidoamine (PAMAM) dendrimers (G4@IONPs) for magnetic hyperthermia treatment of breast cancer in Bagg albino strain C (BALB/c)mice. The survival of breast cancer cells significantly decreased after incubation with G4@IONPs and exposure to an alternating magnetic field (AMF) due to apoptosis and elevation of Bax (Bcl-2 associated X)/Bcl-2(B-cell lymphoma 2) ratio. After intratumoral injection of G4@IONPs, tumor-bearing BALB/c mice were exposed to AMF for 20 min; this procedure was repeated three times every other day. After the last treatment, tumor size was measured every three days. Histopathological and Immunohistochemical studies were performed on the liver, lung, and tumor tissues in treated and control mice. The results did not show any metastatic cells in the liver and lung tissues in the treatment group, while the control mice tissues contained metastatic breast cancer cells. Furthermore, the findings of the present study showed that magnetic hyperthermia treatment inhibited tumor growth by increasing cancer cell apoptosis, as well as reducing the tumor angiogenesis.

Non-invasive depth determination of inclusion in biological tissues using spatially offset Raman spectroscopy with external calibration.

Spatially offset Raman spectroscopy (SORS) allows chemical characterisation of biological tissues at depths of up to two orders of magnitude greater than conventional Raman spectroscopy. In this study, we demonstrate the use of SORS for the non-invasive prediction of depth of an inclusion within turbid media (e.g. biological tissues) using only external calibration data sets, thus extending our previous approach that required internal calibration. As with the previous methodology, the concept is based on relative changes in Raman band intensities of the inclusion that are directly related to the path length of Raman photons travelling through the medium thereby encoding the information of depth of the inclusion. However, here the calibration model is created using data only from external measurements performed at the tissue surface. This new approach facilitates a fully non-invasive methodology applicable potentially to in vivo medical diagnosis without any a priori knowledge. Monte Carlo simulations of photon propagation have been used to provide insight into the relationship between the spatial offset and the photon path lengths inside the tissues enabling one to derive a general scaling factor permitting the use of spatial offset measurements for the depth prediction. The approach was validated by predicting the depth of surface-enhanced Raman scattering (SERS) labelled nanoparticles (NPs) acting as inclusions inside a slab of ex vivo porcine tissue yielding an average root mean square error of prediction of 7.3% with respect to the overall tissue thickness. Our results pave the way for future non-invasive deep Raman spectroscopy in vivo by enabling, for example, the localisation of cancer lesions or cancer biomarkers in early disease diagnosis and targeted treatments.

Smart Gold Nanostructures for Light Mediated Cancer Theranostics: Combining Optical Diagnostics with Photothermal Therapy.

Nanotheranostics, which combines optical multiplexed disease detection with therapeutic monitoring in a single modality, has the potential to propel the field of nanomedicine toward genuine personalized medicine. Currently employed mainstream modalities using gold nanoparticles (AuNPs) in diagnosis and treatment are limited by a lack of specificity and potential issues associated with systemic toxicity. Light-mediated nanotheranostics offers a relatively non-invasive alternative for cancer diagnosis and treatment by using AuNPs of specific shapes and sizes that absorb near infrared (NIR) light, inducing plasmon resonance for enhanced tumor detection and generating localized heat for tumor ablation. Over the last decade, significant progress has been made in the field of nanotheranostics, however the main biological and translational barriers to nanotheranostics leading to a new paradigm in anti-cancer nanomedicine stem from the molecular complexities of cancer and an incomplete mechanistic understanding of utilization of Au-NPs in living systems. This work provides a comprehensive overview on the biological, physical and translational barriers facing the development of nanotheranostics. It will also summarise the recent advances in engineering specific AuNPs, their unique characteristics and, importantly, tunability to achieve the desired optical/photothermal properties.

Magnetic hyperthermia of breast cancer cells and MRI relaxometry with dendrimer-coated iron-oxide nanoparticles.

BACKGROUND: Recently, some studies have focused on dendrimer nanopolymers as a magnetic resonance imaging (MRI) contrast agent or a vehicle for gene and drug delivery. Considering the suitable properties of these materials, they are appropriate candidates for coating iron-oxide nanoparticles which are applied in magnetic hyperthermia. To the best of our knowledge, the novelty of this study is the investigation of fourth-generation dendrimer-coated iron-oxide nanoparticles (G4@IONPs) in magnetic hyperthermia and MRI. METHODS: IONPs were synthesized via co-precipitation and coated with the fourth generation (G4) of polyamidoamine dendrimer. The cytotoxicity of G4@IONPs with different concentrations was assessed in a human breast cancer cell line (MCF7) and human fibroblast cell line (HDF1). Hemolysis and stability of G4@IONPs were investigated, and in addition, the interaction of these particles with MCF7 cells was assessed by Prussian blue staining. Heat generation and specific absorption rate (SAR) were calculated from measurement and simulation results at 200 and 300 kHz. MCF7 and HDF1 cells were incubated with G4@IONPs for 2 h and then put into the magnetic coil for 120 min. Relaxometry experiments were performed with different concentrations of G4@IONPs with T1- and T2-weighted MR images. RESULTS: The TEM results showed that G4@IONPs were 10 ± 4 nm. The in vitro toxicity assessments showed that synthesized nanoparticles had low toxicity. The viability of MCF7 cells incubated with G4@IONPs decreased significantly after magnetic hyperthermia. In addition, MR imaging revealed that G4@IONPs improved transverse relaxivity (r2) significantly. CONCLUSIONS: Our results encouraged the future application of G4@IONPs in magnetic hyperthermia and MR imaging.

Biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles in BALB/c mice.

BACKGROUND: The possibility of using a specific nanoparticle in nanomedicine highly depends on its biodistribution profile and biocompatibility. Due to growing demand for iron oxide nanoparticles (IONPs) and dendrimers in biomedical applications, this study was performed to assess the biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles (G4@IONPs). MATERIALS AND METHODS: IONPs were synthesized via co-precipitation and coated with the fourth generation (G4) of polyamidoamine (PAMAM) dendrimer. To determine the biodistribution, 5 mg/mL G4@IONPs suspension was intraperitoneally injected into tumor-bearing BALB/c mice, and iron levels in blood and various organs, including the lung, liver, brain, heart, tumor, and kidney, were measured by inductively coupled plasma mass spectrometry (ICP-MS) at 4, 8, 12, and 24 h after injection. Also, to investigate the toxicity of G4@IONPs, different concentrations of G4@IONPs were injected into BALB/c mice, and blood, renal, and hepatic factors were measured. Furthermore, histopathological staining was performed to investigate the effect of G4@IONPs on the liver and kidney tissues. RESULTS: The results showed that the iron content was higher in the kidney, liver, and lung tissues 24 h after injection. Toxicity assessments revealed a significant increase in blood urea nitrogen (BUN) and direct bilirubin at the concentration of 10 mg/kg. Also, in this concentration, histopathological abnormalities were detected in liver tissue. CONCLUSION: Although more systematic studies are still required, our results encouraged the future investigations of G4@IONPs in biomedical applications.

Assessment and Comparison of Homogeneity and Conformity Indexes in Step-and-Shoot and Compensator-Based Intensity Modulated Radiation Therapy (IMRT) and Three-Dimensional Conformal Radiation Therapy (3D CRT) in Prostate Cancer.

Intensity modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D CRT) are two treatment modalities in prostate cancer, which provide acceptable dose distribution in tumor region with sparing the surrounding normal tissues. IMRT is based on inverse planning optimization; in which, intensity of beams is modified by using multileaf collimators and also compensators with optimum shapes in step and shoot (SAS) and compensator-based method, respectively. In the recent study, some important parameters were compared in two IMRT and 3D CRT methods. Prescribed dose was 80 Gy for both IMRT procedures and 70 Gy for 3D CRT. Treatment plans of 15 prostate cancer candidates were compared to target the minimum dose, maximum dose, V 76 Gy (for IMRT plans) V 66.5 Gy (for 3D CRT), mean dose, conformity index (CI), and homogeneity index (HI). Dose conformity in compensators-based IMRT was better than SAS and 3D CRT. The same outcome was also achieved for homogeneity index. The target coverage was achieved 95% of prescribed dose to 95% of planning target volume (PTV) in 3D CRT and 95% of prescribed dose to 98% of PTV in IMRT methods. IMRT increases maximum dose of tumor region, improves CI and HI of target volume, and also reduces dose of organs at risks.

Extremely low-frequency electromagnetic field influences the survival and proliferation effect of human adipose derived stem cells.

BACKGROUND: Extremely low-frequency electromagnetic fields (ELF-EMF) can effect on biological systems and alters some cell functions like proliferation rate. Therefore, we aimed to attempt the evaluation effect of ELF-EMF on the growth of human adipose derived stem cells (hADSCs). MATERIALS AND METHODS: ELF-EMF was generated by a system including autotransformer, multi-meter, solenoid coils, teslameter and its probe. We assessed the effect of ELF-EMF with intensity of 0.5 and 1 mT and power line frequency 50 Hz on the survival of hADSCs for 20 and 40 min/day for 7 days by MTT assay. One-way analysis of variance was used to assessment the significant differences in groups. RESULTS: ELF-EMF has maximum effect with intensity of 1 mT for 20 min/day on proliferation of hADSCs. The survival and proliferation effect (PE) in all exposure groups were significantly higher than that in sham groups (P < 0.05) except in group of 1 mT and 40 min/day. CONCLUSION: Our results show that between 0.5 m and 1 mT ELF-EMF could be enhances survival and PE of hADSCs conserving the duration of exposure.