Deep Tissue Research Articles

Combination of deep tissue massage and stretching: Does it affect the healing of low back pain injuries?

Background and Study Aim. Low Back Pain (LBP) is an abnormal condition in the lower back which is accompanied by a painful sensation so that it will experience limitations in moving. Therefore, the need for special treatment in dealing with Low Back Pain (LBP) in order to reduce pain. Material and Methods. This research is a pre-experimental research using the approach one group pretest and posttest design. In this study, the results of the initial test data (pretest) were measured in the form of low back pain results with VAS, Modified Schober Test, Fingertip to Floor, and ODI, then giving treatment by combining deep tissue massage with stretching. Therapy is given to patients 3 times a week for 3 weeks, then the final data measurement (Posttest) is carried out. The subjects of this study were patients at the LKP Rumah Sehat Mandiri clinic for the last 5 months who had experienced low back pain injuries. Sampling in this study used purposive sampling so that there were 20 people with an age range of 20-60 years. The analysis in this study uses the SPSS Version 26 application. Results. The results showed that the indicators of pain, flexion, extension, right flexion, left flexion and function had a significant effect using a combination of deep tissue massage and stretching with a significant value si showing 0.000 < 0.05. In the left flexion indicator, a significance value of 0.001 < 0.05 was obtained, so it can be concluded that there is a significant difference in the deep tissue massage combination of stretching treatment. Conclusions. The results of this study provide evidence that the combination of deep tissue massage and stretching provides a significant reduction in the healing of low back pain injuries in patients. That way a combination of deep tissue massage and stretching can be applied to treat low back pain injury healing.

A transformable and self-oxygenated smart probe for enhanced tumor sonodynamic therapy

Sonodynamic therapy (SDT) is emerging as a promising modality for cancer treatment. However, improving the tumor bioavailability and anti-hypoxia capability of sonosensitizers faces a big challenge. In this work, we present a tumor microenvironment (TME)-mediated nanomorphology transformation and oxygen (O2) self-production strategy to enhance the sonodynamic therapeutic efficacy of tumors. A smart probe Ce6-Leu@Mn2+ that consists of a glutathione (GSH) and leucine amino peptidase (LAP) dual-responsive unit, a 2-cyanobenzothiazole (CBT) group, and a Mn2+-chelated Ce6 as sonosensitizer for tumor SDT was synthesized, and its SDT potential for liver tumor HepG2 in living mice was systematically studied. It was found that the probes could self-assemble into large nanoparticles in physiological condition and spontaneously transformed into small particles under the dual stimulation of GSH and LAP in TME resulting in enhanced tumor accumulation and deep penetration. More notably, Ce6-Leu@Mn2+ could convert endogenous hydrogen peroxide to O2, thereby alleviating the hypoxia and achieving effective SDT against hypoxic tumors under the excitation of ultrasound. We thus believe this smart TME-responsive probe may provide a noninvasive and efficient means for malignant tumor treatment. Statement of significanceSonodynamic therapy (SDT) is emerging as a promising therapeutic modality for cancer treatment. However, how to improve the tumor bioavailability and anti-hypoxia capability of sonosensitizers remains a huge challenge. Herein, we rationally developed a theranostic probe Ce6-Leu@Mn2+ that can transform into small-size nanoparticles from initial large particles under the dual stimulation of LAP and GSH in tumor microenvironment (TME) resulting in enhanced tumor accumulation, deep tissue penetration as well as remarkable O2 self-production for enhanced sonodynamic therapy of human liver HepG2 tumor in living mice. This smart TME-responsive probe may provide a noninvasive and efficient means for hypoxic tumor treatment.

Effects of monopolar pulsed-capacitive dielectric radiofrequency diathermy in patients with chronic low back pain: a randomised clinical trial

Monopolar capacitive diathermy is a physiotherapy technique that uses high-frequency currents to generate heat in deep tissues. This heat can have several therapeutic effects, especially in the treatment of chronic low back pain (CLBP), however, until now there is little evidence of this type of diathermy. The purpose was to evaluate the efficacy of a pulsed monopolar dielectric radiofrequency diathermy (PRF)-capacitive type versus simulated treatment on symptomatology of patients with CLBP. A single-blind randomised controlled trial was conducted. Sixty patients with CLBP were randomly assigned to a PRF-capacitive or a simulated treatment group. All participants received 3 sessions per week for 3 weeks. Disability, pain intensity, movement phobia, lumbar anteflexion, quality of life, and sleep quality were assessed at baseline, after treatment, and at two months. The application of 9 sessions of PRF-capacitive showed significant improvements compared to simulated therapy during the entire follow-up for disability (F = 26.99, p < 0.001), pain intensity (F = 0.550, p < 0.001), the quality of life components of physical function (F = 0.780, p < 0.001), social function (F = 0.780, p < 0.001) and mental health (F = 0.858, p = 0.003) and for sleep duration (F = 0.863, p = 0.004).

Trauma in Neonatal Acute Brain Slices Alters Calcium and Network Dynamics and Causes Calpain-Mediated Cell Death.

Preparing acute brain slices produces trauma that mimics severe penetrating brain injury. In neonatal acute brain slices, the spatiotemporal characteristics of trauma-induced calcium dynamics in neurons and its effect on network activity are relatively unknown. Using multiphoton laser scanning microscopy of the somatosensory neocortex in acute neonatal mouse brain slices (P8-12), we simultaneously imaged neuronal Ca2+ dynamics (GCaMP6s) and cytotoxicity (propidium iodide or PI) to determine the relationship between cytotoxic Ca2+ loaded neurons (GCaMP-filled) and cell viability at different depths and incubation times. PI+ cells and GCaMP-filled neurons were abundant at the surface of the slices, with an exponential decrease with depth. Regions with high PI+ cells correlated with elevated neuronal and neuropil Ca2+ The number of PI+ cells and GCaMP-filled neurons increased with prolonged incubation. GCaMP-filled neurons did not participate in stimulus-evoked or seizure-evoked network activity. Significantly, the superficial tissue, with a higher degree of trauma-induced injury, showed attenuated seizure-related neuronal Ca2+ responses. Calpain inhibition prevented the increase in PI+ cells and GCaMP-filled neurons in the deep tissue and during prolonged incubation times. Isoform-specific pharmacological inhibition implicated calpain-2 as a significant contributor to trauma-induced injury in acute slices. Our results show a calpain-mediated spatiotemporal relationship between cell death and aberrant neuronal Ca2+ load in acute neonatal brain slices. Also, we demonstrate that neurons in acute brain slices exhibit altered physiology depending on the degree of trauma-induced injury. Blocking calpains may be a therapeutic option to prevent acute neuronal death during traumatic brain injury in the young brain.

Relationship between Cephalometric and Ultrasonic Airway Parameters in Adults with High Risk of Obstructive Sleep Apnea.

Background/Objectives: Polysomnography and cephalometry have been used for studying obstructive sleep apnea (OSA) etiology. The association between craniofacial skeleton and OSA severity remains controversial. To study OSA's etiology, cephalometry, fiberoptic pharyngoscopy, polysomnography, and sleep endoscopy have been used; however, airway obstructions cannot be located. Recent research suggested ultrasonography for OSA screening and upper airway obstruction localization. Thus, this study aims to investigate the relationship between specific craniofacial cephalometric and ultrasonic airway parameters in adults at high risk of OSA. Methods: To assess craniofacial structure, lateral cephalograms were taken from thirty-three adults over 18 with a STOP-Bang questionnaire score of three or higher and a waist-to-height ratio (WHtR) of 0.5 or higher. Airway parameters were assessed through submental ultrasound. Results: NSBA correlated with tongue base airspace width, while MP-H correlated with oropharynx, tongue base, and epiglottis airspace width. SNA, SNB, and NSBA correlated with tongue width at the oropharynx. At tongue base, ANB and MP-H correlated with tongue width. SNB and NSBA were associated with deep tissue thickness at the oropharynx, while MP-H correlated with superficial tissue thickness at velum and oropharynx. Conclusions: Cephalometric parameters (SNA, SNB, ANB, NSBA, and MP-H) were correlated with ultrasonic parameters in the velum, oropharynx, tongue base, and epiglottis.

Probing the optical properties and toxicological profile of zinc tungstate nanorods.

Zinc tungstate is a semiconductor known for its favorable photocatalytic, photoluminescence, and scintillation properties, coupled with its relatively low cost, reduced toxicity, and high stability in biological and catalytic environments. In particular, zinc tungstate evinces scintillation properties, namely the ability to emit visible light upon absorption of energetic radiation such as x rays, which has led to applications not only as radiation detectors but also for biomedical applications involving the delivery of optical light to deep tissue, such as photodynamic therapy and optogenetics. Here, we report on the synthesis of zinc tungstate nanorods generated via an optimized but facile method, which allows for synthetic control over the aspect ratio of the as-synthesized anisotropic motifs via rational variation of the solution pH. We investigate the effect of aspect ratio on their resulting photoluminescent and radioluminescent properties. We further demonstrate the potential of these zinc tungstate nanorods for biomedical applications, such as photodynamic therapy for cancer treatment, by analyzing their toxicological profile within cell lines and neurons.

USE OF TAQMAN ARRAY TO INVESTIGATE INFECTION IN DIABETIC FOOT WOUNDS

IntroductionDiabetic foot disease is a major public health problem with an annual NHS expenditure in excess of £1 billion. Infection increases risk of major amputation fivefold. Due to the polymicrobial nature of diabetic foot infections, it is often difficult to isolate the correct organism with conventional culture techniques, to deliver appropriate narrow spectrum antibiotics. Rapid DNA-based technology using multi-channel arrays presents a quicker alternative and has previously been used effectively in intensive care and respiratory medicine.MethodsWe gained institutional and Local Ethics Committee approval for a prospective cohort study of patients with clinically infected diabetic foot wounds. They all had deep tissue samples taken in clinic processed with conventional culture and real-time PCR TaqMan array.Results50 samples were taken from 39 patients between October 2020 and March 2022. 84% of patient were male, 88% had type 2 diabetes. The ulcers were of variable chronicity prior to sampling (range 1–113 weeks) and mean HbA1c was 67.2mmol/mol. Ulcers were on the heel (3), midfoot (6) and forefoot (41). Minimum follow up was 3 months. 6 ulcers healed, 24 patients were admitted due to foot disease, there were 2 major amputations and 4 deaths. TaqMan array results were available a mean of 4.3 days earlier than culture results. 9 patients had negative conventional cultures and 8 were negative onarray testing. 17 patients had the same organisms detected on culture and array. 16 of these 17 had additional organisms detected by array. The most frequent organisms detected on array that were not detected by culture were Staphylococcus spp., Enterobacter, Pseudomonas and fungi.ConclusionTaqMan array shows promise in detecting infecting organisms from diabetic foot wounds and providing earlier results than standard culture, which may enable appropriate and timely antibiotic therapy.

Scoping Review of Wounds in Hospitalized Adults with COVID-19 Over the First Three Years of the Pandemic.

To synthesize the literature on skin failure and pressure injuries among hospitalized patients with COVID-19. An electronic literature search using relevant keywords and controlled vocabulary was conducted in March 2023 on MEDLINE/PubMed, Embase, and CINAHL. Manual citation searches of included articles and grey literature, including the Wound, Ostomy, and Continence Nurses Society website were performed. Articles published in English between 2020 and April 2023 were considered. Articles were included if they reported on COVID-19 positive hospitalized adults with wounds that were not present upon admission. A total of 31 articles met these criteria. Covidence was used to extract the data and was reviewed by multiple team members. Of the 31 studies, 27 reported new onset skin lesions during hospitalization. Wounds were classified as pressure injuries, skin failure, livedo racemosea and/or, retiform purpura, and associated with microvascular thrombosisthrombotic vasculopathy. Most pressure injuries were associated with prone position and affected patients often had multiple comorbidities including hypertension, diabetes mellitus, end-stage renal disease, heart disease, and COPD. Four articles highlighted an increased risk of new onset wounds, and three emphasized the importance of distinguishing deep tissue pressure injuries from ischemic-related lesions in patients with COVID-19. The evidence suggests an increased risk of ischemic lesions and pressure injuries (PI) in patients with COVID-19 infection. This phenomenon may have inflated the numbers of PI during the pandemic and adversely affected nursing quality measures in acute care environments.

A firm-push-to-open and light-push-to-lock strategy for a general chemical platform to develop activatable dual-modality NIR-II probes.

Activatable near-infrared (NIR) imaging in the NIR-II range is crucial for deep tissue bioanalyte tracking. However, designing such probes remains challenging due to the limited availability of general chemical strategies. Here, we introduced a foundational platform for activatable probes, using analyte-triggered smart modulation of the π-conjugation system of a NIR-II-emitting rhodamine hybrid. By tuning the nucleophilicity of the ortho-carboxy moiety, we achieved an electronic effect termed "firm-push-to-open and light-push-to-lock," which enables complete spirocyclization of the probe before sensing and allows for efficient zwitterion formation when the light-pushing aniline carbamate trigger is transformed into a firm-pushing aniline. This platform produces dual-modality NIR-II imaging probes with ~50-fold fluorogenic and activatable photoacoustic signals in live mice, surpassing reported probes with generally below 10-fold activatable signals. Demonstrating generality, we successfully designed probes for hydrogen peroxide (H2O2) and hydrogen sulfide (H2S). We envision a widespread adoption of the chemical platform for designing activatable NIR-II probes across diverse applications.

Nanogel-based nitric oxide-driven nanomotor for deep tissue penetration and enhanced tumor therapy

Antitumor agents often lack effective penetration and accumulation to achieve high therapeutic efficacy in treating solid tumors. Nanomotor-based nanomaterials offer a potential solution to address this obstacle. Among them, nitric oxide (NO) based nanomotors have garnered attention for their potential applications in nanomedicine. However, there widespread clinical adoption has been hindered by their complex preparation processes. To address this limitation, we have developed a NO-driven nanomotor utilizing a convenient and scalable nanogel preparation procedure. These nanomotors, loaded with the fluorescent probe / sonosensitizer chlorin e6 (Ce6), were specifically engineered for sonodynamic therapy. Through comprehensive in vitro investigations using both 2D and 3D cell models, as well as in vivo analysis of Ce6 fluorescent signal distribution in solid tumor models, we observed that the self-propulsion of these nanomotors significantly enhances cellular uptake and tumor penetration, particularly in solid tumors. This phenomenon enables efficient access to challenging tumor regions and, in some cases, results in complete tumor coverage. Notably, our nanomotors have demonstrated long-term in vivo biosafety. This study presents an effective approach to enhancing drug penetration and improving therapeutic efficacy in tumor treatment, with potential clinical relevance for future applications.

“Butterfly-effect” nano-platforms for cascade immune amplification and tumor clearance through multi-modal therapy and immune sensitization

Combined dynamic tumor therapy of photodynamic therapy (PDT), sonodynamic therapy (SDT) and microwave dynamic therapy (MDT) can overcome the limitations of single reactive oxygen species (ROS)-based therapy (including limited tissue penetration depth and low ROS production). However, changes in the tumor microenvironment caused by ROS amplification and oxygen depletion induce severe immunosuppression at the tumor site, indicating effective immunosensitization of the tumors are urgently needed. Here, melanin-hematoporphyrin-chloroquine R837-hyaluronic acid (MHRH) nanoplatform that can simultaneously respond to 980 nm laser /1064 nm laser/ultrasonic/microwave was prepared for PDT/SDT/MDT, achieving outbreak of ROS in deep tumor. More importantly, the photothermal ablation and the participation of chloroquine R837 of MHRH NPs reversed the immunosuppression caused by oxygen depletion after ROS outbreak by promoting DCs maturation and secretion of macrophage exosomes. In summary, the natural MHRH nano-platform supplies an obvious anti-tumor “butterfly effect” through ROS outbreak, thermal ablation and significant immunosuppressive reversal, which provides a new and promising combined strategy of ROS-dynamic therapy and immune agonists in deep tumor tissues.

The role of sonication in microbiology culture yield of the explanted infected implants post fracture fixation: A systematic review

Objective To evaluate the role of sonication in cases of postoperative infection following fracture fixation. Methods A systematic review of studies comparing peri-implant tissue culture (PTC) and sonication fluid culture (SFC) from implants removed due to fracture-related infection was conducted. The inclusion criteria were: published in English, human studies, implants from fracture-related infection, and tests comparing the culture of deep tissue and sonication fluid. The quality of studies was assessed using the Critical Appraisal Skill Program (CASP) tool. The sensitivity, specificity, implant preservation mechanism to avoid contamination, cost, and duration of incubation for PTC and SFC were extracted and compared using descriptive statistics. Results Nine studies with a total of 1,144 participants were included. The overall mean sensitivity of SFC and PTC was 88.9% (95% CI: 84.6-92.4%) and 67.8% (95% CI: 60.9-74.2%), respectively. While the specificity of SFC and PTC was 96.2% (95% CI: 94.7-97.4%) and 98.5% (95% CI: 97.7-99.0%), respectively. However, the cost-effectiveness of sonication as a diagnostic method for sonication remains unclear, as only one study estimated the price of sonication to be $228.00 per test, similar to PTC. Conclusions Sonication fluid culture might improve sensitivity in diagnosing postoperative infection following fracture fixation. This technique can potentially enhance the microbiological output and provide valuable guidance to healthcare professionals in treating infection after fracture fixation. However, more high-quality trials are needed to establish its optimal use, especially cost-effectiveness. Registration The study protocol was registered on PROSPERO (CRD42022338190; 18 June 2022).

Holistic vibrational spectromics assessment of human cartilage for osteoarthritis diagnosis.

Osteoarthritis (OA) is the most common degenerative joint disease, presented as wearing down of articular cartilage and resulting in pain and limited mobility for 1 in 10 adults in the UK [Osteoarthr. Cartil.28(6), 792 (2020)10.1016/j.joca.2020.03.004]. There is an unmet need for patient friendly paradigms for clinical assessment that do not use ionizing radiation (CT), exogenous contrast enhancing dyes (MRI), and biopsy. Hence, techniques that use non-destructive, near- and shortwave infrared light (NIR, SWIR) may be ideal for providing label-free, deep tissue interrogation. This study demonstrates multimodal "spectromics", low-level abstraction data fusion of non-destructive NIR Raman scattering spectroscopy and NIR-SWIR absorption spectroscopy, providing an enhanced, interpretable "fingerprint" for diagnosis of OA in human cartilage. This is proposed as method level innovation applicable to both arthro- or endoscopic (minimally invasive) or potential exoscopic (non-invasive) optical approaches. Samples were excised from femoral heads post hip arthroplasty from OA patients (n = 13) and age-matched control (osteoporosis) patients (n = 14). Under multivariate statistical analysis and supervised machine learning, tissue was classified to high precision: 100% segregation of tissue classes (using 10 principal components), and a classification accuracy of 95% (control) and 80% (OA), using the combined vibrational data. There was a marked performance improvement (5 to 6-fold for multivariate analysis) using the spectromics fingerprint compared to results obtained from solely Raman or NIR-SWIR data. Furthermore, clinically relevant tissue components were identified through discriminatory spectral features - spectromics biomarkers - allowing interpretable feedback from the enhanced fingerprint. In summary, spectromics provides comprehensive information for early OA detection and disease stratification, imperative for effective intervention in treating the degenerative onset disease for an aging demographic. This novel and elegant approach for data fusion is compatible with various NIR-SWIR optical devices that will allow deep non-destructive penetration.

Characterization of the family-level Borreliaceae pan-genome and development of an episomal typing protocol.

The Borreliaceae family includes many obligate parasitic bacterial species which are etiologically associated with a myriad of zoonotic borrelioses including Lyme disease and vector-borne relapsing fevers. Infections by the Borreliaceae are difficult to detect by both direct and indirect methods, often leading to delayed and missed diagnoses. Efforts to improve diagnoses center around the development of molecular diagnostics (MDx), but due to deep tissue sequestration of the causative spirochaetes and the lack of persistent bacteremias, even MDx assays suffer from a lack of sensitivity. Additionally, the highly extensive genomic heterogeneity among isolates, even within the same species, contributes to the lack of assay sensitivity as single target assays cannot provide universal coverage. This within-species heterogeneity is partly due to differences in replicon repertoires and genomic structures that have likely arisen to support the complex Borreliaceae lifecycle in which these parasites have to survive in multiple hosts each with unique immune responses. We constructed a Borreliaceae family-level pangenome and characterized the phylogenetic relationships among the constituent taxa which supports the recent taxonomy of splitting the family into at least two genera. Gene content pro les were created for the majority of the Borreliaceae replicons, providing for the first time their unambiguous molecular typing. Our characterization of the Borreliaceae pan-genome supports the splitting of the former Borrelia genus into two genera and provides for the phylogenetic placement of several non-species designated isolates. Mining this family-level pangenome will enable precision diagnostics corresponding to gene content-driven clinical outcomes while also providing targets for interventions.

Consider Carcinoma Cuniculatum in Recurrent Foot Ulcer: A Case Report and Literature Review

AbstractCarcinoma cuniculatum is a variant of squamous cell carcinoma, characterized by a slow growth with progressive crypt-like invasion of deep tissue. This tumor is frequently misdiagnosed as a benign skin lesion both clinically and histopathologically. The final diagnosis is often delayed as it requires a large sample biopsy. We report the case of a 67-year-old patient who presented to us with a recurring chronic ulcer over a surgical scar of 5 years of evolution.Only after a wide resection of the chronic ulcer was it possible to achieve the correct diagnosis of this large and poorly evolving carcinoma. The subsequent reconstruction with a musculocutaneous gracilis free flap allowed the patient to walk again.

Local recurrence rates of superficial versus deep soft tissue sarcoma.

Soft tissue sarcomas are a group of malignancies that commonly occur in the extremities. As deep lesions may exist within the confines of the muscular fascia, we postulate that local recurrence rates are higher for superficial soft tissue sarcomas managed by the standard of care. A retrospective review was performed on 90 patients who underwent surgical resection of soft tissue sarcomas of the extremity from 2007 to 2015. Patients with minimum 2-year follow-up and adequate operative, pathologic, and clinical outcomes data were included. Mean age was 54 ± 18 years with 49 (54.4%) patients being male. Lesions in 77.8% of cases were deep, and 22.2% were superficial to fascia. Following the index surgical resection, a total of 33 (36.7%) patients had positive margins. A total of 17 (18.9%) patients had a local recurrence. Overall, 3-year survival was 92.7%, and 5-year survival was 79.0%. Five-year recurrence-free survival of deep sarcomas was 91.1% versus 58.2% of superficial lesions (p = 0.006). Patients with higher tumor depth had lower odds of experiencing a local recurrence (HR 0.26 [95% CI 0.09-0.72]). Local recurence rates was also associated with positive surgical margins on initial resection (33.3% versus 12.3%) (p = 0.027). In this series, superficial tumor depth was associated with local recurrence of soft tissue sarcomas of the extremity following surgical resection. Positive surgical margins was also associated with local recurrence.

Boosting the sonodynamic performance of CoBiMn-layered double hydroxide nanoparticles via tumor microenvironment regulation for ultrasound imaging-guided sonodynamic therapy

Sonodynamic therapy (SDT), a promising strategy for cancer treatment with the ability for deep tissue penetration, has received widespread attention in recent years. Sonosensitizers with intrinsic characteristics for tumor-specific curative effects, tumor microenvironment (TME) regulation and tumor diagnosis are in high demand. Herein, amorphous CoBiMn-layered double hydroxide (a-CoBiMn-LDH) nanoparticles are presented as multifunctional sonosensitizers to trigger reactive oxygen species (ROS) generation for ultrasound (US) imaging-guided SDT. Hydrothermal-synthesized CoBiMn-LDH nanoparticles are etched via a simple acid treatment to obtain a-CoBiMn-LDH nanoparticles with abundant defects. The a-CoBiMn-LDH nanoparticles give greater ROS generation upon US irradiation, reaching levels ~ 3.3 times and ~ 8.2 times those of the crystalline CoBiMn-LDH nanoparticles and commercial TiO2 sonosensitizer, respectively. This excellent US-triggered ROS generation performance can be attributed to the defect-induced narrow band gap and promoted electrons and holes (e−/h+) separation. More importantly, the presence of Mn4+ enables the a-CoBiMn-LDH nanoparticles to regulate the TME by decomposing H2O2 into O2 for hypoxia relief and US imaging, and consuming glutathione (GSH) for protection against ROS clearance. Biological mechanism analysis shows that a-CoBiMn-LDH nanoparticles modified with polyethylene glycol can serve as a multifunctional sonosensitizer to effectively kill cancer cells in vitro and eliminate tumors in vivo under US irradiation by activating p53, apoptosis, and oxidative phosphorylation-related signaling pathways.

11.7T Diffusion Magnetic Resonance Imaging and Tractography to Probe Human Brain Organoid Microstructure

BackgroundHuman brain organoids are 3-dimensional cellular models that mimic architectural features of a developing brain. Generated from human induced pluripotent stem cells, these organoids offer an unparalleled physiologically relevant in vitro system for disease modeling and drug screening. In the current study, we sought to establish a foundation for a magnetic resonance imaging (MRI)–based, label-free imaging system that offers high-resolution capabilities for deep tissue imaging of whole organoids. MethodsAn 11.7T Bruker/89 mm microimaging system was used to collect high-resolution multishell 3-dimensional diffusion images of 2 induced pluripotent stem cell–derived human hippocampal brain organoids. The MRI features identified in the study were interpreted on the basis of similarities with immunofluorescence microscopy. ResultsMRI microscopy at ≤40 μm isotropic resolution provided a 3-dimensional view of organoid microstructure. T2-weighted contrast showed a rosette-like internal structure and a protruding spherical structure that correlated with immunofluorescence staining for the choroid plexus. Diffusion tractography methods can be used to model tissue microstructural features and possibly map neuronal organization. This approach complements traditional immunohistochemistry imaging methods without the need for tissue clearing. ConclusionsThis proof-of-concept study shows, for the first time, the application of high-resolution diffusion MRI microscopy to image 2-mm diameter spherical human brain organoids. Application of ultrahigh-field MRI and diffusion tractography is a powerful modality for whole organoid imaging and has the potential to make a significant impact for probing microstructural changes in brain organoids used to model psychiatric disorders, neurodegenerative diseases, and viral infections of the human brain, as well as for assessing neurotoxicity in drug screening.

An Experimental Infection Model in Sheep and Goats to Evaluate Salmonella Colonization in Deep Tissue Lymph Nodes and after Carcass Vascular Rinsing with Bacteriophages in Goats

An animal infection model was evaluated on sheep and goats to confirm which species infected with Salmonella enterica serovar Enteritidis C StR (SE13) would provide a consistent and high frequency of Salmonella colonization in lymph nodes (LNs) without causing undue animal morbidity. Sheep and goats (n = 5) were intradermally inoculated with Salmonella, postincubated for 7 days, and euthanized. Superficial cervical, medial iliac, subiliac, mammary, and popliteal LNs were excised from each carcass. Goat LNs had approximately 53% greater Salmonella level compared to sheep. Also, Salmonella was inconsistently recovered from the sheep LNs. Thus, goats were selected to determine the ability of carcass vascular rinsing (with and without bacteriophages) to reduce Salmonella in infected LNs. Goats with similar characteristics were grouped together before being randomly assigned to 3 postharvest treatments; control (CN, not vascularly rinsed; n = 10), vascularly rinsed with a standard Rinse & Chill® solution (RC; 98.5% water and a blend of saccharides and phosphates; n = 10), or vascularly rinsed with a standard Rinse & Chill® solution plus the addition of bacteriophages (BP; n = 10). Rinse & Chill® system was able to successfully deliver a mean 7.0 log PFU/g to the S. Enteritidis-infected LNs (mean 3.5 log CFU/g). However, neither Rinse & Chill® without bacteriophages nor with bacteriophages caused Salmonella reduction (P > 0.05) compared to the nonrinsed goat carcasses.

A closed-loop smart dressing based on microneedle and electrochemical micropump for early diagnosis and in-time therapy of chronic wound

Early diagnosis combined with in-time treatment is a promising strategy for chronic wound care, preventing wound deterioration and promoting healing. Different smart dressings have recently emerged to enable real-time wound status monitoring and offer active intervention. However, the drawbacks of existing smart dressings, including limited drug loading capacity and poor drug penetration into the deeper wound dermal and subcutaneous tissues, are yet to be addressed, resulting in unsatisfactory therapeutic effectiveness. In this study, a Microneedle-embedded closed-loop smart Dressing (MelD) is developed to simultaneously achieve chronic wound early diagnosis and in-time therapy. The simple impedance sensing electrodes are utilized to monitor wound impedance for chronic wound early diagnosis. Based on the sensing data, the drug delivery micropump in MelD is automatically activated for in-time therapy. By integrating micropump electrodes with a drug reservoir coupled-microneedle array, a practice solution for delivering enough drug fluid into deeper wound dermal/ subcutaneous tissues is developed. Compared to untreated diabetic mice, MelD, delivering sufficient growth factor to the wound and promoting drug entry into deep tissue layers, induces faster wound healing in treated mice. Meanwhile, MelD facilitates tissue formation and nascent collagen deposition. The enhanced drug storage dosage, improved drug penetration and closed-loop operation of Meld enable the first successful attempt of ensuring sufficient and efficient drug delivery by miniaturized all-in-one smart dressing, expanding the usage of closed-loop chronic wound care from laboratorial demonstration on limited kinds of superficial wounds to a wider range of wound types.