A 3D printed microneedle system for transdermal drug delivery of anticancer drugs

Background: Transdermal delivery of drugs is an attractive alternative to the conventional route of administration as oral delivery. The hypodermic injections are painful and less patient compliance. Microneedles (MNs) are micron-sized, minimally invasive needles to deliver a wide range of molecules (e.g., small, DNA, vaccines etc.) to the upper portion of the dermis in a sustained and controlled manner, without causing any pain. The introduction of 3D printing technologies in the fabrication of MN will promote one-step manufacturing tools and scale-up for the delivery devices of anticancer drugs. Methods: The 3D printed MN (3DMN) arrays were fabricated using Stereolithography (SLA), a photopolymerization-based technology, using a biocompatible Class I resin. The printed MN arrays were characterized using Scanning Electron Microscopy (SEM) and the coating was evaluated through Fluorescence Microscopy (FM). The penetration efficiency of 3DMN was investigated through the Optical Coherence Tomography (OCT) into the skin in vitro. The delivery efficiencies of MN arrays to release anticancer drugs in vitro were investigated using Franz diffusion cells and vivo animal studies were carried out to determine the delivery of anticancer drugs and tumour regression effect in mice. Results: 3DMN arrays were successfully fabricated using SLA technology and the dimensions were reproducible. OCT studies have shown more than 80% penetration capability. In vitro and in vivo studies demonstrated the rapid transdermal delivery of anticancer drugs and regression of tumours in mice. Conclusions: These 3DMNs may prove to be of great assistance for the delivery of anticancer drugs in near future in a painless, precise and accurate manner

Development of an Automatic Contextual Agricultural Metadata Collection App

Data is the base of digital agriculture. Farm activities are the metadata for production data that are often recorded manually, hence erroneous and missing data often occur. A metadata collection app for contextual agricultural activities was developed for recording detailed information on who is doing what in which field, when, and how. It was developed for android smartphones and functions as a geofence responsive field recognizer using the GPS location of the app user. It records the accessed crop fields automatically with time and facilitates a rules-driven chatbot with validated options for collecting detailed metadata about the conducted activities in that accessed field. The app was designed as a multiple-user app for multi-crop and multi-field usage and storing collected data in a cloud database. The app automatically records time, location, and operator\u27s name, which reduces the chance of missing data, and the chatbot with validated options reduces errors in recording

An Extremely Indolent T-cell Leukemia: An 18-year Follow-Up.

T-cell prolymphocytic leukemia (T-PLL) is a rare malignancy that comprises about 2% of all mature lymphoid neoplasms. Patients usually present with prominent peripheral blood lymphocytosis, splenomegaly, hepatomegaly, lymphadenopathy, B symptoms, and occasionally with skin lesions.¹ The disease follows an aggressive clinical course with rapid progression and typically has a median survival of less than 1 year. In some cases, the disease is indolent for a period of time before becoming aggressive.² In 2002, 7 years after initial diagnosis in 1995, the case discussed herein was reported as a rare, indolent form of T-PLL.³ We now present 11 additional years of follow-up of this case, during which time the patient remained asymptomatic with respect to his lymphoid neoplasm

The potential role of flow cytometry in the diagnosis of small cell carcinoma.

CONTEXT: Virtually no information exists in the medical literature on the immunophenotyping of small cell carcinoma by flow cytometry. CD56, or neural cell adhesion molecule, is widely expressed by small cell carcinoma and easily measured by flow cytometry. OBJECTIVE: To determine the potential usefulness of flow cytometry in the diagnosis of small cell carcinoma. DESIGN AND SETTING: Retrospective data and archival material on 27 patients were obtained from community hospitals. Specimens (needle aspirations and tissue biopsies) from all patients demonstrated cytomorphologic and flow cytometric features consistent with small cell carcinoma. All measurements were performed at a large reference laboratory. Routine 3- and 4-color flow cytometry using a lymphoma antibody panel, including anti-CD56, was performed. Anti-cytokeratin antibody was also used in the last 12 cases. Immunohistochemical staining with a panel of conventional markers for neuroendocrine neoplasms was performed on available tissue for purposes of confirmation of small cell carcinoma. PATIENTS: Twenty-seven patients whose tissue specimens showed a clearly defined population of CD45-CD56+ cells by flow cytometry and cytomorphologic features consistent with small cell carcinoma. INTERVENTIONS: Needle aspiration (n = 3) and tissue biopsy (n = 24) from a variety of sites. RESULTS: CD56 positivity by flow cytometry was 100 to 1000 times that of the matched isotype control in 25 cases and 10 to 100 times that of the control in 2 cases. Cytokeratin positivity by flow cytometry was found in 12 of 12 cases. Immunohistochemical staining showed positivity for at least 1 cytokeratin and 1 or more neuroendocrine markers in 26 of 27 cases and confirmed the diagnosis of small cell carcinoma. CONCLUSIONS: Routine flow cytometry can identify a neuroendocrine phenotype that shows a strong correlation with confirmatory immunohistochemical markers in cases exhibiting cytomorphologic features of small cell carcinoma. Flow cytometry appears to complement and may possibly be a satisfactory alternative to immunohistochemical staining when small cell carcinoma is suspected

Valence and Core Photoelectron Spectra of Aqueous I3− from Multi-Reference Quantum Chemistry

The I3− molecule is known to undergo substantial structural reorganization upon solvation by a protic solvent, e.g., water. However, the details of this process are still controversially discussed in the literature. In the present study, we combined experimental and theoretical efforts to disentangle this controversy. The valence (5p), N4,5 (4d), and M4,5 (3d) edge photoelectron spectra were measured in an aqueous solution and computed using high-level multi-reference methods. Our previous publication mainly focused on obtaining reliable experimental evidence, whereas in the present article, we focused primarily on theoretical aspects. The complex electronic structure of I3− requires the inclusion of both static and dynamic correlation, e.g., via the multi-configurational perturbation theory treatment. However, the resulting photoelectron spectra appear to be very sensitive to problems with variational stability and intruder states. We attempted to obtain artifact-free spectra, allowing for a more reliable interpretation of experiments. Finally, we concluded that the 3d Photoelectron Spectrum (PES) is particularly informative, evidencing an almost linear structure with a smaller degree of bond asymmetry than previously reported.Deutsche ForschungsgemeinschaftPeer Reviewe

Common GBA Variants in Parkinson\u27s Disease and Lewy Body Dementia Patients

Parkinson’s disease (PD) and Lewy Body Dementias (LBD) are two distinct synucleinopathies with a great amount of symptomatic and genetic overlap. This overlap can often lead to misdiagnosis. Misdiagnosis can result in improper therapy and therefore a poorer prognosis. LBD is a neuropath diagnosis with subcategories, but for the purpose of this project we discuss LBD as a whole. GBA is a gene common to both diseases with different effect sizes in each, although increasing severity of disease for both. Common is defined as a presence greater than 1% in healthy controls. GBA is found in 2-37% of Parkinson cases worldwide, with Ashkenazi Jews having the highest frequency of mutation. Our PD cohort is a clinical series, whereas our LBD cohort is a pathological series. A clinical LBD series can skew results as they are often misdiagnosed, so there is more certainty behind a pathological series. Here, we screened ~200 samples for E365K and T408M, two common GBA variants. We have reviewed the clinical implications of being a GBA carrier for both diseases and have identified differences. We have genotyped ~1200 LBD samples for these two common variants. Now that we know GBA plays a role in each disease, we can better understand the mechanism of pathogenesis and can identify potential therapy targets for GBA carriers. These therapeutic targets could be a gateway to cures and therapies for an otherwise incurable condition

Carbon−Phosphorus Bond Activation of Tri(2-thienyl)phosphine at Dirhenium and Dimanganese Centers

Reaction of [Re2(CO)9(NCMe)] with tri(2-thienyl)phosphine (PTh3) in refluxing cyclohexane affords three substituted dirhenium complexes: [Re2(CO)9(PTh3)] (1), [Re2(CO)8(NCMe)(PTh3)] (2), and [Re2(CO)8(PTh3)2] (3). Complex 2 was also obtained from the room-temperature reaction of [Re2(CO)8(NCMe)2] with PTh3 and is an unusual example in which the acetonitrile and phosphine ligands are coordinated to the same rhenium atom. Thermolysis of 1 and 3 in refluxing xylene affords [Re2(CO)8(μ-PTh2)(μ-η1:κ1-C4H3S)] (4) and [Re2(CO)7(PTh3)(μ-PTh2)(μ-H)] (5), respectively, both resulting from carbon−phosphorus bond cleavage of a coordinated PTh3 ligand. Reaction of [Re2(CO)10] and PTh3 in refluxing xylene gives a complex mixture of products. These products include 3−5, two further binuclear products, [Re2(CO)7(PTh3)(μ-PTh2)(μ-η1:κ1-C4H3S)] (6) and [Re2(CO)7(μ-κ1:κ2-Th2PC4H2SPTh)(μ-η1:κ1-C4H3S)] (7), and the mononuclear hydrides [ReH(CO)4(PTh3)] (8) and trans-[ReH(CO)3(PTh3)2] (9). Binuclear 6 is structurally similar to 4 and can be obtained from reaction of the latter with 1 equiv of PTh3. Formation of 7 involves a series of rearrangements resulting in the formation of a unique new diphosphine ligand, Th2PC4H2SPTh. Reaction of [Mn2(CO)10] with PTh3 in refluxing toluene affords the phosphine-substituted product [Mn2(CO)9(PTh3)] (10) and two carbon−phosphorus bond cleavage products, [Mn2(CO)6(μ-PTh2)(μ-η1:η5-C4H3S)] (11) and [Mn2(CO)5(PTh3)(μ-PTh2)(μ-η1:η5-C4H3S)] (12). Both 11 and 12 contain a bridging thienyl ligand that is bonded to one manganese atom in a η5-fashion. The molecular structures of eight of these new complexes were established by single-crystal X-ray diffraction studies, allowing a detailed analysis of the disposition of the coordinated ligands

Creaky knees: Is there a reason for concern? A qualitative study of the perspectives of people with knee crepitus

Objective: Crepitus is a feature of osteoarthritis that may affect one's participation in exercise. An informed understanding is required of the perceptions that people have of their knee crepitus and how it affects their exercise behaviours. This study aims to investigate the role that crepitus may play in beliefs about exercise and knee health. Methods: Focus group and individual interviews were conducted online with participants who had knee crepitus. The transcripts were thematically analysed through an inductive approach. Results: Five main themes were identified from 24 participants: (1) individual variation of, (2) occurrence of, (3) meaning of knee crepitus, (4) attitudes and exercise behaviours regarding crepitus, and (5) knowledge deficits and needs concerning crepitus during exercise. The variety of crepitus sounds described occurred with a range of exercises or after inactivity. For those already with osteoarthritis or other symptoms, crepitus was of less concern than symptoms such as pain. Most participants had not ceased exercise but may have modified movement due to crepitus and associated symptoms; some had increased intentional strength training to try alleviating it. Participants agreed that more understanding about the processes causing crepitus and what exercise was safe for knee health would be beneficial. Conclusion: Crepitus does not appear to be a major cause of concern for people who experience it. However, it is a factor that influences exercise behaviours as is pain. If health professionals could guide people with concerns about their crepitus, they may be more confident in exercising to benefit their joint health