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Chemistry (Weinheim An Der Bergstrasse,... Jun 2024The multiplexity of cancer has rendered it the second leading cause of mortality worldwide and theragnostic prodrugs have gained popularity in recent years as a means of...
The multiplexity of cancer has rendered it the second leading cause of mortality worldwide and theragnostic prodrugs have gained popularity in recent years as a means of treatment. Theragnostic prodrugs enable the simultaneous diagnosis and therapy of tumors via high-precision real-time drug release monitoring. Herein, we report the development of the small theragnostic prodrug GF, based on the nucleoside anticancer agent gemcitabine and the fluorescent dye 5(6)-carboxyfluorescein. We have successfully demonstrated its efficient internalization in tumor cells, showing localization throughout both the early and late endocytic pathways. Its mechanism of cell internalization was evaluated, confirming its independence from nucleoside transporters. Its cellular localization via confocal microscopy revealed a clathrin-mediated endocytosis mechanism, distinguishing it from analogous compounds studied previously. Furthermore, GF exhibited stability across various pH values and in human blood plasma. Subsequently, its in vitro cytotoxicity was assessed in three human cancer cell lines (A549, U87 and T98). Additionally, its pharmacokinetic profile in mice was investigated and the consequent drug release was monitored. Finally, its in vivo visualization was accomplished in zebrafish xenotransplantation models and its in vivo efficacy was evaluated in A549 xenografts. The results unveiled an intriguing efficacy profile, positioning GF as a compelling candidate warranting further investigation.
PubMed: 38941241
DOI: 10.1002/chem.202401327 -
The International Journal of Medical... Aug 2024The method of stem cell transfer to narrow cochlear canals in vivo to generate hair cells is still an unclear operation. Thus, the development of any possible method...
BACKGROUND
The method of stem cell transfer to narrow cochlear canals in vivo to generate hair cells is still an unclear operation. Thus, the development of any possible method that will ensure the usage of medical microrobots in small cochlear workspaces is a challenging procedure.
METHODS
The current study tries to introduce a macro-micro manipulator system composed of a 6-DoF industrial serial manipulator as a macro manipulator and a proposed 5-DoF parallel manipulator with dual end effectors as a micro manipulator carrying permanent magnets for tetherless microrobot actuation inside the cochlea.
RESULTS
Throughout the study, structural synthesis and kinematic analysis of the proposed micro manipulator were introduced. A prototype of the manipulator was manufactured and its hardware verification procedures were carried out using motion capture cameras and surgical navigation registration methodologies.
CONCLUSIONS
Following motion training, the assembled macro-micro manipulator was successfully utilised to actuate a microrobot placed inside a manufactured cochlea mockup model.
Topics: Equipment Design; Cochlea; Robotic Surgical Procedures; Humans; Motion; Cochlear Implantation; Surgery, Computer-Assisted; Biomechanical Phenomena
PubMed: 38941214
DOI: 10.1002/rcs.2654 -
The International Journal of Oral &... Jun 2024To evaluate the effect of osteotomy preparation technique and implant diameter on primary stability and bone-implant interface of short implants (6mm), when placed in...
PURPOSE
To evaluate the effect of osteotomy preparation technique and implant diameter on primary stability and bone-implant interface of short implants (6mm), when placed in bone with high degree of cancellous content.
MATERIAL AND METHOD
90 short (S) implants (6 mm) divided in nine groups based on width (Narrow 4.2 mm, Regular 4.8 mm, Wide 5.4 mm) (N,R,W) and osteotomy preparation (Standard, Osteotome, Osseodensification) (ST, OT, OD) and placed in porcine tibia plateau bone samples: Group SN-ST; Group SN-OT; Group SN-OD; Group SRST; Group SR-OT; Group SR-OD; Group SW-ST; Group SW-OT and Group SW-OD. Insertion torque and Implant Stability Quotient (ISQ) were measured. Four implants from each group SNST, SN-OT, SN-OD were evaluated histomorphometrically.
RESULTS
Insertion torque was significantly higher for implants of Group SW-OD compared to Group SW-ST (50.00 ±14.14 Ncm vs 28.00 ±10.85 Ncm, p= 0.005) and Group SW-OT compared to Group SW-ST (46.87 ±17.10 Ncm vs 28.00 ±10.85 Ncm, p=0.026). Insertion torque was significantly higher for implants of Group SW-OD compared to Group SN-OD (50.00 ±14.14 Ncm vs 31.5 ±15.82 Ncm, p=0.04). No significant differences were observed for the percentage of bone, marrow space and connective tissue in contact to the implant surface between studied groups.
CONCLUSION
Osteotomy preparation technique at sites with high degree of cancellous content can influence the implant insertion torque for short and wide implants (5.4x6mm). Implant width can influence the insertion torque of short implants placed with the osseodensification technique.
PubMed: 38941166
DOI: 10.11607/jomi.10909 -
The International Journal of Oral &... Jun 2024As the population gets older, the prevalence of complete or partial tooth loss is increasing, significantly impacting people's quality of life. Scientific research...
PURPOSE
As the population gets older, the prevalence of complete or partial tooth loss is increasing, significantly impacting people's quality of life. Scientific research demonstrates that implant-fixed complete dentures offer high levels of satisfaction. In certain cases, tooth loss can lead to significant bone atrophy, necessitating pre-implant bone reconstruction. We conducted a retrospective cohort study involving 43 arches, including or not bone grafts, rehabilitated using a stackable guided approach, which included an immediate loading protocol. The primary outcome measure was the survival rate of the implant at 4 months.
MATERIAL AND METHODS
The digital workflow helps the design of the provisional prothesis before the implant surgery, which will be loaded immediately after the implant's placement. The stacked guides integrate both surgical and prosthetic considerations into a digital workflow.
RESULT
A total of 284 implants were placed. After a 4-month follow-up period, 10 implants (3.5%) exhibited no osseointegration and were subsequently replaced, resulting in an overall success rate of 96.5%. After 1 year of follow-up, a prosthetic success rate of 100% was observed, with all patients being able to progress to the stages for the permanent fixed dentures.
CONCLUSION
Our findings support the use of this protocol for all patients, whether they require bone grafts or not. However, a long-term follow-up is essential for a comprehensive evaluation of these treatment outcomes.
PubMed: 38941165
DOI: 10.11607/jomi.10998 -
Age and Ageing Jun 2024Incontinence is a common, distressing condition, most prevalent in older people. There is an unmet need for effective interventions to support continence. This review...
Effectiveness of non-pharmacological interventions delivered at home for urinary and faecal incontinence with homebound older people: systematic review of randomised controlled trials.
INTRODUCTION
Incontinence is a common, distressing condition, most prevalent in older people. There is an unmet need for effective interventions to support continence. This review focuses on non-pharmacological interventions to reduce incontinence among homebound older people. Aim: to identify interventions with potential to be delivered by care workers, nurses or family members in a person's home.
METHODS
Multiple databases were searched until 15 September 2023 for randomised controlled trials reporting home-based interventions for incontinence for older people (≥65 years) living at home. Two reviewers independently screened titles, abstracts and papers against inclusion criteria, then assessed for the Risk of Bias (RoB2). A third reviewer resolved the discrepancies. Primary data were extracted and synthesised.
RESULTS
A full-text review of 81 papers identified seven eligible papers (1996-2022, all USA), including n = 636 participants (561 women and 75 men). Two studies focusing on multicomponent behavioural interventions showed benefit, as did one study of transcutaneous tibial nerve stimulation self-administered through electrode-embedded socks. Three, which included cognitively impaired people, reported improvement with toileting assistance programmes, but the effects were not all significant. Results were inconclusive from a study examining the effects of fluid intake adjustments. Interventions were delivered by nurses, three in collaboration with family caregivers. No faecal incontinence interventions met the criteria.
CONCLUSION
There is scant evidence for continence supporting interventions delivered in older people's own homes. With an ageing population often reliant on family or social care workers well-placed to support continence promotion and policy drives for services to support older people remaining at home, this evidence gap needs addressing.
Topics: Humans; Fecal Incontinence; Aged; Randomized Controlled Trials as Topic; Urinary Incontinence; Homebound Persons; Home Care Services; Female; Male; Treatment Outcome; Aged, 80 and over
PubMed: 38941119
DOI: 10.1093/ageing/afae126 -
Acta Parasitologica Jun 2024Nothing is known about coccidians (Apicomplexa: Eimeriidae) from the Pacific blue-tailed skink, Emoia caeruleocauda. Here, we report mensural and morphometric data on a...
PURPOSE
Nothing is known about coccidians (Apicomplexa: Eimeriidae) from the Pacific blue-tailed skink, Emoia caeruleocauda. Here, we report mensural and morphometric data on a new species of Isospora from E. caeruleocauda from Guam, US Territory.
METHODS
Feces from four E. caeruleocauda collected by hand in November 2023 were placed in individual vials containing 2.5% potassium dichromate. They were examined for sporulated oocysts after flotation in Sheather's sugar solution, measured, and photographed.
RESULTS
A single (25%) E. caeruleocauda was found to be passing oocysts representing a new species of Isospora. Oocysts of Isospora guamensis n. sp. are ellipsoidal to ovoidal with a bi-layered wall, measure (L × W) 16.5 × 11.8 μm, and have a length/width (L/W) ratio of 1.4; a micropyle and an oocyst residuum were absent but a polar granule was present. Sporocysts are ovoidal and measure 9.4 × 6.5 μm, L/W 1.4; Stieda and sub-Stieda bodies were present but a para-Stieda body was absent. The sporocyst residuum is composed various-sized granules in a compact rounded or irregular mass, sometimes dispersed between the sporozoites. The new species can be differentiated from all other isosporans from skinks by possessing the smallest oocysts known from this host family.
CONCLUSION
This is the first time an isosporan coccidian has been reported from E. caeruleocauda as well as the first report of a coccidian from a Guam-inhabiting skink.
PubMed: 38940982
DOI: 10.1007/s11686-024-00860-9 -
Experimental & Applied Acarology Jun 2024Due to the extensive use of green urban areas as recreation places, city residents are exposed to tick-borne pathogens. The objectives of our study were (i) to determine...
Due to the extensive use of green urban areas as recreation places, city residents are exposed to tick-borne pathogens. The objectives of our study were (i) to determine the occurrence of ticks in urban green areas, focussing on areas used by humans such as parks, schools and kindergartens, and urban forests, and (ii) to assess the prevalence of Borrelia infections in ticks in Zielona Góra, a medium-sized city in western Poland. A total of 161 ticks representing the two species Ixodes ricinus (34 males, 51 females, 30 nymphs) and Dermacentor reticulatus (20 males, 26 females) were collected from 29 of 72 (40.3%) study sites. In total, 26.1% of the ticks (85.7% of I. ricinus and 14.3% of D. reticulatus) yielded DNA of Borrelia. The difference in the infection rate between I. ricinus and D. reticulatus was significant. Among infected ticks, the most frequent spirochete species were B. lusitaniae (50.0%) and B. afzelii (26.2%), followed by B. spielmanii (9.5%), B. valaisiana (7.1%), B. burgdorferi sensu stricto, (4.8%) and B. miyamotoi (2.4%). No co-infections were found. We did not observe a correlation in the occurrence of Borrelia spirochetes in ticks found in individual study sites that differed in terms of habitat type and height of vegetation. Our findings demonstrate that the Borrelia transmission cycles are active within urban habitats, pointing the need for monitoring of tick-borne pathogens in public green areas. They could serve as guidelines for authorities for the proper management of urban green spaces in a way that may limit tick populations and the potential health risks posed by tick-borne pathogens.
PubMed: 38940943
DOI: 10.1007/s10493-024-00932-5 -
European Journal of Applied Physiology Jun 2024To assess the effect of a remote handgrip contraction during wide-pulse high-frequency (WPHF) neuromuscular electrical stimulation (NMES) on the magnitude of extra...
PURPOSE
To assess the effect of a remote handgrip contraction during wide-pulse high-frequency (WPHF) neuromuscular electrical stimulation (NMES) on the magnitude of extra torque, progressive increase in torque during stimulation, and estimates of the persistent inward current (PIC) contribution to motoneuron firing in the plantar flexors.
METHODS
Ten participants performed triangular shaped contractions to 20% of maximal plantar flexion torque before and after WPHF NMES with and without a handgrip contraction, and control conditions. Extra torque, the relative difference between the initial and final torque during stimulation, and sustained electromyographic (EMG) activity were assessed. High-density EMG was recorded during triangular shaped contractions to calculate ∆F, an estimate of PIC contribution to motoneuron firing, and its variation before vs after the intervention referred to as ∆F change score.
RESULTS
While extra torque was not significantly increased with remote contraction (WPHF + remote) vs WPHF (+ 37 ± 63%, p = 0.112), sustained EMG activity was higher in this condition than WPHF (+ 3.9 ± 4.3% MVC EMG, p = 0.017). Moreover, ∆F was greater (+ 0.35 ± 0.30 Hz) with WPHF + remote than control (+ 0.03 ± 0.1 Hz, p = 0.028). A positive correlation was found between ∆F change score and extra torque in the WPHF + remote (r = 0.862, p = 0.006).
DISCUSSION
The findings suggest that the addition of remote muscle contraction to WPHF NMES enhances the central contribution to torque production, which may be related to an increased PIC contribution to motoneuron firing. Gaining a better understanding of these mechanisms should enable NMES intervention optimization in clinical and rehabilitation settings, improving neuromuscular function in clinical populations.
PubMed: 38940932
DOI: 10.1007/s00421-024-05538-8 -
European Radiology Jul 2024
Topics: Humans; Coronary Artery Disease; Tomography, X-Ray Computed; Reproducibility of Results; Radiography, Thoracic; Coronary Angiography; Coronary Vessels; Computed Tomography Angiography; Male; Calcinosis; Female; Vascular Calcification; Middle Aged
PubMed: 38940856
DOI: 10.1007/s00330-023-10472-y -
Alternative Therapies in Health and... Jun 2024This study evaluated the effectiveness of nalbuphine combined with propofol in reducing visceral pain and preserving cognitive function during laparoscopic ovarian tumor...
OBJECTIVE
This study evaluated the effectiveness of nalbuphine combined with propofol in reducing visceral pain and preserving cognitive function during laparoscopic ovarian tumor resection.
METHODS
A total of 100 patients undergoing laparoscopic ovarian tumor resection from January 2019 to January 2022 were randomly assigned to either the control group or the research group (50 patients each). The control group received fentanyl combined with propofol for anesthesia, while the research group received nalbuphine combined with propofol. Various anesthetic parameters, hemodynamics, visceral pain(Visual analog scale was used to evaluate the degree of pain at rest and during movement at 2h, 6h, and 12h after the operation), cognitive function (Mini-Mental State Examination (MMSE) scale was used to assess the cognitive function before the operation and 1 day, 3 days, and 5 days after the operation, including time and place, language, orientation, calculation, delayed memory and useability), and incidence of adverse reactions were assessed and compared between the two groups.
RESULTS
The research group exhibited significantly lower propofol dosage and anesthesia recovery time compared to the control group (P < .05). Hemodynamic stability, as indicated by SBP (Systolic Blood Pressure), DBP (Diastolic Blood Pressure), and SpO2 (Peripheral Capillary Oxygen Saturation)levels, was better maintained in the research group, especially at the beginning of the operation (P < .05). VAS (Visual Analog Scale) scores for pain at rest and during exercise were significantly lower in the research group at 2h and 6h post-operation (P < .05). MMSE (Mini-Mental State Examination) scores were higher in the research group compared to the control group at 1and3 days post-operation (P < .05). Additionally, the incidence of adverse reactions was significantly lower in the research group (8.00%) compared to the control group (20.00%, P < .05).The above results were subjected to t test and χ2 test.
CONCLUSIONS
Nalbuphine combined with propofol effectively alleviates visceral pain during laparoscopic ovarian tumor resection, stabilizes hemodynamics, and preserves cognitive function. This combination demonstrates promising analgesic and sedative effects with high safety, suggesting its potential for widespread clinical use.
PubMed: 38940805
DOI: No ID Found