In this study, the "particle in a box" idea, which was broadly developed in semiconductor quantum dot research, was extended into mid-infrared (IR) cavity modes by applying lateral confinement in an ...optical cavity. The discrete cavity modes hybridized with molecular vibrational modes, resulting in a quartet of polariton states that can support multiple coherence states in the IR regime. We applied tailored pump pulse sequences to selectively prepare these coherences and verified the multi-coherence existence. The simulation based on Lindblad equation showed that because the quartet of polariton states resided in the same cavity, they were specifically robust toward decoherence caused by fluctuations in space. The multiple robust coherences paved the way for entangled states and coherent interactions between cavity polaritons, which would be critical for advancing polariton-based quantum information technology.
Glaucoma is commonly treated using eye drops, which is highly inefficient due to rapid clearance (low residence time) from ocular surface. Contact lenses are ideally suited for controlled drug ...delivery to cornea, but incorporation of any drug loaded particulate system (formulation) affect the optical and physical property of contact lenses. The objective of the present work was to implant timolol maleate (TM) loaded ethyl cellulose nanoparticle-laden ring in hydrogel contact lenses that could provide controlled drug delivery at therapeutic rates without compromising critical lens properties. TM-implant lenses were developed, by dispersing TM encapsulated ethyl cellulose nanoparticles in acrylate hydrogel (fabricated as ring implant) and implanted the same in hydrogel contact lenses (sandwich system). The TM-ethyl cellulose nanoparticles were prepared by double emulsion method at different ratios of TM to ethyl cellulose. The X-ray diffraction studies revealed the transformation of TM to amorphous state. In vitro release kinetic data showed sustained drug release within the therapeutic window for 168h (NP 1:3 batch) with 150μg loading. Cytotoxicity and ocular irritation study demonstrated the safety of TM-implant contact lenses. In vivo pharmacokinetic studies in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC), with TM-implant contact lenses in comparison to eye drop therapy. In vivo pharmacodynamic data in rabbit model showed sustained reduction in intra ocular pressure for 192h. The study demonstrated the promising potential of implantation technology to treat glaucoma using contact lenses, and could serve as a platform for other ocular diseases.
Controlled drug delivery using novel implantation technology to treat glaucoma, without compromising optical and physical properties of contact lenses.
Fig. Change in Intraocular pressure (IOP) in mmHg in rabbits treated with eye drop and timolol maleate laden ring implant hydrogel contact lens (NP 1:3). Each point represents the mean±S.D. (n=6). Display omitted
Hypoxia is a common condition in rapidly proliferating tumors and occurs when oxygen delivery to the tissue is scarce. It is a prevalent feature in ~90% of solid tumors. The family of HIF ...(hypoxia-inducible factor) proteins-HIF1α and HIF2α-are the main transcription factors that regulate the response to hypoxia. These transcription factors regulate numerous downstream gene targets that promote the aggressiveness of tumors and therefore have been linked to worse prognosis in patients. This makes them a potential biomarker to be tested in the clinical setting to predict patient outcomes. However, HIFs have been notoriously challenging to immunolabel, in part due to their fast turnover under normal oxygen conditions. In this work, we developed a multiplexed immunofluorescence (mIF) staining protocol for the simultaneous detection of HIF1α and HIF2α in the same formalin-fixed paraffin-embedded (FFPE) tissue section.
Hypoxia occurs due to inadequate levels of oxygen in tissue and has been implicated in numerous diseases such as cancer, diabetes, cardiovascular, and neurodegenerative diseases. Hypoxia activates ...hypoxia-inducible factors (HIF) which mediate the expression of several downstream genes. Within the context of cancer biology, these genes affect cellular processes including metabolism, proliferation, migration, invasion, and metastasis. Pimonidazole hydrochloride (HCl) is an exogenous marker that is reduced and binds to thiols under hypoxic conditions resulting in adducts that can be visualized using antibodies such as Hypoxyprobe™. This chapter describes a method for using Hypoxyprobe™ to detect hypoxic areas in frozen and FFPE mouse samples by immunofluorescence (IF) and immunohistochemistry (IHC) staining.
•Speed effect on gait of older women with and without hallux valgus (HV) is unknown•Older women with and without HV walked at 1.1 and 1.3 m·s−1•In HV group, ankle ROM and plantarflexor moment did not ...increase with speed•Hip ROM, extensor moment, and work were greater in HV compared to the control group•HV induces a distal-to-proximal redistribution of joint function in older women
Hallux valgus (HV) is a highly prevalent foot deformity in older women. Differences in lower extremity joint function of older women with and without HV during walking at slower and faster speeds are unknown.
Does walking speed affect lower extremity joint range of motion (ROM) and net extensor joint moment and associated work in older women with and without HV?
Thirteen older women with HV and 13 controls completed five walking trials at 1.1 and 1.3 m·s−1 as kinematic marker position and ground reaction force data were collected. Net ankle, knee, and hip joint moments were computed using inverse dynamics during the stance phase. Positive joint work was calculated by integrating hip power in early stance, knee power in mid stance, and ankle power in late stance.
Average ankle ROM and plantarflexor moment did not increase with walking speed in the HV group, while in the control group these variables were greater for the faster compared to the slower speed (p < 0.05). The magnitude of increase in ankle joint work with speed was 12 % lesser in the HV compared to the control group (p = 0.008). The hip ROM, extensor moment, and associated work was greater in the HV compared to the control group (p < 0.05). Knee and hip joint ROM, extensor moments, and work increased with walking speed in both groups (p < 0.05).
Older women with HV compared to older women without HV demonstrate a distal-to-proximal redistribution by increasing hip motion and effort to compensate for reduced ankle contribution during walking.
Breast cancer is the most diagnosed cancer among women. Approximately 15-20% of all breast cancers are highly invasive triple-negative breast cancer (TNBC) and lack estrogen, progesterone, and ERBB2 ...receptors. TNBC is challenging to treat due to its aggressive nature with far fewer targeted therapies than other breast cancer subtypes. Current treatments for patients with TNBC consist of cytotoxic chemotherapies, surgery, radiation, and in some instances PARP inhibitors and immunotherapy. To advance current therapeutics, we repurposed mebendazole (MBZ), an orally available FDA-approved anthelmintic that has shown preclinical efficacy for cancers. MBZ has low toxicity in humans and efficacy in multiple cancer models including breast cancer, glioblastoma multiforme, medulloblastoma, colon cancer, pancreatic and thyroid cancer. MBZ was well-tolerated in a phase I clinical trial of adults recently diagnosed with glioma. We determined that the half-maximal inhibitory concentration (IC
) of MBZ in four breast cancer cell lines is well within the range reported for other types of cancer. MBZ reduced TNBC cell proliferation, induced apoptosis, and caused G2/M cell cycle arrest. MBZ reduced the size of primary tumors and prevented lung and liver metastases. In addition, we uncovered a novel mechanism of action for MBZ. We found that MBZ reduces integrin β4 (ITGβ4) expression and cancer stem cell properties. ITGβ4 has previously been implicated in promoting "cancer stemness," which may contribute to the efficacy of MBZ. Collectively, our results contribute to a growing body of evidence suggesting that MBZ should be considered as a therapeutic to slow tumor progression and prevent metastasis.
Vibrational polaritons have shown potential in influencing chemical reactions, but the exact mechanism by which they impact vibrational energy redistribution, crucial for rational polariton chemistry ...design, remains unclear. In this work, we shed light on this aspect by revealing the role of solvent phonon modes in facilitating the energy relaxation process from the polaritons formed of a
mode of W(CO)
to an IR inactive
mode. Ultrafast dynamic measurements indicate that along with the direct relaxation to the dark
modes, lower polaritons also transition to an intermediate state, which then subsequently relaxes to the
mode. We reason that the intermediate state could correspond to the near-in-energy Raman active
mode, which is populated through a phonon scattering process. This proposed mechanism finds support in the observed dependence of the IR-inactive state’s population on the factors influencing phonon density of states, e.g., solvents. The significance of the Raman mode’s involvement emphasizes the importance of non-IR active modes in modifying chemical reactions and ultrafast molecular dynamics.
Proximal humeral fractures are traditionally treated with open reduction and internal fixation (ORIF), but reverse total shoulder arthroplasty (RTSA) has emerged as an increasingly popular treatment ...option. Although ORIF with angular locking plates is a common treatment for proximal humerus fractures, prior reports suggest high failure and complication rates. Although RTSA has become an increasingly popular option for complex proximal humeral head fractures given its low complication rates, there are concerns it may lead to limited postoperative ROM. Thus, the optimal treatment for patients older than 70 years from a functional and radiographic perspective remains unclear.
(1) In patients older than 70 years with three-part and four-part proximal humerus fractures, does RTSA result in better functional outcome scores (Constant, American Shoulder and Elbow Surgeons ASES, and DASH scores) than ORIF with a locking plate? (2) Does RTSA result in greater ROM than ORIF? (3) Does RTSA result in a lower risk of complications than ORIF? (4) In patients with either procedure, what are the rates of negative radiographic outcomes in those treated with ORIF (such as malunion, bone resorption, malalignment, or avascular necrosis) or those with RTSA (such as resorption, notching, and loosening)? (5) At a minimum of 2 years of follow-up, does ORIF result in a greater number of revision procedures than RTSA?
Between January 1, 2013, and June 30, 2018, we treated 235 patients for a proximal humeral fracture. We considered only patients without previous ipsilateral fracture or surgery, other fractures, or radial nerve injuries; age older than 70 years; and patients without neurologic disease or cognitive dysfunction as potentially eligible. Sixty-nine percent (162 patients) of the patients were eligible; a further 31% (73 patients) were excluded because 18% (13 of 73 patients) did not meet the inclusion criteria, 62% (45 patients) underwent nonoperative treatment, and 21% (15 patients) declined to participate. Patients were nonrandomly allocated to receive RTSA if they had supraspinatus Goutallier/Fuchs Grade 3 or 4 atrophy or ORIF if they had supraspinatus Goutallier/Fuchs Grade 1 or 2 atrophy. This left 81 patients who were treated with RTSA and another 81 patients who were treated with ORIF. Among the 81 patients treated with RTSA, 11% (nine patients) were lost to the minimum study follow-up of 2 years or had incomplete datasets, leaving 89% (72 patients) for analysis. Among the 81 patients treated with ORIF, 19% (15 patients) were lost before the minimal study follow-up of 2 years or had incomplete datasets, leaving 82% (66 patients) for analysis. The median follow-up for both groups was 53 months (range 24 to 72 months). The mean age was 76 ± 2.9 years in the RTSA group and 73 ± 2.9 years in the ORIF group. In the RTSA group, 27 patients had a three-part fracture and 45 patients had a four-part fracture. In the ORIF group, 24 patients had three-part fractures and 42 patients had four-part fractures (p = 0.48). Shoulder function was assessed using functional outcome questionnaires (ASES, DASH, and Constant) and active ROM measurements. A surgical complication was defined as any instance of dislocations, fractures, adhesive capsulitis, nerve injuries, or surgical site infections. Radiographic outcomes after ORIF (malunion, tuberosity resorption, or avascular necrosis) and RTSA (notching and osteolysis) were assessed. In calculating the revision rate, we considered unplanned revision procedures only.
Compared with patients treated with ORIF, patients treated with RTSA had superior improvements in Constant (85.0 ± 7.0 versus 53.0 ± 5.0; mean difference 32 95% CI 30 to 34; p < 0.01), ASES (46.3 ± 3.7 versus 30.0 ± 3.5; mean difference 16 95% CI 15 to 18; p < 0.01), and DASH scores (40.5 ± 4.2 versus 30.5 ± 2.6; mean difference 10 95% CI 9 to 11; p < 0.01). The mean elevation was 135° ± 7° for patients with RTSA and 100° ± 6° for patients with ORIF (mean difference 35 o 95% CI 33 to 37; p < 0.01). The mean abduction was 131° ± 7° for patients with RTSA and 104° ± 6° for those with ORIF (mean difference 27 o 95% CI 25° to 29°; p < 0.01). The mean external rotation was 85° ± 5° for patients with RTSA and 64° ± 5° for those with ORIF (mean difference 21° 95% CI 19° to 23°; p < 0.01). The mean internal rotation was 45° ± 6° for patients with RTSA and 40° ± 6° for those with ORIF (mean difference 5° 95% CI 3° to 7°; p < 0.01). The risk of complications was not different between patients with ORIF and those with RTSA (5% three of 66 versus 1% one of 72; relative risk 3.3 95% CI 0.3 to 30.7; p = 0.30). Among patients with ORIF, 8% had varus malunions (five of 66), 6% had resorption of the greater tuberosity (four of 66), and 2% had avascular necrosis of the humeral head (one of 66). In the RTSA group, 24% (17 of 72 patients) demonstrated reabsorption of periprosthetic bone and 79% of patients (57 of 72) exhibited no notching. The risk of revision was not different between the RTSA and ORIF groups (0% 0 of 72 versus 9% six of 66; relative risk 0.07 95% CI 0.0 to 1.2; p = 0.07).
In patients older than 70 years with three-part and four-part proximal humerus fractures, primary RTSA resulted in better patient-reported outcome scores and better ROM than ORIF with an angular stable locking plate. Our findings might help surgeons decide between internal fixation and arthroplasty to surgically treat these injuries in older patients. Although RTSA seems to be a preferable treatment modality in view of these findings, longer follow-up is required to evaluate its longevity compared with ORIF with an angular locking plate. Dissimilar to ORIF, which is generally stable once healed, arthroplasties are at a continued risk for loosening and infection even after healing is complete.
Level II, therapeutic study.
Hindfoot, midfoot, and forefoot motion during the stance phase of walking provide insights into the forward progression of the body over the feet via the rocker mechanisms. These segmental motions ...are affected by walking speed. Increases in walking speed are accomplished by increasing step length and cadence. It is unknown if taking short, medium, and long steps at the same speed would increase hindfoot, midfoot, and forefoot motion similarly to walking speed. We examined effects of different step lengths at the same preferred walking speed on peak forefoot, midfoot, and hindfoot motions related to the foot rockers. Twelve young healthy adults completed five walking trials under three step length conditions in a random order as feet and lower extremity motion were measured via marker positions for the combined Oxford foot and conventional gait models. Peak hindfoot, midfoot, and forefoot joint angles indicating heel, ankle, and forefoot rockers were identified. When walking at the same preferred speed with increase in step length, there were increases in peak hindfoot-tibia plantarflexion angle (p < 0.001; ηp2 = 0.76) in early stance associated with the heel rocker and peak hindfoot-tibia dorsiflexion angle (p = 0.016; ηp2 = 0.39) in midstance associated with ankle rocker. In late stance, the peak hindfoot-tibia plantarflexion angle, forefoot-hindfoot angle, and forefoot-hallux dorsiflexion angle indicating forefoot rocker motion also increased with step length (p < 0.01). When foot kinematics are compared across different individuals or the same individual across different sessions, researchers and clinicians should consider the influence of step length as a contributor to differences in foot kinematics observed.
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