Hospital Careful Hand Feeding Program Reduced Feeding Tube Use in Patients with Advanced Dementia.

OBJECTIVES: Tube feeding is prevalent among patients with advanced dementia despite empirical data that suggest its lack of benefit. To provide an alternative to tube feeding for end-of-life patients, a careful hand feeding program was launched in a Hong Kong geriatric convalescent hospital in February 2017. We aim to compare the rates of feeding tube insertion before and after program implementation and determine risk factors for feeding tube insertion. For patients on careful hand feeding, we evaluated their sustainability on oral feeding and the rates of hospital readmissions compared with tube feeding patients over the next 12 months. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Advanced dementia patients ≥60 years with indication for tube feeding due to feeding problems admitted from January 2015-June 2019. METHODS: Data was collected on demographic and clinical variables, initial feeding mode (careful hand feeding vs. tube feeding), subsequent feeding mode changes, and hospital admissions over the next 12 months. Rates of feeding tube insertion, sustainability on oral feeding, and hospital readmissions were compared using Chi-square test. Risk factors for feeding tube insertion were assessed using logistic regression models. RESULTS: Among 616 advanced dementia patients admitted with feeding problems, feeding tube insertion rate declined significantly after careful hand feeding program implementation (72% vs 51% p<.001). Independent risk factors for feeding tube insertion were admission prior to program implementation, presence of dysphagia alone, dysphagia combined with poor intake, and lack of advance care planning. Among patients on careful hand feeding, 91% were sustained on oral feeding over the next twelve months and did not differ significantly before or after careful hand feeding program implementation (p=.67). There was no significant difference in hospital readmission rates between careful hand feeding patients and tube feeding patients before (83% vs 86%, p=.55) and after careful hand feeding program implementation (87% vs 85%, p=.63). CONCLUSIONS AND IMPLICATIONS: A hospital careful hand feeding program significantly reduced the feeding tube insertion rate among advanced dementia patients with feeding problems. The vast majority of patients on careful hand feeding were sustained on oral feeding over the next 12 months but their rate of hospital readmissions remained similarly high after program implementation.

Synthesized soliton crystals.

Dissipative Kerr soliton (DKS) featuring broadband coherent frequency comb with compact size and low power consumption, provides an unparalleled tool for nonlinear physics investigation and precise measurement applications. However, the complex nonlinear dynamics generally leads to stochastic soliton formation process and makes it highly challenging to manipulate soliton number and temporal distribution in the microcavity. Here, synthesized and reconfigurable soliton crystals (SCs) are demonstrated by constructing a periodic intra-cavity potential field, which allows deterministic SCs synthesis with soliton numbers from 1 to 32 in a monolithic integrated microcavity. The ordered temporal distribution coherently enhanced the soliton crystal comb lines power up to 3 orders of magnitude in comparison to the single-soliton state. The interaction between the traveling potential field and the soliton crystals creates periodic forces on soliton and results in forced soliton oscillation. Our work paves the way to effectively manipulate cavity solitons. The demonstrated synthesized SCs offer reconfigurable temporal and spectral profiles, which provide compelling advantages for practical applications such as photonic radar, satellite communication and radio-frequency filter.

Demonstration of a stable ultrafast laser based on a nonlinear microcavity.

Ultrashort pulsed lasers, operating through the phenomenon of mode-locking, have had a significant role in many facets of our society for 50 years, for example, in the way we exchange information, measure and diagnose diseases, process materials, and in many other applications. Recently, high-quality resonators have been exploited to demonstrate optical combs. The ability to phase-lock their modes would allow mode-locked lasers to benefit from their high optical spectral quality, helping to realize novel sources such as precision optical clocks for applications in metrology, telecommunication, microchip-computing, and many other areas. Here we demonstrate the first mode-locked laser based on a microcavity resonator. It operates via a new mode-locking method, which we term filter-driven four-wave mixing, and is based on a CMOS-compatible high quality factor microring resonator. It achieves stable self-starting oscillation with negligible amplitude noise at ultrahigh repetition rates, and spectral linewidths well below 130 kHz.

On-chip CMOS-compatible all-optical integrator.

All-optical circuits for computing and information processing could overcome the speed limitations intrinsic to electronics. However, in photonics, very few fundamental 'building blocks' equivalent to those used in multi-functional electronic circuits exist. In this study, we report the first all-optical temporal integrator in a monolithic, integrated platform. Our device--a lightwave 'capacitor-like' element based on a passive micro-ring resonator--performs the time integral of the complex field of an arbitrary optical waveform with a time resolution of a few picoseconds, corresponding to a processing speed of ∼200 GHz, and a 'hold' time approaching a nanosecond. This device, compatible with electronic technology (complementary metal-oxide semiconductor), will be one of the building blocks of next-generation ultrafast data-processing technology, enabling optical memories and real-time differential equation computing units.

Effect of thimerosal on Ca(2+) movement and viability in human oral cancer cells.

The effect of thimerosal on cytosolic free Ca(2+) concentrations ([Ca(2+)](i) ) in human oral cancer cells (OC2) is unclear. This study explored whether thimerosal changed basal [Ca(2+)](i) levels in suspended OC2 cells using fura-2. Thimerosal at concentrations between 1and 50 microM increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was reduced partly by removing extracellular Ca( 2+). Thimerosal-induced Ca(2+) influx was not blocked by L-type Ca(2+) entry inhibitors and protein kinase C modulators (phorbol 12-myristate 13-acetate [PMA] and GF109203X). In Ca(2+)-free medium, 50 microM thimerosal failed to induce a [Ca(2+)](i) rise after pretreatment with thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). Inhibition of phospholipase C with U73122 did not change thimerosal-induced [Ca(2+)](i) rises. At concentrations between 5 and 10 microM, thimerosal killed cells in a concentration-dependent manner. The cytotoxic effect of 8 muM thimerosal was potentiated by prechelating cytosolic Ca(2+) with the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate/acetomethyl (BAPTA/ AM). Flow cytometry data suggested that 1-7 microM thimerosal-induced apoptosis in a concentration-dependent manner. Collectively, in OC2 cells, thimerosal-induced [Ca(2+)](i) rises by causing phospholipase C-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) influx through non-L-type Ca(2+) channels. Thimerosal killed cells in a concentration-dependent manner through apoptosis.

The prognostic influence of prevertebral space involvement in nasopharyngeal carcinoma.

OBJECTIVES: The purpose of this study was to evaluate the effect of prevetebral space involvement on treatment outcomes in patients with nasopharyngeal carcinoma (NPC) who were treated with radiotherapy/concurrent chemoradiotherpy or concurrent chemoradiotherpy with adjuvant chemotherapy. DESIGN: A retrospective review of case notes from the Kaohsiung Veterans General Hospital archives was performed. SETTING: A medical centre in Taiwan. PARTICIPANTS: There were 145 newly diagnosed cases of NPC. Thirty-nine patients were excluded because of the presence of distant metastasis at the time of presentation, loss of follow-up and incomplete image information. MAIN OUTCOME MEASURES: Pearson's chi-square tests were used to analyse correlation between tumour invasion and prevetebral space involvement during univariate analysis and logistic regression was applied during multivariate analysis. Kaplan-Meier survival curves were constructed. Multivariate analysis was performed to examine the impact of various prognostic factors. Pearson's chi-square and Fisher's exact test were also used to evaluate the correlation between failure patterns and treatment modality. RESULTS: A total of 106 patients with newly diagnosed NPC were enrolled in this study. Forty-three patients (41%) in this series were found to have prevertebral space involvement. Patients with prevertebral space involvement conferred a poor overall survival rate and metastasis-free survival rate compared with those without prevertebral space invasion (P = 0.04 and 0.02 respectively). Multivariate analysis showed that prevertebral space invasion was associated with an increased risk for distant metastasis [hazard ratio (HR) 14, 95% confidence interval (CI) 1.0-17.4; P = 0.03)] and overall survival (HR 7, 95% CI 1.1-135; P = 0.04). In patients with prevertebral space involvement, their metastasis-free survival rate, with and without adjuvant chemotherapy, was 100% and 72.7% (P = 0.047). This phenomenon was not observed in NPC patients without prevertebral space invasion. CONCLUSIONS: The present data revealed that prevertebral space involvement has a close relationship with survival rates and recurrence rates of patients with NPC. Nasopharyngeal carcinoma patients with prevertebral space involvement have more recurrence and poorer survival rates and should be the group to benefit from concurrent chemoradiotherapy followed by adjuvant chemotherapy. Inclusion of prevertebral space involvement may be needed to predict prognosis of NPC and help us to identify the high-risk group.

A universal biosensing platform based on optical micro-ring resonators.

The use of optical micro-ring resonators as a platform for quantitative and qualitative biosensing applications was explored. Vertically coupled, high refractive index micro-ring resonators, used as sensing elements, were fabricated on silicon chips by photolithographic techniques. An optical reader system consisting of a near-infrared broad band light source and an optical spectrum analyzer were employed for data acquisition. Micro-ring resonator surfaces were modified with specific target receptors, including antibodies and single-stranded DNA oligonucleotides. The system was successfully used for label-free, specific, and rapid detection of whole bacterial cells, proteins and nucleic acids.

Phosphorylation of the 24p3 protein secreted from mouse uterus in vitro and in vivo.

The 24p3 protein is a 25 KDa glycoprotein, having been purified from mouse uterine fluid. Thr54, Ser88, and Thr128/Ser129 on the protein molecule were predicted to be the phosphorylation site of casein kinase II, protein kinase C, and cAMP-dependent protein kinase, respectively. Incorporation of phosphate to this protein from [gamma-32P]-ATP was tested in the solution suitable for the three kinases. Neither casein kinase II nor cAMP-dependent protein kinase reacted to the 24p3 protein; however, protein kinase C demonstrated phosphorylation to this protein. This phosphorylation may be competing with a polypeptide segment: Arg79-Tyr-Trp-Ilu-Arg-Thr-Phe-Val-Pro-Ser88-Ser-Arg-Ala-Gly-Gln-Phe-Thr-Leu-Gly97 in the 24p3 protein molecule. To support this theory, Ser88 is a phosphorylation site of protein kinase C on 24p3 protein. The enzyme kinetic parameter, based on the Michaelis-Menten equation, determined Km to be 2.96 microM in the phosphorylation of 24p3 protein by the kinase. Both of the phosphorylated and dephosphorylated form of 24p3 protein can enhance the cAMP-dependent protein kinase activity in vitro. In addition, this experiment will show for the first time that serine-phosphorylated 24p3 protein exists in mouse uterine tissue.

A seminal vesicle autoantigen of mouse is able to suppress sperm capacitation-related events stimulated by serum albumin.

We studied the effect of a mouse seminal vesicle autoantigen (SVA) on BSA-stimulated functions of mouse sperm. Uncapacitated, capacitated, and acrosome-reacted stages of sperm were morphologically scored, and the cellular zinc content was examined cytologically in a modified Tyrode solution at 37 degrees C for 80 min. More than 85% of control cells remained uncapacitated. Addition of 0.3% SVA to the cell incubation did not affect the cell status. Approximately 65% of cells were capacitated in the incubation medium containing 0.3% BSA. Only 30% of the cells became capacitated after incubation with 0.3% BSA and 0.3% SVA together. The decapacitation effect by 0.3% SVA could be subdued by more than 3% BSA in the cell incubation. Whereas BSA did, SVA did not cause removal of Zn(2+) from sperm, but SVA could suppress the BSA effect. The tyrosine phosphorylated proteins in sperm were detected after incubation in a modified HEPES medium containing 0.3% BSA and/or 0.3% SVA at 37 degrees C for 90 min. Whereas BSA enhanced greatly, SVA did not cause phosphorylation of proteins in the range of M:(r) 40 000-120 000. The BSA-stimulated protein tyrosine phosphorylation could be suppressed by SVA in the cell incubation.

Expression, immunolocalization and sperm-association of a protein derived from 24p3 gene in mouse epididymis.

The cDNA sequence for 24p3 protein in ICR mouse epididymal tissue was determined by PCR using primers designed according to the cDNA sequence derived from 24p3 protein in mouse uterine tissue. In the present study, 24p3 protein was immunolocalized in the epithelial cells and lumen of mouse epididymis. Both immunoblot analysis for protein and northern blot analysis for mRNA level showed a declining gradient of 24p3 expression from the caput to caudal region of the epididymis. The 24p3 protein was undetectable in the testis. These findings suggest that the 24p3 protein is a caput-initiated secretory protein in the mouse epididymis. A postnatal study revealed that 24p3 gene expression occurred in mice at the age of 14 days, before the completion of epididymal differentiation. This expression remained at a constant level until epididymal differentiation was completed. We also found that the secreted 24p3 protein interacted predominantly with the acrosome of caudal spermatozoa. Our findings suggest that the epididymal 24p3 protein is a caput-initiated and sperm-associated gene product and may be important in the reproductive system.

Pedestal antiresonant reflecting waveguides for robust coupling to microsphere resonators and for microphotonic circuits.

Strip-line pedestal antiresonant reflecting waveguides are high-confinement, silica integrated optical waveguides in which the optical modes are completely isolated from the substrate by thin high-index layers. These waveguides are particularly well suited for whispering-gallery mode excitation in high-Q microspheres. They can also be used in microphotonic circuits, such as for microring resonators. The theory and design of these structures are highlighted. Experiments that show high coupling efficiency to microspheres are also demonstrated.

Filter synthesis for periodically coupled microring resonators.

The theory of filter synthesis using periodically coupled microring resonators is developed as a means to overcome the fabrication sensitivities inherent in conventional higher-order filters, while still achieving desirable spectral characteristics. Each resonator in the array can compensate for deficiencies in any of the others. These filters exhibit a boxlike shape and very high extinction ratios.

Vertical antiresonant reflecting optical waveguide coupler for three-dimensional optical interconnects: optimum design for large tolerance, high coupling efficiency, and short coupling length.

A compact antiresonant-reflecting-optical-waveguide-(ARROW-) type vertical coupler for three-dimensional optical interconnects was demonstrated. The coupler consists of stacked ARROW's channeled by the stripe lateral confinement structure, and each waveguide is completely separated by a thin metal film in the separation region. In the coupling region the intermediate cladding of a previous coupler was made of the same material as that of the first cladding or the core. However, we had to overcome the problem that both the high coupling efficiency and the large fabrication tolerance cannot be achieved simultaneously. Thus we incorporated an intermediate cladding made of a material different from that of the core and the first cladding. The refractive index and the thickness of the intermediate cladding were optimally designed to achieve large fabrication tolerance and a short coupling length with a high coupling efficiency. The coupling length was reduced from 4.1 to 0.8 mm, and a high coupling efficiency of 96% was experimentally demonstrated.

Recurrent inverted papilloma: diagnosis with pharmacokinetic dynamic gadolinium-enhanced MR imaging.

BACKGROUND AND PURPOSE: Dynamic gadolinium-enhanced MR imaging has been used successfully to identify post-treatment recurrence or postoperative changes in rectal and cervical carcinoma. Our purpose was to evaluate the usefulness of dynamic gadolinium-enhanced MR imaging for distinguishing recurrent inverted papilloma (IP) from postoperative changes. METHODS: Fifteen patients with 20 pathologically proved lesions (recurrent IP, 12; fibrosis or granulation tissue, eight) were enrolled in the study. Three observers, blinded to pathologic results, independently evaluated conventional MR images, including T1-weighted (unenhanced and postcontrast), proton-density-weighted, and T2-weighted spin-echo images. Results then were determined by consensus. Dynamic images were obtained using fast spin-echo sequences at 5, 30, 60, 90, 120, 150, 180, and 300 seconds after the injection of gadolinium-diethylene-triamine penta-acetic acid. Time-signal intensity curves of suspected lesions were analyzed by a pharmacokinetic model. The calculated amplitude and tissue distribution time were used to characterize tissue, and their values were displayed as a color-coded overlay. RESULTS: T2-weighted images yielded a sensitivity of 67%, a specificity of 75%, and an accuracy of 70% in the diagnosis of recurrent IP. Contrast-enhanced T1-weighted images yielded a sensitivity of 75%, a specificity of 50%, and an accuracy of 65%. Pharmacokinetic analysis showed that recurrent IP had faster (distribution time, 41 versus 88 seconds) and higher (amplitude, 2.4 versus 1.2 arbitrary units) enhancement than did fibrosis or granulation tissue. A cut-off of 65 seconds for distribution time and 1.6 units for amplitude yielded a sensitivity of 100% and a specificity of 100% for diagnosing recurrent IP. CONCLUSION: Dynamic MR imaging can differentiate accurately recurrent IP from postoperative changes and seems to be a valuable diagnostic tool.

Seminal vesicle autoantigen, a novel phospholipid-binding protein secreted from luminal epithelium of mouse seminal vesicle, exhibits the ability to suppress mouse sperm motility.

Seminal vesicle autoantigen (SVA) is a 19 kDa glycoprotein purified from mouse seminal vesicle secretion. It was quantified to be 0.9% (w/v) in the seminal vesicle fluid. We examined its distribution in the accessory sexual gland, characterized its binding sites on the sperm surface and assessed its effect on sperm motility. It was immunolocalized on the epithelium of the primary and secondary folds in the tissue. Mouse spermatozoa collected from caudal epididymis were devoid of SVA. A cytochemical study illustrated the presence of SVA-binding region on the entire cells. The cytochemical staining intensity for the binding of SVA to spermatozoa remained even when the cells were pretreated with protease digestion, acid or heat at 100 degrees C for 10 min. Moreover, the SVA-sperm binding could be inhibited by the dispersed sperm lipid. The specificity of interaction between (125)I-SVA and phospholipids was studied by TLC overlay techniques. The radiolabelled protein showed strong binding to purified phosphatidylcholine and phosphatidylserine and weak binding to purified sphingomyelin, lysophosphatidylcholine and phosphatidylethanolamine, but did not interact with phosphatidic acid, lysophosphatidic acid or phosphatidylinositol. Among the lipids extracted from spermatozoa, SVA showed strong binding to phosphatidylcholine and weak binding to sphingomyelin and neutral lipids. The assay for SVA-sperm binding with (125)I-SVA determined the IC(50) as being (3.89+/-0.65)x10(-5) M(-1), which is compatible with an apparent dissociation constant of (9.10+/-0.02)x10(-5) M(-1) estimated by fitting the data of phosphatidylcholine-perturbed SVA fluorescence to a modified Scatchard plot. SVA showed an ability to suppress sperm motility. The average path velocity, straight-line velocity and curvilinear velocity of sperm were not detectable by computer-assisted sperm assay after incubation of the cells in the presence of 0.3% SVA at 37 degrees C for more than 40 min.

Ovarian steroids regulate 24p3 expression in mouse uterus during the natural estrous cycle and the preimplantation period.

We examined 24p3 expression in the mouse uterus at various stages of the natural estrous cycle and during the preimplantation period. The level of 24p3 mRNA appeared intensively in proestrus and estrus, then declined sharply from metestrus to diestrus. Consistent with this observation, 24p3 protein was abundant in proestrus, decreased from estrus to metestrus and declined to a very low level in diestrus. The uterine 24p3 expression closely overlapped with the estradiol (E2) surge in proestrus and estrus but it was suppressed when progesterone (P4) rose to a high level during the reproductive cycle. Neither the protein nor its message was detected in the uteri of immature mice or ovariectomized adult animals. While an injection of P4 to these animals was unable to initiate uterine 24p3 expression, administration of estrogenic steroids to these animals markedly stimulated the gene expression. Treatment of these animals with E2 together with P4, on the other hand, did not stimulate the gene expression. In pregnant animals (day 1 (D1)=day of vaginal plug), 24p3 mRNA remained at a high level on D1 and D2 but dropped to an almost undetectable level on D3 and D4. This was accompanied by a decrease in 24p3 protein from D1 to D2 and a decline in the protein to undetectable levels from D3 to D4. The staining patterns of both the immunohistochemical localization of 24p3 protein and in situ hybridization for the detection of 24p3 mRNA in the uterine sections showed that 24p3 expression took place mainly in the luminal and glandular epithelial cells of the endometrium. This together with our previous observation that 24p3 protein is found in uterine luminal fluid indicates that the protein is secreted primarily from these cells to their respective luminal surfaces during proestrus and estrus.

Polarization effects in near-field excitation-collection probe optical microscopy of a single quantum dot.

We solve numerically the three-dimensional vector form of Maxwell's equation for the situation of near-field excitation and collection of luminescence from a single quantum dot, using a scanning near-field optical fibre probe with subwavelength resolution. We highlight the importance of polarization-dependent effects in both the near-field excitation and collection processes. Applying a finite-difference time domain method, we calculate the complete vector fields emerging from a realistic probe structure which is in close proximity to a semiconductor surface. We model the photoluminescence from the quantum dot in terms of electric dipoles of different polarization directions, and determine the near-field luminescence images of the dot captured by the same probe. We show that a collimating effect in the high index semiconductor significantly improves the spatial resolution in the excitation-collection mode. We find that the spatial resolution, image shape and collection efficiency of near-field luminescence imaging strongly depend on the polarization direction as represented by the orientation of the radiating electric dipoles inside the quantum dot.

The hydrophobic pocket of 24p3 protein from mouse uterine luminal fluid: fatty acid and retinol binding activity and predicted structural similarity to lipocalins.

The conformation of 24p3 protein purified from mouse uterine luminal fluid was studied by circular dichroism spectroscopy in 200-300 nm. At pH 7.4, the spectrum in the UV region appears as one negative band with a minimum mean residue ellipticity of -3,600 deg.cm2.dmole(-1) at 217 nm, suggesting a very low or no helical content, but a considerable amount of beta-form, beta-turn, and unordered form in the protein molecule. This agrees with the predicted secondary structures consisting of only one a-helical segment of residues 150-163 and nine segments of residues 28-35, 50-60, 67-72, 78-86, 94-97, 106-114, 119-125, 136-140 and 166-172 in beta-forms, which would construct two orthonormal beta-sheets to form a less polar beta-barrel. The environments around Trp-31 and Trp-81 of this protein were studied by intrinsic fluorescence and solute quenching. They give an emission peak at 332 nm, and only about 21% of them are accessible to quenching by acrylamide. This together with their low accessibility to either CsCI or KI suggests that they are located in the less polar beta-barrel. Hydrophobic compounds such as fatty acids, retinoids, and cholesteryl oleate in the protein solution diminish the protein fluorescence. Analysis of the fluorescence data suggests that the protein has a binding site for hydrophobic ligand. The association constants for the complex formation are 1.03 x 10(6) MM(-1), 1.92 x 10(5) M(-1), 2.38 x 10(5) M(-1) or 1.25 x 10(5) M(-1) for cholesteryl oleate, oleic acid, retinol, or retinoic acid at pH 7.4. Analysis of the equilibrium binding data from binding assay using [H3]-retinol and [H3]-retinoic acid reveals a singular type of retinoid-binding site in the protein with the association constant of 4.92 x 10(5) M(-1) and 1.17 x 10(5) M(-1) for retinol and retinoic acid, respectively. Trp-31 or/ and Trp-81 is in or very near the binding site and the gross conformation of protein changes considerably as the formation of protein-ligand complex.

Track changing by use of the phase response of microspheres and resonators.

A microsphere or resonator that is side coupled to an incident optical beam induces a phase response in the beam. In the so-called overcoupled regime, the amplitude of the incident beam remains unmodulated, whereas the phase goes through a shift of p at resonance. This shift is insensitive to the details of the coupling geometry or the resonant mode. In conjunction with an interferometer, the phase response can be used to switch the beam between two well-defined outputs, thus offering a robust means of deploying microspheres and other microresonators in practical photonic devices.

Second-order filtering and sensing with partially coupled traveling waves in a single resonator.

The counterpropagating waves in a single traveling-wave cavity can be partially coupled by means of a small perturbation such as a notch. When it is side coupled to a waveguide, this single cavity yields a general second-order (Chebyshev) reflection response in the waveguide, which is useful for narrow-bandwidth reflecting applications. In a different application, the cavity amplifies small reflections induced by external perturbations, thus finding use in ultrafine sensing. Amplification factors as great as 10(12) are predicted for the highest-Q microsphere resonators. The analytic theory of these devices is presented.