Non-pharmacological and pharmacological treatments for bone health after stroke: Systematic review with meta-analysis.

BACKGROUND: Hemi-osteoporosis is a common secondary complication of stroke. No systematic reviews of pharmacological and non-pharmacological agents for post-stroke bone health have estimated the magnitude and precision of effect sizes to guide better clinical practice. OBJECTIVES: To examine the benefits and harms of pharmacological and non-pharmacological agents on bone health in post-stroke individuals. METHODS: Eight databases were searched (PubMed, Cochrane library, Scopus, CINAHL Complete, Embase, PEDro, Clinicaltrils.gov and ICTRP) up to June 2023. Any controlled studies that applied physical exercise, supplements, or medications and measured bone-related outcomes in people with stroke were included. PEDro and the GRADE approach were used to examine the methodological quality of included articles and quality of evidence for outcomes. Effect sizes were calculated as standardized mean differences (SMD) and risk ratio (RR). Review Manager 5.4 was used for data synthetization. RESULTS: Twenty-four articles from 21 trials involving 22,500 participants (3,827 in 11 non-pharmacological and 18,673 in 10 pharmacological trials) were included. Eight trials were included in the meta-analysis. The methodological quality of half of the included non-pharmacological studies was either poor or fair, whereas it was good to excellent in 8 of 10 pharmacological studies. Meta-analysis revealed a beneficial effect of exercise on the bone mineral density (BMD) of the paretic hip (SMD: 0.50, 95 % CI: 0.16; 0.85; low-quality evidence). The effects of anti-resorptive medications on the BMD of the paretic hip were mixed and thus inconclusive (low-quality evidence). High-quality evidence showed that the administration of antidepressants increased the risk of fracture (RR: 2.36, 95 % CI 1.64-3.39). CONCLUSION: Exercise under supervision may be beneficial for hip bone health in post-stroke individuals. The effect of anti-resorptive medications on hip BMD is uncertain. The adverse effects of antidepressants on fracture risk among post-stroke individuals warrant further attention. Further high-quality studies are required to better understand this issue. REGISTRATION: PROSPERO CRD42022359186.

miR-145 as a Potential Biomarker and Therapeutic Target in Patients with Non-Small Cell Lung Cancer.

Our previous study found that miR-145 was downregulated in non-small cell lung cancer (NSCLC) tissues and that it could inhibit the cell proliferation in transfected NSCLC cells. In this study, we found that miR-145 was downregulated in NSCLC plasma samples compared to healthy controls. A receiver operating characteristic curve analysis indicated that plasma miR-145 expression was correlated with NSCLC in patient samples. We further revealed that the transfection of miR-145 inhibited the proliferation, migration, and invasion of NSCLC cells. Most importantly, miR-145 significantly delayed the tumor growth in a mouse model of NSCLC. We further identified GOLM1 and RTKN as the direct targets of miR-145. A cohort of paired tumors and adjacent non-malignant lung tissues from NSCLC patients was used to confirm the downregulated expression and diagnostic value of miR-145. The results were highly consistent between our plasma and tissue cohorts, confirming the clinical value of miR-145 in different sample groups. In addition, we also validated the expressions of miR-145, GOLM1, and RTKN using the TCGA database. Our findings suggested that miR-145 is a regulator of NSCLC and it plays an important role in NSCLC progression. This microRNA and its gene targets may serve as potential biomarkers and novel molecular therapeutic targets in NSCLC patients.

MicroRNA-338-5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id-1.

5-Fluorouracil (5-FU) is a chemotherapeutic agent commonly used to treat esophageal squamous cell carcinoma (ESCC), but acquisition of chemoresistance frequently occurs and the underlying mechanisms are not fully understood. We found that microRNA (miR)-338-5p was underexpressed in ESCC cells with acquired 5-FU chemoresistance. Forced expression of miR-338-5p in these cells resulted in downregulation of Id-1, and restoration of both in vitro and in vivo sensitivity to 5-FU treatment. The effects were abolished by reexpression of Id-1. In contrast, miR-338-5p knockdown induced 5-FU resistance in chemosensitive esophageal cell lines, and knockdown of both miR-338-5p and Id-1 resensitized the cells to 5-FU. In addition, miR-338-5p had suppressive effects on migration and invasion of ESCC cells. Luciferase reporter assay confirmed a direct interaction between miR-338-5p and the 3'-UTR of Id-1. We also found that miR-338-5p was significantly downregulated in tumor tissue and serum samples of patients with ESCC. Notably, low serum miR-338-5p expression level was associated with poorer survival and poor response to 5-FU/cisplatin-based neoadjuvant chemoradiotherapy. In summary, we found that miR-338-5p can modulate 5-FU chemoresistance and inhibit invasion-related functions in ESCC by negatively regulating Id-1, and that serum miR-338-5p could be a novel noninvasive prognostic and predictive biomarker in ESCC.

Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy.

Metastasis is the most lethal hallmark of esophageal squamous cell carcinoma (ESCC). The aim of the study is to identify key signaling pathways that control metastasis in ESCC. Highly invasive ESCC sublines (designated I3 cells) were established through three rounds of selection of cancer cells invading through matrigel-coated chambers. Gene expression profile of one of the I3 sublines was compared with that of its parental cell line using cDNA microarray analysis. Gene ontology and pathway analyses of the differentially expressed genes (both upregulated and downregulated) indicated that genes associated with cellular movement and the AKT pathway were associated with increased cancer cell invasiveness. Western blot analysis confirmed increased phosphorylated AKT (p-AKT), N-cadherin and decreased E-cadherin expression in the I3 cells. Immunohistochemistry was used to evaluate the clinical significance of p-AKT expression in ESCC, and the results showed higher p-AKT nuclear expression in lymph node metastases when compared with primary carcinoma. Inactivation of the PI3K/AKT pathway with specific inhibitors, or with PTEN overexpression, resulted in reversed cadherin switching and inhibited cancer cell motility. Inhibition of the pathway by treatment with wortmannin markedly suppressed experimental metastasis in nude mice. Our data demonstrated the importance of the PI3K/AKT signaling pathway in ESCC metastasis and support PI3K/AKT as a valid therapeutic target in treatment of metastatic ESCC.

Silent genetic alterations identified by targeted next-generation sequencing in pheochromocytoma/paraganglioma: A clinicopathological correlations.

AIMS: The goal of this pilot study was to develop a customized, cost-effective amplicon panel (Ampliseq) for target sequencing in a cohort of patients with sporadic phaeochromocytoma/paraganglioma. METHODS: Phaeochromocytoma/paragangliomas from 25 patients were analysed by targeted next-generation sequencing approach using an Ion Torrent PGM instrument. Primers for 15 target genes (NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, MEN1, KIF1Bß, EPAS1, CDKN2 & PHD2) were designed using ion ampliseq designer. Ion Reporter software and Ingenuity® Variant Analysis™ software (www.ingenuity.com/variants) from Ingenuity Systems were used to analysis these results. RESULTS: Overall, 713 variants were identified. The variants identified from the Ion Reporter ranged from 64 to 161 per patient. Single nucleotide variants (SNV) were the most common. Further annotation with the help of Ingenuity variant analysis revealed 29 of these 713variants were deletions. Of these, six variants were non-pathogenic and four were likely to be pathogenic. The remaining 19 variants were of uncertain significance. The most frequently altered gene in the cohort was KIF1B followed by NF1. Novel KIF1B pathogenic variant c.3375+1G>A was identified. The mutation was noted in a patient with clinically confirmed neurofibromatosis. Chromosome 1 showed the presence of maximum number of variants. CONCLUSIONS: Use of targeted next-generation sequencing is a sensitive method for the detecting genetic changes in patients with phaeochromocytoma/paraganglioma. The precise detection of these genetic changes helps in understanding the pathogenesis of these tumours.

Self-aligned multi-channel superconducting nanowire single-photon detectors.

We describe a micromachining process to allow back-side coupling of an array of single-mode telecommunication fibers to individual superconducting nanowire single photon detectors (SNSPDs). This approach enables a back-illuminated detector structure which separates the optical access and electrical readout on two sides of the chip and thus allows for compact integration of multi-channel detectors. As proof of principle, we show the integration of four detectors on the same silicon chip with two different designs and their performances are compared. In the optimized design, the device shows saturated system detection efficiency of 16% while the dark count rate is less than 20 Hz, all achieved without the use of metal reflectors or distributed Bragg reflectors (DBRs). This back-illumination approach also eliminates the cross-talk between different detection channels.

Cascaded optical transparency in multimode-cavity optomechanical systems.

Electromagnetically induced transparency has great theoretical and experimental importance in many areas of physics, such as atomic physics, quantum optics and, more recent, cavity optomechanics. Optical delay is the most prominent feature of electromagnetically induced transparency, and in cavity optomechanics, the optical delay is limited by the mechanical dissipation rate of sideband-resolved mechanical modes. Here we demonstrate a cascaded optical transparency scheme by leveraging the parametric phonon-phonon coupling in a multimode optomechanical system, where a low damping mechanical mode in the unresolved-sideband regime is made to couple to an intermediate, high-frequency mechanical mode in the resolved-sideband regime of an optical cavity. Extended optical delay and higher transmission as well as optical advancing are demonstrated. These results provide a route to realize ultra-long optical delay, indicating a significant step towards integrated classical and quantum information storage devices.

Prevalence and risk factors for age-related macular degeneration in the elderly Chinese population in south-western Taiwan: the Puzih eye study.

AIM: This study aimed to ascertain the prevalence of and the risk factors associated with early and late age-related macular degeneration (AMD) among Chinese individuals aged ≥65 years residing in Puzih, Taiwan. METHODS: This population-based cross-sectional study graded digital colour photographs of the ocular fundus of 673 individuals using the Wisconsin Age-Related Maculopathy Grading System. We compared the characteristics of individuals with early and late AMD using χ(2)-analyses and described risk factors for early and late AMD using odds ratios and 95% confidence intervals. RESULTS: Individuals with late AMD were significantly older and more likely to have hypertension. Further, their sunlight exposure time was longer than that of those with early AMD, only drusen, or no AMD lesions (P<0.01). A history of hyperlipidaemia for >10 years was a significant risk factor for early AMD, while old age, hypertension for >10 years, and exposure to sunlight for >8 h per day were associated with late AMD. CONCLUSIONS: The prevalence rate of early AMD in the present study was 15.0%, which is similar to that reported for Caucasians and Japanese included in the European Eye Study and the Hisayama Study, respectively. The late AMD prevalence rate of 7.3% found among our study participants was comparable to that reported by the Greenland Inuit Eye Study and Reykjavik Study, but considerably lower than that reported for Caucasians, indicating that late AMD might be less prevalent among Asians than Caucasians.

Electrical tuning and switching of an optical frequency comb generated in aluminum nitride microring resonators.

Aluminum nitride (AlN) has been shown to possess both strong Kerr nonlinearity and electro-optic Pockels effect. By combining these two effects, here we demonstrate on-chip reversible on/off switching of the optical frequency comb generated by an AlN microring resonator. We optimize the design of gating electrodes and the underneath resonator structure to effectively apply an electric field without increasing the optical loss. The switching of the comb is monitored by measuring one of the frequency comb peaks while varying the electric field. The controlled comb electro-optic response is investigated for direct comparison with the transient thermal effect.

Optical frequency comb generation from aluminum nitride microring resonator.

Aluminum nitride (AlN) is an appealing nonlinear optical material for on-chip wavelength conversion. Here we report optical frequency comb generation from high-quality-factor AlN microring resonators integrated on silicon substrates. By engineering the waveguide structure to achieve near-zero dispersion at telecommunication wavelengths and optimizing the phase matching for four-wave mixing, frequency combs are generated with a single-wavelength continuous-wave pump laser. Further, the Kerr coefficient (n2) of AlN is extracted from our experimental results.

Clinical impacts of mammalian target of rapamycin expression in human colorectal cancers.

This study investigated the clinicopathologic roles of mammalian target of rapamycin (mTOR) expression and its relationship to carcinogenesis and tumor progression in a colorectal adenoma-adenocarcinoma model. Two colon cancer cell lines with different pathologic stages (SW480 and SW48) and 1 normal colonic epithelial cell line (FHC) were used, in addition to 119 colorectal adenocarcinomas and 32 adenomas. mTOR expression profiles at messenger RNA (mRNA) and protein levels were investigated in the cells and tissues using real-time quantification polymerase chain reaction and immunohistochemistry. The findings were correlated with the clinicopathologic features of the tumors. The colon cell line from stage III cancer (SW48) showed higher expression of mTOR mRNA than that from stage II cancer (SW480). At the tissue level, mTOR showed higher mRNA and protein expression in colorectal carcinoma than in adenoma. The mRNA and protein expression was correlated with each other in approximately one-third of the carcinomas and adenomas. High levels of mTOR mRNA expression were noted more in carcinoma or adenoma arising from the distal portion of the large intestine (P = .025 and .019, respectively). Within the colorectal cancer population, a high level of expression of mTOR mRNA was related to the presence of lymph node metastases (P = .031), advanced pathologic stage (P = .05), and presence of persistent disease or tumor recurrence (P = .035). To conclude, the study has indicated that mTOR is likely to be involved in the development and progression of colorectal cancer and is linked to cancer initiation, invasiveness, and progression.

Thermographic imaging during nasal peanut challenge may be useful in the diagnosis of peanut allergy.

BACKGROUND: Double-blinded challenges are widely used for diagnosing food allergy but are time-consuming and cause severe reactions. Outcome relies on subjective interpretation of symptoms, which leads to variations in outcome between observers. Facial thermography combined with nasal peanut challenge was evaluated as a novel objective indicator of clinical allergy. METHODS: Sixteen children with positive blinded peanut challenge underwent nasal challenge with 10 µg peanut protein or placebo. Mean skin temperatures were recorded from the mouth and nose using infrared thermography over 18 min. RESULTS: The area under curve of nasal skin temperature was significantly elevated after peanut vs placebo (18.2 vs 4.8°Cmin). The maximum increase in temperature was also significantly greater after peanut: mean difference +0.9°C. CONCLUSION: This feasibility study shows thermography can detect inflammation caused by nasal challenges whilst employing one thousand-fold less peanut than an oral challenge. This novel technique could be developed to provide a rapid, safe and objective clinical allergy test.

Near-infrared distributed feedback solgel lasers by intensity modulation and polarization modulation.

Near-infrared distributed feedback (DFB) laser actions of Oxazine 725 dye in zirconia thin films and in silica bulks were investigated. Intensity modulation and polarization modulation were used to generate the DFB lasing. Wideband tuning of the output wavelength was achieved by varying the period of the modulation generated by a nanosecond Nd:YAG laser at 532 nm. Tuning ranges were 716-778 nm and 724-813 nm for the thin film lasers and the bulk lasers, respectively. The laser output showed different polarization characteristics and threshold energy variation when the feedback mechanism was changed from intensity modulation to polarization modulation.

GHz optomechanical resonators with high mechanical Q factor in air.

We demonstrate wheel-shaped silicon optomechanical resonators for resonant operation in ambient air. The high finesse of optical whispering gallery modes (loaded optical Q factor above 500,000) allows for efficient transduction of the wheel resonator's mechanical radial contour modes of frequency up to 1.35 GHz with high mechanical Q factor around 4,000 in air.

Tunable optical coupler controlled by optical gradient forces.

We demonstrate optical gradient force-tunable directional couplers in free-standing silicon nitride slot waveguides. Utilizing device geometries optimized for strong optomechanical interactions allows us to control the optical transmission without the aid of a cavity. Static, wideband tuning as well as low-power optical modulation is achieved.

Integrated GaN photonic circuits on silicon (100) for second harmonic generation.

We demonstrate second order optical nonlinearity in a silicon architecture through heterogeneous integration of single-crystalline gallium nitride (GaN) on silicon (100) substrates. By engineering GaN microrings for dual resonance around 1560 nm and 780 nm, we achieve efficient, tunable second harmonic generation at 780 nm. The χ2 nonlinear susceptibility is measured to be as high as 16 ± 7 pm/V. Because GaN has a wideband transparency window covering ultraviolet, visible and infrared wavelengths, our platform provides a viable route for the on-chip generation of optical wavelengths in both the far infrared and near-UV through a combination of χ2 enabled sum-/difference-frequency processes.

A longitudinal study of resolution of allergy to well-cooked and uncooked egg.

BACKGROUND: Egg allergy is common and although resolution to uncooked egg has been demonstrated, there is lack of evidence to guide reintroduction of well-cooked egg. OBJECTIVES: To examine the rate of resolution to well-cooked, compared with uncooked egg in children, and safety of egg challenges. METHOD: A longitudinal study of egg-allergic children from 2004 to 2010, who underwent challenge with well-cooked and if negative, uncooked egg. Participants underwent repeat annual challenges and egg-specific IgE measurement. RESULTS: One hundred and eighty-one open egg challenges were performed in 95 children whose median age of allergy onset was 12 months. Fifty-three of 95 (56%) had at least one annual repeat challenge. Pre-study historical reactions occurred to baked egg in five (5%), lightly cooked in 58 (61%) and uncooked in nine (9%); respiratory reactions occurred in 11 (12%) and seven (7%) had anaphylaxis; adrenaline was used during five reactions. There were 77 well-cooked and 104 uncooked egg challenges. Tolerance was gained twice as rapidly to well-cooked than uncooked egg (median 5.6 vs. 10.3 years; P<0.0001) and continued to 13 years; hazard ratio 2.23 (95% confidence interval 1.6-3.9). Nearly 1/3 had resolved allergy to well-cooked egg at 3 years and 2/3 at 6 years. Of 28/77 (37%) positive well-cooked egg challenges, 65% had cutaneous symptoms, 68% gastrointestinal and 39% rhinitis, with no other respiratory reactions. Adrenaline was not required. CONCLUSIONS AND CLINICAL RELEVANCE RESOLUTION: of egg allergy takes place over many years, with children outgrowing allergy to well-cooked egg approximately twice as quickly as they outgrow allergy to uncooked egg. There were no severe reactions to well-cooked egg challenge, and adrenaline was not required. Our data support initiation of home reintroduction of well-cooked egg from 2 to 3 years of age in children with previous mild reactions and no asthma. Resolution continues to occur in older children, so that despite an earlier positive challenge, attempts at reintroduction should be continued.

Efficacy and safety of high-dose peanut oral immunotherapy with factors predicting outcome.

BACKGROUND: Peanut allergy is severe and rarely resolves. OBJECTIVE: To test the efficacy and safety of a new oral immunotherapy (OIT) protocol for peanut allergy. METHOD: Twenty-two peanut-allergic children underwent oral challenge. OIT was administered by gradual updosing with 2-weekly increments (8-38 weeks) to 800 mg of protein (5 peanuts/day) followed by 30-week maintenance. Oral challenge was repeated after 6 and 30 weeks maintenance. RESULTS: Twenty-two children (median 11 years) had positive challenges (threshold 1-110 mg). Nineteen of 22 (86%) tolerated updosing and maintenance at 800 mg protein/day. One of 22 dropped out; 2/22 tolerated updosing and maintenance at 200-400 mg protein. Reactions, mostly mild, occurred in 86% during immunotherapy, adrenaline was not required. Eight of 8 with pre-immunotherapy peanut IgE<27.3 kU/L required no dose adjustment compared with 5/13 with pre-immunotherapy peanut IgE≥27.3 kU/L. Twelve of 22 (54%) required a transient dose reduction because of reactions possibly related to extrinsic factors: tiredness, infection and exercise. After 6 weeks, 12/22 (54%) had no reaction to a 2.6 g protein challenge. After 30 weeks, 14/22 (64%) tolerated 6.6 g protein. The median tolerated peanut dose increased 1000-fold following immunotherapy, from 6 to 6459 mg of protein. CONCLUSIONS AND CLINICAL RELEVANCE: We used a novel protocol using gradual updosing, and higher maintenance dose resulting in a better outcome compared with rush protocols. There was a 1000-fold increase in the amount of peanut tolerated with a good safety profile. No serious adverse events occurred. Most subjects tolerated five peanuts and all were protected against amounts likely during accidental ingestion. New information is provided on 'extrinsic factors', updosing method and factors associated with success (trial registration http://ClinicalTrials.gov- ID number NCT01259804).

Immediately sequential bilateral cataract surgery versus delayed sequential bilateral cataract surgery: potential hospital cost savings.

OBJECTIVE: Cataract surgery represents a substantial cost to health care systems around the world. Canada's socialized medical system allows an opportunity to accurately track costing because of the institutional record keeping necessary for public reporting to provincial governments. Cataract surgical costs consist of medical costs, hospital costs, and social costs. Our study compared the hospital costs of immediately sequential bilateral cataract surgery (ISBCS) with delayed sequential bilateral cataract surgeries (DSBCS), minimizing other interfering variables. DESIGN: Retrospective chart review with collection of associated costing information from the hospital. PARTICIPANTS: Twenty-two consecutive patients undergoing ISBCS with posterior chamber intraocular lens implantation and a randomly selected group of 22 patients undergoing similar DSBCS during the same period. METHODS: Hospital costs were determined using the London Health Sciences Centre case-costing system. Average costs were calculated and compared statistically. RESULTS: Average hospital costs were significantly reduced when performing ISBCS (p < 0.0001); 2 separate unilateral cataract surgeries totaled $1566.30, compared with $1059.10 for one bilateral cataract surgery (32.4% reduction). Pre- and post-operative in-hospital care accounted for a significant portion of this difference (54%), as 2 separate surgeries cost $547.92 compared with $273.96 for ISBCS. CONCLUSIONS: ISBCS provided considerable hospital cost savings compared to DSBCS.