Association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and macular degeneration in patients with diabetes: a nationwide population-based study in Taiwan.

AIMS: Evidence showed that SGLT2 inhibitors have greater protective effects against retinal diseases compared to other hypoglycemic agents. Thus, we explore the association between SGLT2 inhibitor usage and macular degeneration (MD) in Taiwanese patients with diabetes. METHODS: The National Health Insurance (NHI) program's claim data are released as the National Health Insurance Research Database (NHIRD). This database covers more than 99% of the residents in Taiwan. We included data on patients who were newly diagnosed with type 2 diabetes mellitus (ICD-9-CM: 250, exclude 250.1x; ICD-10-CM: E11), with an age at diagnosis of over 20 years as our study population. Patients who received (sodium-glucose cotransporter 2 inhibitor) SGLT2i (ATC code: A10BK) over 90 days in 2016-2019 were defined as the SGLT2i cohort. Conversely, patients who did never received SGLT2i were defined as the non-SGLT2i cohort. The exclusion criteria were having MD before the index date, receiving SGLT2i within 1-89 days, and missing data on sex, age, or days of SGLT2i usage. Two cohorts were matched by 1:1 propensity score matching, which was based on age, sex, payroll bracket grade, urbanization, comorbidities, and medications. RESULTS: Compared to non-SGLT2i cohort, patients who received SGLT2i had a significantly lower risk of MD (adjusted hazard ratio = 0.70, 95%CI = 0.66-0.75). CONCLUSIONS: We found that SGLT2is has a strong protective effect against MD in patients with diabetes. SGLT2is may have benefits beyond glycemic control in patients with DR. However, additional clinical and experimental studies are required.

Self-powered broadband photodetection enabled by facile CVD-grown MoS2/GaN heterostructures.

Achieving self-powered photodetection without biasing is a notable challenge for photodetectors. In this work, we demonstrate the successful fabrication of large-scale van der Waals epitaxial molybdenum disulfide (MoS2) on a p-GaN/sapphire substrate using a straightforward chemical vapor deposition (CVD) technique. Our research primarily centers on the characterization of these photodetectors produced through this method. The MoS2/GaN heterojunction photodetector showcases a broad and extensive photoresponse spanning from ultraviolet A (UVA) to near-infrared (NIR). When illuminated by a 532 nm laser, its self-powered photoresponse is characterized by a rise time (τr) of ∼18.5 ms and a decay time (τd) of ∼123.2 ms. The photodetector achieves a responsivity (R) of ∼0.13 A W-1 and a specific detectivity (D*) of ∼3.8 × 1010 Jones at zero bias. Additionally, while utilizing a 404 nm laser, the photodetector reaches a maximum R and D* of ∼1.7 × 104 A/W and ∼1.6 × 1013 Jones, respectively, at Vb = 5 V. The operational mechanism of the device can be explained by the diode characteristics involving a tunneling current in the presence of reverse bias. The exceptional performance of these photodetectors can be attributed to the pristine interface between the CVD-grown MoS2 and GaN, providing an impeccably clean tunneling surface. Additionally, our investigation has unveiled that MoS2/GaN heterostructure photodetectors, featuring MoS2 coverage percentages spanning from 20% to 50%, exhibit improved responsivity capabilities at an external bias voltage. As a result, this facile CVD growth technique for MoS2 photodetectors holds significant potential for large-scale production in the manufacturing industry.

A 6-Month Open-Label Study of Vortioxetine among Cancer Patients with Major Depressive Disorder (MDD).

OBJECTIVE: Vortioxetine is a monoaminergic drug with a novel multimodal mechanism of action. We investigated its efficacy on depressive symptoms, cognitive function, and quality of life among cancer patients. METHODS: In this multicenter, open-label, single-arm, observational study, patients received flexible doses of Vortioxetine for a period of six months. All participants were assessed at baseline and scheduled for monitoring at weeks 2, 4, 8, 12, 16, 20, and 24. Depression severity was assessed using Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) scale. The Perceived Deficiency Questionnaire (PDQ-5) assessed the perceived cognitive difficulties in concentration, executive functioning, and memory. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) was used to assess the patients' quality of life. Side effects of vortioxetine were monitored using the Antidepressant Side-Effect Checklist (ASEC). RESULTS: Patients experienced a reduction in MADRS scores from 29.89 ± 5.997 at baseline to 11.59 ± 4.629 by Week 24. The PDQ-5 scores showed significant change from Week-4, whereas the EORTC role, emotional, and cognitive functioning scores showed a significant change from Week 2 onwards. CGI-Severity scores decreased from a baseline of 4.39 ± 0.746 to 2.41 ± 1.085 by Week 24. During the 24-Weeks of therapy, around three-quarters of the patients (73.3%) had one or more adverse events reported on the ASEC. The most frequently reported TEAEs were dry mouth, insomnia, somnolence, and headache, with more than a 30% incidence rate. CONCLUSION: Vortioxetine seems promising in the management of depression and enhancement of cognitive function and quality of life of cancer patients with Major Depressive Disorder.
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Dual-mode frequency multiplier in graphene-base hot electron transistor.

Since quantum computers have been gradually introduced in countries around the world, the development of the many related quantum components that can operate independently of temperature has become more important for enabling mature products with low power dissipation and high efficiency. As an alternative to studying cryo-CMOSs (complementary metal-oxide-semiconductors) to achieve this goal, quantum tunneling devices based on 2D materials can be examined instead. In this work, a vertical graphene-based quantum tunneling transistor has been used as a frequency modulator. The transistor can operate via different quantum tunneling mechanisms and generates, by applying the appropriate bias, voltage-resistance curves characteristic of variable nonlinear resistance for both base and emitter voltages. We experimentally demonstrate frequency modulation from input signals over the range of 100 kHz to 10 MHz, enabling a tunable frequency doubler or tripler in just a single transistor. This frequency multiplication with a tunneling mechanism makes the graphene-based tunneling device a promising option for frequency electronics in the emerging field of quantum technologies.

Defect-engineered room temperature negative differential resistance in monolayer MoS2 transistors.

The negative differential resistance (NDR) effect has been widely investigated for the development of various electronic devices. Apart from traditional semiconductor-based devices, two-dimensional (2D) transition metal dichalcogenide (TMD)-based field-effect transistors (FETs) have also recently exhibited NDR behavior in several of their heterostructures. However, to observe NDR in the form of monolayer MoS2, theoretical prediction has revealed that the material should be more profoundly affected by sulfur (S) vacancy defects. In this work, monolayer MoS2 FETs with a specific amount of S-vacancy defects are fabricated using three approaches, namely chemical treatment (KOH solution), physical treatment (electron beam bombardment), and as-grown MoS2. Based on systematic studies on the correlation of the S-vacancies with both the device's electron transport characteristics and spectroscopic analysis, the NDR has been clearly observed in the defect-engineered monolayer MoS2 FETs with an S-vacancy (VS) amount of ∼5 ± 0.5%. Consequently, stable NDR behavior can be observed at room temperature, and its peak-to-valley ratio can also be effectively modulated via the gate electric field and light intensity. Through these results, it is envisioned that more electronic applications based on defect-engineered layered TMDs will emerge in the near future.

Twisted Light-Induced Photocurrent in a Silicon Nanowire Field-Effect Transistor.

Light can possess orbital angular momentum (OAM), in addition to spin angular momentum (SAM), which offers nearly infinite possible values of momentum states, allowing a wider degree of freedom for information processing and communications. The OAM of light induces a selection rule that obeys the law of conservation of angular momentum as it interacts with a material, affecting the material's optical and electrical properties. In this work, silicon nanowire field-effect transistors are subjected to light with OAM, also known as twisted light. Electrical measurements on the devices consequently reveal photocurrent enhancements after incrementing the OAM of the incident light from 0ℏ (fundamental mode) to 5ℏ. Such a phenomenon is attributed to the enhancements of the photogating and the photoconductive effects under the influence of the OAM of light, the underlying mechanism of which is proposed and discussed using energy band diagrams. With these observations, a strategy for controlling photocurrent has been introduced, which can be a realization of the application in the field of optoelectronics technology.

The three-dimensional quadriceps vector is most parallel to the spherical axis in Japanese varus osteoarthritic knees.

BACKGROUND: The quadriceps femoris may be a reliable reference to proper alignment in total knee arthroplasty (TKA). We previously showed the quadriceps vector (QV) to be the most parallel to the spherical axis (SA-center hip to center medial condyle) for healthy knees. The purpose of this study was to determine whether the QV is the most parallel to the SA in knees with varus osteoarthritis (OA). METHODS: CT imaging for 35 varus OA and 40 healthy Japanese knees was used to construct 3D models of the femur, patella and each quadriceps component for each subject. The QV was calculated using principal component analysis for direction and was compared with the relationship of the QV to the measurement axes of the lower extremity, including the anatomical, mechanical and spherical axes. RESULTS: The direction of the QV for the OA knee group was different from that for the healthy knee group in 3D space (medio-lateral direction: women, p = 0.532, men, p = 0.540; antero-posterior direction: women, p = 0.141, men, p < 0.001). However, the angle of the QV in relation to measurement axes in the coronal plane was closest to the SA in both groups (around 1°), with no difference between the groups (women, p = 0.382, men, p = 0.943). CONCLUSION: In the coronal plane, the SA most closely approximates the QV for both healthy and OA knees. The more posterior QV position in the 3D space may affect the patellofemoral joint.

High-Frequency Graphene Base Hot-Electron Transistor.

The integration of graphene and other two-dimensional (2D) materials with existing silicon semiconductor technology is highly desirable. This is due to the diverse advantages and potential applications brought about by the consequent miniaturization of the resulting electronic devices. Nevertheless, such devices that can operate at very high frequencies for high-speed applications are eminently preferred. In this work, we demonstrate a vertical graphene base hot-electron transistor that performs in the radio frequency regime. Our device exhibits a relatively high current density (∼200 A/cm2), high common base current gain (α* ∼ 99.2%), and moderate common emitter current gain (ß* ∼ 2.7) at room temperature with an intrinsic current gain cutoff frequency of around 65 GHz. Furthermore, cutoff frequency can be tuned from 54 to 65 GHz by varying the collector-base bias. We anticipate that this proposed transistor design, built by the integrated 2D material and silicon semiconductor technology, can be a potential candidate to realize extra fast radio frequency tunneling hot-carrier electronics.

Spontaneously induced magnetic anisotropy in an ultrathin Co/MoS2 heterojunction.

Magnetic anisotropy (MA) is a material preference that involves magnetization aligned along a specific direction and provides a basis for spintronic devices. Here we report the first observation of strong MA in a cobalt-molybdenum disulfide (Co/MoS2) heterojunction. Element-specific magnetic images recorded with an X-ray photoemission electron microscope (PEEM) reveal that ultrathin Co films, of thickness 5 monolayers (ML) and above, form micrometer (µm)-sized domains on monolayer MoS2 flakes of size tens of µm. Image analysis shows that the magnetization of these Co domains is oriented not randomly but in directions apparently correlated with the crystal structure of the underlying MoS2. Evidence from micro-area X-ray photoelectron spectra (µ-XPS) further indicates that a small amount of charge is donated from cobalt to sulfur upon direct contact between Co and MoS2. As the ferromagnetic behavior found for Co/MoS2 is in sharp contrast with that reported earlier for non-reactive Fe/MoS2, we suggest that orbital hybridization at the interface is what makes Co/MoS2 different. Our report provides micro-magnetic and micro-spectral evidence that consolidates the knowledge required to build functional heterojunctions based on two-dimensional (2D) materials.

Nonvolatile molecular memory with the multilevel states based on MoS2 nanochannel field effect transistor through tuning gate voltage to control molecular configurations.

A new flexible memory element is crucial for mobile and wearable electronics. A new concept for memory operation and innovative device structure with new materials is certainly required to address the bottleneck of memory applications now and in the future. We report a new nonvolatile molecular memory with a new operating mechanism based on two-dimensional (2D) material nanochannel field-effect transistors (FETs). The smallest channel length for our 2D material nanochannel FETs was approximately 30 nm. The modified molecular configuration for charge induced in the nanochannel of the MoS2 FET can be tuned by applying an up-gate voltage pulse, which can vary the channel conductance to exhibit memory states. Through controlling the amounts of triggered molecules through either different gate voltage pulses or gate duration time, multilevel states were obtained in the molecular memory. These new molecular memory transistors exhibited an erase/program ratio of more than three orders of current magnitude and high sensitivity, of a few picoamperes, at the current level. Reproducible operation and four-level states with stable retention and endurance were achieved. We believe this prototype device has potential for use in future memory devices.

Risk Factors and Behaviours of Schoolchildren with Myopia in Taiwan.

Importance: Because of the high prevalence of myopia in Taiwan, understanding the risk factors for its development and progression is important to public health. Background: This study investigated the risk factors for myopia and their influence on the progression of myopia in schoolchildren in Taiwan. Design: Patients' clinical records were obtained retrospectively from ophthalmologists. Questionnaires were given to collect demographic information, family background, hours spent on daily activities, myopia progression, and treatment methods. Participants: From a regional medical hospital in northern Taiwan, 522 schoolchildren with myopia participated in the study. Written informed consent was obtained from participants of legal age or the parents or legal guardians of younger children. Methods: Multivariable regression analyses were performed. Myopia measured in cycloplegic spherical equivalent (SE) was analysed, controlling for patients' family and demographic information as well as their daily activity behaviours. Main Outcome Results: Children with high myopic parents were more myopic. Earlier onset age of myopia was associated with a higher level of myopia and greater annual myopic progression. Children reporting longer time usage of electronic devices had greater progression of myopia. Boys tended to be more myopic than girls. Lower levels of myopia were associated with more outdoor activities, and better vision care knowledge in children and parents. Conclusions and Relevance: In addition to genetics, education and environment can influence the development of myopia. Health policies for schoolchildren should promote protective activities and vision care knowledge at a young age, to protect the eyesight of schoolchildren.

Symmetrical cruciate-retaining versus medial pivot prostheses: The effect of intercondylar sagittal conformity on knee kinematics and contact mechanics.

BACKGROUND: A total knee arthroplasty should restore the mechanical function of the knee and enable patients to perform desired daily activities. The joint kinematics and contact mechanics performance are important determinants of the success of total knee arthroplasty devices. The purpose of this study was to determine the effect of intercondylar sagittal conformity on kinematics and contact mechanics. METHODS: An explicit dynamic finite element method was used to investigate the differences in the performances of constrained cruciate-retaining (CR), unconstrained CR, and medial pivot designs during gait, squatting, descending stairs, and climbing stairs. The predicted kinematic results were verified through an in vitro experiment during the gait cycle. RESULTS: The results confirmed that the medial pivot design improved the kinematic behavior with no paradoxical anterior motion, which was found in the unconstrained prosthesis during the four activities. However, a small femoral internal rotation was found during gait (3.9°), descending stairs (2.2°), and climbing stairs (3.6°), which may produce anterolateral pain. An enlarged contact area and a lower peak contact pressure were observed on the medial side of the medial pivot prosthesis. Conversely, on the lateral side of the medial pivot prosthesis, the contact area and peak contact pressure were equal to those of the unconstrained prosthesis, which could potentially result in wear. CONCLUSION: In summary, although the medial pivot prosthesis may provide qualitatively similar kinematics as the average measurements of tibiofemoral motion, further in vivo analysis and long-term studies on the femoral internal rotation and high contact pressure on the lateral side are still required.

Macrophage Migration Inhibitory Factor Acts as the Potential Target of a Newly Synthesized Compound, 1-(9'-methyl-3'-carbazole)-3, 4-dihydro-ß-carboline.

For a newly synthesized compound, identifying its target protein is a slow but pivotal step toward understand its pharmacologic mechanism. In this study, we systemically synthesized novel manzamine derivatives and chose 1-(9'-methyl-3'-carbazole)-3, 4-dihydro-ß-carboline (MCDC) as an example to identify its target protein and function. MCDC had potent toxicity against several cancer cells. To identify its target protein, we first used a docking screen to predict macrophage migration inhibitory factor (MIF) as the potential target. Biochemical experiments, including mutation analysis and hydrogen-deuterium exchange assays, validated the binding of MCDC to MIF. Furthermore, MCDC was shown by microarrays to interfere with the cell cycle of breast cancer MCF7 cells. The activated signaling pathways included AKT phosphorylation and S phase-related proteins. Our results showed MIF as a potential direct target of a newly synthesized manzamine derivative, MCDC, and its pharmacologic mechanisms.

The role of motivational interview in the request for termination of pregnancy: A case report

@#In Malaysia, induced termination of pregnancy is legal, if a registered medical practitioner is the one who terminates the pregnancy, and is acting in good faith without the risk to the life or injury to the mental health of the pregnant woman; in the event that continuation of the pregnancy is greater than the risk if the pregnancy is terminated. This case report highlights the approach of motivational interviewing in evoking a change of the behaviour of a patient wishing termination of pregnancy for psychosocial reasons.

Psychological morbidities amongst house officers in Sarawak General Hospital Kuching

@#Introduction: Psychological morbidities are common amongst healthcare professionals particularly among junior house officers (HO) who are in a transitional stage from being a medical student to a doctor. They undergo many stressors during this period and hence might suffer from higher psychological morbidities such as depression, anxiety and stress. Objectives: To determine the prevalence of depression, anxiety and stress among HO in Sarawak General Hospital (SGH), Kuching, Sarawak. The socialdemographic factors were also evaluated to identify the high-risk groups. Materials and methods: This is a descriptive cross-sectional study involving 227 house officers in SGH over a period of three months. The social-demographic data such as age, sex, marital status, current posting, duration of posting, place of graduate and state of origin were obtained from interviews with the respondents. The Depression, Anxiety and Stress scale (DASS) questionnaire was completed to assess the psychological morbidities. Results: HO were found to have high prevalence of psychiatric morbidities such as depression (42%), anxiety (50%) and stress (42.7%). Foreign graduates showed a significantly higher odds of depression (odds ratio, OR: 3.851; 95% confidence interval, 95%CI: 2.165, 6.851), anxiety (OR: 2.427; 95%CI: 1.394, 4.225) and stress (OR: 2.524; 95%CI: 1.439, 4.427) as compared to local graduates.. Further, non-Sarawakians were observed to have higher odds of developing anxiety (OR: 1.772; 95%CI: 1.022, 3.073) as compared to the Sarawakians. Conclusion: HO in SGH had high prevalence of depression, anxiety and stress. Therefore, psychiatric morbidities should be screened regularly amongst the HOs in Malaysia.

Validation of an informant-based cognitive screening tool for Parkinson disease.

INTRODUCTION: The objective of this study was to establish the psychometric properties of the AD8 Dementia Screening Interview in patients with Parkinson disease (PD) with or without cognitive impairment using the Montreal Cognitive Assessment Tool (MoCA) for comparison. METHODS: The AD8 was translated into Malay for Malay-speaking participants. A correlation analysis and a receiver operator characteristic curve were generated to establish the psychometric properties of the AD8 in relation to the MoCA. RESULTS: One hundred fifty patients and their caretakers completed the AD8 and MoCA. Using a cutoff score of 1/8, the AD8 had 81% sensitivity and 59% specificity for the detection of cognitive impairment in PD. With a cutoff score of 2/8, the AD8 had 83% specificity and 64% sensitivity. The area under the receiver operator characteristic curve was 80%, indicating good-to-excellent discriminative ability. DISCUSSION: These findings suggest that the AD8 can reliably differentiate between cognitively impaired and cognitively normal patients with PD and is a useful caregiver screening tool for PD.

Stress-induced premature senescence of dermal papilla cells compromises hair follicle epithelial-mesenchymal interaction.

BACKGROUND: Hair follicle is miniorgan constituted by keratinocytes and its distinctive mesenchyme of dermal papilla. Its aging is characterized by organ atrophy and impaired stem cell activation and differentiation. The contribution of dermal papilla to hair follicle aging change is not well understood. OBJECTIVE: This work was aimed at exploring the possible role of premature dermal papilla senescence in the pathogenesis of hair follicle aging. METHODS: Dermal papilla cells were challenged with H2O2 to induce premature senescence and the proliferation, apoptosis, gene expression and protein secretion were characterized. Its effect on epithelial-mesenchymal interaction was analyzed by co-culture in vitro and implantation of protein-coated beads in vivo. RESULT: Dermal papilla cells were more resistant to oxidative stress-induced apoptosis than dermal fibroblasts. The surviving dermal papilla cells showed signs of senescence but still preserved key dermal papilla signature gene expression. In addition to the failure to respond to mitogenic stimulation from keratinocytes, they lost the ability to induce hair follicle neogenesis, promoted interfollicular epidermal differentiation, inhibited follicular differentiation and, importantly, suppressed clonal growth of hair follicle stem cells. They produced higher levels of multiple inflammatory cytokines, including IL-6. Functionally, IL-6 inhibited clonal keratinocyte growth in vitro and blocked the transition from telogen to anagen in vivo. CONCLUSION: Stress-induced premature dermal papilla senescence can contribute to hair follicle aging change due to compromised epithelial-mesenchymal interaction.

The Quadriceps Vector is Most Parallel to the Spherical Axis With Minimal Difference for Gender or Ethnicity.

BACKGROUND: The extensor mechanism may be the key to kinematic alignment of total knee arthroplasty. The purpose of this study was to determine any differences in the direction of the quadriceps vector based on gender or ethnicity and to determine which anatomically derived alignment axis is closest to the quadriceps vector. METHODS: Computed tomography scans and patient records for 14 Caucasians (9 men and 5 women) and 40 Japanese (19 men and 21 women) were evaluated. Three axes of alignment-anatomic, mechanical, and spherical-were identified, measured, and compared to the quadriceps vector in each case. Principal component analysis was used to determine the quadriceps vector by using 3-dimensional models of muscles on computed tomography scans. RESULTS: No statistically significant differences in the orientation of the quadriceps vector were found based on gender or ethnicity, and the quadriceps vector was most closely aligned with the spherical axis. CONCLUSION: Because the quadriceps is the primary knee extensor, the spherical axis therefore may be a ubiquitous guide to alignment of the arthroplasty knee based on motion.

Psychometric properties of Malay neuropsychiatry unit cognitive assessment tool among Alzheimer's disease patients in comparison to Malay Montreal Cognitive Assessment.

This study aims to establish psychometric properties of the Malay Neuropsychiatry Unit Cognitive Assessment Tool (Malay NuCOG) in Alzheimer's disease. NuCOG was translated to Malay language and compared with Montreal Cognitive Assessment Tool on 80 individuals. The Malay NuCOG showed good internal consistency and reliability (Cronbach's alpha = 0.895). It demonstrated 100% sensitivity and 87.5% specificity at the cutoff score of 78.50/100. The Malay NuCOG is a valid and reliable cognitive instrument that is sensitive and specific for the detection of dementia and has clinical advantages in its ability to examine individual cognitive domains.