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AnteayerPLOS ONE Medicine&Health

PIK3CA regulates development of diabetes retinopathy through the PI3K/Akt/mTOR pathway

by Ruijuan Guan, Zefeng Kang, Ling Li, Xin Yan, Tianpeng Gao

Objective

To explore their association with the development of diabetes retinopathy (DR), single nucleotide polymorphism (SNP) mutations were screened out by high-throughput sequencing and validated in patients diagnosed with DR. To understand the role of PIK3CA in the pathogenesis of DR and explore the relationship between PIK3CA,phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR),and DR, the effect of PIK3CA.rs17849079 mutation was investigated in a DR cell model.

Methods

Twelve patients diagnosed with DR at the Qinghai Provincial People’s Hospital from September 2020 to June 2021 were randomly selected as the case group, while 12 healthy subjects of similar age and gender who underwent physical examination in Qinghai Provincial People’s Hospital physical examination center during the same period were randomly selected as the control group. Blood samples (2 mL) were collected from both groups using EDTA anticoagulant blood collection vessels and frozen at −20°C for future analysis. SNP mutations were detected by high-throughput sequencing, and the shortlisted candidates were subjected by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The detected SNP candidates were verified by expanding the sample size (first validation: 56 patients in the case group and 58 controls; second validation: 157 patients in the case group and 96 controls). A lentivirus vector carrying mutated or wild-type PIK3CA.rs17849079 was constructed. ARPE-19 cells were cultured in a medium supplemented with 10% fetal bovine serum (FBS) to establish a DR cell model. PIRES2-PIK3CA-MT and PIRES2-PIK3CA-WT vectors were transfected into DR model cells, which were categorized into control, mannitol, model, empty vector, PIK3CA wild-type, and PIK3CA mutant-type groups. Cell activity was detected by the cell counting kit (CCK)-8 assay, and cellular apoptosis was evaluated by flow cytometry. Glucose concentration and levels of cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β were detected using enzyme-linked immunosorbent assay kits. The expression of PIK3CA, AKT1, mTOR, and VEGF genes was detected by real-time quantitative polymerase chain reaction (RT-qPCR), while the expression of PI3K, p-PI3K, AKT1, p-AKT1, mTOR, p-mTOR, and VEGF proteins was detected by western blotting.

Results

The mutated SNPs were mainly enriched in the PI3K/AKT pathway, calcium ion pathway, and glutamatergic synaptic and cholinergic synaptic signaling pathways. Seven SNPs, including PRKCE.rs1533476, DNAH11.rs10485983, ERAP1.rs149481, KLHL1.rs1318761, APOBEC3C.rs1969643, FYN.rs11963612, and KCTD1.rs7240205, were not related to the development of DR. PIK3CA.rs17849079 was prone to C/T mutation. The risk of DR increased with the presence of the C allele and decreased in the presence of the T allele. High glucose induced the expression of PIK3CA and VEGF mRNAs as well as the expression of PI3K, p-PI3K, p-AKT1, p-mTOR, and VEGF proteins in ARPE-19 cells, which led to secretion of inflammatory factors TNF-αand IL-1, cell apoptosis, and inhibition of cell proliferation. The PIK3CA.rs17849079 C allele accelerated the progression of DR. These biological effects were inhibited when the C allele of PIK3CA.rs17849079 was mutated to T allele.

Conclusion

The mutated SNP sites in patients with DR were mainly enriched in PI3K/AKT, calcium ion, and glutamatergic synaptic and cholinergic synaptic signaling pathways. The rs17849079 allele of PIK3CA is prone to C/T mutation where the C allele increases the risk of DR. High glucose activates the expression of PIK3CA and promotes the phosphorylation of PI3K, which leads to the phosphorylation of AKT and mTOR. These effects consequently increase VEGF expression and accelerate the development of DR. The C to T allele mutation in PIK3CA.rs17849079 can play a protective role and reduce the risk of DR.

Association between physical performance and bone mass in community-dwelling postmenopausal Japanese women: The Unzen study

by Masahiro Suiko, Satoshi Mizukami, Kazuhiko Arima, Hiroki Nakashima, Takayuki Nishimura, Yoshihito Tomita, Yasuyo Abe, Natsumi Tanaka, Yuzo Honda, Michiko Kojima, Tetsuji Okawachi, Maiko Hasegawa, Youko Sou, Ritsu Tsujimoto, Mitsuo Kanagae, Makoto Osaki, Kiyoshi Aoyagi

Background

Low bone mass is an independent risk factor for osteoporotic fractures. We examined the association between physical performance and bone mass using quantitative ultrasound in community-dwelling postmenopausal Japanese women.

Methods

We conducted a cross-sectional study on 524 community-dwelling postmenopausal Japanese women who were not being administered osteoporosis medications. Physical performance was assessed on the basis of grip strength, chair stand time, and functional reach. The stiffness index was measured as a quantitative ultrasound parameter for heel bone mass.

Results

Physical performance, assessed by grip strength, chair stand time, and functional reach, and the stiffness index significantly decreased with age (both p Conclusions

Physical performance was significantly associated with heel bone mass in community-dwelling postmenopausal Japanese women.

Efficacy of preoperative lymphoscintigraphy in predicting surgical outcomes of lymphaticovenous anastomosis in lower extremity lymphedema: Clinical correlations in gynecological cancer-related lymphedema

by Min Young Yoo, Kyong-Je Woo, Seo Young Kang, Byung Seok Moon, Bom Sahn Kim, Hai-Jeon Yoon

Background

Lymphaticovenous anastomosis (LVA) is a promising microsurgical treatment for lower extremity lymphedema (LEL). Lymphoscintigraphy effectively assesses lower limb lymphatic systems before LVA, but its role in predicting the therapeutic outcomes of LVA is indeterminate. In this study we investigate the efficacy of preoperative lymphoscintigraphy using clinical findings to predict outcomes in gynecological cancer-related LEL patients who underwent LVA.

Methods

A retrospective review was conducted on consecutive gynecological cancer patients with LEL who had undergone LVA between June 2018 and June 2021. The therapeutic efficacy was assessed by measuring the change rate of the lower extremity lymphedema index (LELi) six months after surgery. Clinical data and lymphoscintigraphic findings were analyzed to assess therapeutic efficacy of LVA.

Results

Out of the 60 evaluated legs, 83.3% of the legs showed improved results after LVA. Univariable linear regression analysis revealed that higher preoperative LELi, and ovarian cancer were associated with superior LELi change rate (LC rate). Absence of dermal backflow (DBF) on lymphoscintigraphy was associated with inferior LC rate. Multivariable linear regression analysis identified ovarian cancer and higher preoperative LELi were independently correlated with favorable outcomes, while the absence of DBF was independently correlated with inferior outcomes.

Conclusion

The results of this study emphasizes the effectiveness of preoperative lymphoscintigraphy, preoperative LELi, and primary malignancy as predictors of LVA outcomes in gynecological cancer-related LEL patients.

The role of basic psychological needs in the relationships between identity orientations and adolescent mental health: A protocol for a longitudinal study

by Veljko Jovanović, Aleksandar Tomašević, Dušana Šakan, Milica Lazić, Vesna Gavrilov-Jerković, Marija Zotović-Kostić, Vojana Obradović

Research into the role of identity orientations (the relative importance an individual places on different personal and social attributes and characteristics when defining her or his identity) in adolescent mental health is extremely limited. Furthermore, the potential mechanisms that might explain the associations between identity orientations and adolescent mental health are poorly understood. This study protocol describes a one-year longitudinal study across three time points to be initiated with the purpose of investigating the mediating role of basic psychological needs satisfaction and frustration in the relationship between identity orientations and various mental health indicators in adolescence. We aim to recruit a large sample of Serbian adolescents (N = 2,000 at Time 1), using a two-stage stratified random sampling. The data will be analyzed using the random intercept cross-lagged panel model (RI-CLPM), and the results will be contrasted with the traditional CLPM. The goal of this study is to make a theoretical contribution to research in the fields of identity, self-determination theory, and adolescent mental health, as well as to provide insights towards the development of evidence-based recommendations for creating prevention and promotion programs aimed at improving the well-being of adolescents.

Diversity and characterization of culturable fungi associated with the marine sea cucumber <i>Holothuria scabra</i>

by Lakkhana Kanhayuwa Wingfield, Jirawalan Atcharawiriyakul, Ninadia Jitprasitporn

Fungi associated with the marine echinoderm, Holothuria scabra, produces extracellular enzymes and bioactive metabolites, and mycoviruses that could be used for biotechnological and pharmaceutical applications. The species identification based on molecular and morphological characteristics classified the culturable fungi into twenty-three genera belonging to eight orders, Chaetothyriales, Eurotiales, Hypocreales, Mucorales, Mycosphaerellales, Onygenales, Pleosporales and Venturiales, from four classes, Eurotiomycetes, Dothideomycetes, Mucoromycetes and Sordariomycetes of the two phyla Ascomycota and Mucoromycota. The most frequent genera were Aspergillus (relative frequency, 45.30%) and Penicillium (relative frequency, 22.68%). The Menhinick species richness and Shannon species diversity indices were 1.64 and 2.36, respectively, indicating a high diversity of fungi. An enzymatic production test revealed that sixteen isolates could produce proteases and amylases at different levels. The presence of mycoviruses was detected in eight isolates with different genomic profiles. Thirty-two of the 55 isolates produced antimicrobial metabolites which had an inhibitory effect on various microbial pathogens. Most of these active isolates were identified as Aspergillus, Penicillium and Trichoderma. Notably, Aspergillus terreus F10M7, Trichoderma harzianum F31M4 and T. harzianum F31M5 showed the most potent activity against both Gram-positive and Gram-negative bacteria and human pathogenic fungi. Our study represents the first report of the mycobiota associated with the marine echinoderm Holothuria scabra.

“High blood pressure comes from thinking too much”: Understandings of illness among couples living with cardiometabolic disorders and HIV in Malawi

by Jane Jere, Allison Ruark, Julie T. Bidwell, Rita M. Butterfield, Torsten B. Neilands, Sheri D. Weiser, Nancy Mulauzi, James Mkandawire, Amy A. Conroy

Cardiometabolic disorders (CMD) such as hypertension and diabetes are increasingly prevalent in sub-Saharan Africa, placing people living with HIV at risk for cardiovascular disease and threatening the success of HIV care. Spouses are often the primary caregivers for people living with CMD, and understanding patients’ and partners’ conceptions of CMD could inform care. We conducted semi-structured interviews with 25 couples having a partner living with HIV and either hypertension or diabetes. Couples were recruited from HIV clinics in Malawi and were interviewed on beliefs around symptoms, causation, prevention, and treatment for CMD. Data were analyzed at the individual and dyadic levels using framework analysis and Kleinman’s theory of explanatory models as a lens. On average, participants were 51 years old and married for 21 years. Approximately 57%, 14%, and 80% had hypertension, diabetes, and HIV. Couples endorsed a combination of biomedical explanatory models (beliefs around physical and mental health) and traditional explanatory models (beliefs around religion and natural remedies), although tended to emphasize the biomedical model. Half of couples believed stress was the main cause of hypertension. For diabetes, diet was believed to be a common cause. In terms of prevention, dietary changes and physical activity were most frequently mentioned. For disease management, medication adherence and diet modifications were emphasized, with some couples also supporting herbal remedies, stress reduction, and faith in God as strategies. Participants were generally more concerned about CMD than HIV due to poor access to CMD medications and beliefs that CMD could lead to sudden death. Within couples, partners often held many of the same beliefs but diverged around which etiological or preventive factors were most important (e.g., stress versus diet) and the best diet for CMD. Health education programs should involve primary partners to build knowledge of CMD and address overlap with HIV, and reinforce accurate information on lifestyle factors for the prevention and treatment of CMD.

Crawling toward obsolescence: The extended lifespan of amylase for pancreatitis

by Naga Sasidhar Kanaparthy, Andrew J. Loza, Ronald George Hauser

The correlation between hyperamylasemia and acute pancreatitis was discovered in 1929, yet another test, lipase, was shown to provide better diagnostic performance in the late 1980s and early 1990s. Subsequent studies demonstrated co-ordering amylase with lipase did not provide additional benefit, only added cost. We sought to investigate the impact of studies advocating for the obsolescence of amylase on its clinical demand. We reviewed 1.3 million reportable results for amylase over 14 years (2009–2022). The trend in utilization of amylase over this period declined by 66% along a linear trajectory (R2 = 0.97). Despite demand for amylase decreasing by an average of 17,003 tests per year, the last year of the study (2022) recorded over 100,000 results for amylase. By interpolating the decline of amylase until the utilization reached zero, we calculated amylase orders will continue for 6 more years until 2028. Tests for creatinine and lipase changed

Influence of horizontal resistance loads on spatiotemporal and ground reaction force variables during maximal sprint acceleration

by Norihide Sugisaki, Kai Kobayashi, Takaya Yoshimoto, Naotoshi Mitsukawa, Hiroyasu Tsuchie, Yohei Takai, Hiroaki Kanehisa

This study aimed to elucidate the influence of horizontal resistance loads on the spatiotemporal and ground reaction force (GRF) variables during maximal sprint acceleration. Nine male sprinters (20.2 ± 1.2 years; 175.3 ± 4.5 cm, 69.7 ± 6.1 kg) performed sprint-running with six loading conditions of one unresisted and five resisted loads of 4, 6, 8, 10, and 12 kg using a resistance training device with intelligent drag technology. During the trials, the GRFs for all steps were determined using a 50-m force plate system. The spatiotemporal and GRF variables at running velocity of every 0.5 m/s were obtained and compared across the loading conditions. The maximal running velocity under 0, 4, 6, 8, 10, and 12 kg loading conditions were 9.84 ± 0.41, 8.55 ± 0.41, 8.09 ± 0.33, 7.62 ± 0.34, 7.11 ± 0.31, and 6.71 ± 0.29 m/s, respectively. ANOVA revealed significant main effects of load on the measured variables (η2 = 0.236–0.715, p

Non-infectious diseases in infectious disease consultation: A descriptive study in a tertiary care teaching hospital

by Yoshiro Hadano, Takanori Matsumoto

In this retrospective study, we aimed to investigate the frequency, trend, and nature of non-infectious diseases (non-IDs) as the final diagnosis for patients during an infectious disease (ID) consultation in an acute care hospital in Japan. This study included adult inpatients who underwent ID consultations between October 2016 and March 2018. The demographic data, clinical manifestations, and final non-ID diagnoses of cases were explored. Among the 502 patients who underwent ID consultations, 45 (9.0%) were diagnosed with non-IDs. The most common diagnoses were tumors (22.2%, n = 10), connective tissue and collagen vascular diseases (13.3%, n = 6), other inflammatory diseases (8.9%, n = 4), and drug-induced fever (8.9%, n = 4). Multiple logistic regression analysis showed that the presence of consultations for diagnosis (odds ratio [OR], 22.0; 95% confidence interval [CI], 10.1–48.2; p

Automated, high-throughput quantification of EGFP-expressing neutrophils in zebrafish by machine learning and a highly-parallelized microscope

by John Efromson, Giuliano Ferrero, Aurélien Bègue, Thomas Jedidiah Jenks Doman, Clay Dugo, Andi Barker, Veton Saliu, Paul Reamey, Kanghyun Kim, Mark Harfouche, Jeffrey A. Yoder

Normal development of the immune system is essential for overall health and disease resistance. Bony fish, such as the zebrafish (Danio rerio), possess all the major immune cell lineages as mammals and can be employed to model human host response to immune challenge. Zebrafish neutrophils, for example, are present in the transparent larvae as early as 48 hours post fertilization and have been examined in numerous infection and immunotoxicology reports. One significant advantage of the zebrafish model is the ability to affordably generate high numbers of individual larvae that can be arrayed in multi-well plates for high throughput genetic and chemical exposure screens. However, traditional workflows for imaging individual larvae have been limited to low-throughput studies using traditional microscopes and manual analyses. Using a newly developed, parallelized microscope, the Multi-Camera Array Microscope (MCAM™), we have optimized a rapid, high-resolution algorithmic method to count fluorescently labeled cells in zebrafish larvae in vivo. Using transgenic zebrafish larvae, in which neutrophils express EGFP, we captured 18 gigapixels of images across a full 96-well plate, in 75 seconds, and processed the resulting datastream, counting individual fluorescent neutrophils in all individual larvae in 5 minutes. This automation is facilitated by a machine learning segmentation algorithm that defines the most in-focus view of each larva in each well after which pixel intensity thresholding and blob detection are employed to locate and count fluorescent cells. We validated this method by comparing algorithmic neutrophil counts to manual counts in larvae subjected to changes in neutrophil numbers, demonstrating the utility of this approach for high-throughput genetic and chemical screens where a change in neutrophil number is an endpoint metric. Using the MCAM™ we have been able to, within minutes, acquire both enough data to create an automated algorithm and execute a biological experiment with statistical significance. Finally, we present this open-source software package which allows the user to train and evaluate a custom machine learning segmentation model and use it to localize zebrafish and analyze cell counts within the segmented region of interest. This software can be modified as needed for studies involving other zebrafish cell lineages using different transgenic reporter lines and can also be adapted for studies using other amenable model species.

Cardiac response to water activities in children with Long QT syndrome type 1

by Anna Lundström, Urban Wiklund, Annika Winbo, Håkan Eliasson, Marcus Karlsson, Annika Rydberg

Background

Swimming is a genotype-specific trigger in long QT syndrome type 1 (LQT1).

Objective

To examine the autonomic response to water activities in children and adolescents with LQT1.

Methods

In this cross-sectional study, LQT1 patients were age and sex matched to one healthy control subject. Electrocardiograms (ECGs) were recorded during face immersion (FI), swimming, diving, and whole-body submersion (WBS). Heart rate (HR) and heart rate variability (HRV) was measured. The high frequency (HF) component of HRV was interpreted to reflect parasympathetic activity, while the low frequency (LF) component was interpreted as reflecting the combined influence of sympathetic and parasympathetic activity on autonomic nervous modulation of the heart.

Results

Fifteen LQT1 patients (aged 7–19 years, all on beta-blocker therapy) and fifteen age and sex matched non-medicated controls were included. No significant ventricular arrhythmias were observed in the LQT1 population during the water activities. Out of these 15 matched pairs, 12 pairs managed to complete FI and WBS for more than 10 seconds and were subsequently included in HR and HRV analyses. In response to FI, the LQT1 group experienced a drop in HR of 48 bpm, compared to 67 bpm in the control group (p = 0.006). In response to WBS, HR decreased by 48 bpm in the LQT1 group and 70 bpm in the control group (p = 0.007). A significantly lower PTOT (p Conclusion

A significantly lower HR decrease in response to water activities was observed in LQT1 subjects on beta-blocker therapy, compared to matched non-medicated controls. The data suggests an impaired parasympathetic response in LQT1 children and adolescents. An aberrant autonomic nervous system (ANS) response may cause an autonomic imbalance in this patient group.

Radiographers’ perceptions on the quality of managing general radiographic paediatric examinations through the use of a reflective tool

by Kate Caruana, Chris Hayre, Chandra Makanjee

Introduction

Paediatric patients are a vulnerable population that require additional care by healthcare professionals. Quality managing these examinations ensures that effective and quality care is provided to individual patients, whilst encouraging consistency within the medical imaging department. This study explored radiographers’ perspectives on quality management strategies of general radiographic paediatric examinations using a paediatric imaging reflective checklist.

Methods

A quantitative descriptive research design with qualitative questions was used through a purposive sampling method from both public and private Australian diagnostic imaging qualified radiographers who had experience in paediatric imaging examinations. The paediatric imaging service reflective tool consisted of 65 items in total. Data analysis entailed Microsoft Excel version 16.16.6 and Jamovi version 2.3.21 for the closed-ended questions and for the open-ended responses a thematic analysis.

Results

The participation rate was 13.2% and the most significant findings were: lead shielding was still being used at their organisation, despite recent recommendations to suspend its use; access to paediatric patient related information resources is limited; there was no involvement of families and communities regarding policy development or quality improvement measures as advocated in literature; and there was a need for enhanced specialised paediatric education, training and protocols.

Conclusion

Using the paediatric patient-centred imaging reflective checklist, radiographers had an opportunity to identify quality improvement indicators as well as issues that could further enhance best practice principles. Further studies could inform on the validity of this reflective tool.

The association between cardiopulmonary exercise testing and postoperative outcomes in patients with lung cancer undergoing lung resection surgery: A systematic review and meta-analysis

by Nabeela Arbee-Kalidas, Hlamatsi Jacob Moutlana, Yoshan Moodley, Moses Mogakolodi Kebalepile, Palesa Motshabi Chakane

Background

Exercise capacity should be determined in all patients undergoing lung resection for lung cancer surgery and cardiopulmonary exercise testing (CPET) remains the gold standard. The purpose of this study was to investigate associations between preoperative CPET and postoperative outcomes in patients undergoing lung resection surgery for lung cancer through a review of the existing literature.

Methods

A search was conducted on PubMed, Scopus, Cochrane Library and CINAHL from inception until December 2022. Studies investigating associations between preoperative CPET and postoperative outcomes were included. Risk of bias was assessed using the QUIPS tool. A random effect model meta-analysis was performed. I2 > 40% indicated a high level of heterogeneity.

Results

Thirty-seven studies were included with 6450 patients. Twenty-eight studies had low risk of bias. V˙O2 peak is the oxygen consumption at peak exercise and serves as a marker of cardiopulmonary fitness. Higher estimates of V˙O2 peak, measured and as a percentagege of predicted, showed significant associations with a lower risk of mortality [MD: 3.66, 95% CI: 0.88; 6.43 and MD: 16.49, 95% CI: 6.92; 26.07] and fewer complications [MD: 2.06, 95% CI: 1.12; 3.00 and MD: 9.82, 95% CI: 5.88; 13.76]. Using a previously defined cutoff value of > 15mL/kg/min for V˙O2 peak, showed evidence of decreased odds of mortality [OR: 0.55, 95% CI: 0.28–0.81] and but not decreased odds of postoperative morbidity [OR: 0.82, 95% CI: 0.64–1.00]. There was no relationship between V˙E/V˙CO2 slope, which depicts ventilatory efficiency, with mortality [MD: -9.60, 95% CI: -27.74; 8.54] however, patients without postoperative complications had a lower preoperative V˙E/V˙CO2 [MD: -2.36, 95% CI: -3.01; -1.71]. Exercise load and anaerobic threshold did not correlate with morbidity or mortality. There was significant heterogeneity between studies.

Conclusions

Estimates of cardiopulmonary fitness as evidenced by higher V˙O2 peak, measured and as a percentage of predicted, were associated with decreased morbidity and mortality. A cutoff value of V˙O2 peak > 15mL/kg/min was consistent with improved survival but not with fewer complications. Ventilatory efficiency was associated with decreased postoperative morbidity but not with improved survival. The heterogeneity in literature could be remedied with large scale, prospective, blinded, standardised research to improve preoperative risk stratification in patients with lung cancer scheduled for lung resection surgery.

Application of Skyline software for detecting prohibited substances in doping control analysis

by Hyeon-Jeong Lee, Mijin Jeon, Yoondam Seo, Inseon Kang, Wooyeon Jeong, Junghyun Son, Eugene C. Yi, Hophil Min

As the number of prohibited drugs has been progressively increasing and analytical methods for detecting such substances are renewed continuously for doping control, the need for more sensitive and accurate doping analysis has increased. To address the urgent need for high throughput and accurate analysis, liquid chromatography with tandem mass spectrometry is actively utilized in case of most of the newly designated prohibited substances. However, because all mass spectrometer vendors provide data processing software that is incapable of handling other instrumental data, it is difficult to cover all doping analysis procedures, from method development to result reporting, on one platform. Skyline is an open-source and vendor-neutral software program invented for the method development and data processing of targeted proteomics. Recently, the utilization of Skyline has been expanding for the quantitative analysis of small molecules and lipids. Herein, we demonstrated Skyline as a simple platform for unifying overall doping control, including the optimization of analytical methods, monitoring of data quality, discovery of suspected doping samples, and validation of analytical methods for detecting newly prohibited substances. For method optimization, we selected the optimal collision energies for 339 prohibited substances. Notably, 195 substances exhibited a signal intensity increase of >110% compared with the signal intensity of the original collision energy. All data related to method validation and quantitative analysis were efficiently visualized, extracted, or calculated using Skyline. Moreover, a comparison of the time consumed and the number of suspicious samples screened in the initial test procedure highlighted the advantages of using Skyline over the commercially available software TraceFinder in doping control.

The effect of a brinzolamide/brimonidine fixed combination on optic nerve head blood flow in rabbits

by Nana Takahashi, Kota Sato, Naoki Kiyota, Mai Yamazaki, Eriko Kunikane, Toru Nakazawa

Purpose

The purpose of this study was to investigate the effect of a 1% brinzolamide and 0.1% brimonidine fixed combination (BBFC) on ONH blood flow (BF) in rabbits.

Methods

A crossover study was conducted on pigmented rabbits; a physiological saline solution, brinzolamide, or BBFC was administered for eight days. ONH BF, intraocular pressure (IOP) and systemic parameters were measured before the eighth day’s first dose and at 6, 9, 12, and 14 hours after the dose. ONH BF was assessed using laser speckle flowgraphy, and mean blur rate (MBR) values were calculated. The percentage against baseline of each parameter was calculated, and intergroup comparisons were performed at each time point.

Results

There were no significant differences in the percentage change in systemic parameters. At 6 hours after administration, the BBFC group showed a significantly higher percentage change in large vessel area-MBR (%MV) compared to the control group (98.6±16.8%MV vs. 81.3±7.9%MV, P = 0.03). On the other hand, the brinzolamide group did not show a significant difference. Both the brinzolamide and BBFC groups had significantly lower percentage change in IOP (%IOP) compared to the control group (90.6±5.0%IOP, 93.3±2.9%IOP, and 99.2±1.7%IOP, respectively, P Conclusion

BBFC effectively reduces IOP and mitigates diurnal fluctuation-induced decreases in ONH BF.

A Semantic Segment Encoder (SSE): Improving human face inversion quality through minimized learning space

by Byungseok Kang, Youngjae Jo

Recently, Generative Adversarial Networks (GAN) has been greatly developed and widely used in image synthesis. A Style-Based Generator Architecture for Generative Adversarial Networks (StyleGAN) which is the foremost, continues to develop human face inversion domain. StyleGAN uses insufficient vector space to express more than one million pixels. It is difficult to apply in real business due to distortion-edit tradeoff problem in latent space. To overcome this, we propose a novel semantic segment encoder (SSE) with improved face inversion quality by narrowing the size of restoration latent space. Encoder’s learning area is minimized to logical semantic-segment units that can be recognized by humans. The proposed encoder does not affect other segments because only one segment is edited at a time. To verify the face inversion quality, we compared with the latest encoders both Pixel2style2Pixel and RestyleEncoder. Experimental result shows that the proposed encoder improved distortion quality around 20% while maintain editing performance.

Clarithromycin overcomes stromal cell-mediated drug resistance against proteasome inhibitors in myeloma cells via autophagy flux blockage leading to high NOXA expression

by Shota Moriya, Hiromi Kazama, Hirotsugu Hino, Naoharu Takano, Masaki Hiramoto, Shin Aizawa, Keisuke Miyazawa

We previously reported that macrolide antibiotics, such as clarithromycin (CAM), blocked autophagy flux, and simultaneous proteasome and autophagy inhibition by bortezomib (BTZ) plus CAM resulted in enhanced apoptosis induction in multiple myeloma (MM) cells via increased endoplasmic reticulum (ER) stress loading. However, in actual therapeutic settings, cell adhesion-mediated drug resistance between bone marrow stromal cells (BMSC) and MM cells has been known to be a barrier to treatment. To investigate whether CAM could enhance BTZ-induced cytotoxicity in MM cells under direct cell adhesion with BMSC, we established a co-culture system of EGFP-labeled MM cells with BMSC. The cytotoxic effect of BTZ on MM cells was diminished by its interaction with BMSC; however, the attenuated cytotoxicity was recovered by the co-administration of CAM, which upregulates ER stress loading and NOXA expression. Knockout of NOXA in MM cells canceled the enhanced cell death by CAM, indicating that NOXA is a key molecule for cell death induction by the co-administration of CAM. Since NOXA is degraded by autophagy as well as proteasomes, blocking autophagy with CAM resulted in the sustained upregulation of NOXA in MM cells co-cultured with BMSC in the presence of BTZ. Our data suggest that BMSC-associated BTZ resistance is mediated by the attenuation of ER stress loading. However, the addition of CAM overcomes BMSC-associated resistance via upregulation of NOXA by concomitantly blocking autophagy-mediated NOXA degradation and transcriptional activation of NOXA by ER stress loading.

Chronic kidney disease prediction using boosting techniques based on clinical parameters

by Shahid Mohammad Ganie, Pijush Kanti Dutta Pramanik, Saurav Mallik, Zhongming Zhao

Chronic kidney disease (CKD) has become a major global health crisis, causing millions of yearly deaths. Predicting the possibility of a person being affected by the disease will allow timely diagnosis and precautionary measures leading to preventive strategies for health. Machine learning techniques have been popularly applied in various disease diagnoses and predictions. Ensemble learning approaches have become useful for predicting many complex diseases. In this paper, we utilise the boosting method, one of the popular ensemble learnings, to achieve a higher prediction accuracy for CKD. Five boosting algorithms are employed: XGBoost, CatBoost, LightGBM, AdaBoost, and gradient boosting. We experimented with the CKD data set from the UCI machine learning repository. Various preprocessing steps are employed to achieve better prediction performance, along with suitable hyperparameter tuning and feature selection. We assessed the degree of importance of each feature in the dataset leading to CKD. The performance of each model was evaluated with accuracy, precision, recall, F1-score, Area under the curve-receiving operator characteristic (AUC-ROC), and runtime. AdaBoost was found to have the overall best performance among the five algorithms, scoring the highest in almost all the performance measures. It attained 100% and 98.47% accuracy for training and testing sets. This model also exhibited better precision, recall, and AUC-ROC curve performance.

The burden of non-disabled frailty and its associated factors among older adults in Bangladesh

by Sabuj Kanti Mistry, A. R. M. Mehrab Ali, Uday Narayan Yadav, Saruna Ghimire, Afsana Anwar, Md. Nazmul Huda, Fouzia Khanam, Rashidul Alam Mahumud, Ateeb Ahmad Parray, Shovon Bhattacharjee, David Lim, Mark Fort Harris

Objective

The present study aims to measure the prevalence of non-disabled frailty and its associated factors among Bangladeshi older adults.

Methods

This cross-sectional study was conducted during September and October 2021 among 1,045 Bangladeshi older adults (≥60 years). Telephone interviews, using a semi-structured questionnaire, were undertaken to collect data on participants’ characteristics and level of frailty. The non-disabled frailty was measured using the ‘Frail Non-Disabled (FiND)’ questionnaire. A multinomial logistic regression model assessed the factors associated with frailty among the participants.

Results

Around a quarter of the participants (24.8%) were frail. The multinomial regression analysis showed that older participants aged ≥80 years (RRR = 3.23, 95% CI: 1.41–7.37) were more likely to be frail compared to participants aged 60–69 years. Likewise, the participants living in a large family with ≥4 members (RRR = 1.39, 95% CI: 1.01–1.92) were more likely to be frail compared to those living in smaller families. Also, participants having memory or concentration problems (RRR = 1.56, 95% CI: 1.12–2.17) were more likely to be frail compared to those who were not suffering from these problems. Moreover, participants whose family members were non-responsive to their day-to-day assistance (RRR = 1.47, 95% CI: 1.06–2.03) were more likely to be frail compared to those whose family members were responsive. Furthermore, participants who were feeling lonely (RRR = 1.45, 95% CI: 1.07–1.98) were more likely to be frail than their counterparts who were not feeling lonely.

Conclusions

The findings of the present study suggest developing tailored interventions to address the burden of frailty among the older populations in Bangladesh. In particular, providing long-term care and health promotion activities can be of value in preventing frailty and reducing adverse health outcomes among this vulnerable population group.

Healthcare data quality assessment for improving the quality of the Korea Biobank Network

by Ki-Hoon Kim, Seol Whan Oh, Soo Jeong Ko, Kang Hyuck Lee, Wona Choi, In Young Choi

Numerous studies make extensive use of healthcare data, including human materials and clinical information, and acknowledge its significance. However, limitations in data collection methods can impact the quality of healthcare data obtained from multiple institutions. In order to secure high-quality data related to human materials, research focused on data quality is necessary. This study validated the quality of data collected in 2020 from 16 institutions constituting the Korea Biobank Network using 104 validation rules. The validation rules were developed based on the DQ4HEALTH model and were divided into four dimensions: completeness, validity, accuracy, and uniqueness. Korea Biobank Network collects and manages human materials and clinical information from multiple biobanks, and is in the process of developing a common data model for data integration. The results of the data quality verification revealed an error rate of 0.74%. Furthermore, an analysis of the data from each institution was performed to examine the relationship between the institution’s characteristics and error count. The results from a chi-square test indicated that there was an independent correlation between each institution and its error count. To confirm this correlation between error counts and the characteristics of each institution, a correlation analysis was conducted. The results, shown in a graph, revealed the relationship between factors that had high correlation coefficients and the error count. The findings suggest that the data quality was impacted by biases in the evaluation system, including the institution’s IT environment, infrastructure, and the number of collected samples. These results highlight the need to consider the scalability of research quality when evaluating clinical epidemiological information linked to human materials in future validation studies of data quality.
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