Hasil untuk "Medical technology"

Jiawei Hao, Ping Wang, Quan Shen et al.

Abstract The lysosome is a cell’s endogenous machinery responsible for degrading proteins. Here we describe two lysosome-targeting live attenuated vaccine approaches, LYTAR 1.0 and LYTAR 2.0, by harnessing the lysosome to conditionally degrade viral proteins of influenza virus. LYTAR 1.0 incorporates a conditionally removable lysosome-targeting motif at the N- or C-terminus of viral proteins. LYTAR 2.0 allows flexible placement of lysosome-targeting motifs at internal or terminal sites of viral proteins. The resulting lysosome-targeting vaccine strains are attenuated by lysosome-mediated viral protein degradation in conventional cells, while maintaining replication efficiencies comparable to the wild-type virus in producer cell lines. In mouse models, these vaccine candidates are attenuated, induce strong and broad adaptive immune responses, and provide cross-reactive protection against H1N1 and H3N2 influenza viral challenges. This study establishes a lysosome-targeting vaccine platform for developing safe and effective live attenuated vaccines.

Muhammad Danish Mujib, Nayab Mubashir, Ahmad Zahid Rao et al.

<b>Background</b>: The global prevalence of Alzheimer’s disease (AD) has reached 55.2 million. AD is characterized by progressive deterioration in cognition and working memory (WM), which are essential for attention, reasoning, and learning. These impairments are associated with pathological changes in cortical and subcortical regions. Binaural beats (BBs), a non-invasive auditory neuromodulation technique, have demonstrated cognitive enhancement effects in healthy individuals; however, their impact on WM in patients with AD remains largely unexplored. <b>Methods</b>: This study investigated the effects of BB stimulation on WM and cognitive function in the temporal lobe of patients with AD using standardized Low-Resolution Electromagnetic Tomography (sLORETA). Twenty-five patients with AD were randomly assigned to either an experimental group (<i>n</i> = 15) that received BB stimulation or a control group (<i>n</i> = 10) that received standard auditory stimulation. EEG recordings were obtained before and after the intervention. <b>Results</b>: Paired <i>t</i>-tests conducted on timeframe and frequency-wise sLORETA images revealed significant increases (<i>p</i> < 0.05) in theta, alpha1, and alpha2 frequency bands in the experimental group. Activated regions included the inferior, middle, superior, and transverse temporal gyri; Brodmann areas (BA) 20, 21, 22, 40, and 42; as well as networks associated with working memory and cognition. <b>Conclusions</b>: These findings suggest that BB stimulation induces temporal lobe activation, thereby enhancing working memory and cognitive function in patients with AD.

Wanyu Deng, Zhen Luo, Haifei Yu et al.

IntroductionChronic hepatitis B virus (HBV) infection continues to pose a significant global health burden, and current therapies rarely target the viral covalently closed circular DNA reservoir. Kaempferol (KP), a major flavonoid found in various herbs and plants, exhibits diverse bioactivities, but its potential anti-HBV activity remains unclear. This study aims to investigate the anti-HBV potential of KP and to elucidate its underlying mechanisms.MethodsThe HBV-infected Huh7DhNTCP cell, viral stable transfection cell HepG2.2.15, as well as a hydrodynamic injection-based chronic HBV infection mouse model, were established to evaluate the antiviral effects of KP. The levels of HBV RNAs, DNA and proteins were detected using ELISA, western blot, qPCR, immunofluorescence and immunohistochemistry. To investigate the mechanisms, viral promoter activities were assessed via dual-luciferase reporter assays, and relevant transcription factors were validated through qPCR and western blot analysis.ResultsKP dose- and time-dependently reduced the levels of viral antigens, RNA, and DNA in vitro, and also significantly lowered viral markers and attenuated HBV-induced hepatic pro-inflammatory cytokines expression in vivo. Furthermore, KP acted in combination with the nucleoside analog entecavir to suppress HBV replication. Mechanistically, KP strongly inhibited the transcriptional activity of the HBV core promoter (Cp), and enhanced the phosphorylation of both extracellular signal-regulated kinase (ERK) and its downstream target forkhead box protein O1 (FOXO1). Importantly, the ERK-specific inhibitor U0126 completely abolished the antiviral effects of KP, confirming that its antiviral activity depended on the ERK/FOXO1 pathway.DiscussionCollectively, our results indicate that KP activates ERK-dependent FOXO1 phosphorylation, leading to transcriptional repression of the HBV Cp and thereby suppression of viral replication. These findings identify KP as a potential candidate for developing novel therapeutics against chronic HBV infection.

Hao Zhang, Hao Zhang, Hao Zhang et al.

BackgroundHigh-altitude hypoxia disrupts intestinal homeostasis by impairing the epithelial barrier, triggering inflammation, and promoting microbial translocation. Berberine (BER), a natural isoquinoline alkaloid with antimicrobial and anti-inflammatory properties, has shown potential in protecting intestinal integrity; however, its efficacy under hypoxic conditions and its interaction with the gut microbiota remain unclear.MethodsA chronic hypoxia mouse model was used to investigate the protective effects of BER against intestinal injury. Microbiota dependency was assessed through antibiotic-mediated depletion and fecal microbiota transplantation (FMT), combined with 16S rRNA gene sequencing, metabolomics, and immune profiling. The functional role of a BER-responsive bacterium was validated by oral administration in antibiotic-treated mice.ResultsBER supplementation restored epithelial barrier integrity, including tight junctions, antimicrobial peptide expression, and goblet cell function, while reducing inflammation and epithelial apoptosis under hypoxic conditions. BER also reshaped gut microbial composition and network structure, accompanied by coordinated alterations in cecal metabolites, particularly purine metabolites and bile acids. Microbiota depletion abolished the protective effects of BER, whereas FMT from BER-treated donors recapitulated these effects, confirming a microbiota-dependent mechanism. Among BER-responsive taxa, Bacteroides thetaiotaomicron (B. thetaiotaomicron) emerged as a key effector, correlating with metabolite profiles and barrier integrity. Oral administration of B. thetaiotaomicron alone protected against hypoxia-induced intestinal injury, restoring mucin production and antimicrobial peptide expression, and attenuating inflammation and apoptosis. Mechanistically, both BER and B. thetaiotaomicron reactivated bile acid–FXR signaling and normalized intestinal immune homeostasis, including T-cell subset distribution.ConclusionThese findings demonstrate that BER protects against hypoxia-induced intestinal injury through microbiota-dependent metabolic and immune regulation. B. thetaiotaomicron acts as a central mediator of this protective effect, highlighting microbiota-targeted strategies as potential interventions for maintaining intestinal homeostasis under hypoxic stress.

Yi Shuai, Bo Chen, Tao Jiang et al.

Abstract Background Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe, therapy-refractory condition driven by ferroptotic disruption of jawbone-derived mesenchymal stem cells (MSCs) biology. We dissect this mechanism to validate ferroptosis as a therapeutic target. Methods We first demonstrated that miR-145-3p is mechanistically coupled to ferroptosis and osteogenesis in BRONJ model by gain- and loss-of-function studies. To evaluate therapeutic efficacy under pathologically relevant conditions, we designed three models: (i) Local BRONJ repair model: miR-145-3p-enriched exosomes were encapsulated in an injectable hydrogel scaffold and grafted into necrotic alveolar bone to assess direct BRONJ resolution. After local BRONJ treatment, endogenous MSCs were re-isolated, and both cellular and exosomal miR-145-3p levels were quantified. (ii) Osteoporosis treatment model: The reprogrammed MSCs derived from treated BRONJ rats were then administered intravenously to osteoporotic littermates to evaluate whether these MSCs retain systemic osteogenic competence. (iii) Critical-sized calvarial defect repair model: To further dissect the intrinsic osteogenic capacity, reprogrammed MSCs derived from treated BRONJ rats were fabricated into cell-sheet/HA-TCP “sandwich” constructs and transplanted into calvarial defects. Results BRONJ markedly compromised MSCs viability while elevating hallmarks of ferroptosis that were reversed by the ferroptosis inhibitor. Concomitantly, osteogenic capacity declined, as shown by reduced ALP activity, mineralized nodules, new bone formation and expression of RUNX2 and OCN. Mechanistically, we identified a miR-145-3p/IREB2 regulatory circuit that governs ferroptosis in BRONJ-derived MSCs; exosome-mediated delivery of miR-145-3p reinstated this axis, thereby reactivating the MSCs osteogenesis and driving in situ bone regeneration. Critically, after local BRONJ therapy, the reprogrammed MSCs were (i) infused via tail vein into osteoporotic rats, significantly elevating bone mass, and (ii) engineered into cell-sheet/HA-TCP “sandwich” constructs that achieved robust repair of critical-sized calvarial defects. These data establish exosomal miR-145-3p as a therapeutic that mitigates ferroptosis and restores the osteogenic competence of jawbone-derived MSCs for bone regeneration. Conclusion Collectively, our findings establish the miR-145-3p/IREB2/ferroptosis axis as an important regulator of BRONJ pathology and demonstrate that exosomal delivery of miR-145-3p not only ameliorates localized BRONJ but also substantially reinstates the systemic osteogenic potential of jawbone-derived MSCs, offering a pre-clinical promising strategy to combat both BRONJ and associated bone loss disorders. Graphical Abstract

Salem Hannoun, Grace Fayad, Nabil K. El Ayoubi et al.

Abstract Background Brain age estimation is an emerging biomarker for assessing neurodegeneration in multiple sclerosis (MS). However, MS-related lesions can distort structural measurements, potentially leading to inaccuracies in age prediction models. Lesion filling has been proposed as a corrective step, but its impact on brain age estimation and its associations with clinical and structural markers remains unclear. Methods We analyzed 571 relapsing-remitting MS patients using the BrainAgeR pipeline to estimate brain age from both non-lesion-filled and lesion-filled T1-weighted images. Bias correction was applied to remove age-related prediction bias. Brain Age Gap (BAG) was computed as the difference between corrected predicted brain age and chronological age. Multivariable linear regression models were used to assess associations between BAG and clinical outcomes (EDSS, 9HPT, SDMT, 25FWT) and volumetric measures. Results Non-lesion-filled and lesion-filled brain age estimates showed excellent agreement (r = 0.97; ICC = 0.962), with a mean difference of 1.23 years and slightly lower mean absolute error for lesion-filled predictions (8.12 vs. 9.40 years). Both BAG measures were significantly associated with EDSS, 9HPT, and SDMT, though effect sizes were modest. Lesion-filled BAG showed stronger and more consistent associations with gray matter, thalamic, and hippocampal volumes, and these associations remained significant after Bonferroni correction. Conclusion Lesion filling modestly improves structural interpretability of brain age estimates in MS but has limited effect on clinical correlations. The high concordance between lesion-filled and non-lesion-filled estimates confirms the robustness of brain age as a biomarker, while supporting the use of lesion correction when structural precision is essential.

Dong Wang, Wenzhe Chen, Jiali Chen et al.

In individuals afflicted with hemophilia, characterized by a deficiency of coagulation factor VIII (FVIII), the occurrence of spontaneous recurrent intra-articular hemorrhage precipitates the emergence of hemophilic arthropathy (HA). Although clotting factor replacement therapy reduces joint bleeding clinically, clotting factors need to be injected frequently due to the rapid diffusion of the drug. Hence, a novel drug delivery approach may be developed to improve the drug therapy. Platelet-derived extracellular vesicles (PEVs) are known to possess anti-inflammatory and hemostatic properties and could be used as a potential HA therapy. In this study, we constructed a PEV-LS@FVIII nanotherapeutic system by combining thioketal (TK), liposomes (LS), and FVIII to form the LS@FVIII complexes, and then hybridizing PEV with LS@FVIII. Our results demonstrated that PEV-LS@FVIII could efficiently facilitate FVIII delivery and specifically target the injured knee joint. Both in vitro and in vivo studies showed a reduction in the M1 phenotype of macrophages and an enhancement of the M2 phenotype, compared to FVIII free control. Furthermore, PEV-LS@FVIII appeared to alleviate HA-induced cartilage damage. In conclusion, our findings demonstrate that PEV-LS@FVIII could delay the progression of HA by targeting bleeding joints, modulating macrophage polarization to suppress inflammation, and mitigating cartilage damage.

Jie Liu, Danping Zeng, Zhihui Jiang et al.

Abstract Backgroud Intussusception is a common acute abdominal disease in children, often leading to acute ileus in infants and young children. Objective This study aimed to develop and validate a nomogram for predicting recurrent intussusception in children within 48 h after pneumatic reduction of primary intussusception. Methods Clinical data of children with acute intussusception admitted to multiple hospitals from March 2019 to March 2021 were retrospectively analyzed. The children were divided into a successful reductioncontrol group (control group) and a recurrent intussusception group (RI group) according to the results of pneumatic reduction. Results A total of 2406 cases were included in this study, including 2198 control group and 208 RI group. In the total sample, 1684 cases were trained and 722 cases were verified. A logistic regression analysis was conducted to establish a predictive model based on age, abdominal pain time, white blood cells count, and hypersensitive C-reactive protein levels as independent predictors of intussusception recurrence. The nomogram successfully predicted recurrent intussusception after pneumatic reduction. Conclusion In this study, a nomogram was developed based on clinical risk factors to predict recurrent intussusception following pneumatic reduction in children. Age, abdominal pain time, white blood cell counts, and hypersensitive C-reactive protein levels were identified as predictors and incorporated into the nomogram. Internal validation demonstrated that this nomogram can offer a clear and convenient tool for identifying risk factors for recurrence of intussusception in children undergoing pneumatic reduction.

Han Na Suh, Sung-Hoon Yoon, Yoo Min Park et al.

Xiaohang Yang, Jingjing Yin, Yu Fu et al.

Abstract Introduction Myometrial invasion is a prognostic factor for lymph node metastases and decreased survival in non-endometrioid endometrial carcinoma patients. Herein, we explored the mode of myometrial invasion diagnosis in FIGO stage I non-endometrioid carcinoma and evaluated the differences in diagnostic efficiency among intraoperative frozen section (IFS), intraoperative gross examination (IGE), magnetic resonance imaging (MRI), and computed tomography (CT) in clinical practice. Finally, we suggested which test should be routinely performed. Method This was a historical cohort study nationwide with 30 centers in China between January 2000 and December 2019. Clinical data, including age, histology, method of myometrial invasion evaluation (MRI, CT, IGE, and IFS), and final diagnosis of postoperative paraffin sections, were collected from 490 non-endometrioid endometrial carcinoma (serous, clear cell, undifferentiated, mixed carcinoma, and carcinosarcoma) women in FIGO stage I. Results Among the 490 patients, 89.59% presented myometrial invasion. The methods reported for myometrial invasion assessment were IFS in 23.47%, IGE in 69.59%, MRI in 37.96%, and CT in 10.20% of cases. The highest concordance was detected between IFS and postoperative paraffin sections (Kappa = 0.631, accuracy = 93.04%), followed by IGE (Kappa = 0.303, accuracy = 82.40%), MRI (Kappa = 0.131, accuracy = 69.35%), and CT (Kappa = 0.118, accuracy = 50.00%). A stable diagnostic agreement between IFS and the final results was also found through the years (2000–2012: Kappa = 0.776; 2013–2014: Kappa = 0.625; 2015–2016: Kappa = 0.545; 2017–2019: Kappa = 0.652). Conclusion In China, the assessment of myometrial invasion in non-endometrioid endometrial carcinoma is often performed via IGE, but the reliability is relatively low in contrast to IFS. In clinical practice, IFS is a reliable method that can help accurately assess myometrial invasion and intraoperative decision-making (lymph node dissection or not). Hence, it should be routinely performed in non-endometrioid endometrial carcinoma patients.

Mingzhu Zhou, Mingyu Mao, Fan Yang et al.

BackgroundLong non-coding RNAs (lncRNAs) are increasingly recognized as essential players in various biological processes due to their interactions with DNA, RNA, and protein. Emerging studies have demonstrated lncRNAs as prognostic biomarkers in multiple cancers. However, the prognostic effect of lncRNA AL161431.1 in head and neck squamous cell carcinoma (HNSCC) patients has not been reported.MethodsIn the present study, we conducted a series of analyses to identify and validate the prognostic value of lncRNA AL161431.1 in HNSCC, which included differential lncRNAs screening, survival analysis, Cox regression analysis, time ROCanalysis, nomogram prediction, enrichment analysis, tumor infiltration of immune cells, drug sensitivity analysis, and quantitative real-time polymerase chain reaction (qRT-PCR).ResultsIn this study, we performed a comprehensive survival and predictive analysis and demonstrated that AL161431.1 was an independent prognostic factor of HNSCC, for which a high AL161431.1 level indicated poor survival in HNSCC. Functional enrichment analyses found that cell growth and immune-related pathways were significantly enriched in HNSCC, suggesting that AL161431.1 may play a role in tumor development and tumor microenvironment (TME). AL161431.1-related immune cells infiltration analysis demonstrated that AL161431.1 expression is significantly positively associated with M0 macrophages in HNSCC (P&lt;0.001). Using "OncoPredict", we recognized chemotherapy drugs sensitive to the high expression group. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to identify the expression level of AL161431.1 in HNSCC, and the results further validated our findings.ConclusionsOur findings suggest that AL161431.1 is a reliable prognostic marker for HNSCC and can potentially be an effective therapeutic target.

Guanyun Wei, Xu Zhang, Xu Zhang et al.

Most cases of acquired hearing loss are due to degeneration and subsequent loss of cochlear hair cells. Whereas mammalian hair cells are not replaced when lost, in zebrafish, they constantly renew and regenerate after injury. However, the molecular mechanism among this difference remains unknown. Dual-specificity phosphatase 14 (DUSP14) is an important negative modulator of mitogen-activated protein kinase (MAPK) signaling pathways. Our study was to investigate the effects of DUSP14 on supporting cell development and hair cell regeneration and explore the potential mechanism. Our results showed that dusp14 gene is highly expressed in zebrafish developing neuromasts and otic vesicles. Behavior analysis showed that dusp14 deficiency resulted in hearing defects in zebrafish larvae, which were reversed by dusp14 mRNA treatment. Moreover, knockdown of dusp14 gene caused a significant decrease in the number of neuromasts and hair cells in both neuromast and otic vesicle, mainly due to the inhibition of the proliferation of supporting cells, which results in a decrease in the number of supporting cells and ultimately in the regeneration of hair cells. We further found significant changes in a series of MAPK pathway genes through transcriptome sequencing analysis of dusp14-deficient zebrafish, especially mapk12b gene in p38 signaling. Additionally, inhibiting p38 signaling effectively rescued all phenotypes caused by dusp14 deficiency, including hair cell and supporting cell reduction. These results suggest that DUSP14 might be a key gene to regulate supporting cell development and hair cell regeneration and is a potential target for the treatment of hearing loss.

Tzu-Yu Hsu, Tzu-Yu Hsu, Hsin-Yi Wang et al.

The pupil constricts in response to an increase in global luminance level, commonly referred to as the pupil light reflex. Recent research has shown that these reflex responses are modulated by high-level cognition. There is larger pupil constriction evoked by a bright stimulus when the stimulus location spatially overlaps with the locus of attention, and these effects have been extended to saccade planning and working memory (here referred to as pupil local-luminance modulation). Although research in monkeys has further elucidated a central role of the frontal eye field (FEF) and superior colliculus in the pupil local-luminance modulation, their roles remain to be established in humans. Through applying continuous theta-burst transcranial magnetic stimulation over the right FEF (and vertex) to inhibit its activity, we investigated the role of the FEF in human pupil local-luminance responses. Pupil light reflex responses were transiently evoked by a bright patch stimulus presented during the delay period in the visual- and memory-delay tasks. In the visual-delay task, larger pupil constriction was observed when the patch location was spatially aligned with the target location in both stimulation conditions. More interestingly, after FEF stimulation, larger pupil constriction was obtained when the patch was presented in the contralateral, compared to the ipsilateral visual field of the stimulation. In contrast, FEF stimulation effects were absence in the memory-delay task. Linear mixed model results further found that stimulation condition, patch location consistency, and visual field significantly modulated observed pupil constriction responses. Together, our results constitute the first evidence of FEF modulation in human pupil local-luminance responses.

Mahdi NoroozOliaei, Hamid Riazi Esfahani, Mohammad Sadegh Abrishamian

The absorption of light is very important task for retina photoreceptors. Graphene is an energy harvesting material and one of the best models for the electromagnetic wave absorption and its conversion into signals. In this paper, an electromagnetic modeling of human retinal photoreceptors has been presented based on graphene coated material as a receiver antenna. The proposed electromagnetic model based on dielectric resonator antenna (DRA) is being analyzed for retina photoreceptors of human eye (cones and rods) by Finite Integral Method (FIM) collaborated with CST MWS. The results show that the model is good for vision spectrum with a proper field enhancement in cone photoreceptor due to its sensitivity to light. The results indicate proper S11 (return loss below −10 dB) with invaluable resonances in a wide range of frequencies from 405 THz to 790 THz (vision spectrum), suitable S21 (insertion loss 3-dB bandwidth), very good field distribution for flowing the power within desired radiation characteristics. The drawbacks of conventional model (no coating) have been resolved by presenting this one at blue spectrum specifically. Finally, mfERG clinical and experimental results show that this model can stimulate the electrochemical voltages and currents in photoreceptor cells.

Hailu Gemechu Benti, Abraham Debebe Woldeyohannes, Belete Sirahbizu Yigezu

The challenge of enhancing cutting tool life has been dealt with by many research studies. However, this challenge seems endless with growing technological advancement which brings about incremental improvement in tool life. The objective of this review paper is focused at assessing filtered cathodic vacuum arc deposition techniques applied on cutting tools and their effect on tool efficiency. The paper particularly picks filtered cathodic vacuum arc deposition (FCVAD) among other well-identified methods of coating like the Chemical Vapor Deposition (CVD) and Physical Vapor Deposition (PVD). Filtered Cathodic Vacuum Arc Deposition is the state of art in the coating technology finding wide application in the electronics industry and medical industry in addition to the machining industry, which is the concern of this review paper. This review is made in order to summarize and present the various techniques of FCVAD coatings and their applications, as investigated by various researches in the area.

Xiuhua April Si, Jinxiang Xi

Respiratory diseases often show no apparent symptoms at their early stages and are usually diagnosed when permanent damages have been made to the lungs. A major site of lung pathogenesis is the small airways, which make it highly challenging to detect using current techniques due to the diseases’ location (inaccessibility to biopsy) and size (below normal CT/MRI resolution). In this review, we present a new method for lung disease detection and treatment in small airways based on exhaled aerosols, whose patterns are uniquely related to the health of the lungs. Proof-of-concept studies are first presented in idealized lung geometries. We subsequently describe the recent developments in feature extraction and classification of the exhaled aerosol images to establish the relationship between the images and the underlying airway remodeling. Different feature extraction algorithms (aerosol density, fractal dimension, principal mode analysis, and dynamic mode decomposition) and machine learning approaches (support vector machine, random forest, and convolutional neural network) are elaborated upon. Finally, future studies and frequent questions related to clinical applications of the proposed aerosol breath testing are discussed from the authors’ perspective. The proposed breath testing has clinical advantages over conventional approaches, such as easy-to-perform, non-invasive, providing real-time feedback, and is promising in detecting symptomless lung diseases at early stages.

Gabriela Brzuska, Gabriela Pastuch-Gawolek, Monika Krawczyk et al.

Tick-borne encephalitis virus (TBEV) transmitted by ticks is a pathogen of great medical importance. As still no effective antiviral treatment is available, in the present study, a series of uridine glycoconjugates containing amide or/and 1,2,3-triazole moiety in the linker structure was synthesized and evaluated for the antiviral activity against two strains of TBEV: a highly virulent Hypr strain and less virulent Neudoerfl strain, using standardized previously in vitro assays. Our data have shown that four compounds from the series (<b>18–21</b>) possess strong activity against both TBEV strains. The half maximal inhibitory concentration (IC₅₀) values of compounds <b>18–21</b> were between 15.1 and 3.7 μM depending on the virus strain, which along with low cytotoxicity resulted in high values of the selectivity index (SI). The obtained results suggest that these compounds may be promising candidates for further development of new therapies against flaviviruses.

William A. Pettinger, Edwin K. Jackson

It was indeed a Don Quixote-like pursuit of the mechanism of essential hypertension when we serendipitously discovered α2-adrenoceptors (α2-ARs) in skin-lightening experiments in the frog. Now α2-ARs lurk on the horizon involving hypertension causality, renal denervation for hypertension, injury from falling in the elderly and prazosin’s mechanism of action in anxiety states such as posttraumatic stress disorder (PTSD). Our goal here is to focus on this horizon and bring into clear view the role of α2-AR-mediated mechanisms in these seemingly unrelated conditions. Our narrative begins with an explanation of how experiments in isolated perfused kidneys led to the discovery of a sodium-retaining process, a fundamental mechanism of hypertension, mediated by α2-ARs. In this model system and in the setting of furosemide-induced sodium excretion, α2-AR activation inhibited adenylate cyclase, suppressed cAMP formation, and caused sodium retention. Further investigations led to the realization that renal α2-AR expression in hypertensive animals is elevated, thus supporting a key role for kidney α2-ARs in the pathophysiology of essential hypertension. Subsequent studies clarified the molecular pathways by which α2-ARs activate prohypertensive biochemical systems. While investigating the role of α1-adrenoceptors (α1-ARs) versus α2-ARs in renal sympathetic neurotransmission, we noted an astonishing result: in the kidney α1-ARs suppress the postjunctional expression of α2-ARs. Here, we describe how this finding relates to a broader understanding of the role of α2-ARs in diverse disease states. Because of the capacity for qualitative and quantitative monitoring of α2-AR-induced regulatory mechanisms in the kidney, we looked to the kidney and found enlightenment.

Xuan Thi Thanh Le, Anh Kim Dang, Jayson Toweh et al.

This is the first time in Vietnam that people have undergone “social distancing” to minimize the spreading of infectious disease, COVID-19. These deliberate preemptive strategies may have profound impacts on the mental health of the population. Therefore, this study aimed to identify the psychological impacts of COVID-19 on Vietnamese people and associated factors. We conducted a cross-sectional study during a one-week social distancing and isolation from April 7 to 14, 2020, in Vietnam. A snowball sampling technique was carried out to recruit participants. Impact of Event Scale-Revised (IES-R) was utilized to assess the psychological impacts of the COVID-19. Of all participants, 233 (16.4%) reported low level of PTSS; 76 (5.3%) rated as moderate, and 77 (5.4%) reported extreme psychological conditions. Being female, above 44 years old, or having a higher number of children in the family were positively associated with a higher level of psychological distress. Being self-employed/unemployed/retired was associated with a higher score of intrusion and hyperarousal subscale. Individuals who have a history of touching objects with the possibility of spreading coronavirus (utensils) were related to a higher level of avoidance. There were relatively high rates of participants suffering from PTSS during the first national lockdown related to COVID-19. Comprehensive strategies for the screen of psychological problems and to support high-risk groups are critical, especially females, middle-aged adults and the elderly, affected laborers, and health care professionals.

Jankowska-Polańska B, Dudek K, Szymanska-Chabowska A et al.

Beata Jankowska-Polańska,1 Krzysztof Dudek,2 Anna Szymanska-Chabowska,3 Izabella Uchmanowicz1 1Department of Clinical Nursing, Faculty of Health Science, Wroclaw Medical University, 2Department of Logistic and Transport Systems, Faculty of Mechanical Engineering, Wroclaw University of Technology, 3Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland Background: Hypertension affects about 80% of people older than 80 years; however, diagnosis and treatment are difficult because about 55% of them do not adhere to treatment recommendations due to low socioeconomic status, comorbidities, age, physical limitations, and frailty syndrome.Aims: The purposes of this study were to evaluate the influence of frailty on medication adherence among elderly hypertensive patients and to assess whether other factors influence adherence in this group of patients.Methods and results: The study included 296 patients (mean age 68.8&plusmn;8.0) divided into frail (n=198) and non-frail (n=98) groups. The Polish versions of the Tilburg Frailty Indicator (TFI) for frailty assessment and 8-item Morisky Medication Adherence Scale for adherence assessment were used. The frail patients had lower medication adherence in comparison to the non-frail subjects (6.60&plusmn;1.89 vs 7.11&plusmn;1.42; P=0.028). Spearman&rsquo;s rank correlation coefficients showed that significant determinants with negative influence on the level of adherence were physical (rho =-0.117), psychological (rho =-0.183), and social domain (rho =-0.163) of TFI as well as the total score of the questionnaire (rho =-0.183). However, multiple regression analysis revealed that only knowledge about complications of untreated hypertension (&beta;=0.395) and satisfaction with the home environment (&beta;=0.897) were found to be independent stimulants of adherence level.Conclusion: Frailty is highly prevalent among elderly hypertensive patients. Higher level of frailty among elderly patients can be considered as a determinant of lower adherence. However, social support and knowledge about complications of untreated hypertension are the most important independent determinants of adherence to pharmacological treatment. Keywords: frailty syndrome, ageing, hypertension, medication adherence, geriatric syndrome