Hasil untuk "Medicine"

J. Acosta, G. Falcone, P. Rajpurkar et al.

G. Sirugo, Scott M. Williams, S. Tishkoff

Giorgio Sirugo,1,2,6,* Scott M. Williams,5,6,* and Sarah A. Tishkoff3,4,6,* 1Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA 2Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA 3Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA 4Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA 5Departments of Population and Quantitative Health Sciences, and Genetics and Genome Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH 44106, USA 6All three authors contributed equally *Correspondence: giorgio.sirugo@pennmedicine.upenn.edu (G.S.), smw154@case.edu (S.M.W.), tishkoff@pennmedicine.upenn.edu (S.A.T.) https://doi.org/10.1016/j.cell.2019.02.048

Qing-Wen Zhang, Ligen Lin, W. Ye

Natural medicines were the only option for the prevention and treatment of human diseases for thousands of years. Natural products are important sources for drug development. The amounts of bioactive natural products in natural medicines are always fairly low. Today, it is very crucial to develop effective and selective methods for the extraction and isolation of those bioactive natural products. This paper intends to provide a comprehensive view of a variety of methods used in the extraction and isolation of natural products. This paper also presents the advantage, disadvantage and practical examples of conventional and modern techniques involved in natural products research.

Yanhong Shi, H. Inoue, Joseph C. Wu et al.

B. Hill

Damian R. Griffin, Damian R. Griffin, Edward J. Dickenson et al.

J. Olesen

Yutaro Hama, Yuko Fujioka, Hayashi Yamamoto et al.

In mammals, autophagosome formation, a central event in autophagy, is initiated by the ULK complex comprising ULK1/2, FIP200, ATG13, and ATG101. However, the structural basis and mechanism underlying the ULK complex assembly have yet to be fully clarified. Here, we predicted the core interactions organizing the ULK complex using AlphaFold, which proposed that the intrinsically disordered region of ATG13 engages the bases of the two UBL domains in the FIP200 dimer via two phenylalanines and also binds the tandem microtubule-interacting and transport domain of ULK1, thereby yielding the 1:1:2 stoichiometry of the ULK1–ATG13–FIP200 complex. We validated the predicted interactions by point mutations and demonstrated direct triad interactions among ULK1, ATG13, and FIP200 in vitro and in cells, wherein each interaction was additively important for autophagic flux. These results indicate that the ULK1–ATG13–FIP200 triadic interaction is crucial for autophagosome formation and provides a structural basis and insights into the regulation mechanism of autophagy initiation in mammals.

Shi-Cheng Jin, Zi-Long Zhao, Xuyang Zhang et al.

Summary: Stanford type B aortic dissections often exhibit helical morphology. However, the influences of structural helicity on periprocedural and mid-to long-term adverse events after thoracic endovascular aortic repair (TEVAR) remain unclear. In this article, a total of 197 patients who underwent TEVAR between October 2019 and December 2020 were studied. Among them, 93 patients were excluded, and 104 patients were analyzed. The maximum helical angles and the maximum twists were measured using an efficient morphological method based on computed tomography angiography images. The whole dissecting aorta was divided into five zones. The visceral aortic zone exhibited the most pronounced structural helicity compared with other zones. Patients with the maximum helical angle larger or smaller than 200° were categorized into two groups, i.e., the groups of strong helicity and weak helicity. The patients in the strong helicity group exhibited a greater likelihood of experiencing adverse events after TEVAR.

Adrian Singer, Katharina Tropschuh, Marc von Gernler et al.

Abstract Background Progestogens, synthetic analogues of progesterone, are widely used in clinical practice for contraception, hormone replacement therapy, and the management of gynecological disorders. Understanding the specific impacts of different progestogens on the renin-angiotensin-aldosterone system (RAAS) is crucial due to their potential effects on cardiovascular and renal outcomes. Objective This systematic review aims to synthesize existing research on the effects of various progestogens on the RAAS and associated clinical outcomes. Methods We conducted a comprehensive search of databases up to the search date, including randomized controlled trials (RCTs), cohort studies, case-control studies, cross-sectional studies, and qualitative studies. The NIH Study Quality Assessment Tool for Controlled Intervention Studies was used to evaluate the quality of the included studies. Data extraction and quality assessment were performed independently by two reviewers, with discrepancies resolved through discussion. Results Forty-two studies on drospirenone (DRSP) were the most extensively investigated, showing either decreased or unchanged blood pressure (BP), mostly unchanged serum sodium, and an increased risk of hyperkalemia only in patients with mild renal impairment. Sixteen studies on norethindrone (NET/NETA) presented conflicting results on BP and a higher risk of hyperkalemia. Other progestogens, such as levonorgestrel (LNG) and medroxyprogesterone acetate (MPA), showed varied effects on RAAS parameters. Notably, changes in plasma renin activity (PRA), serum aldosterone, and angiotensin II levels were inconsistent across different progestogens and study designs. Conclusion The effects of progestogens on the RAAS are complex and varied, influenced by the type of progestogen, dosage, and combination with estrogen. While some progestogens like DRSP may offer benefits in BP management with minimal electrolyte disturbances, others like NET/NETA might require more careful monitoring due to their associated risks. These findings highlight the importance of personalized medicine approaches in the use of progestogens, tailored to individual patient characteristics and specific hormonal profiles. Further research with standardized methodologies is needed to clarify these effects and guide clinical practice. Trial registration This review was prospectively registered with PROSPERO.

Majed Alluqmani, Abdulfatah M. Alayoubi, Jamil A. Hashmi et al.

BackgroundVariants in a gene encoding sodium voltage-gated channel alpha subunit 1 (SCN1A) are known to cause a broad clinical spectrum of epilepsy and associated features, including Dravet syndrome (MIM 607208), non-Dravet developmental and epileptic encephalopathy (MIM 619317), familial febrile seizures (MIM 604403), familial hemiplegic migraine (MIM 609634), and generalized epilepsy with febrile seizures (MIM 604403).MethodsIn this study, we examined a patient with Parkinson’s disease (PD) without any clinical manifestations of epilepsy and associated features. Genomic nucleic acid was extracted, and a complete coding sequence of the human genome (whole-exome sequencing) was sequenced. Moreover, Sanger sequencing of variants of interest was performed to validate the exome-discovered variants.ResultsWe identified a heterozygous pathogenic missense mutation (c.1498C>T; p.Arg500Trp) in the SCN1A gene in the patient using the whole-exome sequencing approach. The onset of PD features in our patient occurred at the age of 30 years. Biochemical investigations were carried out to rule out any secondary cause of the disease, including Wilson's disease or another metabolic disorder. MRI of the brain and spinal images were unremarkable. Moreover, a dramatic response to carbidopa–levodopa treatment was also observed in the patient.ConclusionOur results suggest that the pathogenic variant in SCN1A may lead to PD features without epilepsy.

Wentao HU, Hui LAO, Ao QIU et al.

In recent years, silicon photomultipliers (SiPMs) have emerged as preferred photoelectric conversion devices in positron emission tomography (PET) due to their outstanding performance. SiPMs possess single-photon resolution capability and time resolution below 100 ps, enabling precise photon arrival time measurements. These advances paved the way for emerging applications such as time-of-flight PET (TOF-PET), photon counting CT, and positron emission lifetime imaging, presenting new challenges to SiPM performance, the advancing of which to their physical limits has become a key focus area in next-generation SiPM research. In traditional SiPM architectures, signal processing and analog-to-digital conversion introduce noise and degrade time performance, thereby limiting the full SiPM potential. With the recent and rapid development of semiconductor manufacturing processes, SiPMs could be manufactured on standard CMOS process nodes, which marks a significant breakthrough in the SiPM field, allowing for the integration of digital logic within SiPM devices. This advancement opens the possibility of achieving more precise time, energy, and position information within a single SiPM, thereby providing potential possibilities to push SiPMs to their performance limits. In this study, we reviewed the development history, working principles, and performance parameters of SiPMs. We analyzed the limitations of traditional SiPMs, outlined key aspects of digital SiPM research, and introduced various current digital SiPM architectures. Finally, we summarized and anticipated key technologies in digital SiPMs.

J. Harkness, J. E. Wagner

Sharli Paphitis, Fatima Akilu, Natasha Chilambo et al.

Background Despite theoretical support for including mental health and psychosocial support (MHPSS) with peacebuilding, few programmes in conflict-affected regions fully integrate these approaches. Aims To describe and assess preliminary outcomes of the Counselling on Wheels programme delivered by the NEEM Foundation in the Borno State of North-East Nigeria. Method We first describe the components of the Counselling on Wheels programme, including education and advocacy for peace and social cohesion through community peacebuilding partnerships and activities, and an MHPSS intervention open to all adults, delivered in groups of eight to ten people. We then conducted secondary analysis of data from 1550 adults who took part in the MHPSS intervention, who provided data at baseline and 1–2 weeks after the final group session. Vulnerability to violent extremism was assessed with a locally developed 80-item scale. Symptoms of common mental disorders were assessed with the Depression, Anxiety and Stress Scale (DASS-21) and Post-Traumatic Stress Disorder Scale (PTSD-8). Data were analysed through a mixed-effect linear regression model, accounting for clustering by community and adjusted for age and gender. Results After taking part in group MHPSS, scores fell for depression (−5.8, 95% CI −6.7 to −5.0), stress (−5.5, 95% CI −6.3 to −4.6), post-traumatic stress disorder (−2.9, 95% CI −3.4 to −2.4) and vulnerability to violent extremism (−44.6, 95% CI −50.6 to −38.6). Conclusions The Counselling on Wheels programme shows promise as a model for integrating MHPSS with community peacebuilding activities in this conflict-affected region of Africa.

Gillian Yeowell, Rachel Leech, Susan Greenhalgh et al.

S. Giguère

Salma M Abdalla, MBBS, MPH, Shui Yu, MPH, Sandro Galea, MD, DrPH

Introduction: Income inequality between the richest 20% and the poorest 80% in the United States has been increasing over the past two decades. Emerging evidence indicates widening disparities between the two groups in cardiovascular disease prevalence as well. However, the mechanisms behind this trend remains unclear. This analysis examines whether a similar trend exists in the levels of biomarkers and risk factors of cardiovascular disease in the United States. Methods: We conducted a serial cross-sectional analysis of a nationally representative data from the National Health and Nutrition Examination Survey (NHANES) for participants age 20 or older between 1999 and 2018. We calculated trends in age-standardized means of body mass index (BMI), systolic blood pressure (SBP), and high-density lipoproteins (HDL) and the trend in prevalence of obesity, high SBP, and low HDL by income group. Results: This analysis included 49,764 participants. Age-standardized mean BMI increased every two years by an average of 0.15 kg/m 2 among the richest 20% and by an average of 0.21 kg/m 2 among the poorest 80%. Age-standardized mean SBP decreased every two years by an average of 0.13 mm Hg among the richest 20% and by an average of 0.10 mm Hg among the poorest 80%. Age-standardized mean HDL increased every two years by an average of 0.39 mg/dL among the richest 20% and by an average of 0.19 mg/dL among the poorest 80%. When adjusted for demographic factors and time, the richest 20% had lower mean BMI (OR = −0.67, 95% CI: −0.89, - 0.44), lower mean SBP (OR = −0.72, 95% CI: −1.24, −0.20), and higher mean HDL (OR = 3.04, 95% CI: 2.46, 3.62) compared to the poorest 80% Conclusion: There are increasing disparities in cardiovascular disease biomarkers by income in the US. Between 1999 and 2018, improvement in biomarkers overwhelmingly occurred among the richest 20%

Yangling Ma, Yixin Luo

Automated fracture detection is an essential part in a computer-aided tele-medicine system. Fractures often occur in human's arbitrary bone due to accidental injuries such as slipping. In fact, many hospitals lack experienced surgeons to diagnose fractures. Therefore, computer-aided diagnosis (CAD) reduces the burden on doctors and identifies fracture. We present a new classification network, Crack-Sensitive Convolutional Neural Network (CrackNet), which is sensitive to fracture lines. In this paper, we propose a new two-stage system to detect fracture. Firstly, we use Faster Region with Convolutional Neutral Network (Faster R-CNN) to detect 20 different types of bone regions in X-ray images, and then we recognize whether each bone region is fractured by using CrackNet. Total of 1052 images are used to test our system, of which 526 are fractured images and the rest are non-fractured images. We assess the performance of our proposed system with X-ray images from Haikou People's Hospital, achieving 90.11% accuracy and 90.14% F-measure. And our system is better than other two-stage systems.

Florian Köhler, Felix Bormann, Günter Raddatz et al.

Abstract Background Hutchinson-Gilford progeria syndrome (HGPS) is a progeroid disease characterized by the early onset of age-related phenotypes including arthritis, loss of body fat and hair, and atherosclerosis. Cells from affected individuals express a mutant version of the nuclear envelope protein lamin A (termed progerin) and have previously been shown to exhibit prominent histone modification changes. Methods Here, we analyze the possibility that epigenetic deregulation of lamina-associated domains (LADs) is involved in the molecular pathology of HGPS. To do so, we studied chromatin accessibility (Assay for Transposase-accessible Chromatin (ATAC)-see/-seq), DNA methylation profiles (Infinium MethylationEPIC BeadChips), and transcriptomes (RNA-seq) of nine primary HGPS fibroblast cell lines and six additional controls, two parental and four age-matched healthy fibroblast cell lines. Results Our ATAC-see/-seq data demonstrate that primary dermal fibroblasts from HGPS patients exhibit chromatin accessibility changes that are enriched in LADs. Infinium MethylationEPIC BeadChip profiling further reveals that DNA methylation alterations observed in HGPS fibroblasts are similarly enriched in LADs and different from those occurring during healthy aging and Werner syndrome (WS), another premature aging disease. Moreover, HGPS patients can be stratified into two different subgroups according to their DNA methylation profiles. Finally, we show that the epigenetic deregulation of LADs is associated with HGPS-specific gene expression changes. Conclusions Taken together, our results strongly implicate epigenetic deregulation of LADs as an important and previously unrecognized feature of HGPS, which contributes to disease-specific gene expression. Therefore, they not only add a new layer to the study of epigenetic changes in the progeroid syndrome, but also advance our understanding of the disease’s pathology at the cellular level.

Andrew Riley, Yasmin Akther, Mohammed Noor et al.

Abstract Background Almost 900,000 Rohingya refugees currently reside in refugee camps in Southeastern Bangladesh. Prior to fleeing Myanmar, Rohingya experienced years of systematic human rights violations, in addition to other historical and more recent traumatic events such as the burning of their villages and murder of family members, friends and neighbors. Currently, many Rohingya struggle to meet basic needs in refugee camps in Bangladesh and face mental health-related concerns that appear linked to such challenges. The purpose of this study is to describe systematic human rights violations, traumatic events, daily stressors, and mental health symptoms and to examine relationships between these factors. Methods Cross-sectional data was collected from a representative sample of 495 Rohingya refugee adults residing in camps in Bangladesh in July and August of 2018. Results Respondents reported high levels of systematic human rights violations in Myanmar, including restrictions related to expressing thoughts, meeting in groups, travel, religious practices, education, marriage, childbirth, healthcare, and more. Events experienced in Myanmar included exposure to gunfire (99%), destruction of their homes (93%), witnessing dead bodies (92%), torture (56%), forced labor (49%), sexual assault (33%), and other events. More than half (61%) of participants endorsed mental health symptom levels typically indicative of PTSD, and more than two thirds (84%) endorsed levels indicative of emotional distress (symptoms of anxiety and depression). Historic systematic human rights violations, traumatic events, and daily stressors were associated with symptoms of posttraumatic stress, as well as depression and anxiety. Respondents reported numerous stressors associated with current life in the camps in Bangladesh as well as previous stressors, such as harassment, encountered in Myanmar. Conclusions Findings underscore the impact of systematic human rights violations, targeted violence, and daily stressors on the mental health of Rohingya in Bangladesh. Those working with Rohingya should consider the role of such factors in contributing to poor mental health. This research has the potential to inform interventions targeting such elements. Future research should examine the relationships between mental health and human rights violations over time.