Extracellular vesicles (EVs) function as potent mediators of intercellular communication for many in vivo processes, contributing to both health and disease related conditions. Given their biological origins and diverse functionality from correspondingly unique “cargo” compositions, both endogenous and modified EVs are garnering attention as promising therapeutic modalities and vehicles for targeted therapeutic delivery applications. Their diversity in composition, however, has revealed a significant need for more comprehensive analytical-based characterization methods, and manufacturing processes that are consistent and scalable. In this review, we explore the dynamic landscape of EV research and development efforts, ranging from novel isolation approaches, to their analytical assessment through novel characterization techniques, and to their production by industrial-scale manufacturing process considerations. Expanding the horizon of these topics to EVs for in-human applications, we underscore the need for stringent development and adherence to Good Manufacturing Practice (GMP) guidelines. Wherein, the intricate interplay of raw materials, production in bioreactors, and isolation practices, along with analytical assessments compliant with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, in conjunction with reference standard materials, collectively pave the way for standardized and consistent GMP production processes.

Perianeurysmal cysts are a rare and poorly understood finding in patients both with treated and untreated aneurysms. While the prior literature suggests that a minority of perianeurysmal cysts develop 1-4 years following endovascular aneurysm treatment, this updated review demonstrates that nearly half of perianeurysmal cysts were diagnosed following aneurysm coiling, with the other half diagnosed concurrently with an associated aneurysm prior to treatment. 64% of perianeurysmal cysts were surgically decompressed, with a 39% rate of recurrence requiring re-operation. We report a case of a 71-year-old woman who presented with vertigo and nausea and was found to have a 3.4 cm perianeurysmal cyst 20 years after initial endovascular coiling of a ruptured giant ophthalmic aneurysm. The cyst was treated with endoscopic fenestration followed by open fenestration upon recurrence. The case represents the longest latency from initial aneurysm treatment to cyst diagnosis reported in the literature and indicates that the diagnosis of perianeurysmal cyst should remain on the differential even decades after treatment. Based on a case discussion and updated literature review, this report highlights proposed etiologies of development and management strategies for a challenging lesion.

BACKGROUND: Overweight, obesity, and cardiovascular disease risk factors are prevalent among firefighters in some developed countries. It is unclear whether physical activity and cardiopulmonary fitness reduce cardiovascular disease risk and the cardiovascular workload at work in firefighters. The present study investigated the relationship between leisure-time physical activity, cardiopulmonary fitness, cardiovascular disease risk factors, and cardiovascular workload at work in firefighters in Hong Kong. METHODS: Male firefighters (n = 387) were randomly selected from serving firefighters in Hong Kong (n = 5,370) for the assessment of cardiovascular disease risk factors (obesity, hypertension, diabetes mellitus, dyslipidemia, smoking, known cardiovascular diseases). One-third (Target Group) were randomly selected for the assessment of off-duty leisure-time physical activity using the short version of the International Physical Activity Questionnaire. Maximal oxygen uptake was assessed, as well as cardiovascular workload using heart rate monitoring for each firefighter for four "normal" 24-hour working shifts and during real-situation simulated scenarios. RESULTS: Overall, 33.9% of the firefighters had at least two cardiovascular disease risk factors. In the Target Group, firefighters who had higher leisure-time physical activity had a lower resting heart rate and a lower average working heart rate, and spent a smaller proportion of time working at a moderateintensity cardiovascular workload. Firefighters who had moderate aerobic fitness and high leisuretime physical activity had a lower peak working heart rate during the mountain rescue scenario compared with firefighters who had low leisure-time physical activities. CONCLUSION: Leisure-time physical activity conferred significant benefits during job tasks of moderate cardiovascular workload in firefighters in Hong Kong.
Cardiovascular Diseases ; Developed Countries ; Diabetes Mellitus ; Dyslipidemias ; Firefighters* ; Heart Rate ; Hong Kong ; Humans ; Hypertension ; Leisure Activities* ; Male ; Motor Activity* ; Obesity ; Overweight ; Oxygen ; Risk Factors* ; Smoke ; Smoking

BACKGROUND: Within the lateral pillar classification of the Legg-Calve-Perthes (LCP) disease, hips seem quite variable in the pattern of fragmentation as seen in radiographs. The purpose of this study was to determine: if it is possible to reliably subdivide the lateral pillar groups into femoral head fragmentation patterns, and if such a subdivision of the lateral pillar groupings is clinically useful in managing LCP disease. METHODS: Two hundred and ninety-three anteroposterior radiographs taken at the maximal fragmentation stage (189 lateral pillar B, 57 B/C border, and 47 C hips; mean bone/chronologic age at the time of first visit, 6.2/7.9 years) and at skeletal maturity (mean age, 16.6 years) were analyzed. We distinguished 3 fragmentation patterns in each pillar group based on the region of major involvement. We tested the inter- and intraobserver reliability of our classification system and analyzed the relationships between the fragmentation patterns and the Stulberg outcomes as well as other factors such as surgical treatment and age. RESULTS: Inter- and intraobserver consistency in fragmentation pattern assignments was found to be substantial to excellent. A statistically significant trend (p = 0.001) in the proportion of Stulberg III or IV outcomes in comparison with Stulberg I and II was only found for the different fragmentation patterns in our lateral pillar B patients: fragmentation patterns having mainly lateral-central necrosis led to poor outcomes. No significant association was found between fragmentation patterns and Stulberg outcomes in pillar groups B/C border and C. CONCLUSIONS: Our results are consistent with the lateral pillar classification itself. Therefore, fragmentation patterns in each lateral pillar classification did not provide clinical usefulness in the management of LCP disease.
Adolescent ; Child ; Femur Head/*radiography ; Femur Head Necrosis/classification/radiography ; Humans ; Legg-Calve-Perthes Disease/*classification/radiography ; Observer Variation ; Prognosis ; Retrospective Studies ; Young Adult

INTRODUCTIONThis study aimed to assess the outcome of percutaneous transluminal angioplasty (PTA) as the primary treatment for transplant renal artery stenosis (TxRAS).

MATERIALS AND METHODSA retrospective review of PTA of TxRAS from April 1999 to December 2008 was performed. Twenty-seven patients (17 males (M):10 females (F)) with the mean age of 49.5 years underwent PTA of TxRAS in the review period. Indications for PTA were suboptimal control of hypertension (n=12), impaired renal function (n=6) and both suboptimal control of hypertension and impaired renal function (n=9). All patients had doppler ultrasound scans prior to their PTA. In addition, 5 of these patients had computed tomography angiography (CTA) and another 7 had magnetic resonance angiography (MRA) evaluation. Mean follow-up period was 57.0 months (range, 7 to 108 months).

RESULTSThe stenotic lesions were located proximal to the anastomosis (n=2), at the anastomosis (n=15), and distal to the anastomosis (n=14). Technical success rate was 96.3%. One case was complicated by extensive dissection during PTA, resulting in subsequent graft failure. The overall clinical success rate was 76.9%. Seven out of 26 patients had restenoses (26.9% of cases). These were detected at a mean of 14.3 months post angioplasty (range, 5 to 38 months). All 7 patients underwent a second PTA successfully. Three of these patients required more than 1 repeat PTA.

CONCLUSIONPTA is safe and effective in the management of symptomatic TxRAS and should be the primary treatment of choice. Close surveillance for restenosis is required and when diagnosed, re-angioplasty can be performed.

Adult ; Angioplasty ; Female ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; Postoperative Complications ; surgery ; Renal Artery Obstruction ; surgery ; Retrospective Studies ; Time Factors

Anticoagulants ; therapeutic use ; Atrial Fibrillation ; etiology ; genetics ; therapy ; Catheter Ablation ; Humans ; Thromboembolism ; prevention & control ; United States

The evolutionarily conserved RNA Polymerase II Rpb4/7 sub-complex has been thoroughly studied in yeast and impacts gene expression at multiple levels including transcription, mRNA processing and decay. In addition Rpb4/7 exerts differential effects on gene expression in yeast and Rpb4 is not obligatory for yeast (S. cerevisiae) survival. Specialised roles for human (hs) Rpb4/7 have not been extensively described and we have probed this question by depleting hsRpb4/7 in established human cell lines using RNA interference. We find that Rpb4/7 protein levels are inter-dependent and accordingly, the functional effects of depleting either protein are co-incident. hsRpb4/7 exhibits gene-specific effects and cells initially remain viable upon hsRpb4/7 depletion. However prolonged hsRpb4/7 depletion is cytotoxic in the range of cell lines tested. Protracted cell death occurs by an unknown mechanism and in some cases is accompanied by a pronounced elongated cell morphology. In conclusion we provide evidence for a gene-specific role of hsRpb4/7 in human cell viability.
Cell Line ; Cell Nucleus ; metabolism ; Cell Survival ; drug effects ; Gene Expression Profiling ; HeLa Cells ; Humans ; RNA Interference ; RNA Polymerase II ; antagonists & inhibitors ; genetics ; metabolism ; RNA, Small Interfering ; pharmacology

To identify the 'physiatry' in a single word is difficult. This may be due that physiatry originated from two different fields, physical medicine and rehabilitation and focuses on assisting the general improvement of functional recovery in disabled patients. In addition, physiatry has new markets to develop; health and welfare. Therefore, the identity of physiatry will change depending on how physiatrists act in these fields. We attempt to define the physiatry from several aspects.
Humans ; Physical and Rehabilitation Medicine

INTRODUCTION: Psychiatric comorbidity is common in patients with functional dyspepsia (FD) but a good screening tool for psychiatric disorders in gastrointestinal clinical practice is lacking. Aims: 1) Evaluate the performance and optimal cut-off of 12-item General Health Questionnaire (GHQ-12) as a screening tool for psychiatric disorders in FD patients; 2) Compare health-related quality of life (HRQoL) in FD patients with and without psychiatric comorbidities. METHODS: Consecutive patients fulfilling Rome III criteria for FD without medical co-morbidities and gastroesophageal reflux disease were recruited in a gastroenterology clinic. The followings were conducted at 4 weeks after index oesophagogastroduodenoscopy: self-administrated questionnaires on socio-demographics, dyspeptic symptom severity (4-point Likert scale), GHQ-12, and 36-item short-form health survey (SF-36). Psychiatric disorders were diagnosed with Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) by a trained psychiatrist, which served as reference standard. RESULTS: 55 patients underwent psychiatrist-conducted interview and questionnaire assessment. 27 (49.1%) had current psychiatric disorders as determined by SCID (anxiety disorders: 38.2%, depressive disorders: 16.4%). Receiver operating characteristic curve analysis of GHQ-12 revealed an area under curve of 0.825 (95%CI: 0.698-0.914). Cut-off of GHQ-12 at > or =3 gave a sensitivity of 63.0% (95%CI = 42.4-80.6%) and specificity of 92.9% (95%CI = 76.5%-98.9%). Subjects with co-existing psychiatric disorders scored significantly lower in multiple domains of SF-36 (mental component summary, general health, vitality and mental health). By multivariate linear regression analysis, current psychiatric morbidities (Beta = -0.396, p = 0.002) and family history of psychiatric illness (Beta = -0.299, p = 0.015) were independent risk factors for poorer mental component summary in SF-36, while dyspepsia severity was the only independent risk factor for poorer physical component summary (Beta = -0.332, p = 0.027). CONCLUSIONS: Concomitant psychiatric disorders adversely affect HRQoL in FD patients. The use of GHQ-12 as a reliable screening tool for psychiatric disorders allows early intervention and may improve clinical outcomes of these patients.
Area Under Curve ; Axis, Cervical Vertebra ; Comorbidity ; Diagnostic and Statistical Manual of Mental Disorders ; Dyspepsia ; Early Intervention (Education) ; Gastroenterology ; Gastroesophageal Reflux ; Health Surveys ; Humans ; Linear Models ; Mass Screening ; Mental Disorders ; Psychiatry ; Quality of Life ; Surveys and Questionnaires ; Risk Factors ; ROC Curve ; Rome ; Sensitivity and Specificity

INTRODUCTIONThe Framingham Risk Score (FRS) is a well-validated epidemiologic tool used to assess the risk for a fi rst cardiac event. Because young patients presenting with a fi rst myocardial infarction (MI) tend to have less significant risk profiles compared with older patients, we hypothesized that FRS may underestimate cardiac risk in these patients.

MATERIALS AND METHODSWe studied 1267 patients between January 2002 and November 2007 presenting with a fi rst MI. Patients with pre-existing diabetes mellitus and vascular disease were excluded. FRS was calculated for each patient. Patients were divided based on their age: group A (<40 years), group B (40 to 64 years) and group C (> or =65 years).

RESULTSThe mean age was 54.7 +/- 11 years, 88.4% of the patients were males. Younger patients were more likely to be assigned with lower scores. Based on FRS, 63.0%, 29.3% and 14.2% of group A, B and C patients were classified as low risk (10-year risk for cardiac events<10%) respectively, P <0.001. The sensitivity of FRS in identifying at least intermediate risk subjects (10-year risk for cardiac events >10%) was 37.0% in group A vs 85.8% in group C (P <0.001). The incidence of newly diagnosed diabetes mellitus was higher in younger patients (12.0% vs 13.2% vs 7.1 % in groups A, B and C respectively, P = 0.027).

CONCLUSIONSFRS inadequately predicts cardiac risk in young patients presenting with a fi rst MI. This could be because a significant proportion of these young patients have undiagnosed diabetes mellitus, a coronary artery disease risk equivalent.

Adult ; Age Factors ; Aged ; Algorithms ; Diabetes Complications ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; complications ; diagnosis ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Sex Factors