Assessment of aortic hemodynamics in patients with thoracoabdominal aortic aneurysm using four-dimensional magnetic resonance imaging: a cross-sectional study.

Background: Thoracoabdominal aortic aneurysms (TAAAs) are rare but complicated aortic pathologies that can result in high morbidity and mortality. The whole-aorta hemodynamic characteristics of TAAA survivors remains unknown. This study sought to obtain a comprehensive view of flow hemodynamics of the whole aorta in patients with TAAA using four-dimensional flow (4D flow) magnetic resonance imaging (MRI). Methods: This study included patients who had experienced TAAA or abdominal aortic aneurysm (AAA) and age- and sex-matched volunteers who had attended China Hospital from December 2021 to December 2022 in West. Patients with unstable ruptured aneurysm or other cardiovascular diseases were excluded. 4D-flow MRI that covered the whole aorta was acquired. Both planar parameters [(regurgitation fraction (RF), peak systolic velocity (Vmax), overall wall shear stress (WSS)] and segmental parameters [pulse wave velocity (PWV) and viscous energy loss (VEL)] were generated during postprocessing. The Student's t-test or Mann-Whitney test was used to compare flow dynamics among the three groups. Results: A total of 11 patients with TAAA (mean age 53.2±11.9 years; 10 males), 19 patients with AAA (mean age 58.0±11.7 years; 16 males), and 21 controls (mean age 55.4±15.0 years; 19 males) were analyzed. The patients with TAAA demonstrated a significantly higher RF and lower Vmax in the aortic arch compared to healthy controls. The whole length of the aorta in patients with TAAA was characterized by lower WSS, predominantly in the planes of pulmonary artery bifurcation and the middle infrarenal planes (all P values <0.001). As for segmental hemodynamics, compared to controls, patients with TAAA had a significantly higher PWV in the thoracic aorta (TAAA: median 11.41 m/s, IQR 9.56-14.32 m/s; control: median 7.21 m/s, IQR 5.57-7.79 m/s; P<0.001) as did those with AAA (AAA: median 8.75 m/s, IQR 7.35-10.75 m/s; control: median 7.21 m/s, IQR 5.57-7.79 m/s; P=0.024). Moreover, a greater VEL was observed in the whole aorta and abdominal aorta in patients with TAAA. Conclusions: Patients with TAAA exhibited a stiffer aortic wall with a lower WSS and a greater VEL for the whole aorta, which was accompanied by a higher RF and lower peak velocity in the dilated portion of the aorta.

The necessity for popularizing varicella-zoster virus vaccine programs worldwide: An age-period-cohort analysis for the Global Burden of Disease study 2019.

BACKGROUND: Varicella-zoster virus (VZV) causes varicella and herpes zoster (VHZ), which is endemic worldwide. Although infection with VZV represents a considerable health threat, the global, regional and national burden of VZV infection, especially the probable relationship between VZV vaccines and the epidemiology of VZV infection, is poorly known. We sought to estimate the global spatial patterns and temporal trends of VHZ burden in 204 countries and territories from 1990 to 2019. METHODS: Numbers and age-standardized rates (ASR) of VHZ incidence, and disability-adjusted life years (DALYs) were estimated using data from the Global Burden of Diseases Study (GBD) 2019. Spatiotemporal trends in ASR were evaluated by estimated annual percentage change (EAPC). RESULTS: Worldwide, in 2019, there were approximately 84.0 million incidence and 0.9 million DALYs due to VHZ. The corresponding ASIR (age-standardized incidence rate) and ASDR (age-standardized DALY rate) drastically decreased in children (aged <20 years old), while the ASIR and ASDR of VHZ significantly increased in middle- and old-aged adults (aged >50 years old), with highest ASIR and ASDR in the High-income Asia Pacific and Western Sub-Saharan Africa, respectively. From 1990-2019, the corresponding EAPC in ASIR were 0.03 (95% uncertainty interval [UI]: 0.02-0.04). Whereas the global EAPC in ASDR decreased in all regions (-1.59, 95% UI: -1.64 to -1.55), expect for Australasia (0.46, [0.05, 0.88]). Notably, in 2019, age-specific rates of VHZ DALYs presented a rapid growth trend after 70 years old. CONCLUSION: The spatiotemporal trends of VHZ were heterogeneous across countries from 1990 to 2019. The spatiotemporal trend in ASIR is highest in the High sociodemographic index (SDI) region, however the EAPC in ASDR is lowest, in part probably due to VHZ vaccination. Therefore, reducing morbidity and burden strategies such as vaccines programs for the prevention of VHZ should be promoted in those regions with high growth incidence and/or burden, especially for the population after 70 years old.

Accurate Proteoform Identification and Quantitation Using pTop 2.0.

The remarkable advancement of top-down proteomics in the past decade is driven by the technological development in separation, mass spectrometry (MS) instrumentation, novel fragmentation, and bioinformatics. However, the accurate identification and quantification of proteoforms, all clearly-defined molecular forms of protein products from a single gene, remain a challenging computational task. This is in part due to the complicated mass spectra from intact proteoforms when compared to those from the digested peptides. Herein, pTop 2.0 is developed to fill in the gap between the large-scale complex top-down MS data and the shortage of high-accuracy bioinformatic tools. Compared with pTop 1.0, the first version, pTop 2.0 concentrates mainly on the identification of the proteoforms with unexpected modifications or a terminal truncation. The quantitation based on isotopic labeling is also a new function, which can be carried out by the convenient and user-friendly "one-key operation," integrated together with the qualitative identifications. The accuracy and running speed of pTop 2.0 is significantly improved on the test data sets. This chapter will introduce the main features, step-by-step running operations, and algorithmic developments of pTop 2.0 in order to push the identification and quantitation of intact proteoforms to a higher-accuracy level in top-down proteomics.

Assessment of the Novel, Practical, and Prognosis-Relevant TNM Staging System for Stage I-III Cutaneous Melanoma.

Background: The clinical TNM staging system does not differ between the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging manual. A more practical TNM staging system for patients with stage I-III cutaneous melanoma are needed. Methods: Data were accessed from the Surveillance, Epidemiology, and End Results (SEER) open database. We divided the patients into 32 groups based on the T and N categories. The Kaplan-Meier survival curves and treatment guidelines were used to proposed a new TNM staging system. Cox proportional hazards model and 1000-person-years were used to verify accuracy. Results: This retrospective study included 68 861 patients from 2010 to 2015. The new proposed staging system was as follows: stage IA, T1aN0M0; stage IB, T1b/T2aN0M0; stage IIA, T3-4aN0M0 and T2bN0M0; stage IIB, T1-4aN1-2M0 and T3-4bN0M0; and stage III, T1-4aN3M0 and T1-4bN1-3M0. Hazard ratios for the new stages IB, IIA, IIB, and III, with stage IA as reference, were 4.311 (95% confidence interval [CI]: 3.217-5.778), 8.993 (95% CI: 6.637-12.186), 13.179 (95% CI: 9.435-18.407), and 20.693 (95% CI: 13.655-31.356), respectively (all p-values < 0.001). Cancer-specific mortality rates per 1000-person-years were 0.812 (95% CI: 0.674-0.978), 6.612 (95% CI: 5.936-7.364), 22.228 (95% CI: 20.128-24.547), 50.863 (95% CI: 47.472-54.496) and 120.318 (95% CI: 112.596-128.570) for stages IA, IB, IIA, IIB and III, respectively. Conclusion: We developed a more practical and prognosis-relevant staging system than that of the 8th edition AJCC manual for patients with stage I-III cutaneous melanoma. Treatments using this new model would improve the quality of life and survival rates of patients with melanoma.

Water resource use and driving forces analysis for crop production in China coupling irrigation and water footprint paradigms.

The crop water relationship quantification is conducive to decision-making for regional food safety and resource conservation. However, irrigation water and crop water footprint (CWF) was observed separately in previous studies, which leads to incomplete evaluation of water resource occupation in agricultural system. The crop water resource use (WRU), combining WF and irrigation water accounting, in 31 provinces of China from 1999 to 2018 was estimated in current paper. The driving forces of WRU were analyzed using the logarithmic mean divisia index (LMDI) model, based on its spatial and temporal patterns demonstration. The results showed that national WRU increased from 1051.6 Gm3 in 1999 to 1676.4 Gm3 in 2018, with an average annual growth rate of 2.48%. The provinces with high WRU were mainly distributed in North China and Northeast China. Hebei, Shandong, and Henan jointly contributed 28.9% of the national WRU. In addition, economic level was the largest contributor to promote the growth of WRU, and water use intensity was the most important contributor to inhibit the growth of WRU. Economic level, resource endowment, and population size had a promoting effect on WRU in Northeast, Northwest, North China, and Southeast provinces, while water use intensity, irrigation technique, and urbanization degree showed inhibitory effect in Northeast, Northwest, and Southwest provinces. It is meaningful to combine water footprint and irrigation water use for agricultural water management and conservation. The arid North China Plain should adopt water-saving irrigation and rainwater recycling technologies to control WRU, and the Northeast granary should reduce WRU by strengthening water pollution prevention and improving water resources scheduling to ensure food security and sustainable use of water resources.

Surgical Disparities of Parathyroid Carcinoma: Long-Term Outcomes and Deep Excavation Based on a Large Database.

PURPOSE: Parathyroid carcinoma (PC) is an uncommon endocrine disease, and surgery is considered the only potential cure. PC does not have a mature staging system because of the small number of PC patients. Our aim is to further investigate the prognostic factors associated with PC and explore the optimal extent of resection for PC patients. METHODS: Univariate and multivariate Cox regression analyses were conducted to explore the influence of relevant factors on cancer-specific survival (CSS) and overall survival (OS). Survival curves were generated using the Kaplan-Meier method and analyzed using the log-rank test. The mortality rates per 1,000 person-years were calculated to evaluate patients' follow-up data. We also performed subgroup analysis based on the extent of resection. RESULTS: The extent of resection was related to both CSS and OS, whereas race and extent of disease had a significant positive correlation with OS (all P < 0.05). Patients who underwent parathyroidectomy had remarkably better CSS and OS than patients who did not undergo definitive treatment. CONCLUSION: The extent of resection is related to CSS and OS in patients with PC. No significant difference in prognosis was observed between patients who underwent parathyroidectomy and those who underwent en bloc resection, which may provide useful parameters for the treatment of PC.

Global, regional and national incidence, mortality and disability-adjusted life-years of skin cancers and trend analysis from 1990 to 2019: An analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Information about global and local epidemiology and trends of skin cancers is limited, which increases the difficulty of cutaneous cancer control. METHODS: To estimate the global spatial patterns and temporal trends of skin cancer burden. Based on the GBD 2019, we collected and analyzed numbers and age-standardized rates (ASR) of skin cancer incidence, disability-adjusted life years (DALYs) and mortality (ASIR, ASDR, and ASMR) in 204 countries from 1990 through 2019 were estimated by age, sex, subtype (malignant skin melanoma [MSM], squamous-cell carcinoma [SCC], and basal-cell carcinoma [BCC]), Socio-demographic Index (SDI), region, and country. Temporal trends in ASR were also analyzed using estimated annual percentage change. RESULTS: Globally, in 2019, there were 4.0 million BCC, 2.4 million SCC, and 0.3 million MSM. There were approximately 62.8 thousand deaths and 1.7 million DALYs due to MSM, and 56.1 thousand deaths and 1.2 million DALYs were attributed to SCC, respectively. The men had higher ASR of skin cancer burden than women. The age-specific rates of global skin cancer burden were higher in the older adults, increasing trends observed from 55 years old. Geographically, the numbers and ASR of skin cancers varied greatly across countries, with the largest burden of ASIR in high SDI regions. However, an unexpected increase was observed in some regions from 1990 to 2019, such as East Asia, and Sub-Saharan Africa. Although there was a slight decrease of the ASMR and ASDR, the global ASIR of MSM dramatically increased, 1990-2019. Also, there was a remarkable increase in ASR of BCC and SCC burden. CONCLUSIONS: Skin cancer remains a major global public health threat. Reducing morbidity and mortality strategies such as primary and secondary prevention should be reconsidered, especially in the most prevalent and unexpected increased regions, especially for those areas with the greatest proportions of their population over age 55.

Anterograde Neuronal Circuit Tracers Derived from Herpes Simplex Virus 1: Development, Application, and Perspectives.

Herpes simplex virus type 1 (HSV-1) has great potential to be applied as a viral tool for gene delivery or oncolysis. The broad infection tropism of HSV-1 makes it a suitable tool for targeting many different cell types, and its 150 kb double-stranded DNA genome provides great capacity for exogenous genes. Moreover, the features of neuron infection and neuron-to-neuron spread also offer special value to neuroscience. HSV-1 strain H129, with its predominant anterograde transneuronal transmission, represents one of the most promising anterograde neuronal circuit tracers to map output neuronal pathways. Decades of development have greatly expanded the H129-derived anterograde tracing toolbox, including polysynaptic and monosynaptic tracers with various fluorescent protein labeling. These tracers have been applied to neuroanatomical studies, and have contributed to revealing multiple important neuronal circuits. However, current H129-derived tracers retain intrinsic drawbacks that limit their broad application, such as yet-to-be improved labeling intensity, potential nonspecific retrograde labeling, and high toxicity. The biological complexity of HSV-1 and its insufficiently characterized virological properties have caused difficulties in its improvement and optimization as a viral tool. In this review, we focus on the current H129-derived viral tracers and highlight strategies in which future technological development can advance its use as a tool.

Assessment of Talaromyces Marneffei Infection of the Intestine in Three Patients and a Systematic Review of Case Reports.

BACKGROUND: Hematogenous dissemination of Talaromyces marneffei can result in multiorgan involvement (skin, lung, and reticuloendothelial system involvement); however, few studies have reported intestinal T marneffei infections. We investigated clinical features, management, and patient outcomes concerning Talaromyces-related intestinal infections. METHODS: Patients with Talaromycosis between August 2012 and April 2019 at The First Affiliated Hospital of Guangxi Medical University, China, were retrospectively analyzed. Patients presenting with intestinal Talaromycosis and endoscopy-confirmed diagnoses were investigated. We also undertook a systematic review of the relevant English and Chinese literature. RESULTS: Of 175 patients diagnosed with Talaromycosis, 33 presented with gastrointestinal symptoms, and 31 underwent stool cultures, 1 of which tested positive. Three patients had gastrointestinal symptoms and negative stool cultures, and endoscopic tissue biopsy confirmed a pathological diagnosis. A systematic review of 14 reports on human Talaromycosis identified an additional 16 patients. Fever, weight loss, and anemia were the most common symptoms, along with abdominal pain, diarrhea, and bloody stools. Abdominal computed tomography showed intestinal wall edema and thickening and/or abdominal lymphadenopathy. Endoscopy showed erosion, hyperemia, edema, and multiple intestinal mucosal ulcers. Of the 19 patients, 16 received antifungal therapy, 14 of whom recovered and 2 died. Three patients received no therapy and died. CONCLUSIONS: Gastrointestinal disseminated Talaromycosis is not rare and can affect the stomach, duodenum, and colon, and may involve the entire digestive tract. Colon is the most common site. Endoscopy is needed for patients presenting with gastrointestinal symptoms in T marneffei-infected endemic areas. Systemic application of effective antifungal therapy can improve the prognosis.

Trends in prevalence and incidence of scabies from 1990 to 2017: findings from the global Burden of disease study 2017.

Scabies remains a significant public health concern globally, affecting people of all ages, races, and socioeconomic groups. The epidemic characteristics of scabies are yet unravelled, especially in high-income countries and elderly population. In this study, we sought to investigate incidence and prevalence and their trends of scabies worldwide from 1990 to 2017 via the Global Burden of Disease (GBD) Study 2017. The prevalence and incidence of scabies tend to a moderate increase after age 70. The annual percentage change in ASR of scabies prevalence and incidence increased in high SDI countries and High-income North America. Current prevention strategies should be reoriented, and much more targeted strategies should be established in some populations to forestall the increase in scabies.

2D/3D CMR tissue tracking versus CMR tagging in the assessment of spontaneous T2DM rhesus monkeys with isolated diastolic dysfunction.

BACKGROUND: Spontaneous T2DM in rhesus monkeys manifests as isolated diastolic dysfunction in the early stage of diabetic cardiomyopathy, similar to humans. Myocardial deformation measurements have emerged as a superior way to measure left ventricular (LV) function in the early stage of cardiac dysfunction, making it possible to further evaluate early-stage LV dysfunction in spontaneous T2DM rhesus monkeys. METHODS: Spontaneous T2DM rhesus monkeys with isolated diastolic dysfunction (T2DM-DD, n = 10) and corresponding nondiabetic healthy animals (ND, n = 9) were prospectively scanned for a CMR study. Circumferential and longitudinal peak systolic strain (Ecc, Ell), time to peak strain (tEcc, tEll) and peak diastolic strain rate (CSR, LSR) obtained from 2D/3D CMR-TT were compared with those obtained from CMR tagging separately. In addition, all CMR imaging protocols were performed twice in 9 ND animals to assess test-retest reproducibility. RESULTS: Compared with the ND group, the T2DM-DD monkeys demonstrated significantly impaired LV Ecc (- 10.63 ± 3.23 vs - 14.18 ± 3.19, p < 0.05), CSR (65.50 ± 14.48 vs 65.50 ± 14.48, p < 0.01), Ell (- 9.11 ± 2.59 vs - 14.17 ± 1.68, p < 0.05), and LSR (59.43 ± 19.17 vs 108.46 ± 22.33, p < 0.01) with the tagging. Only Ecc (- 13.10 ± 2.47 vs - 19.03 ± 3.69, p < 0.01) and CSR (148.90 ± 31.27 vs 202.00 ± 51.88, p < 0.01) were significantly reduced with 2D CMR-TT, and only Ecc (- 13.77 ± 1.98 vs - 17.26 ± 3.78, p < 0.05) was significantly reduced with 3D CMR-TT. Moreover, 2D/3D CMR-TT-derived Ecc and CSR correlated with the corresponding tagging values collectively, with a statistically significant ICC value (p < 0.05). Test-retest repeatability analysis showed that most tagging-derived biomarkers had acceptable repeatability (p < 0.01). In addition, 2D CMR-TT-derived indicators were poorer than those derived from the tagging method but better than those obtained using the 3D method, with larger ICCs except for tEcc (p < 0.05). CONCLUSIONS: LV systolic and diastolic deformations were impaired in spontaneous T2DM rhesus monkeys previously diagnosed with isolated diastolic dysfunction by echocardiography. The 2D CMR-TT-derived Ecc and CSR were effective in the evaluation of the myocardial systolic and diastolic functions of early-diabetic cardiomyopathy, with relatively higher test-retest reproducibility and acceptable correlation with the tagging method compared with the 3D CMR-TT method.

Optimal linear combination of ARFI, transient elastography and APRI for the assessment of fibrosis in chronic hepatitis B.

BACKGROUND & AIMS: Accurate assessment of liver fibrosis in patients with chronic hepatitis B (CHB) is necessary not only to predict the long-term clinical course but also to determine an appropriate antiviral therapy scheme. Several noninvasive approaches - serum markers and elastography - have been proposed as alternatives for the histopathological analysis of liver biopsies. The aim of this study was to evaluate two ultrasound elastography methods (ARFI and TE) and one biochemical test (APRI), as well as their optimal linear combination, in the assessment of liver fibrosis in CHB. METHODS: Ninety five patients with CHB and 16 volunteers underwent ARFI, TE and APRI; and liver fibrosis was staged in the patients by a liver biopsy. An optimal linear combination of the three methods was developed, and its diagnostic performance was evaluated by a 10-fold cross-validation. RESULTS: The accuracy of the linear combination was 83.86% and 91.88% for significant fibrosis (≥F2) and cirrhosis (F4), respectively, higher than those obtained for ARFI (83.50%, 88.76%), TE (75.27%, 87.61%) and APRI (73.29% and 81.67%). The combination also increased the sensitivity and the negative predictive values for the diagnosis of significant fibrosis and cirrhosis. CONCLUSIONS: The optimal linear combination algorithm is effective for noninvasive staging of liver fibrosis in CHB. However, linear combination has its own limitations; nonlinear methods may eventually reveal even clearer diagnostic results.

Assessment of liver fibrosis: the relationship between point shear wave elastography and quantitative histological analysis.

BACKGROUND AND AIM: Traditional pathological scoring systems for liver fibrosis progression are predominantly based on the description of architectural changes with no consideration of the amount of collagen fiber deposition. Our purpose was to explore a true histological standard in accordance with the liver stiffness measured by point shear wave elastography (PSWE) in patients with chronic hepatitis B. METHODS: A total of 78 patients with liver neoplasms underwent liver stiffness measurements with PSWE as well as biochemical investigations within 3 days before partial hepatectomy. One tissue section of the liver specimens was stained with HE trichrome and evaluated traditionally with the Scheuer scoring system. The other tissue section was stained with picroSirius red and was evaluated according to the semiquantitative Chevallier et al. scoring system. In addition, this second tissue section was evaluated for the collagen proportionate area (CPA) with computer-assisted digital image analysis. The reproducibility of PSWE technology was explored through the intra-class correlation coefficient of a reliability analysis. RESULTS: The PSWE technology revealed good reproducibility in liver stiffness measurements, and the PSWE values increased with the pathological severity of liver fibrosis on both the Scheuer scoring system and the semiquantitative Chevallier et al. scoring system. PSWE values exhibited more reasonable relationships with CPA (r = 0.628, P = 0.00 < 0.05) than with the Scheuer scoring system (r = 0.473, P = 0.00 < 0.05) or the Chevallier et al. semiquantitative scoring system (r = 0.487, P = 0.00 < 0.05). CONCLUSION: CPA is a better pathological parameter than traditional semiquantitative scoring systems in accordance with liver stiffness measured by PSWE technology.

[Real-time elastography for quantitative assessment of liver fibrosis in a rat model].

OBJECTIVE: To investigate the feasibility of real-time elastography for quantitative evaluation of liver fibrosis in a rat model. METHODS: A total of 70 male Wistar rats were included in the group for dimethylnitrosamine (DMN)-induced liver injury, and 10 saline-injected rats were used as normal control. Hepatic injury was induced by a single intraperitoneal injection of DMN at a dose of 50 mg/kg of body weight. Nine or ten rats in the group with DNM injected and one or two rats in the normal control group were randomly selected and sacrificed at each of the following post-injection time: day 5, 7, 10, 14, 21, 24, and 28. And their livers were taken for pathology analysis. All the rats underwent real-time elastography before sacrificed in order to acquire area ratio of low-strain region (% AREA) and liver fibrosis index (LF index) which were compared with the stage of liver fibrosis and grade of necroinflammatory pathologically. By the different data, Spearman correlation analysis, rank-sum test or receiver operating characteristic curve was used. RESULTS: Among 58 successfully modeled rats, there were nine, 13, 14 and 12 rats of S1, S2, S3 and S4 liver fibrosis on pathology, respectively, which were with or without mild necroinflammatory. The other 10 rats were found to be S0 with severe necroinflammatory. Values of LF index and % AREA both increased with liver fibrosis stage (P less than 0.05). There was certain correlation between LF index and liver fibrosis stage (r=0.643, P=0.000), so was % AREA and liver fibrosis stage (r=0.662, P=0.000). As for LF index, Areas under the receiver operating characteristic curve (Az) was 0.943, 0.890, 0.743 and 0.821 for the diagnosis of hepatic fibrosis S1 or higher, S2 or higher, S3 or higher and S4, respectively; as for % AREA, they were 0.948, 0.883, 0.772 and 0.842, respectively. However, we found a significant difference for LF index or % AREA between S0 with and without severe inflammatory activity rats (P=0.005 and P=0.017). CONCLUSION: Real-time elastography is available for quantitative assessment of liver fibrosis in rats induced by DMN, but severe inflammatory activity can affect its accuracy.

Exploring risk factors for depression among older men residing in Macau.

AIM: To determine the prevalence of depression level of older men in Macau and identify factors that predict depression. BACKGROUND: Studies have revealed the contribution of psychosocial factors such as stress, dissatisfaction at work and stressful life events to older men and the mental health burdens pose a grave threat to their quality of life. DESIGN: A descriptive survey. METHOD: The study was conducted from July-August 2004 in six parishes in Macau; 839 older men aged 60+ completed a structured questionnaire. OUTCOME MEASURES: Predisposing characteristics, social and daily activities, health history and need/behaviours and depression level were collected. Multiple logistic regression models were used to identify factors to predict older men who will have depression. RESULTS: The prevalence rate of depression of older men was 8·6%. It showed that a history of stroke (p=0·039), insomnia (p<0·001), palpitations (p=0·014), poor social network (p=0·005) and self-perceived health status (p=0·001) and perceived low ability to meet living costs (p<0·001) were significant risk factors for depression. CONCLUSION: We should focus on older men by reducing their burden to meet living costs, improving their sleep quality and helping them to expand their social network. These should help in both prevention and recognition of the onset of depression. Those with the low social network scores could be targeted for more intensive support from the beginning. RELEVANCE TO CLINICAL PRACTICE: It is important to screen regularly for depression status among older men in the community. Attention to poor perceived health and not enough on the ability to meet living costs were needed and important to follow up.

In vivo assessment of mitochondrial toxicity of metacavir in Rhesus monkeys after three months of intravenous administration.

AIM: To explore the potential mitochondrial toxicities and their severities of intravenously administered metacavir, a nucleoside analog, in rhesus monkeys. METHODS: Totally 21 rhesus monkeys were randomly divided into 4 groups: metacavir 120 mg/kg group, metacavir 40 mg/kg group, zidovudine(AZT) 50 mg/kg group, and blank control group. Animals were killed after the completion of dosing or further observed in a 4-week recovery phase. Changes of structure of mitochondria in liver, kidney, skeletal muscles, and cardiac muscles were observed under transmission electron microscope(TEM). Changes of the activities of mitochondrial respiratory chain complexes and mitochondrial DNA were also determined. RESULTS: In metacavir 120 mg/kg group, some mitochondrial injuries were found in skeletal muscle, cardiac muscle, and liver, including that some cristae was broken and became sparse in density in the skeletal muscle, the morphology and size of mitochondria remained unchanged. Metacavir decreased the activities of respiratory chain complexes I and II and the mtDNA contents in three tissues in a dose-dependent manner; however, the extent of such decrease was lower than that in AZT 50 mg/kg group. The mitochondrial injuries in metacavir 40 mg/kg group were mild in each tissue and no obvious change in mitochondrial function was noted. On week 4 in the recovery phase, results showed that all these injuries were reversible after drug withdrawal. CONCLUSION: These results suggest that metacavir has not a high risk for potential mitochondrial-related effects in rhesus monkeys.